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AMERICAN JOINT COMMITTEE ON CANCER (AJCC)

AMERICAN JOINT COMMITTEE ON CANCER
AJCC
CANCER STAGING
AT L A S
EDITORS
FREDERICK L. GREENE, m.d.
Chair, Department of General Surgery
Carolinas Medical Center
Charlotte, North Carolina
CAROLYN C. COMPTON, m.d., ph.d
Director of Biorepositories and Biospeciment Research
National Cancer Institute
Bethesda, Maryland
APRIL G. FRITZ, c .t .r., r.h.i.t.
Division of Cancer Control and Population Sciences
National Cancer Institute
Bethesda, Maryland
JATIN P. SHAH, m.d.
Chief, Head and Neck Service
Memorial Sloan-Kettering Cancer Center
N e w  Yo r k , N e w  Yo r k
DAVID P. WINCHESTER, m.d.
Professor and Chair, Department of Surgery
Evanston Northwestern Healthcare
Evanston, Illinois
AJCC
CANCER STAGING
AT L A S
AMERICAN JOINT COMMITTEE ON CANCER
Executive Office
633 North Saint Clair Street
Chicago, Illinois 60611
FOUNDING ORGANIZATIONS
American Cancer Society
American College of Physicians
American College of Radiology
American College of Surgeons
College of American Pathologists
National Cancer Institute
SPONSORING ORGANIZATIONS
American Cancer Society
American College of Surgeons
American Society of Clinical Oncology
Centers for Disease Control and Prevention
LIAISON ORGANIZATIONS
American Urological Association
Association of American Cancer Institutes
National Cancer Registrars Association
North American Association of Central Cancer Registries
American Society of Colon and Rectal Surgeons
Society of Gynecologic Oncologists
Society of Urologic Oncology
American Joint Committee on Cancer
Executive Office
633 North Saint Clair Street
Chicago, IL 60611, USA
Editors:
Frederick L. Greene, M.D. Carolyn C. Compton, M.D., PH.D.
April G. Fritz, C.T.R., R.H.I.T. Jatin P. Shan, M.D.
David P. Winchester, M.D.
Illustrator: Alice Y. Chen
This atlas was prepared and published through the support of the American Cancer Society, the Amer-ican College of Surgeons, the American Society of Clinical Oncology, the Centers for Disease Control
and Prevention, and the International Union Against Cancer.
Library of Congress Control Number: 2005932559
ISBN-10: 0-387-29014-1
ISBN-13: 978-0387-29014-0
Printed on acid-free paper.
© 2006 Springer Science+Business Media, Inc.
All rights reserved. This work may not be translated or copied in whole or in part without the
written permission of the publisher (Springer Science+Business Media, Inc., 233 Spring Street,
New York, NY 10013, USA), except for brief excerpts in connection with reviews or scholarly
analysis. Use in connection with any form of information storage and retrieval, electronic
adaptation, computer software, or by similar or dissimilar methodology now known or hereafter
developed is forbidden.
The use in this publication of trade names, trademarks, service marks, and similar terms, even if
they are not identified as such, is not to be taken as an expression of opinion as to whether or
not they are subject to proprietary rights.
While the advice and information in this book are believed to be true and accurate at the date of
going to press, neither the authors nor the editors nor the publisher can accept any legal respon-sibility for any errors or omissions that may be made. The publisher makes no warranty, express
or implied, with respect to the material contained herein.
Printed in the United States of America. (BS/EB)
987654321
springeronline.com
American Joint Committee on Cancer • 2006 v
Preface
This first edition of the AJCC Cancer Staging Atlas has been created as a com-pendium to the  AJCC Cancer Staging Manual and Handbook which have
now been developed through six editions and which continue to promulgate
the importance of anatomical and pathological staging in the management of
cancer. This Atlas has been viewed as a companion to illustrate the TNM clas-sifications of all the regions included under the head and neck, digestive, tho-racic, musculoskeletal, soft tissue, breast, genital, urinary and gynecologic sites.
This monograph has been fully illustrated to give meaningful visualization to
the TNM classifications and stage groupings and will serve as a useful reference
for the clinician and patient alike.
Since there have been changes in staging strategies in the 6th Edition of the
AJCC Cancer Staging Manual, the differences between the 5th edition and 6th
edition have been included throughout the Atlas. This will provide a meaning-ful comparison for the experienced clinician as well as serve as a teaching refer-ence for the student and trainee.
The 432 outstanding illustrations have been developed exclusively for the
AJCC Cancer Staging Atlas by Alice Y. Chen, our exceptional medical illustrator.
Every illustration provides detailed and thorough anatomic depictions to clarify
critical structures and to allow the reader to instantly visualize the progressive
extent of malignant disease. Appropriate labeling has been incorporated to iden-tify significant anatomic structures. A significant number (28%) of the illustra-tions are devoted solely to the representation of the TNM changes which are
new in the AJCC Cancer Staging Manual, 6th Edition. Throughout all anatomic
sites, the newly developed illustrations reflect concepts that are more completely
discussed in the AJCC Cancer Staging Manual and Handbook.
The AJCC Cancer Staging Atlas is an official publication of the American
Joint Committee on Cancer and reinforces the AJCC’s position as the leader in
disseminating state of the art information on TNM staging. The AJCC contin-ues to have as its mission the education of physicians, registrars and patients.
The Atlas, a portable and easily referenced representation of the AJCC mono-graphs, continues to enhance this mission. This project has been fully supported
by our publishing colleagues at Springer and especially Laura diZerega and Bill
Curtis, our longtime friends and AJCC supporters.
The editors of this most recent AJCC project wish to reinforce the concept
that TNM is a universal “language” which must be applied by all clinicians caring
for the cancer patients. In order to make this language come alive, a pictorial
representation of clinical and pathological staging is necessary. We dedicate this
work to all of our patients and colleagues and hope that they too will benefit
from this illustrated resource.
Frederick L. Greene, m.d.
Carolyn C. Compton, m.d., ph .d.
April G. Fritz, c .t .r., r.h.i.t .
Jatin P. Shah, m.d.
David P. Winchester, m.d.
American Joint Committee on Cancer • 2006 vii
Contents
Preface  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v
1. Purposes and Principles of Staging  . . . . . . . . . . . . . . . . . . . . . . . 1
Part I  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
Head and Neck Sites
2. Introduction to Head and Neck Sites  . . . . . . . . . . . . . . . . . . . . . 13
3. Lip and Oral Cavity  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
4. Pharynx (Including Base of Tongue, Soft Palate,
and Uvula) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
5. Larynx  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
6. Nasal Cavity and Paranasal Sinuses  . . . . . . . . . . . . . . . . . . . . . . . 53
7. Major Salivary Glands (Parotid, Submandibular,
and Sublingual)  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61
8. Thyroid  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67
Part II  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75
Digestive System
9. Esophagus  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77
10. Stomach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89
11. Small Intestine  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101
12. Colon and Rectum  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 107
13. Anal Canal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119
14. Liver (Including Intrahepatic Bile Ducts)  . . . . . . . . . . . . . . . . . . . 127
15. Gallbladder  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133
16. Extrahepatic Bile Ducts  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139
17. Ampulla of Vater  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147
18. Exocrine Pancreas  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 155
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Part III  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 165
Thorax
19. Lung  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 167
20. Pleural Mesothelioma  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 177
Part IV  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 183
Musculoskeletal Sites
21. Bone  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 185
22. Soft Tissue Sarcoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 191
Part V . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 195
Skin
23. Carcinoma of the Skin (Excluding Eyelid, Vulva,
and Penis)  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 197
24. Melanoma of the Skin  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 207
Part VI  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 217
Breast
25. Breast . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 219
Part VII  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 235
Gynecologic Sites
26. Vulva  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 237
27. Vagina  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 243
28. Cervix Uteri . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 249
29. Corpus Uteri  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 259
30. Ovary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 265
31. Fallopian Tube  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 273
32. Gestational Trophoblastic Tumors  . . . . . . . . . . . . . . . . . . . . . . . . 279
Part VIII  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 285
Genitourinary Sites
33. Penis  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 287
34. Prostate  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 293
American Joint Committee on Cancer • 2006 ix
35. Testis  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 303
36. Kidney  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 315
37. Renal Pelvis and Ureter  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 323
38. Urinary Bladder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 329
39. Urethra  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 337
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 347
American Joint Committee on Cancer • 2006 1
1
Purposes and Principles of Staging
PHILOSOPHY OF CLASSIFICATION AND STAGING
BY THE TNM SYSTEM
A clinically useful classification scheme for cancer must encompass the attrib-utes of the tumor that define its behavior. The American Joint Committee on
Cancer (AJCC) classification is based on the premise that cancers of the same
anatomic site and histology share similar patterns of growth and similar
outcomes.
As the size of the untreated primary cancer (T) increases, regional lymph
node involvement (N) and/or distant metastasis (M) become more frequent. A
simple classification scheme, which can be incorporated into a form for staging
and can be universally applied, is the goal of the TNM system as proposed by
the AJCC. This classification is identical to that of the  International Union
Against Cancer (UICC).
The three significant events in the life history of a cancer—local tumor
growth (T), spread to regional lymph nodes (N), and metastasis (M)—are used
as they appear (or do not appear) on clinical examination, before definitive
therapy begins, to indicate the anatomic extent of the cancer. This shorthand
method of indicating the extent of disease (TNM) at a particular designated
time is an expression of the stage of the cancer at that time in its progression.
Spread to regional lymph nodes and/or distant metastasis occur before they
are discernible by clinical examination. Thus, examination during the surgical
procedure and histologic examination of the surgically removed tissues may
identify significant additional indicators of the prognosis of the patient (T, N,
and M) as different from what could be discerned clinically before therapy.
Because this is the pathologic (pTNM) classification and stage grouping (based
on examination of a surgically resected specimen with sufficient tissue to eval-uate the highest T, N, or M classification), it is recorded in addition to the clin-ical classification. It does not replace the clinical classification. Both should be
maintained in the patient’s permanent medical record. The clinical stage is used
as a guide to the selection of primary therapy. The pathologic stage can be used
as a guide to the need for adjuvant therapy, to estimation of prognosis, and to
reporting end results.
Therapeutic procedures, even if not curative, may alter the course and life
history of a cancer patient. Although cancers that recur after therapy may be
staged with the same criteria that are used in pretreatment clinical staging, the
significance of these criteria may not be the same. Hence, the “restage” classifi-cation of recurrent cancer (rTNM) is considered separately for therapeutic guid-ance, estimation of prognosis, and end-results reporting at that time in the
patient’s clinical course.
The significance of the criteria for defining anatomic extent of disease
differs for tumors at different anatomic sites and of different histologic types.
Therefore, the criteria for T, N, and M must be defined for tumors of each
anatomic site to attain validity. With certain types of tumors, such as Hodgkin’s
disease and lymphomas, a different system for designating the extent of the
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disease and its prognosis, and for classifying its stage grouping, is necessary to
achieve validity. In these exceptional circumstances, other symbols or descrip-tive criteria are used in place of T, N, and M.
The combination of the T, N, and M classifications into stage groupings is
thus a method of designating the anatomic extent of a cancer and is related to
the natural history of the particular type of cancer. It is intended to provide a
means by which this information can readily be communicated to others, to
assist in therapeutic decisions, and to help estimate prognosis. Ultimately, it pro-vides a mechanism for comparing similar groups of patients when evaluating
different potential therapies.
For most cancer sites, the staging recommendations in this atlas are con-cerned only with the anatomic extent of disease, but in several instances, histo-logic grade (soft-tissue sarcoma) and age (thyroid carcinoma) are factors that
significantly influence prognosis and must be considered. In the future, biologic
markers or genetic mutations may have to be included along with those of
anatomic extent in classifying cancer, but at present they are supplements to,
and not necessarily components of, the TNM stage based on anatomic extent of
the cancer.
In addition to anatomic extent, the histologic type and histologic grade of
the tumor may be important prognostic determinants in the classification for
staging. These factors are also important variables affecting choices of treatment.
For sarcomas, the tumor grade may prove to be the most important variable.
Philosophy of Changes. The introduction of new types of therapeutic interven-tions or new technologies may require modification of the classification and
staging systems. These dynamic processes may alter treatment and outcomes. It
is essential to recognize the kinetics of change of staging systems. However,
changes in the staging system make it difficult to compare outcomes of current
therapy with those of past treatment. Because of this, changes to the staging
system must be undertaken with caution. In this edition, only factors validated
in multiple large studies have been incorporated into the staging system.
NOMENCLATURE OF THE MORPHOLOGY OF CANCER
Cancer therapy decisions are made after an assessment of the patient and the
tumor, using many methods that often include sophisticated technical proce-dures. For most types of cancer, the anatomic extent to which the disease has
spread is probably the most important factor determining prognosis and must
be given prime consideration in evaluating and comparing different therapeu-tic regimens.
Staging classifications are based on documentation of the anatomic extent
of disease, and their design requires a thorough knowledge of the natural history
of each type of cancer. Such knowledge has been and continues to be derived
primarily from morphologic studies, which also provide us with the definitions
and classifications of tumor types.
An accurate histologic diagnosis, therefore, is an essential element in a
meaningful evaluation of the tumor. In certain types of cancer, biochemical,
molecular, genetic, or immunologic measurements of normal or abnormal cel-lular function have become important elements in classifying tumors precisely.
Increasingly, definitions and classifications should include function as a com-
American Joint Committee on Cancer • 2006 3
ponent of the pathologist’s anatomic diagnosis. One may also anticipate that
special techniques such as immunohistochemistry, cytogenetics, and molecular
markers will be used more routinely for characterizing tumors and their
behavior.
The most comprehensive and best-known English-language compendium
of the macroscopic and microscopic characteristics of tumors and their associ-ated behavior is the Atlas of Tumor Pathology series, published in many volumes
by the Armed Forces Institute of Pathology in Washington, DC. These are revised
periodically and are used as a basic reference by pathologists throughout the
world.
RELATED CLASSIFICATIONS
Since 1958 the World Health Organization (WHO) has had a program aimed at
providing internationally acceptable criteria for the histologic classification of
tumors of various anatomic sites. This has resulted in the  International Histo-logical Classification of Tumours, which contains, in an illustrated 25-volume
series, definitions, descriptions, and multiple illustrations of tumor types and
proposed nomenclature.
The WHO International Classification of Diseases for Oncology  (ICD-O).
Third Edition, is a numerical coding system for neoplasms by topography and
morphology. The coded morphology nomenclature is identical to the
morphology field for neoplasms in the Systematized Nomenclature of Medicine
(SNOMED) published by the College of American Pathologists.
In the interest of promoting national and international collaboration in
cancer research, and specifically to facilitate appropriate comparison of data
among different clinical investigations, use of the  International Histological
Classification of Tumours  for classification and definition of tumor types, and
use of the ICD-O codes for storage and retrieval of data, are recommended.
BIBLIOGRAPHY
Atlas of tumor pathology, 3rd series. Washington, DC: Armed Forces Institute of
Pathology, 1991–2002.
International Union Against Cancer (UICC): prognostic factors in cancer, 2nd ed.
Gospodarowicz MK, Henson DE, Hutter RVP, O’Sullivan B, Sobin LH, Wittekind
Ch (Eds.). New York: Wiley-Liss, 2001.
International Union Against Cancer (UICC) TNM supplement: a commentary on
uniform use, 2nd ed. Wittekind Ch, Henson DE, Hutter RVP, Sobin LH (Eds.).
New York: Wiley-Liss, 2001.
World Health Organization: ICD-O International classification of diseases for
oncology, 3rd ed. Geneva: WHO, 2000.
World Health Organization: International histological classification of tumours, 2nd
ed. Berlin-Heidelberg. New York: Springer-Verlag, 1988–1997.
GENERAL RULES FOR STAGING OF CANCER
The practice of dividing cancer cases into groups according to stage arose from
the observation that survival rates were higher for cases in which the disease was
localized than for those in which the disease had extended beyond the organ or
site of origin. These groups were often referred to as “early cases” and “late cases,”
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implying some regular progression with time. Actually, the stage of disease at
the time of diagnosis may be a reflection not only of the rate of growth and
extension of the neoplasm, but also of the type of tumor and of the tumor-host
relationship.
The staging of cancer is used to analyze and compare groups of patients. It
is preferable to reach agreement on the recording of accurate information about
the anatomic extent of the disease for each site, because the precise clinical
description and histopathologic classification of malignant neoplasms may serve
a number of related objectives, such as (1) selection of primary and adjuvant
therapy, (2) estimation of prognosis, (3) assistance in evaluation of the results
of treatment, (4) facilitation of the exchange of information among treatment
centers, and (5) contribution to the continuing investigation of human cancers.
The principal purpose served by international agreement on the classifica-tion of cancer cases by anatomic extent of disease, however, is to provide a
method of conveying clinical experience to others without ambiguity.
There are many classification schemes: the clinical and pathologic anatomic
extent of disease; the reported duration of symptoms or signs; the sex and age
of the patient; and the histologic type and grade. All of these represent variables
that are known to affect or can predict the outcome of the patient. Classifica-tion by anatomic extent of disease as determined clinically and histopathologi-cally (when possible) is the classification to which the attention of the AJCC and
the UICC is primarily directed.
The clinician’s immediate task is to select the most effective course of treat-ment and estimate the prognosis. This decision and this judgment require,
among other things, an objective assessment of the anatomic extent of the
disease.
To meet these stated objectives, a system of classification is needed that (1)
has basic principles applicable to all anatomic sites regardless of treatment, and
(2) allows the clinical appraisal to be supplemented by later information derived
from surgery, histopathology, and other staging studies. The TNM system
fulfills these requirements.
GENERAL RULES OF THE TNM SYSTEM
The TNM system is an expression of the anatomic extent of disease and is based
on the assessment of three components:
T The extent of the primary tumor
N The absence or presence and extent of regional lymph node metastasis
M The absence or presence of distant metastasis
The use of numerical subsets of the TNM components indicates the pro-gressive extent of the malignant disease.
T0, T1, T2, T3, T4
N0, N1, N2, N3
M0, M1
In effect, the system is a shorthand notation for describing the clinical and
pathologic anatomic extent of a particular malignant tumor. The following
general rules apply to all sites.
American Joint Committee on Cancer • 2006 5
1. All cases should use the following time guidelines for evaluating stage:
through the first course of surgery or 4 months, whichever is longer.
2. All cases should be confirmed microscopically for TNM classification
(including clinical classification). Rare cases that do not have biopsy or
cytology of the tumor can be staged but should be analyzed separately and
should not be included in survival analyses.
3. Four classifications are described for each site:
• Clinical classification, designated cTNM or TNM
• Pathologic classification, designated pTNM
• Retreatment classification, designated rTNM
• Autopsy classification, designated aTNM
Clinical classification is based on evidence acquired before primary
treatment. Clinical assessment uses information available prior to first definitive
treatment, including but not limited to physical examination, imaging,
endoscopy, biopsy, and surgical exploration. Clinical stage is assigned prior to
any cancer-directed treatment and is not changed on the basis of subsequent
information. Clinical staging ends if a decision is made not to treat the patient.
The clinical stage is essential to selecting and evaluating primary therapy.
Pathologic classification uses the evidence acquired before treatment, sup-plemented or modified by the additional evidence acquired during and from
surgery, particularly from pathologic examination. The pathologic stage
provides additional precise data used for estimating prognosis and calculating
end results.
• The pathologic assessment of the primary tumor (pT) entails resection of
the primary tumor sufficient to evaluate the highest pT category and, with
several partial removals, may necessitate an effort at reasonable reconstruc-tion to approximate the native size prior to manipulation.
• The complete pathologic assessment of the regional lymph nodes (pN)
ideally entails removal of a sufficient number of lymph nodes to evaluate
the highest pN category.
Exception: Sentinel node assessment may be appropriate for some sites and
is clarified in chapter guidelines for those sites.*
*Note: The sentinel lymph node is the first lymph node to receive lymphatic
drainage from a primary tumor. If it contains metastatic tumor, this indicates
that other lymph nodes may contain tumor. If it does not contain metastatic
tumor, other lymph nodes are not likely to contain tumor. Occasionally there is
more than one sentinel lymph node.
• If pathologic assessment of lymph nodes reveals negative nodes but the
number of examined lymph nodes is less than the suggested number for
lymph node dissection, classify the N category as pN0.
• Isolated tumor cells (ITC) are single tumor cells or small clusters of cells
not more than 0.2 mm in greatest dimension that are usually detected by
immunohistochemistry or molecular methods. Cases with ITC in lymph
nodes or at distant sites should be classified as N0 or M0, respectively. The
same applies to cases with findings suggestive of tumor cells or their com-ponents by nonmorphologic techniques such as flow cytometry or DNA
analysis. These cases should be analyzed separately and have special record-ing rules in the specific organ site.
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• The pathologic assessment of metastases may be either clinical or patho-logic when the T and/or N categories meet the criteria for pathologic staging
(pT, pN, cM, or pM).
Pathologic classification of the extent of the primary tumor (T) and lymph
nodes (N) is essential. Pathologic staging depends on the proven anatomic extent
of disease, whether or not the primary lesion has been completely removed. If
a biopsied primary tumor technically cannot be removed, or when it is unrea-sonable to remove it, and if the highest T and N categories or the M1 category
of the tumor can be confirmed microscopically, the criteria for pathologic clas-sification and staging have been satisfied without total removal of the primary
cancer.
Retreatment classification  is assigned when further treatment (such as
chemotherapy) is planned for a caner that recurs after a disease-free interval. All
information available at the time of retreatment should be used in determining
the stage of the recurrent tumor (rTNM). Biopsy confirmation of the recurrent
cancer is useful if clinically feasible, but with pathologic proof of the primary
site, clinical evidence of distant metastases (usually by radiographic or related
methodologies) may be used.
Autopsy classification occurs when classification of a cancer by postmortem
examination is done after the death of a patient (cancer was not evident prior
to death). The classification of the stage is identified as aTNM and includes all
pathologic information obtained at the time of death.
4. Stage grouping. After the assignment of cT, cN, and cM and/or pT, pN, and
pM categories, these may be grouped into stages. Both TNM classifications
and stage groupings, once established, remain in the medical record. If there
is doubt concerning the T, N, or M classification to which a particular case
should be assigned, then the lower (less advanced) category should be
assigned. The same principle applies to the stage grouping. Carcinoma  in
situ (CIS) is an exception to the stage grouping guidelines. By definition,
CIS has not involved any structures in the primary organ that would allow
tumor cells to spread to regional nodes or distant sites. Therefore, pTis, cN0,
cM0, clinical stage group 0 is appropriate.
5. Multiple tumors. In the case of multiple, simultaneous tumors in one
organ, the tumor with the highest T category is the one selected for classi-fication and staging, and the multiplicity or the number of tumors is
indicated in parentheses: for example, T2(m) or T2(5). For simultaneous
bilateral cancers in paired organs, the tumors are classified separately as
independent tumors in different organs. In the case of tumors of the
thyroid, liver, and ovary, multiplicity is a criterion of T classification.
6. Subsets of TNM. Definitions of TNM categories and stage grouping may
be telescoped (expanded as subsets of existing classifications) for research
purposes as long as the original definitions are not changed. For instance,
any of the published T, N, or M classifications can be divided into subgroups
for testing and, if validated, may be submitted to the American Joint Com-mittee on Cancer or the TNM Process Subcommittee of the UICC to be
evaluated for inclusion in the classification system.
7. Unknown primary. In the case of a primary of unknown origin, staging
can only be based on clinical suspicion of the primary origin (e.g., T0 N1
M0).
American Joint Committee on Cancer • 2006 7
ANATOMIC REGIONS AND SITES
The sites in this classification are listed by code number of the International Clas-sification of Diseases for Oncology, Third Edition (ICD-O Third Edition, World
Health Organization, 2000).
DEFINITIONS OF TNM
Primary Tumor (T)
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
Tis Carcinoma in situ
T1, T2, T3 T4 Increasing size and/or local extent of the primary tumor
Regional Lymph Nodes (N)
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1, N2, N3 Increasing involvement of regional lymph nodes
Note: Direct extension of the primary tumor into a lymph node(s) is
classified as a lymph node metastasis.
Note: Metastasis in any lymph node other than regional is classified as a
distant metastasis.
Distant Metastasis (M)
MX Distant metastasis cannot be assessed
M0 No distant metastasis
M1 Distant metastasis
Note: For pathologic stage grouping, if sufficient tissue to evaluate the
highest T and N categories has been removed for pathologic examination, M1
may be either clinical (cM1) or pathologic (pM1). If only a metastasis has had
microscopic confirmation, the classification is pathologic (pM1) and the stage
is pathologic.
The category M1 may be further specified according to the following
notation:
Pulmonary PUL
Osseous OSS
Hepatic HEP
Brain BRA
Lymph nodes LYM
Bone marrow MAR
Pleura PLE
Peritoneum PER
Adrenals ADR
Skin SKI
Other OTH
Subdivisions of TNM. Subdivisions of some main categories are available for
those who need greater specificity (e.g., T1a, 1b or N2a, 2b as with breast and
prostate).
1
8 American Joint Committee on Cancer • 2006
HISTOLOGIC GRADE (G)
The histologic grade is a qualitative assessment of the differentiation of the
tumor expressed as the extent to which a tumor resembles the normal tissue at
that site. Grade is expressed in numerical grades of differentiation from most
differentiated (Grade 1) to least differentiated (Grade 4), e.g., squamous cell car-cinoma, moderately differentiated, Grade 2. The term  grade  is also used when
other predictive, tissue-based parameters are used for prediction, particularly
nuclear grade and mitotic count.
GX Grade cannot be assessed
G1 Well differentiated
G2 Moderately differentiated
G3 Poorly differentiated
G4 Undifferentiated
For the purpose of this atlas, Grade has been included only in those chap-ters in which it appears in the Stage Grouping: bone, soft tissue sarcoma, and
prostate.
DESCRIPTORS
For identification of special cases of TNM or pTNM classifications, the m suffix
and “y,”“r,” and “a” prefixes are used. Although they do not affect the stage group-ing, they indicate cases that require separate analysis.
m Suffix. Indicates the presence of multiple primary tumors in a single site and
is recorded in parentheses: pT(m)NM.
y Prefix. Indicates those cases in which classification is performed during or
following initial multimodality therapy. The cTNM or pTNM category is iden-tified by a “y” prefix. The ycTNM or ypTNM categorizes the extent of tumor
actually present at the time of that examination. The “y” categorization is not
an estimate of the extent of tumor prior to multimodality therapy.
r Prefix. Indicates a recurrent tumor when staged after a disease-free interval,
and is identified by the “r” prefix: rTNM. (See reclassification, r above as rTNM).
a Prefix. Designates the stage determined at autopsy: aTNM.
OTHER DESCRIPTORS
Lymphatic Vessel Invasion (L)
LX Lymphatic vessel invasion cannot be assessed
L0 No lymphatic vessel invasion
L1 Lymphatic vessel invasion
Venous Invasion (V)
VX Venous invasion cannot be assessed
V0 No venous invasion
V1 Microscopic venous invasion
V2 Macroscopic venous invasion
American Joint Committee on Cancer • 2006 9
Residual Tumor (R)
The absence or presence of residual tumor after treatment is described by the
symbol R.
TNM and pTNM describe the anatomic extent of cancer in general without
consideration of treatment. TNM and pTNM can be supplemented by the R
classification, which deals with the tumor status after treatment. It reflects the
effects of therapy, influences further therapeutic procedures, and is a strong
predictor of prognosis.
The R categories are
RX Presence of residual tumor cannot be assessed
R0 No residual tumor
R1 Microscopic residual tumor
R2 Macroscopic residual tumor
STAGE GROUPING
Classification by the TNM system achieves reasonably precise description and
recording of the anatomic extent of disease. A tumor with 4 categories of T, 3
categories of N, and 2 categories of M has 24 TNM combinations. For purposes
of tabulation and analysis, except in very large series, it is necessary to condense
these combinations into a convenient number of TNM stage groupings.
The grouping adopted ensures, as far as possible, that each stage group is
relatively homogencous with respect to survival and that the survival rates of
these stage groupings for each cancer site are distinct. Carcinoma in situ is cat-egorized Stage 0; for most sites, a case with distant metastasis is categorized Stage
IV. Stages I, II, and III indicated relatively greater anatomic extent of cancer
within the range from Stage 0 to Stage IV.
1
American Joint Committee on Cancer • 2006 13
2
Introduction to Head and Neck Sites
2
SUMMARY OF CHANGES
• Across the board for all head and neck sites, a uniform description of advanced
tumors has been recommended whereby T4 lesions are divided into T4a
(resectable) and T4b (unresectable). This will allow assignment of patients with
advanced stage disease to three categories: Stage IVA, advanced resectable disease;
Stage IVB, advanced unresectable disease; and Stage IVC, advanced distant
metastatic disease.
• In general, every effort has been made to bring the stage groupings to a relatively
uniform combination of T, N, and M categories for all sites, including paranasal
sinuses, salivary tumors, and thyroid tumors.
• No changes have been made in the N staging for any sites except that a descrip-tor has been added for nodal metastasis in the upper neck or in the lower neck,
designated by (U) and (L) respectively. This descriptor will not influence nodal
staging.
INTRODUCTION
Cancers of the head and neck may arise from any of the lining membranes of
the upper aerodigestive tract. The T classifications indicating the extent of the
primary tumor are generally similar but differ in specific details for each site
because of anatomic considerations. The N classification for cervical lymph
node metastasis is uniform for all mucosal sites except nasopharynx. The N clas-sifications for thyroid and nasopharynx are unique to those sites and are based
on tumor behavior and prognosis. The staging systems presented in this section
are all clinical staging based on the best estimate of the extent of disease before
first treatment. Imaging techniques (computed tomography [CT], magnetic res-onance imaging [MRI], and ultrasonography) may be applied and, in more
advanced tumor stages, have added to the accuracy of primary (T) and nodal
(N) staging, especially in the nasopharyngeal, paranasal sinuses, and regional
lymph nodal areas. Appropriate imaging studies should be obtained whenever
the clinical findings are uncertain. Similarly, endoscopic evaluation of the
primary tumor, when appropriate, is desirable for detailed assessment of the
primary tumor for accurate T staging. Fine-needle aspiration (FNAB) may
confirm the presence of tumor and its histopathologic nature, but it cannot rule
out the presence of tumor.
Any diagnostic information that contributes to the overall accuracy of the
pretreatment assessment should be considered in clinical staging and treatment
planning. When surgical treatment is carried out, cancer of the head and neck
can be staged (pathologic stage [pTNM]) using all information available from
clinical assessment, as well as from the pathologic study of the resected speci-men. The pathologic stage does not replace the clinical stage, which should be
reported as well.
In reviewing the staging systems, several changes in the T classifications as
well as the stage groupings are made to reflect current practices of treatment,
14 American Joint Committee on Cancer • 2006
clinical relevance, or contemporary data. Uniform T staging for oral cavity,
oropharynx, salivary, and thyroid cancers greatly simplifies the systems and will
improve compliance by clinicians. T4 tumors are subdivided into advanced
resectable (T4a) and advanced unresectable (T4b) categories. Regrouping of
Stage IV disease for all sites into advanced resectable (Stage IVA), advanced
unresectable (Stage IVB), and distant metastatic (Stage IVC) also simplifies
advanced-disease staging.
Chapters 3 through 8 present the illustrated staging classification for six
major head and neck regions: the oral cavity, the pharynx (nasopharynx,
oropharynx, and hypopharynx), the larynx, the paranasal sinuses, the salivary
glands, and the thyroid gland.
ANATOMY
Regional Lymph Nodes. The status of the regional lymph nodes in head and
neck cancer is of such prognostic importance that the cervical nodes must be
assessed for each patient and tumor. The lymph nodes may be subdivided into
specific anatomic subsites and grouped into seven levels for ease of description.
Level I: Submental
Submandibular
Level II: Upper jugular
Level III: Mid-jugular
Level IV: Lower jugular
Level V: Posterior triangle (spinal accessory and transverse cervical)
(upper, middle, and lower, corresponding to the levels that
define upper, middle, and lower jugular nodes)
Level VI: Prelaryngeal (Delphian)
Pretracheal
Paratracheal
Level VII: Upper mediastinal
Other groups: Sub-occipital
Retropharyngeal
Parapharyngeal
Buccinator (facial)
Preauricular
Periparotid and intraparotid
The location of the lymph node levels conforms to the following clinical
descriptions, which also correlate with surgical landmarks at the time of surgi-cal neck exploration (Figures 2.1, 2.2, 2.3).
Level I: Contains lymph nodes in the submental and submandibular trian-gles bounded by the anterior and posterior bellies of the digastric
muscle, and the hyoid bone inferiorly, and the body of the mandible
superiorly.
Level II: Contains lymph nodes in the upper jugular lymph nodes and
extends from the level of the skull base superiorly to the hyoid bone
inferiorly.
Level III: Contains the middle jugular lymph nodes from the hyoid bone
superiorly to the level of the lower border of the cricoid cartilage
inferiorly.
American Joint Committee on Cancer • 2006 15
2I
I
VI
II II
IV
III
V
FIGURE 2.1. Schematic diagram indicating the location of the lymph node levels
in the neck as described in the text.
Buccal
Preauricular
and intraparotid
Retroauricular
and sub-occipital
FIGURE 2.2. Location of parotid, buccal, retroauricular and occipital nodes.
Retropharyngeal
FIGURE 2.3. Location of retropharyngeal nodes.
16 American Joint Committee on Cancer • 2006
Level  IV: Contains the lower jugular lymph nodes from the level of the cricoid
cartilage superiorly to the clavicle inferiorly.
Level V: Contains the lymph nodes in the posterior triangle bounded by
the anterior border of the trapezius muscle posteriorly, the poste-rior border of the sternocleidomastoid muscle anteriorly, and
the clavicle inferiorly. For descriptive purposes, Level V may be
further subdivided into upper, middle, and lower levels correspon-ding to the superior and inferior planes that define Levels II, III,
and IV.
Level VI: Contains the lymph nodes of the anterior central compartment
from the hyoid bone superiorly to the suprasternal notch inferiorly.
On each side, the lateral boundary is formed by the medial border
of the carotid sheath.
Level VII: Contains the lymph nodes inferior to the suprasternal notch in the
superior mediastinum.
The pattern of the lymphatic drainage varies for different anatomic sites.
However, the location of the lymph node metastases has prognostic significance
in patients with squamous cell carcinoma of the head and neck. Survival is sig-nificantly worse when metastases involve lymph nodes beyond the first echelon
of lymphatic drainage and, particularly, lymph nodes in the lower region of the
neck, i.e., Level IV and Level V (supraclavicular region). Consequently, it is rec-ommended that each N staging category be recorded to show, in addition to the
established parameters, whether the nodes involved are located in the upper (U)
or lower (L) regions of the neck, depending on their location above or below
the lower border of the cricoid cartilage.
The natural history and response to treatment of cervical nodal metastases
from nasopharynx primary sites are different, in terms of their impact on prog-nosis, so they justify a different N classification scheme. Regional nodal metas-tases from well-differentiated thyroid cancer do not significantly affect the
ultimate prognosis and therefore also justify a unique staging system for thyroid
cancers.
Histopathologic examination is necessary to exclude the presence of tumor
in lymph nodes. No imaging study (as yet) can identify microscopic tumor foci
in regional nodes or distinguish between small reactive nodes and small malig-nant nodes.
When enlarged lymph nodes are detected, the actual size of the nodal
mass(es) should be measured. It is recognized that most masses over 3 cm in
diameter are not single nodes but are confluent nodes or tumor in soft tissues
of the neck. Imaging studies showing amorphous spiculated margins of involved
nodes or involvement of intranodal fat resulting in loss of normal oval to round
nodal shape strongly suggest extracapsular (extranodal) tumor spread. Patho-logic examination is necessary for documentation of tumor extent in terms of
the location or level of the lymph node(s) involved, the number of nodes that
contain metastases, and the presence or absence of extracapsular spread of
tumor.
Metastatic Sites. The most common sites of distant spread are in the lungs
and bones; hepatic and brain metastases occur less often. Mediastinal lymph
node metastases are considered distant metastases.
American Joint Committee on Cancer • 2006 17
Regional Lymph Nodes (N) (Figure 2.4)
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
*N1 Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest
dimension
*N2 Metastasis in a single ipsilateral lymph node, more than 3 cm but not
more than 6 cm in greatest dimension; or in multiple ipsilateral lymph
nodes, none more than 6 cm in greatest dimension; or in bilateral
or contralateral lymph nodes, none more than 6 cm in greatest
dimension
*N2a Metastasis in single ipsilateral lymph node more than 3 cm but not more
than 6 cm in greatest dimension
*N2b Metastasis in multiple ipsilateral lymph nodes, none more than 6 cm in
greatest dimension
*N2c Metastasis in bilateral or contralateral lymph nodes, none more than 6
cm in greatest dimension
*N3 Metastasis in a lymph node more than 6 cm in greatest dimension
*Note:  A designation of “U” or “L” may be used to indicate metastasis in the
lateral neck above the lower border of the cricoid (U) or below the lower border
of the cricoid (L).
2
N0 N1 N2a
N2b N2c N3
Ipsilateral ❤ cm Ipsilateral 3-6 cm
Bilateral or contralateral  <6 cmIpsilateral multiple <6 cm >6 cm
FIGURE 2.4. Regional lymph node (N) classification for all head and neck cancer
sites except nasopharynx and thyroid cancers.
18 American Joint Committee on Cancer • 2006
Distant Metastasis (M)
MX Distant metastasis cannot be assessed
M0 No distant metastasis
M1 Distant metastasis
American Joint Committee on Cancer • 2006 19
3
Lip and Oral Cavity
(Nonepithelial tumors such as those of lymphoid tissue, soft tissue, bone,
and cartilage are not included.)
3
SUMMARY OF CHANGES
• T4 lesions have been divided into T4a (resectable) and T4b (unresectable),
leading to the division of Stage IV into Stage IVA, Stage IVB, and Stage IVC.
C00.0 External upper lip
C00.1 External lower lip
C00.2 External lip, NOS
C00.3 Mucosa of upper lip
C00.4 Mucosa of lower lip
C00.5 Mucosa of lip, NOS
C00.6 Commissure of lip
C00.8 Overlapping lesion of
lip
C00.9 Lip, NOS
C02.0 Dorsal surface of
tongue, NOS
C02.1 Border of tongue
C02.2 Ventral surface of
tongue, NOS
C02.3 Anterior two-thirds of
tongue, NOS
C02.8 Overlapping lesion of
tongue
C02.9 Tongue, NOS
C03.0 Upper gum
C03.1 Lower gum
C03.9 Gum, NOS
C04.0 Anterior floor of the
mouth
C04.1 Lateral floor of the
mouth
C04.8 Overlapping lesion of
floor of mouth
C04.9 Floor of mouth,
NOS
C05.0 Hard palate
C05.8 Overlapping lesion of
palate
C05.9 Palate, NOS
C06.0 Cheek mucosa
C06.1 Vestibule of mouth
C06.2 Retromolar area
C06.8 Overlapping lesion of
other and unspecified
parts of mouth
C06.9 Mouth, NOS
ANATOMY
Primary Site. The oral cavity extends from the skin-vermillion junction of the
lips to the junction of the hard and soft palate above and to the line of circum-vallate papillae below (Figures 3.1, 3.2, 3.3, 3.4) and is divided into the follow-ing specific:
Sites Lip. The lip begins at the junction of the vermillion border with the skin
and includes only the vermillion surface or that portion of the lip that comes
into contact with the opposing lip. It is well defined into an upper and lower lip
joined at the commissures of the mouth.
Buccal Mucosa. This includes all the membrane lining of the inner surface of
the cheeks and lips from the line of contact of the opposing lips to the line of
attachment of mucosa to the alveolar ridge (upper and lower) and pterygo-mandibular raphe.
Lower Alveolar Ridge. This refers to the mucosa overlying the alveolar process
of the mandible which extends from the line of attachment of mucosa in the
buccal gutter to the line of free mucosa of the floor of the mouth. Posteriorly it
extends to the ascending ramus of the mandible.
Upper Alveolar Ridge. This refers to the mucosa overlying the alveolar process
of the maxilla which extends from the line of attachment of mucosa in the upper
20 American Joint Committee on Cancer • 2006
C00.0
C00.6
C00.1
FIGURE 3.1. Anatomical subsites of the lip.
C06.1
C03.0
C00.4
C05.0
C06.0
C06.2
C05.1
Oropharynx
C05.2
C06.2
C03.1C03.1
C06.1
C00.3
FIGURE 3.2. Anatomical sites and subsites of the oral cavity.
C02.0
C00.3
C02.1
C02.1
C00.4
FIGURE 3.3. Anatomical sites and subsites of the oral cavity.
American Joint Committee on Cancer • 2006 21
gingival buccal gutter to the junction of the hard palate. Its posterior margin is
the upper end of the pterygopalatine arch.
Retromolar Gingiva (Retromolar Trigone). This is the attached mucosa overly-ing the ascending ramus of the mandible from the level of the posterior surface
of the last molar tooth to the apex superiorly, adjacent to the tuberosity of the
maxilla.
Floor of the Mouth. This is a semilunar space over the myelohyoid and hyo-glossus muscles, extending from the inner surface of the lower alveolar ridge to
the undersurface of the tongue. Its posterior boundary is the base of anterior
pillar of the tonsil. It is divided into two sides by the frenulum of the tongue
and contains the ostia of the submaxillary and sublingual salivary glands.
Hard Palate. This is the semilunar area between the upper alveolar ridge and
mucous membrane covering the palatine process of the maxillary palatine
bones. It extends from the inner surface of the superior alveolar ridge to the pos-terior edge of the palatine bone.
Anterior Two-thirds of the Tongue (Oral Tongue). This is the freely mobile
portion of the tongue that extends anteriorly from the line of circumvallate
papillae to the undersurface of the tongue at the junction of the floor of the
mouth. It is composed of four areas: the tip, the lateral borders, the dorsum, and
the undersurface (nonvillous ventral surface of the tongue). The undersurface
of the tongue is considered a separate category by the World Health Organiza-tion (WHO).
Regional Lymph Nodes. Mucosal cancer of the oral cavity may spread to
regional lymph node(s). Tumors of each anatomic site have their own pre-dictable patterns of regional spread. The risk of regional metastases is generally
related to the T category and, probably more important, to the depth of infil-tration of the primary tumor. Cancer of the lip carries a low metastatic risk and
initially involves adjacent submental and submandibular nodes, then jugular
nodes. Cancers of the hard palate and alveolar ridge likewise have a low metasta-tic potential and involve buccinator, submandibular, jugular, and occasionally
retropharyngeal nodes. Other oral cancers will spread primarily to sub-3
C02.2
C04.0
FIGURE 3.4. Anatomical sites and subsites of the oral cavity.
22 American Joint Committee on Cancer • 2006
mandibular and jugular nodes and uncommonly to posterior triangle/supra-clavicular nodes. Cancer of the anterior oral tongue may spread directly to lower
jugular nodes. The closer to the midline the primary, the greater the risk of bilat-eral cervical nodal spread. Any previous treatment to the neck, surgical and/or
radiation, may alter normal lymphatic drainage patterns, resulting in unusual
distribution of regional spread of disease to the cervical lymph nodes. In general,
cervical lymph node involvement from oral cavity primary sites is predictable
and orderly, spreading from the primary to upper, then middle, and subse-quently lower cervical nodes. However, disease in the anterior oral cavity may
also spread directly to the mid-cervical lymph nodes. The risk of distant metas-tasis is more dependent on the N than on the T status of the head and neck
cancer. Midline nodes are considered ipsilateral. In addition to the components
to describe the N category, regional lymph nodes should also be described
according to the level of the neck that is involved. It is recognized that the level
of involved nodes in the neck is prognostically significant (lower is worse), as is
the presence of extracapsular extension of metastatic tumor from individual
nodes. Imaging studies showing amorphous spiculated margins of involved
nodes or involvement of internodal fat resulting in loss of normal oval-to-round
nodal shape strongly suggest extracapsular (extranodal) tumor spread; however,
pathologic examination is necessary for documentation of the extent of such
disease. No imaging study (as yet) can identify microscopic foci of cancer in
regional nodes or distinguish between small reactive nodes and small malignant
nodes (unless central radiographic inhomogeneity is present). For pN, a selec-tive neck dissection will ordinarily include six or more lymph nodes, and a
radical or modified radical neck dissection will ordinarily include 10 or more
lymph nodes. Negative pathologic examination of a lesser number of nodes still
mandates a pN0 designation.
Metastatic Sites. The lungs are the commonest site of distant metastases; skele-tal and hepatic metastases occur less often. Mediastinal lymph node metastases
are considered distant metastases.
DEFINITIONS
Primary Tumor (T)
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
Tis Carcinoma in situ
T1 Tumor 2 cm or less in greatest dimension (Figures 3.5A, B)
T2 Tumor more than 2 cm but not more than 4 cm in greatest dimension
(Figures 3.6A, B)
T3 Tumor more than 4 cm in greatest dimension (Figures 3.7A–C)
T4a (Lip) Tumor invades through cortical bone, inferior alveolar nerve, floor
of mouth, or skin of face, i.e., chin or nose(1)
(Figure 3.8)
T4a (Oral Cavity) Tumor invades through cortical bone, into deep [extrinsic]
muscle of tongue (genioglossus, hyoglossus, palatoglossus, and styloglos-sus), maxillary sinus, or skin of face (Figure 3.9)
T4b Tumor involves masticator space, pterygoid plates, or skull base and/or
encases internal carotid artery (Figure 3.10)
American Joint Committee on Cancer • 2006 23
3
T1
£2 cmA
£2 cm
T1
B
FIGURE 3.5. A. T1 is defined as a tumor 2 cm or less in greatest dimension. B. T1
is defined as a tumor 2 cm or less in greatest dimension.
T2
2-4 cm
A
FIGURE 3.6. A. T2 is defined as a tumor more than 2 cm but not more than 4 cm
in greatest dimension. B. T2 is defined as a tumor more than 2 cm but not more
than 4 cm in greatest dimension.
2-4 cm
T2
B
Regional Lymph Nodes (N) (see Figure 2.4)
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest
dimension
N2 Metastasis in a single ipsilateral lymph node, more than 3 cm but not
more than 6 cm in greatest dimension; or in multiple ipsilateral lymph
nodes, none more than 6 cm in greatest dimension; or in bilateral or con-tralateral lymph nodes, none more than 6 cm in greatest dimension
24 American Joint Committee on Cancer • 2006
T3
>4 cm
A
>4 cm
T3
B
T4 (Lip)
FIGURE 3.8. T4a (Lip) is defined as tumor invading through cortical bone, inferior
alveolar nerve, floor of mouth, or skin of face, i.e., chin or nose (as shown).(1)
T3
>4 cm
C
FIGURE 3.7. A. T3 is defined as tumor more than 4 cm in greatest dimension. B.
T3 is defined as tumor more than 4 cm in greatest dimension. C. T3 is defined as
tumor more than 4 cm in greatest dimension.
American Joint Committee on Cancer • 2006 25
N2a Metastasis in single ipsilateral lymph node more than 3 cm but not more
than 6 cm in greatest dimension
N2b Metastasis in multiple ipsilateral lymph nodes, none more than 6 cm in
greatest dimension
N2c Metastasis in bilateral or contralateral lymph nodes, none more than
6 cm in greatest dimension
N3 Metastasis in a lymph node more than 6 cm in greatest dimension
Distant Metastasis (M)
MX Distant metastasis cannot be assessed
M0 No distant metastasis
M1 Distant metastasis
3
T4a (Oral Cavity)
FIGURE 3.9. T4a (Oral Cavity) is defined as tumor invading through cortical
bone, into deep [extrinsic] muscle of tongue (genioglossus, hyoglossus,
palatoglossus, and styloglossus), maxillary sinus, or skin of face.
Pterygoid plate
Masticator space
T4b
FIGURE 3.10. T4b is defined as tumor involves masticator space, pterygoid plates
(as shown), or skull base and/or encases internal carotid artery.
26 American Joint Committee on Cancer • 2006
STAGE GROUPING
0 Tis N0 M0
IT1N0M0
II T2 N0 M0
III T3 N0 M0
T1 N1 M0
T2 N1 M0
T3 N1 M0
IVA T4a N0 M0
T4a N1 M0
T1 N2 M0
T2 N2 M0
T3 N2 M0
T4a N2 M0
IVB Any T N3 M0
T4b Any N M0
IVC Any T Any N M1
NOTE
1. Superficial erosion alone of bone/tooth socket by gingival primary is not suffi-cient to classify as T4.
American Joint Committee on Cancer • 2006 27
4
Pharynx (Including Base of Tongue, Soft Palate,
and Uvula)
(Nonepithelial tumors, such as those of lymphoid tissue, soft tissue, bone, and cartilage,
are not included.)
4
SUMMARY OF CHANGES
• For oropharynx and hypopharynx only, T4 lesions have been divided into T4a
(resectable) and T4b (unresectable), leading to the division of Stage IV into Stage
IVA, Stage IVB, and Stage IVC.
C01.9 Base of tongue,
NOS
C02.4 Lingual tonsil
C05.1 Soft palate, NOS
C05.2 Uvula
C09.0 Tonsillar fossa
C09.1 Tonsillar pillar
C09.8 Overlapping lesion
C09.9 Tonsil, NOS
C10.0 Vallecula
C10.2 Lateral wall of
oropharynx
C10.3 Posterior pharyngeal
wall
C10.4 Branchial cleft
C10.8 Overlapping lesion
C10.9 Oropharynx, NOS
C11.0 Superior wall of
nasopharynx
C11.1 Posterior wall of
nasopharynx
C11.2 Lateral wall of
nasopharynx
C11.3 Anterior wall of
nasopharynx
C11.8 Overlapping lesion
C11.9 Nasopharynx, NOS
C12.9 Pyriform sinus
C13.0 Postcricoid region
C13.1 Hypopharyngeal
aspect of aryepiglottic
fold
C13.2 Posterior wall of
hypopharnyx
C13.8 Overlapping lesion
C13.9 Hypopharnyx,
NOS
C14.0 Pharynx, NOS
C14.2 Waldeyer’s ring
C14.8 Overlapping lesion of
lip, oral cavity, and
pharynx
ANATOMY
Primary Sites and Subsites. The pharynx is divided into three regions:
nasopharynx, oropharynx, and hypopharynx (Figures 4.1, 4.2, 4.3). Each region
is further subdivided into specific sites as summarized in the following:
Nasopharynx. The nasopharynx begins anteriorly at the posterior choana and
extends along the plane of the airway to the level of the free border of the soft
palate. It includes the vault, the lateral walls (including the fossae of Rosenmuller
and the mucosa covering the torus tubaris forming the Eustachian tube orifice),
and the posterior wall. The floor is the superior surface of the soft palate. The
posterior margins of the choanal orifices and of the nasal septum are included
in the nasal fossa.
Parapharyngeal involvement denotes posterolateral infiltration of tumor
beyond the pharyngobasilar fascia. Involvement of the masticator space denotes
extension of tumor beyond the anterior surface of the lateral pterygoid muscle,
or lateral extension beyond the posterolateral wall of the maxillary antrum, and
the pterygomaxillary fissure.
Oropharynx. The oropharynx is the region in continuity of the pharynx extend-ing from the plane of the superior surface of the soft palate to the superior
surface of the hyoid bone (or floor of the vallecula). It includes the base of the
28 American Joint Committee on Cancer • 2006
tongue, the inferior (anterior) surface of the soft palate and the uvula, the
anterior and posterior tonsillar pillars, the glossotonsillar sulci, the pharyngeal
tonsils, and the lateral and posterior pharyngeal walls.
Hypopharynx. The hypopharynx is that portion of the pharynx extending from
the plane of the superior border of the hyoid bone (or floor of the vallecula) to
the plane corresponding to the lower border of the cricoid cartilage. It connects
C09.0
C09.9C09.1C01.9
C05.1
C10.2
C10.1
Nasopharynx
Oropharynx
Hypopharynx
FIGURE 4.1. Sagittal view of the face and neck depicting the subdivisions of the
pharynx as described in the text.
C01.9
C10.1
C10.3C10.3
C10.0
C09.1
C09.0
C09.9
C09.0
C09.1
FIGURE 4.2. Anatomical sites and subsites of the oropharynx.
American Joint Committee on Cancer • 2006 29
the two pyriform sinuses at the post cricoid region, thus forming the anterior
wall of the hypopharynx. The pyriform sinus extends from the pharyn-goepiglottic fold to the upper end of the esophagus at the lower border of the
cricoid cartilages. The posterior pharyngeal wall extends from the level of the
superior surface of the hyoid bone (or floor of the vallecula) to the inferior
border of the cricoid cartilage and from the apex of one pyriform sinus to the
other.
Regional Lymph Nodes. The risk of regional lymph nodal spread from
cancers of the pharynx is high. Primary nasopharyngeal tumors commonly
spread to retropharyngeal, upper jugular, and spinal accessory nodes, often bilat-erally. Oropharyngeal cancers involve upper and mid-jugular lymph nodes and
(less commonly) submental/submandibular nodes. Hypopharyngeal cancers
spread to adjacent parapharyngeal, paratracheal, and mid- and lower jugular
nodes. Bilateral lymphatic drainage is common.
In clinical evaluation, the maximum size of the nodal mass should be meas-ured. Most masses over 3 cm in diameter are not single nodes but, rather, are
confluent nodes or tumor in soft tissues of the neck. There are three categories
of clinically involved nodes for the nasopharynx, oropharynx, and hypophar-ynx: N1, N2, and N3. The use of subgroups a, b, and c is not required but is
recommended. Midline nodes are considered ipsilateral nodes. In addition to
4
Nasopharynx
C11
C11.2
C11.1C11.0
Oropharynx
C10
Hypopharynx
C13
Esophagus
C15
C11.2
C11.3
C10.3
C13.1
C12.9
C13.2
C13.0
C15.0
FIGURE 4.3. Anatomical sites and subsites of the nasopharynx, oropharynx,
hypopharynx, and esophagus.
30 American Joint Committee on Cancer • 2006
the components to describe the N category, regional lymph nodes should also
be described according to the level of the neck that is involved. The level of
involved nodes in the neck is prognostically significant (lower is worse), as is the
presence of extracapsular extension of metastatic tumor from individual nodes.
Imaging studies showing amorphous spiculated margins of involved nodes
or involvement of internodal fat resulting in loss of normal oval-to-round
nodal shape strongly suggest extracapsular (extranodal) tumor spread; however,
pathologic examination is necessary for documentation of such disease extent.
No imaging study (as yet) can identify microscopic foci of cancer in regional
nodes or distinguish between small reactive nodes and small malignant nodes
(unless central radiographic inhomogeneity is present). For pN, a selective neck
dissection will ordinarily include six or more lymph nodes, and a radical or
modified radical neck dissection will ordinarily include 10 or more lymph
nodes. Negative pathologic examination of a lesser number of nodes still man-dates a pN0 designation.
Metastatic Sites. The lungs are the commonest site of distant metastases;
skeletal and hepatic metastases occur less often. Mediastinal lymph node metas-tases are considered distant metastases.
DEFINITIONS
Primary Tumor (T)
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
Tis Carcinoma in situ
Nasopharynx
T1 Tumor confined to the nasopharynx (Figure 4.4)
T2 Tumor extends to soft tissues (Figure 4.4)
T2a Tumor extends to the oropharynx and/or nasal cavity without parapha-ryngeal extension(1)
(Figure 4.5)
T2b Any tumor with parapharyngeal extension(1)
(Figure 4.6)
T3 Tumor involves bony structures and/or paranasal sinuses (Figure 4.7)
T1 T2
FIGURE 4.4. For nasopharynx, T1 is defined as tumor confined to the
nasopharynx (left) whereas T2 extends to soft tissues.
American Joint Committee on Cancer • 2006 31
4
T2a
FIGURE 4.5. T2a is defined as tumor extending to the oropharynx and/or nasal
cavity without parapharyngeal extension.
T2b
FIGURE 4.6. T2b is defined as any nasopharynx tumor with parapharyngeal
extension.
T3
FIGURE 4.7. T3 tumors involve bony structures and/or paranasal sinuses.
32 American Joint Committee on Cancer • 2006
T4 Tumor with intracranial extension and/or involvement of cranial nerves,
infratemporal fossa, hypopharynx, orbit, or masticator space (Figures
4.8A, B)
Oropharynx
Tl Tumor 2 cm or less in greatest dimension (Figure 4.9)
T2 Tumor more than 2 cm but not more than 4 cm in greatest dimension
(Figure 4.10)
T3 Tumor more than 4 cm in greatest dimension (Figure 4.11)
T4a Tumor invades the larynx, deep/extrinsic muscle of tongue, medial ptery-goid, hard palate, or mandible (Figure 4.12)
T4b Tumor invades lateral pterygoid muscle, pterygoid plates, lateral
nasopharynx, or skull base or encases carotid artery (Figure 4.13)
Hypopharynx
T1 Tumor limited to one subsite of hypopharynx and 2 cm or less in great-est dimension (Figures 4.14A–C)
T4
Intracranial extension
A
T4
Cranial
nerves
B
FIGURE 4.8. A,B. T4 is defined as a tumor with intracranial extension (A) and/or
involvement of cranial nerves (B), infratemporal fossa, hypopharynx, orbit, or
masticator space.
4
?2 cm
T1FIGURE 4.9. T1 tumors of the oropharynx
are 2 cm or less in greatest dimension and are
confined to one subsite.
2-4 cm
T2
FIGURE 4.10. T2 tumors of the
oropharynx invade more than one
subsite or an adjacent site and measure
more than 2 cm but not more than
4 cm.
>4 cm
T3
FIGURE 4.11. T3 tumors of the
oropharynx are more than 4 cm in
greatest dimension.
34 American Joint Committee on Cancer • 2006
T4a
FIGURE 4.12. T4a tumor of the oropharynx is described as a tumor that invades
the larynx, deep/extrinsic music of tongue, medial pterygoid, hard plate, or
mandible.
T4b
Submucosal extension
to pterygoid fossa
FIGURE 4.13. T4b tumor of oropharynx showing submucosal extension to the
pterygoid fossa.
T2 Tumor invades more than one subsite of hypopharynx or an adjacent site,
or measures more than 2 cm but not more than 4 cm in greatest diame-ter without fixation of hemilarynx (Figures 4.15A–E)
T3 Tumor measures more than 4 cm in greatest dimension or with fixation
of hemilarynx (Figures 4.16A–C)
American Joint Committee on Cancer • 2006 35
4
T1
£2 cm
A
T1
£2 cmC
T1
≤2 cmB
FIGURE 4.14. A. T1 tumor of the hypopharynx with involvement of the pyriform
sinus. B. T1 tumor of the hypopharynx with involvement of the posterior wall.
C. T1 tumor of the hypopharynx with involvement of the post-cricoid area.
T2
C
T2
D
T2
E
FIGURE 4.15. A. T2 tumor of the hypopharynx with involvement of the posterior
wall of the hypopharynx. B. T2 tumor of the hypopharynx with involvement of the
post-cricoid area. C. T2 tumor of the hypopharynx with involvement of the
pyriform sinus and the aryepiglottic fold. D. T2 tumor of the hypopharynx with
involvement of the pyriform sinus and the posterior wall. E. T2 tumor of the
hypopharynx with involvement of the pyriform sinus and the post-cricoid area.
T2
2-4 cm
A
T2
2-4 cm
B
36 American Joint Committee on Cancer • 2006
T3
>4 cm
A
T3
B
T3
C
FIGURE 4.16. A. T3 tumor of the hypopharynx greater than 4 cm in diameter and
with involvement of the posterior wall. B. T3 tumor of the hypopharynx with
fixation of the hemilarynx and invasion of the pyriform sinus, aryepiglottic fold,
and posterior wall. C. T3 tumor of the hypopharynx with fixation of the
hemilarynx with invasion of the pyriform sinus and post-cricoid area.
T4a
Hyoid bone
Thyroid cartilage
Thyroid gland
A
T4a
Esophagus
B
FIGURE 4.17. A. T4a tumor of the hypopharynx with invasion of the hyoid bone,
thyroid cartilage and thyroid gland. B. T4a tumor of the hypopharynx with
invasion of the esophagus.
T4a Tumor invades thyroid/cricoid cartilage, hyoid bone, thyroid gland,
esophagus or central compartment soft tissue(2)
(Figures 4.17A, B)
T4b Tumor invades prevertebral fascia, encases carotid artery, or involves
mediastinal structures (Figure 4.18)
Regional Lymph Nodes (N)
Nasopharynx
The distribution and the prognostic impact of regional lymph node spread from
nasopharynx cancer (particularly of the undifferentiated type) are different from
those of other head and neck mucosal cancers and justify the use of a different
N classification scheme as illustrated in Figures 4.19, 4.20, and 4.21.
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
American Joint Committee on Cancer • 2006 37
4
T4b
Carotid
artery
Vertebral
body
FIGURE 4.18. T4b tumor the hypopharynx with invasion of the carotid artery and
prevertebral fascia.
N1
£6 cm
FIGURE 4.19. N1 for nasopharynx cancer is
defined as unilateral metastasis in lymph
node(s), 6 cm or less in greatest dimension,
above the supraclavicular fossa.
N2
£6 cm
FIGURE 4.20. N2 for nasopharynx cancer is
defined as bilateral metastasis in lymph
node(s), 6 cm or less in greatest dimension,
above the supraclavicular fossa.
38 American Joint Committee on Cancer • 2006
N1 Unilateral metastasis in lymph node(s), 6 cm or less in greatest dimen-sion, above the supraclavicular fossa(3)
(Figure 4.19)
N2 Bilateral metastasis in lymph node(s), 6 cm or less in greatest dimension,
above the supraclavicular fossa(3)
(Figure 4.20)
N3 Metastasis in a lymph node(s) >6 cm and/or to supraclavicular fossa
N3a Greater than 6 cm in dimension (Figure 4.21)
N3b Extension to the supraclavicular fossa(3)
(Figure 4.21)
Oropharynx and Hypopharynx (see Figure 2.4)
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest
dimension
N2 Metastasis in a single ipsilateral lymph node, more than 3 cm but not
more than 6 cm in greatest dimension, or in multiple ipsilateral lymph
nodes, none more than 6 cm in greatest dimension, or in bilateral or con-tralateral lymph nodes, none more than 6 cm in greatest dimension
N2a Metastasis in a single ipsilateral lymph node more than 3 cm but not more
than 6 cm in greatest dimension
N2b Metastasis in multiple ipsilateral lymph nodes, none more than 6 cm in
greatest dimension
N2c Metastasis in bilateral or contralateral lymph nodes, none more than
6 cm in greatest dimension
N3 Metastasis in a lymph node more than 6 cm in greatest dimension
Distant Metastasis (M)
MX Distant metastasis cannot be assessed
M0 No distant metastasis
M1 Distant metastasis
N3a
N3
N3b
>6 cm
FIGURE 4.21. N3 for nasopharynx cancer may be categorized as N3a (left) for
metastasis in a lymph node(s) greater than 6 cm in dimension and/or N3b (right)
metastatic to the supraclavicular fossa.
American Joint Committee on Cancer • 2006 39
STAGE GROUPING: NASOPHARYNX
0 Tis N0 M0
IT1N0M0
IIA T2a N0 M0
IIB T1 N1 M0
T2 N1 M0
T2a N1 M0
T2b N0 M0
T2b N1 M0
III T1 N2 M0
T2a N2 M0
T2b N2 M0
T3 N0 M0
T3 N1 M0
T3 N2 M0
IVA T4 N0 M0
T4 N1 M0
T4 N2 M0
IVB Any T N3 M0
IVC Any T Any N M1
STAGE GROUPING: OROPHARYNX AND HYPOPHARYNX
0 Tis N0 M0
IT1N0M0
II T2 N0 M0
III T3 N0 M0
T1 N1 M0
T2 N1 M0
T3 N1 M0
IVA T4a N0 M0
T4a N1 M0
T1 N2 M0
T2 N2 M0
T3 N2 M0
T4a N2 M0
IVB T4b Any N M0
Any T N3 M0
IVC Any T Any N M1
NOTES
1. Parapharyngeal extension denotes posterolateral infiltration of tumor beyond the
pharyngobasilar fascia.
2. Central compartment soft tissue includes prelaryngeal strap muscles and subcuta-neous fat.
3. Midline nodes are considered ipsilateral nodes.
4
American Joint Committee on Cancer • 2006 41
5
Larynx
(Nonepithelial tumors such as those of lymphoid tissue, soft tissue, bone,
and cartilage are not included.)
5
ANATOMY
Primary Site. The following anatomic definition of the larynx allows classifi-cation of carcinomas arising in the encompassed mucous membranes but
excludes cancers arising on the lateral or posterior pharyngeal wall, pyriform
fossa, postcricoid area, or base of tongue.
The anterior limit of the larynx is composed of the anterior or lingual
surface of the suprahyoid epiglottis, the thyrohyoid membrane, the anterior
commissure, and the anterior wall of the subglottic region, which is composed
of the thyroid cartilage, the cricothyroid membrane, and the anterior arch of the
cricoid cartilage.
The posterior and lateral limits include the laryngeal aspect of the
aryepiglottic folds, the arytenoid region, the interarytenoid space, and the pos-terior surface of the subglottic space, represented by the mucous membrane cov-ering the surface of the cricoid cartilage.
The superolateral limits are composed of the tip and the lateral borders of
the epiglottis. The inferior limits are made up of the plane passing through the
inferior edge of the cricoid cartilage.
For purposes of this clinical stage classification, the larynx is divided into
three regions: supraglottis, glottis, and subglottis (Figures 5.1, 5.2). The supra-glottis is composed of the epiglottis (both its lingual and laryngeal aspects),
aryepglottic folds (laryngeal aspects), arytenoids, and the ventricular bands
(false cords). The epiglottis is divided for staging purposes into suprahyoid
and infrahyoid portions by a plane at the level of the hyoid bone. The inferior
boundary of the supraglottis is a horizontal plane passing through the lateral
margin of the ventricle at its junction with the superior surface of the vocal cord.
The glottis is composed of the superior and inferior surfaces of the true vocal
cords, including the anterior and posterior commissures. It occupies a horizon-tal plane 1 cm in thickness, extending inferiorly from the lateral margin of the
ventricle. The subglottis is the region extending from the lower boundary of the
glottis to the lower margin of the cricoid cartilage.
SUMMARY OF CHANGES
• T4 lesions have been divided into T4a (resectable) and T4b (unresectable),
leading to the division of Stage IV into Stage IVA, Stage IVB, and Stage IVC.
C10.1 Anterior (lingual)
surface of
epiglottis
C32.0 Glottis
C32.1 Supraglottis (laryn-geal surface)
C32.2 Subglottis
C32.2 Laryngeal cartilage
C32.8 Overlapping lesion of
larynx
C32.9 Larynx, NOS
42 American Joint Committee on Cancer • 2006
The division of the larynx is summarized as follows:
Site Subsite
Supraglottis Suprahyoid epiglottis
Infrahyoid epiglottis
Aryepiglottic folds (laryngeal aspect)
Arytenoids
Ventricular bands (false cords)
Glottis True vocal cords, including anterior and posterior commissures
Subglottis Subglottis
Regional Lymph Nodes. The incidence and distribution of cervical nodal
metastases from cancer of the larynx vary with the site of origin and the T
classification of the primary tumor. The true vocal cords are nearly devoid of
lymphatics, and tumors of that site alone rarely spread to regional nodes. By
C32.1 (i)
Supraglottis
Subglottis
Glottis
C32.1 (ii)
C12.9
C32.0
C32.2
C32.1 (v)
C32.1 (iv)
FIGURE 5.1. Anatomical sites and subsites of the three regions of the larynx:
supraglottis, glottis, and subglottis. Supraglottis (C32.1) subsites include
suprahyoid epiglottis (i), aryepiglottic fold, laryngeal aspect (ii), infrahyoid
epiglottis (iv), and ventricular bands or false cords (v).
C32.0 (ii)
C32.1 (i)
C32.0 (i)
C32.1 (ii)
C32.1 (iii)
C32.1 (v)
C32.0 (iii)
FIGURE 5.2. Anatomical sites and subsites of the supraglottis and glottis.
Supraglottis (C32.1) subsites include suprahyoid epiglottis (i), aryepiglottic fold,
laryngeal aspect (ii), arytenoids (iii), and ventricular bands or false cords (v).
Glottis (C32.0) subsites include vocal cords (i), anterior commissure (ii), and
posterior commissure (iii).
American Joint Committee on Cancer • 2006 43
contrast, the supraglottis has a rich and bilaterally interconnected lymphatic
network, and primary supraglottic cancers are commonly accompanied by
regional lymph node spread. Glottic tumors may spread directly to adjacent soft
tissues and prelaryngeal, pretracheal, paralaryngeal, and paratracheal nodes, as
well as to upper, mid-, and lower jugular nodes. Supraglottic tumors commonly
spread to upper and midjugular nodes, considerably less commonly to sub-mental or submandibular nodes, and occasionally to retropharyngeal nodes. The
rare subglottic primary tumors spread first to adjacent soft tissues and prela-ryngeal, pretracheal, paralaryngeal and paratracheal nodes, then to mid- and
lower jugular nodes. Contralateral lymphatic spread is common.
In clinical evaluation, the physical size of the nodal mass should be mea-sured. Most masses over 3 cm in diameter are not single nodes but, rather, are
confluent nodes or tumor in soft tissues of the neck. There are three categories
of clinically positive nodes: N1, N2, and N3. Midline nodes are considered ipsi-lateral nodes. In addition to the components to describe the N category, regional
lymph nodes should also be described according to the level of the neck that is
involved. Pathologic examination is necessary for documentation of such disease
extent. Imaging studies showing amorphous spiculated margins of involved
nodes or involvement of internodal fat resulting in loss of normal oval-to-round
nodal shape strongly suggest extracapsular (extranodal) tumor spread; however,
pathologic examination is necessary for documentation of such disease extent.
No imaging study (as yet) can identify microscopic foci of cancer in regional
nodes or distinguish between small reactive nodes and small malignant nodes
without central radiographic inhomogeneity.
Metastatic Sites. Distant spread is common only for patients who have bulky
regional lymphadenopathy. When distant metastases occur, spread to the lungs
is most common; skeletal or hepatic metastases occur less often. Mediastinal
lymph node metastases are considered distant metastases.
DEFINITIONS
Primary Tumor (T)
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
Tis Carcinoma in situ
Supraglottis
T1 Tumor limited to one subsite of supraglottis with normal vocal cord
mobility (Figures 5.3A, B)
T2 Tumor invades mucosa of more than one adjacent subsite of supraglottis
or glottis or region outside the supraglottis (e.g., mucosa of base of
tongue, vallecula, medial wall of pyriform sinus) without fixation of the
larynx (Figures 5.4A, B)
T3 Tumor limited to larynx with vocal cord fixation and/or invades any
of the following: postcricoid area, pre-epiglottic tissues, paraglottic
space, and/or minor thyroid cartilage erosion (e.g., inner cortex) (Figures
5.5A, B)
T4a Tumor invades through the thyroid cartilage and/or invades tissues
beyond the larynx (e.g., trachea, soft tissues of neck including deep
5
44 American Joint Committee on Cancer • 2006
T1
A
FIGURE 5.3. A. T1 is defined as tumor limited to one subsite of supraglottis
(shown here in the epiglottis) with normal vocal cord mobility. B. T1 is defined as
tumor limited to one subsite of supraglottis (shown here in the ventricular bands)
with normal vocal cord mobility.
T1
B
American Joint Committee on Cancer • 2006 45
5
T2
A
T2
B
FIGURE 5.4. A. T2 is defined as tumor invading the mucosa of more than one
adjacent subsite of supraglottis or glottis or region outside the supraglottis (e.g.,
mucosa of base of tongue, vallecula, medial wall of pyriform sinus) without
fixation of the larynx (shown here with tumor involvement in the suprahyoid and
mucosa of the infrahyoid epiglottis). B. T2 with invasion of ventricular bands (false
cords) and the epiglottis.
46 American Joint Committee on Cancer • 2006
T3
A
FIGURE 5.5. A. T3 is defined as tumor limited to larynx with vocal cord fixation
and/or invading any of the following: postcricoid area, pre-epiglottic tissues,
paraglottic space, and/or minor thyroid cartilage erosion (e.g., inner cortex), here
with invasion of the supraglottis and vocal cord with vocal cord fixation. B. T3
with invasion of the pre-epiglottic tissues with vocal cord fixation.
T3
B
American Joint Committee on Cancer • 2006 47
5
T4a
FIGURE 5.6. T4a is defined as tumor invading through the thyroid cartilage and/or
invading tissues beyond the larynx (e.g., trachea, soft tissues of neck including deep
extrinsic muscle of the tongue, strap muscles, thyroid, or esophagus). Here, tumor
has invaded beyond the larynx into the vallecula and base of the tongue as well as
into soft tissues of the neck.
Pre-epiglottic
space
Epiglottis
T4b
FIGURE 5.7. Cross-sectional illustration of T4b tumor, which is defined as
invading prevertebral space, encasing the carotid artery (shown), or invading
mediastinal structures.
extrinsic muscle of the tongue, strap muscles, thyroid, or esophagus)
(Figure 5.6)
T4b Tumor invades prevertebral space, encases carotid artery, or invades medi-astinal structures (Figure 5.7)
Glottis
T1 Tumor limited to the vocal cord(s) (may involve anterior or posterior
commissure) with normal mobility (Figure 5.8)
T1a Tumor limited to one vocal cord (Figure 5.8)
T1b Tumor involves both vocal cords (Figure 5.8)
48 American Joint Committee on Cancer • 2006
T1 T1a
T1b
FIGURE 5.8. T1 tumors of the glottis are limited to the vocal cord(s) with normal
mobility (may involve anterior or posterior commissure). T1a tumors are limited
to one vocal cord (top right) and T1b tumors involve both vocal cords (bottom
right).
T2
FIGURE 5.9. T2 tumors of the glottis extend to supraglottis and/or subglottis, or
with impaired vocal cord mobility.
T2 Tumor extends to supraglottis and/or subglottis, or with impaired vocal
cord mobility (Figure 5.9)
T3 Tumor limited to the larynx with vocal cord fixation, and/or invades para-glottic space, and/or minor thyroid cartilage erosion (e.g., inner cortex)
(Figure 5.10)
American Joint Committee on Cancer • 2006 49
5
T3
FIGURE 5.10. T3 tumors of the glottis are limited to the larynx with vocal cord
fixation (shown), and/or invade paraglottic space, and/or minor thyroid cartilage
erosion (e.g., inner cortex).
T4a
FIGURE 5.11. T4a tumors of the glottis invade through the thyroid cartilage
and/or invade tissues beyond the larynx (e.g., trachea, soft tissues of neck including
deep extrinsic muscle of the tongue, strap muscles, thyroid, or esophagus).
T4a Tumor invades through the thyroid cartilage and/or invades tissues beyond
the larynx (e.g., trachea, soft tissues of neck including deep extrinsic muscle
of the tongue, strap muscles, thyroid, or esophagus) (Figure 5.11)
T4b Tumor invades prevertebral space, encases carotid artery, or invades medi-astinal structures
Subglottis
T1 Tumor limited to the subglottis (Figure 5.12)
T2 Tumor extends to vocal cord(s) with normal or impaired mobility (Figure
5.13)
50 American Joint Committee on Cancer • 2006
T1
FIGURE 5.12. T1 tumors of the subglottis are limited to subglottis.
T2
FIGURE 5.13. T2 tumors of the subglottis extend to vocal cord(s), with normal or
impaired mobility.
T3 Tumor limited to larynx with vocal cord fixation (Figure 5.14)
T4a Tumor invades cricoid or thyroid cartilage and/or invades tissues beyond
the larynx (e.g., trachea, soft tissues of neck including deep extrinsic
muscles of the tongue, strap muscles, thyroid, or esophagus) (Figure 5.15)
T4b Tumor invades prevertebral space, encases carotid artery, or invades medi-astinal structures
Regional Lymph Nodes (N) (see Figure 2.4)
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest
dimension
American Joint Committee on Cancer • 2006 51
5
T3
FIGURE 5.14. T3 tumors of the subglottis are limited to larynx with vocal cord
fixation.
T4a
FIGURE 5.15. T4a tumors of the subglottis invade cricoid or thyroid cartilage
and/or invade tissues beyond the larynx (e.g., trachea, soft tissues of neck including
deep extrinsic muscles of the tongue, strap muscles, thyroid, or esophagus).
N2 Metastasis in a single ipsilateral lymph node, more than 3 cm but not more
than 6 cm in greatest dimension, or in multiple ipsilateral lymph nodes,
none more than 6 cm in greatest dimension, or in bilateral or contralat-eral lymph nodes, none more than 6 cm in greatest dimension
N2a Metastasis in a single ipsilateral lymph node, more than 3 cm but not more
than 6 cm in greatest dimension
N2b Metastasis in multiple ipsilateral lymph nodes, none more than 6 cm in
greatest dimension
N2c Metastasis in bilateral or contralateral lymph nodes, none more than 6 cm
in greatest dimension
N3 Metastasis in a lymph node, more than 6 cm in greatest dimension
52 American Joint Committee on Cancer • 2006
Distant Metastasis (M)
MX Distant metastasis cannot be assessed
M0 No distant metastasis
M1 Distant metastasis
STAGE GROUPING
0 Tis N0 M0
IT1N0M0
II T2 N0 M0
III T3 N0 M0
T1 N1 M0
T2 N1 M0
T3 N1 M0
IVA T4a N0 M0
T4a N1 M0
T1 N2 M0
T2 N2 M0
T3 N2 M0
T4a N2 M0
IVB T4b Any N M0
Any T N3 M0
IVC Any T Any N M1
American Joint Committee on Cancer • 2006 53
6
Nasal Cavity and Paranasal Sinuses
(Nonepithelial tumors such as those of lymphoid tissue, soft tissue, bone,
and cartilage are not included.)
6
ANATOMY
Primary Sites. Cancer of the maxillary sinus is the most common of the
sinonasal malignancies. Ethmoid sinuses and nasal cavity cancers are equal in
frequency but considerably less common than maxillary sinus cancers. Tumors
of the sphenoid and frontal sinuses are rare.
The location as well as the extent of the mucosal lesion within the maxil-lary sinus has prognostic significance. Historically, Ohngren’s line, connecting
the medial canthus of the eye to the angle of the mandible, is used to divide the
maxillary sinus into an anteroinferior portion (infrastructure), which is associ-ated with a good prognosis, and a superoposterior portion (suprastructure),
which has a poor prognosis (Figure 6.1). The poorer outcome associated with
superoposterior cancers reflects early extension of these tumors to critical struc-tures, including the eye, skull base, pterygoids, and infratemporal fossa.
For the purpose of staging, the nasoethmoidal complex is divided into two
sites: nasal cavity and ethmoid sinuses. The ethmoids are further subdivided into
two sites: left and right, separated by the nasal septum. The nasal cavity is divided
into four subsites: the septum, floor, lateral wall, and vestibule.
Site Subsite
Maxillary sinus Left/right
Nasal cavity Septum
Floor
Lateral wall
Vestibule
C30.0 Nasal cavity C31.0 Maxillary sinus C31.1 Ethmoid sinus
SUMMARY OF CHANGES
• A new site has been added for inclusion into the staging system. In addition to
maxillary sinus, the nasoethmoid complex is described as a second site with two
regions within this site: nasal cavity and ethmoid sinuses.
• The nasal cavity region is further divided into four subsites: septum, floor, lateral
wall, and vestibule. The ethmoid sinus region is divided into two subsites: right
and left.
• The T staging of ethmoid lesions has been revised to reflect nasoethmoid
tumors, and appropriate descriptions for the T staging have been added.
• For maxillary sinus, T4 lesions have been divided into T4a (resectable) and T4b
(unresectable), leading to the division of Stage IV into Stage IVA, Stage IVB, and
Stage IVC.
54 American Joint Committee on Cancer • 2006
Ethmoid sinus Left
Right
Regional Lymph Nodes. Regional lymph node spread from cancer of nasal
cavity and paranasal sinuses is relatively uncommon. Involvement of buccina-tor, submandibular, upper jugular, and (occasionally) retropharyngeal nodes
may occur with advanced maxillary sinus cancer which involve adjacent struc-tures, including soft tissues of the cheek, upper alveolus, palate, and buccal
mucosa. Ethmoid sinus cancers are less prone to regional lymphatic spread.
When only one side of the neck is involved, it should be considered ipsilateral.
Bilateral spread may occur with advanced primary cancer, particularly with
spread of the primary beyond the midline.
In clinical evaluation, the physical size of the nodal mass should be mea-sured. Most masses over 3 cm in diameter are not single nodes but, rather, are
confluent nodes or tumor in soft tissues of the neck. There are three categories
of clinically positive nodes: N1, N2, and N3. Midline nodes are considered ipsi-lateral nodes. In addition to the components to describe the N category, regional
lymph nodes should also be described according to the level of the neck that is
involved. Pathologic examination is necessary for documentation of such disease
Ethmoid
sinuses
Maxillary
sinus
Ethmoid
sinuses
Maxillary
sinus
Sphenoid sinus
Frontal sinus
FIGURE 6.1. Sites of origin of tumors of the paranasal sinuses.
American Joint Committee on Cancer • 2006 55
extent. Imaging studies showing amorphous spiculated margins of involved
nodes or involvement of internodal fat resulting in loss of normal oval-to-round
nodal shape strongly suggest extracapsular (extranodal) tumor spread; however,
pathologic examination is necessary for documentation of such disease extent.
No imaging study (as yet) can identify microscopic foci of cancer in regional
nodes or distinguish between small reactive nodes and small malignant nodes
without central radiographic inhomogeneity.
For pN, a selective neck dissection will ordinarily include 6 or more lymph
nodes, and a radical or modified radical neck dissection will ordinarily include
10 or more lymph nodes. Negative pathologic examination of a lesser number
of lymph nodes still mandates a pN0 designation.
Metastatic Disease. Distant spread usually occurs to lungs but occasionally
there is spread to bone.
DEFINITIONS
Primary Tumor (T)
Maxillary Sinus
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
Tis Carcinoma in situ
T1 Tumor limited to the maxillary sinus mucosa with no erosion or destruc-tion of bone (Figure 6.2)
T2 Tumor causing bone erosion or destruction including extension into the
hard palate and/or middle nasal meatus, except extension to posterior wall
of maxillary sinus and pterygoid plates (Figure 6.3)
T3 Tumor invades any of the following: bone of the posterior wall of maxil-lary sinus, subcutaneous tissues, floor or medial wall of orbit, pterygoid
fossa, ethmoid sinuses (Figure 6.4)
T4a Tumor invades anterior orbital contents, skin of cheek, pterygoid plates,
infratemporal fossa, cribriform plate, sphenoid or frontal sinuses
(Figures 6.5A, B)
6
T1
FIGURE 6.2. T1 is limited to the maxillary sinus mucosa.
56 American Joint Committee on Cancer • 2006
T2 FIGURE 6.3. T2 causes bone erosion or destruction
including extension into the hard palate and/or middle
nasal meatus with the exception of extension to
posterior wall of maxillary sinus and pterygoid plates.
T3 T3 FIGURE 6.4. Two views of T3.
T4a
Anterior
orbit
A
T4a
Sphenoid
sinus
Cribiform plate
B
FIGURE 6.5. A. T4a showing tumor invasion of anterior orbital contents. B. T4a
showing tumor invasion of sphenoid sinus and cribriform plate.
Tumor invades any of the following:
bone of the posterior wall of maxillary
sinus, subcutaneous tissues, floor or
medial wall of orbit, pterygoid fossa,
ethmoid sinuses.
American Joint Committee on Cancer • 2006 57
T4b Tumor invades any of the following: orbital apex, dura, brain, middle
cranial fossa, cranial nerves other than maxillary division of trigeminal
nerve V2, nasopharynx, or clivus (Figure 6.6)
Nasal Cavity and Ethmoid Sinus
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
Tis Carcinoma in situ
T1 Tumor restricted to any one subsite, with or without bony invasion
(Figure 6.7)
6
T4b
Orbital
apex
Middle
cranial
fossa
FIGURE 6.6. Coronal view of T4b shows tumor invades orbital apex and or dura,
brain or middle cranical fossa.
T1
FIGURE 6.7. In the nasal cavity and ethmoid
sinus, T1 is defined as tumor restricted to any
one subsite, with or without bony invasion.
58 American Joint Committee on Cancer • 2006
T2 Tumor invading two subsites in a single region or extending to involve an
adjacent region within the nasoethmoidal complex, with or without bony
invasion (Figure 6.8)
T3 Tumor extends to invade the medial wall or floor of the orbit, maxillary
sinus, palate, or cribriform plate (Figure 6.9)
T4a Tumor invades any of the following: anterior orbital contents, skin of nose
or cheek, minimal extension to anterior cranial fossa, pterygoid plates,
sphenoid or frontal sinuses (Figure 6.10)
T4b Tumor invades any of the following: orbital apex, dura, brain, middle
cranial fossa, cranial nerves other than V2, nasopharynx, or clivus
(Figure 6.11)
Regional Lymph Nodes (N) (see Figure 2.4)
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest
dimension
N2 Metastasis in a single ipsilateral lymph node, more than 3 cm but not more
than 6 cm in greatest dimension, or in multiple ipsilateral lymph nodes,
none more than 6 cm in greatest dimension, or in bilateral or contralat-eral lymph nodes, none more than 6 cm in greatest dimension
N2a Metastasis in a single ipsilateral lymph node, more than 3 cm but not more
than 6 cm in greatest dimension
N2b Metastasis in multiple ipsilateral lymph nodes, none more than 6 cm in
greatest dimension
Nasal
cavity
T2
FIGURE 6.8. T2 is defined as invading two subsites in a single region or extending
to involve an adjacent region within the nasoethmoidal complex, here the nasal
cavity, and ethmoid with or without bony invasion.
American Joint Committee on Cancer • 2006 59
6
Ethmoid
sinuses
Maxillary
sinus
T3
Orbit
T3
FIGURE 6.9. Two views of T3 showing tumor invading maxillary sinus and palate
(left) and extending to the floor of the orbit and cribriform plate (right).
T4a
FIGURE 6.10. T4a invades any of the following: anterior orbital contents, skin of
nose or cheek, minimal extension to anterior cranial fossa, pterygoid plates,
sphenoid or frontal sinuses.
60 American Joint Committee on Cancer • 2006
N2c Metastasis in bilateral or contralateral lymph nodes, none more than 6 cm
in greatest dimension
N3 Metastasis in a lymph node, more than 6 cm in greatest dimension
Distant Metastasis (M)
MX Distant metastasis cannot be assessed
M0 No distant metastasis
M1 Distant metastasis
STAGE GROUPING
0 Tis N0 M0
IT1N0M0
II T2 N0 M0
III T3 N0 M0
T1 N1 M0
T2 N1 M0
T3 N1 M0
IVA T4a N0 M0
T4a N1 M0
T1 N2 M0
T2 N2 M0
T3 N2 M0
T4a N2 M0
IVB T4b Any N M0
Any T N3 M0
IVC Any T Any N M1
T4b
Maxillary
sinus
Clivus
FIGURE 6.11. Two views of T4b. The coronal view on the left shows invasion in
the orbital apex and brain. On the right, tumor invades the clivus.
American Joint Committee on Cancer • 2006 61
7
Major Salivary Glands (Parotid, Submandibular,
and Sublingual)
7
INTRODUCTION
This staging system is based on an extensive retrospective review of the world
literature regarding malignant tumors of the major salivary glands. Numerous
factors affect patient survival, including the histologic diagnosis, cellular differ-entiation of the tumor (grade), site, size, degree of fixation or local extension,
facial nerve involvement, and the status of regional lymph nodes as well as
distant metastases. The classification involves the four dominant clinical vari-ables: tumor size, local extension of the tumor, nodal metastasis, and distant
metastasis. The T4 category has been divided into T4a and T4b. T4a indicates
advanced lesions that are resectable with grossly clear margins; T4b reflects
extension to areas that preclude resection with clear margins. Histologic grade,
patient age, and tumor site are important additional factors that should be
recorded for future analysis and potential inclusion in the staging system.
ANATOMY
Primary Site. The major salivary glands include the parotid, submandibular,
and sublingual glands. Tumors arising in minor salivary glands (mucus-secreting glands in the lining membrane of the upper aerodigestive tract) are
staged according to the anatomic site of origin (e.g., oral cavity, sinuses, etc.).
Primary tumors of the parotid constitute the largest proportion of salivary
gland tumors. Sublingual primary cancers are rare and may be difficult to dis-tinguish with certainty from minor salivary gland primary tumors of the ante-rior floor of the mouth.
Regional Lymph Nodes. Regional lymphatic spread from salivary gland
cancer is less common than from head and neck mucosal squamous cancers and
varies according to the histology and size of the primary tumor. Most nodal
metastases will be clinically apparent on initial evaluation.
C07.9 Parotid gland
C08.0 Submandibular gland
C08.1 Sublingual gland
C08.8 Overlapping lesion of
major salivary glands
C08.9 Major salivary gland,
NOS
SUMMARY OF CHANGES
• In order to maintain internal consistency of T staging across all sites, the descrip-tion for T3 has been revised. In addition to tumors having extraparenchymal
extension, all tumors larger than 4 cm are considered T3.
• T4 lesions have been divided into T4a (resectable) and T4b (unresectable),
leading to the division of Stage IV into Stage IVA, Stage IVB, and Stage IVC.
62 American Joint Committee on Cancer • 2006
Low-grade tumors rarely metastasize to regional nodes, whereas the risk of
regional spread is substantially higher from high-grade cancers. Regional dis-semination tends to be orderly, progressing from intraglandular to adjacent
(periparotid, submandibular) nodes, then to upper and midjugular nodes, and
occasionally to retropharyngeal nodes. Bilateral lymphatic spread is rare.
For pN, a selective neck dissection will ordinarily include 6 or more lymph
nodes, and a radical or modified radical neck dissection will ordinarily include
10 or more lymph nodes. Negative pathologic examination of a lesser number
of lymph nodes still mandates a pN0 designation.
Metastatic Sites. Distant spread is most frequently to the lungs.
DEFINITIONS
Primary Tumor (T)
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
T1 Tumor 2 cm or less in greatest dimension without extraparenchymal
extension(1)
(Figure 7.1)
T2 Tumor more than 2 cm but not more than 4 cm in greatest dimension
without extraparenchymal extension(1)
(Figure 7.2)
T3 Tumor more than 4 cm and/or tumor having extraparenchymal exten-sion(1)
(Figures 7.3A, B)
T4a Tumor invades skin, mandible, ear canal, and/or facial nerve (Figures
7.4A–D)
£2 cm
Hypoglossal
nerve
Lingual nerve
Myelohyoid
muscle
T1
FIGURE 7.1. T1 is defined as a tumor 2 cm or less in greatest dimension without
extraparenchymal extension (a coronal section thru the floor of the mouth with
tumor of the submandibular gland is shown).
7
2-4 cm
Facial
nerve
Masseter
muscle
Isthmus of
parotid gland
Facial nerve
Mastoid
process
T2FIGURE 7.2. T2 is defined as
a tumor greater than 2 cm
but not more than 4 cm in
greatest dimension without
extraparenchymal extension
(an axial section with tumor of
the deep lobe of the parotid
gland is shown).
>4 cm
T3
A
FIGURE 7.3. A. T3 is defined as greater than 4 cm and/or tumor having
extraparenchymal extension (a tumor of the superficial lobe of the parotid gland is
shown). B. Cross-sectional diagram of T3 tumor with extraparenchymal extension
from the parotid gland.
T3
Masseter muscle
Medial pterygoid
muscle
Tumor
Parotid gland
B
64 American Joint Committee on Cancer • 2006
T4a
Facial nerve
A
T4a
Masseter muscleMedial pterygoid
muscle
Mandible
Skin
Parotid gland
B
T4a
Masseter muscle
Medial
pterygoid
muscle
Mandible
Skin
C
FIGURE 7.4. A. T4a is defined as tumor invading skin, mandible, ear canal, and/or
facial nerve (as illustrated here). B. Cross-sectional diagram of T4a tumor invading
skin. C. Cross-sectional diagram of T4a tumor invading mandible. D. Coronal
section of T4 tumor invading ear canal.
T4a
Ear canal
D
American Joint Committee on Cancer • 2006 65
7
FIGURE 7.5. A. T4b is defined as tumor invading skull base and/or pterygoid
plates and/or encasing carotid artery. In this cross-sectional diagram, the
tumor encases the carotid artery. B. Coronal section of T4b tumor invading skull
base.
T4b Tumor invades skull base and/or pterygoid plates and/or encases carotid
artery (Figures 7.5A, B)
Regional Lymph Nodes (N) (see Figure 2.4)
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest
dimension
N2 Metastasis in a single ipsilateral lymph node, more than 3 cm but not more
than 6 cm in greatest dimension, or in multiple ipsilateral lymph nodes,
none more than 6 cm in greatest dimension, or in bilateral or contralat-eral lymph nodes, none more than 6 cm in greatest dimension
N2a Metastasis in a single ipsilateral lymph node, more than 3 cm but not more
than 6 cm in greatest dimension
N2b Metastasis in multiple ipsilateral lymph nodes, none more than 6 cm in
greatest dimension
N2c Metastasis in bilateral or contralateral lymph nodes, none more than 6 cm
in greatest dimension
N3 Metastasis in a lymph node, more than 6 cm in greatest dimension
Distant Metastasis (M)
MX Distant metastasis cannot be assessed
M0 No distant metastasis
M1 Distant metastasis
T4b
Carotid
artery
A
T4b
Skull
base
B
66 American Joint Committee on Cancer • 2006
STAGE GROUPING
IT1N0M0
II T2 N0 M0
III T3 N0 M0
T1 N1 M0
T2 N1 M0
T3 N1 M0
IVA T4a N0 M0
T4a N1 M0
T1 N2 M0
T2 N2 M0
T3 N2 M0
T4a N2 M0
IVB T4b Any N M0
Any T N3 M0
IVC Any T Any N M1
NOTE
1. Extraparenchymal extension is clinical or macroscopic evidence of invasion of soft
tissues. Microscopic evidence alone does not constitute extraparenchymal exten-sion for classification purposes.
American Joint Committee on Cancer • 2006 67
8
Thyroid
8
INTRODUCTION
Although staging for cancers in other head and neck sites is based entirely on
the anatomic extent of disease, it is not possible to follow this pattern for the
unique group of malignant tumors that arise in the thyroid gland. Both the his-tologic diagnosis and the age of the patient are of such importance in the behav-ior and the prognosis of thyroid cancer that these factors are included in this
staging system.
ANATOMY
Primary Site. The thyroid gland ordinarily is composed of a right and a left
lobe lying adjacent and lateral to the upper trachea and esophagus. An isthmus
connects the two lobes, and in some cases a pyramidal lobe is present extend-ing upward anterior to the thyroid cartilage (Figure 8.1).
Regional Lymph Nodes. Regional lymph node spread from thyroid cancer is
common but of less prognostic significance in patients with well-differentiated
tumors (papillary, follicular) than in medullary cancers. The adverse prognos-tic influence of lymph node metastasis in patients with differentiated carcino-mas is observed only in the older age group. The first echelon of nodal metastasis
consists of paralaryngeal, paratracheal, and prelaryngeal (Delphian) nodes adja-cent to the thyroid gland in the central compartment of the neck generally
described as Level VI. Metastases secondarily involve the mid- and lower jugular,
C73.9 Thyroid gland
SUMMARY OF CHANGES
• Tumor staging (T) has been revised and the categories redefined.
• T4 is now divided into T4a and T4b.
• Nodal staging (N) has been revised.
• All anaplastic carcinomas are considered T4. The T4 category for anaplastic
carcinomas is divided into T4a (intrathyroidal anaplastic carcinoma—
surgically resectable) and T4b (extrathyroidal anaplastic carcinoma—surgically
unresectable).
• For papillary and follicular carcinomas, the stage grouping for patients older
than 45 has been revised. Stage III includes tumors with minimal extrathyroid
extension. Stage IVA includes tumors of any size extending beyond the thyroid
capsule to invade subcutaneous soft tissues, larynx, trachea, esophagus, or recur-rent laryngeal nerve. Stage IVB includes tumors that invade prevertebral fascia,
carotid artery, or mediastinal vessels. Stage IVC includes advanced tumors with
distant metastasis.
68 American Joint Committee on Cancer • 2006
the supraclavicular, and (much less commonly) the upper deep jugular and
spinal accessory lymph nodes. Lymph node metastasis to submandibular and
submental lymph nodes is very rare. Upper mediastinal (Level VII) nodal spread
occurs frequently both anteriorly and posteriorly. Retropharyngeal nodal metas-tasis may be seen, usually in the presence of extensive lateral cervical metasta-sis. Bilateral nodal spread is common. The components of the N category are
described as follows: first echelon (central compartment/Level VI) or N1a, and
lateral cervical and/or superior mediastinal or N1b. The lymph node metastasis
should also be described according to the level of the neck that is involved. Nodal
metastases from medullary thyroid cancer carry a much more ominous prog-nosis, although they follow a similar pattern of spread.
For pN, histologic examination of a selective neck dissection will ordinar-ily include 6 or more lymph nodes, whereas histologic examination or a radical
or a modified radical comprehensive neck dissection will ordinarily include 10
or more lymph nodes. Negative pathologic evaluation of a lesser number of
nodes still mandates a pN0 designation.
Metastatic Sites. Distant spread occurs by hematogenous routes—for
example to lungs and bones—but many other sites may be involved.
DEFINITIONS
Primary Tumor (T)
All categories may be subdivided: (a) solitary tumor, (b) multifocal tumor (the
largest determines the classification).
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
T1 Tumor 2 cm or less in greatest dimension limited to the thyroid
(Figure 8.2)
T2 Tumor more than 2 cm but not more than 4 cm in greatest dimension
limited to the thyroid (Figure 8.3)
T3 Tumor more than 4 cm in greatest dimension limited to the thyroid or
any tumor with minimal extrathyroid extension (e.g., extension to ster-nothyroid muscle or perithyroid soft tissues) (Figure 8.4)
C73.9
Hyoid bone
Thyroid cartilage
Trachea
Thyroid gland
FIGURE 8.1. Thyroid gland.
American Joint Committee on Cancer • 2006 69
8
£2 cm
T1FIGURE 8.2. T1 is defined as tumor 2 cm or less in
greatest dimension limited to the thyroid.
2-4 cm
T2
FIGURE 8.3. T2 is defined as tumor more than 2
cm but not more than 4 cm in greatest dimension
limited to the thyroid.
T3T3
>4 cm
FIGURE 8.4. Two views of T3: on the left, a tumor
more than 4 cm in greatest dimension limited to the
thyroid; on the right, a tumor with minimal
extrathyroid extension (to either sternothyroid
muscle or perithyroid soft tissues).
70 American Joint Committee on Cancer • 2006
T4a Tumor of any size extending beyond the thyroid capsule to invade sub-cutaneous soft tissues, larynx, trachea, esophagus, or recurrent laryngeal
nerve (Figures 8.5A, B)
T4b Tumor invades prevertebral fascia or encases carotid artery or mediasti-nal vessels (Figure 8.6)
All anaplastic carcinomas are considered T4 tumors.
T4a Intrathyroidal anaplastic carcinoma—surgically resectable
T4b Extrathyroidal anaplastic carcinoma—surgically unresectable
Regional Lymph Nodes (N)
Regional lymph nodes are the central compartment, lateral cervical, and upper
mediastinal lymph nodes.
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Regional lymph node metastasis
T4a
A
Subcutaneous
soft tissue
T4a
Trachea
Esophagus
B
FIGURE 8.5. A. T4a is defined as a tumor of any size extending beyond the thyroid
capsule to invade subcutaneous soft tissues, larynx, trachea, esophagus, or
recurrent laryngeal nerve. B. Cross-sectional diagram of three different parameters
of T4a: tumor invading subcutaneous soft tissues; tumor invading trachea; tumor
invading esophagus.
American Joint Committee on Cancer • 2006 71
8
T4b
Carotid
artery
Vertebral
body
FIGURE 8.6. T4b is defined as tumor invading prevertebral fascia or encasing
carotid artery or mediastinal vessels. Cross-sectional diagram of two different
parameters of T4b: tumor encases carotid artery; tumor invades vertebral body.
N1a Metastasis to Level VI (pretracheal, paratracheal, and prelaryngeal/
Delphian lymph nodes) (Figure 8.7)
N1b Metastasis to unilateral, bilateral, or contralateral cervical or superior
mediastinal lymph nodes (Figure 8.8)
Distant Metastasis (M)
MX Distant metastasis cannot be assessed
M0 No distant metastasis
M1 Distant metastasis
N1a
FIGURE 8.7. N1a is defined as metastasis to Level VI (pretracheal, paratracheal,
and prelaryngeal/Delphian lymph nodes).
72 American Joint Committee on Cancer • 2006
N1b
FIGURE 8.8. N1b is defined as metastasis to unilateral, bilateral, or contralateral
cervical or superior mediastinal lymph nodes.
STAGE GROUPING
Separate stage groupings are recommended for papillary or follicu-lar, medullary, and anaplastic (undifferentiated) carcinoma.
Papillary or Follicular
Under 45 years
I Any T Any N M0
II Any T Any N Ml
Papillary or Follicular
45 years and older
IT1N0M0
II T2 N0 M0
III T3 N0 M0
T1 N1a M0
T2 N1a M0
T3 N1a M0
IVA T4a N0 M0
T4a N1a M0
T1 N1b M0
T2 N1b M0
T3 N1b M0
T4a N1b M0
American Joint Committee on Cancer • 2006 73
IVB T4b Any N M0
IVC Any T Any N M1
Medullary Carcinoma
IT1N0M0
II T2 N0 M0
III T3 N0 M0
T1 N1a M0
T2 N1a M0
T3 N1a M0
IVA T4a N0 M0
T4a N1a M0
T1 N1b M0
T2 N1b M0
T3 N1b M0
T4a N1b M0
IVB T4b Any N M0
IVC Any T Any N M1
Anaplastic Carcinoma
IVA T4a Any N M0
IVB T4b Any N M0
IVC Any T Any N M1
8
American Joint Committee on Cancer • 2006 77
9
Esophagus
(Sarcomas are not included.)
9
INTRODUCTION
Occurring more often in males, cancer of the esophagus accounts for 5.5% of
all malignant tumors of the gastrointestinal tract and for less than 1% of all
cancers in the United States. However, during the past 20 years, there has been
a dramatic shift in the epidemiology of esophageal cancer in North America and
most Western countries, characterized by a very rapid rise in the incidence of
this disease and a marked shift from squamous cell carcinomas occurring pre-dominantly in the middle third and distal esophagus and the esophagogastric
(EG) junction. Predisposing factors for squamous cell carcinomas include a high
alcohol intake and heavy use of tobacco or nutritional deficiencies of vitamins
and minerals. In contrast, EG junction adenocarcinomas arise most frequently
in Barrett’s epithelium. The underlying causes for this marked epidemiologic
change remain undefined.
Esophageal cancers, regardless of histologic type, may extend over wide
areas of the mucosal surface. Squamous cell carcinomas often arise as
multifocal tumors, presumably as a result of field carcinogenesis. Adenocarci-nomas may have varying lengths of mucosal and submucosal disease, particu-larly in patients with long segments of Barrett’s mucosa. However, only the depth
of penetration into the esophageal wall and nodal status are considered in
staging.
Many patients are asymptomatic during the early stages of disease. Early
symptoms include those related to gastroesophageal reflux and associated
Barrett’s esophagus or odynophagia caused by esophageal ulceration. Unfortu-nately, the most common clinical symptom for all lesions is dysphagia, which
occurs with large tumors that obstruct the lumen and deeply invade the
esophageal wall. Therefore, most patients already have locally advanced or
metastatic disease at diagnosis.
C15.0 Cervical esophagus
C15.1 Thoracic esophagus
C15.2 Abdominal esophagus
C15.3 Upper third of
esophagus
C15.4 Middle third of
esophagus
C15.5 Lower third of
esophagus
C15.8 Overlapping lesion of
esophagus
C15.9 Esophagus, NOS
SUMMARY OF CHANGES
• The definitions of TNM and the Stage Grouping for this chapter have not
changed from the Fifth Edition.
78 American Joint Committee on Cancer • 2006
ANATOMY
Primary Site. Beginning at the hypopharynx, the esophagus lies posterior to
the trachea and the heart, passing through the posterior mediastinum and enter-ing the stomach through an opening in the diaphragm called the hiatus. Figure
9.1 illustrates the anatomical subsites of the esophagus, including the average
measurement of each region from the incisors (front teeth).
Histologically, the esophagus has four layers: mucosa, submucosal, muscle
coat or muscularis propria, and adventitia. There is no serosa.
16-20 cm Thoracic
C15.0
C15.3
C15.4
C15.5
22-26 cm Tracheal
bifurcation
30-34 cm
38-42 cm Esophagogastric
junction
FIGURE 9.1. The anatomical subsites of the esophagus, including the average
measurement of each region from the incisors. The exact measurement is body
size/height dependent.
American Joint Committee on Cancer • 2006 79
For classification, staging, and reporting of cancer, the esophagus is divided
into four regions. Because the behavior of esophageal cancer and its treatment
vary with the anatomic divisions, these regions should be recorded and reported
separately. The location of esophageal cancer at the time of endoscopy is often
measured from the incisors (front teeth).
Cervical Esophagus. The cervical esophagus begins at the level of the lower
border of the cricoid cartilage and ends at the thoracic inlet (the suprasternal
notch), approximately 18 cm from the upper incisor teeth.
Intrathoracic and Abdominal Esophagus. This region is divided into two por-tions: The  upper thoracic portion extends from the thoracic inlet to the level
of the tracheal bifurcation, approximately 24 cm from the upper incisor
teeth. The midthoracic portion of the esophagus lies between the tracheal bifur-cation and the distal esophagus just above the esophagogastric junction.
The lower level of this portion is approximately 32 cm from the upper incisor
teeth.
Lower Thoracic and Abdominal Portion. Approximately 3 cm in length, the
lower esophagus also includes the intraabdominal portion of the esophagus and
the EG junction, which is located approximately 40 cm from the upper incisor
teeth. Most adenocarcinomas arise from the EG junction and involve both the
distal esophagus and the proximal stomach. Controversy exists over how to dis-tinguish proximal gastric cancers involving the EG junction from distal
esophageal and EG junction adenocarcinomas extending inferiorly to involve
the gastric cardia. In the absence of underlying Barrett’s mucosa, making this
distinction can be difficult. Siewert has proposed classifying EG junction cancers
into types I, II, and III, depending on the relative extent of involvement of either
the esophagus or the stomach. Further validation of this classification is needed
to determine whether it is reliable for staging or for prognosis. In clinical prac-tice, tumors arising within the EG junction and gastric cardia that have minimal
(2 cm or less) involvement of the esophagus are considered primary gastric
cancers.
Regional Lymph Nodes. Figure 9.2 illustrates the regional lymph nodes of the
esophagus. Specific regional lymph nodes are listed as follows:
Cervical esophagus
Scalene
Internal jugular
Upper and lower cervical
Periesophageal
Supraclavicular
Intrathoracic esophagus—upper, middle, and lower
Upper periesophageal (above the azygous vein)
Subcarinal
Lower periesophageal (below the azygous vein)
9
80 American Joint Committee on Cancer • 2006
Gastroesophageal junction
Lower esophageal (below the azygous vein)
Diaphragmatic
Pericardial
Left gastric
Celiac
Involvement of more distant lymph nodes (such as cervical or celiac axis
nodes for intrathoracic tumors) is currently considered distant metastasis
(M1a). However, recent analyses suggest that extensive nodal disease is associ-ated with a better overall survival than visceral metastases and with an approx-imately 10% chance of cure at 5 years after surgical resection. On this basis, it
has been suggested that the involvement of distant lymph nodes be classified as
C77.0
Cervical
esophagus
Intra-thoracic
esophagus
C77.1, 2
(partly)
FIGURE 9.2. For intrathoracic tumors involvement of more distant lymph nodes
(such as cervical or celiac axis nodes) is currently considered distant metastasis
(M1a).
American Joint Committee on Cancer • 2006 81
N2 disease rather than M1a, but such a change in classification requires further
study.
The nomenclature used to indicate the location of involved lymph nodes
has most frequently been that shown above, which provides a general anatom-ical description. More recently, a lymph node map that extends the nomencla-ture and numbering system used for the staging of non–small cell lung cancer
has been developed and used in clinical trials. This map, which is shown in
Figure 9.1, makes possible the more precise identification of involved lymph
nodes.
Metastatic Sites. The liver, lungs, and pleura are the most common sites of
distant metastases. Occasionally, the tumor may extend directly into mediasti-nal structures before distant metastasis is evident. This occurs most frequently
with tumors of the intrathoracic esophagus, which may extend directly into the
aorta, trachea, and pericardium.
DEFINITIONS
Primary Tumor (T)
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
Tis Carcinoma in situ
T1 Tumor invades lamina propria or submucosal (Figure 9.3)
T2 Tumor invades muscularis propria (Figure 9.3)
T3 Tumor invades adventitia (Figure 9.4)
T4 Tumor invades adjacent structures (Figure 9.5)
Regional Lymph Nodes (N)
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Regional lymph node metastasis (Figures 9.6, 9.7, 9.8, 9.9)
Distant Metastasis (M)
MX Distant metastasis cannot be assessed
M0 No distant metastasis
M1 Distant metastasis (Figure 9.6)
Tumors of the lower thoracic esophagus:
M1a Metastasis in celiac lymph nodes (Figure 9.7)
M1b Other distant metastasis (Figure 9.7)
Tumors of the midthoracic esophagus:
M1a Not applicable
Mlb Nonregional lymph nodes and/or other distant metastasis (Figure
9.8)
Tumors of the upper thoracic esophagus:
M1a Metastasis in cervical nodes (Figure 9.9)
M1b Other distant metastasis (Figure 9.9)
9
82 American Joint Committee on Cancer • 2006
T1 T2
Epithelium
Muscularis mucosae
Lamina propria
Submucosa
Muscularis propria
Adventitia
Mucosa
FIGURE 9.3. On the left, two views of T1, tumor which is defined as tumor that invades lamina propria (left side of T1
illustration) or submucosa (right side of T1 illustration). T2 tumor invades muscularis propria as illustrated on the right.
American Joint Committee on Cancer • 2006 83
9
T3
FIGURE 9.4. T3 tumor invades adventitia.
T4
Figure 9.5. T4 tumor that invades adjacent structures (tracheobronchial
involvement is shown).
Cervical including
supra-clavicular
Mediastinal
Celiac
Perigastric
N1
Carcinoma of Cervical Esophagus
M1
Figure 9.6. For carcinomas of the cervical esophagus, lymph node involvement
outside the cervical and supraclavicular region, as illustrated here in the
mediastinal region, is defined as M1 disease.
American Joint Committee on Cancer • 2006 85
9
Cervical including
supra-clavicular
Mediastinal
Celiac
Perigastric
M1b
Carcinoma of Lower Thoracic Esophagus
N1
M1a
Figure 9.7. Lymph node involvement outside the regional lymph nodes of the
lower thoracic esophagus, as illustrated here, is defined as M1a for metastasis in
celiac lymph nodes and M1b for other distant metastasis.
86 American Joint Committee on Cancer • 2006
Cervical including
supra-clavicular
Mediastinal
Celiac
Perigastric
M1b
Carcinoma of Mid-thoracic Esophagus
N1
M1b
Figure 9.8. In carcinoma of the mid-thoracic esophagus, any nonregional lymph
node involvement and/or other distant metastasis is defined as M1b disease.
American Joint Committee on Cancer • 2006 87
9
Cervical including
supra-clavicular
Mediastinal
Celiac
Perigastric
M1a
Carcinoma of Upper Thoracic Esophagus
N1
M1b
Figure 9.9. Lymph node involvement outside the regional lymph nodes of the
upper thoracic esophagus, as illustrated here, is defined as M1a for metastasis in
cervical lymph nodes and M1b for other distant metastasis.
88 American Joint Committee on Cancer • 2006
STAGE GROUPING
0 Tis N0 M0
IT1N0M0
IIA T2 N0 M0
T3 N0 M0
IIB T1 N1 M0
T2 N1 M0
III T3 N1 M0
T4 Any N M0
IV Any T Any N M1
IVA Any T Any N M1a
IVB Any T Any N M1b
American Joint Committee on Cancer • 2006 89
10
Stomach
(Lymphomas, sarcomas, and carcinoid tumors are not included.)
10
INTRODUCTION
Gastric adenocarcinoma has declined significantly in the United States over the
past 70 years, but even so, during the early twenty-first century, an estimated
22,000 patients develop the disease each year. Of these patients, 13,000 die,
mainly because of nodal and metastatic disease present at the time of initial
diagnosis. When worldwide figures are analyzed, the United States ranks forty-fourth in both male and female death rates from gastric adenocarcinoma. The
highest rates of this disease continue to be in areas of Asia and Russia. Trends
in survival rates from the 1970s to the 1990s have unfortunately shown very
little improvement. During the 1990s, 20% of gastric carcinoma cases were
diagnosed while localized to the gastric wall, whereas 30% had evidence of
regional nodal disease. Disease resulting from metastasis to other solid organs
within the abdomen, as well as to extra-abdominal sites, represents 35% of
all cases. Although overall 5-year survival is approximately 15–20%, the 5-year
survival is approximately 55% when disease is localized to the stomach. The
involvement of regional nodes reduces the 5-year survival to approximately
20%.
A notable shift in the site of gastric cancer reflects a proportionate increase
in disease of the proximal stomach over the past several decades. Previously,
there was a predominance of distal gastric cancers presenting as mass lesions or
ulceration. Although other malignancies occur in the stomach, approximately
90% of all gastric neoplasms are adenocarcinomas. Tumors of the gastroe-sophageal (GE) junction may be difficult to stage as either a gastric or an
esophageal primary, especially in view of the increased incidence of adenocar-cinoma in the esophagus that presumably results from acid reflux disease. By
convention, if more than 50% of the cancer involves the esophagus, the cancer
is classified as esophageal. Similarly, if more than 50% of the tumor is below the
GE junction, it is classified as gastric in origin. If the tumor is located equally
above and below the GE junction, the histology determines the origin of the
C16.0 Cardia, NOS
C16.1 Fundus of stomach
C16.2 Body of stomach
C16.3 Gastric antrum
C16.4 Pylorus
C16.5 Lesser curvature of
the stomach, NOS
C16.8 Greater curvature of
stomach, NOS
C16.8 Overlapping lesion of
stomach
C16.9 Stomach, NOS
SUMMARY OF CHANGES
• T2 lesions have been divided into T2a and T2b.
• T2a is defined as a tumor that invades the muscularis propria.
• T2b is defined as a tumor that invades into subserosa.
90 American Joint Committee on Cancer • 2006
primary—squamous cell, small cell, and undifferentiated carcinomas are classi-fied as esophageal, and adenocarcinoma and signet ring cell carcinoma are clas-sified as gastric. When Barrett’s esophagus (internal metaplasia) is present,
adenocarcinoma in both the gastric cardia and lower esophagus is most likely
to be esophageal in origin.
ANATOMY
Primary Site. The anatomic subsites of the stomach are illustrated in Figure
10.1. The stomach is the first division of the abdominal portion of the alimen-tary tract, beginning at the gastroesophageal junction and extending to the
pylorus. The proximal stomach is located immediately below the diaphragm and
is termed the cardia. The remaining portions are the fundus (body) of the
stomach and the distal portion of the stomach known as the antrum. The
pylorus is a muscular ring that controls the flow of food content from the
stomach into the first portion of the duodenum. The medial and lateral curva-tures of the stomach are known as the lesser and greater curvatures, respectively.
Histologically, the wall of the stomach has five layers: mucosal, submucosal,
muscular, subserosal, and serosal.
Staging of primary gastric adenocarcinoma is dependent on the depth of
penetration of the primary tumor. The T2 designation has been subdivided into
T2a (invasion of the muscularis propria) and T2b (invasion of the subserosa)
in order to discriminate between these intramural locations, even though there
is no change in the designation in the stage grouping that involves T2a or T2b
lesions.
Pylorus
C16.4
C16.3
C16.2
C16.1
Cardia
Fundus
Body
Antrum
FIGURE 10.1. Anatomical subsites of the stomach.
American Joint Committee on Cancer • 2006 91
Regional Lymph Nodes. The regional lymph nodes of the stomach are illus-trated in Figures 10.2A, B. Several groups of regional lymph nodes drain the wall
of the stomach. These perigastric nodes are found along the lesser and greater
curvatures. Other major nodal groups follow the main arterial and venous
vessels from the aorta and portal circulation. Adequate nodal dissection of these
regional nodal areas is important to ensure appropriate designation of the pN
determination. Although it is suggested that at least 15 regional nodes be
assessed pathologically, a pN0 determination may be assigned on the basis of
the actual number of nodes evaluated microscopically.
10
2
1
3
5
6
4b
4a
Distant (M)
Diaphragm
Regional (N)
A
7
9
8
11
10
12
Regional (N)
B
FIGURE 10.2. A. 1, 3, 5: perigastric nodes of the lesser curvature. 2, 4a, 4b, 6:
perigastric nodes along the greater curvature. Involvement of nodes above the
diaphragm is defined as distant metastasis. B. Regional lymph nodes of the
stomach. 7: left gastric nodes; 8: nodes along the common hepatic artery; 9:
nodes along the celiac artery; 10 and 11: nodes along the splenic artery; 12:
hepatoduodenal nodes.
Regional Lymph Nodes of the Stomach.
92 American Joint Committee on Cancer • 2006
Involvement of other intra-abdominal lymph nodes, such as the hepato-duodenal, retropancreatic, mesenteric, and para-aortic, is classified as distant
metastasis. The specific nodal areas are as follows:
Greater Curvature of the Stomach:
Greater curvature, greater omental, gastroduodenal, gastroepiploic, pyloric, and
pancreaticoduodenal
Pancreatic and Splenic Area:
Pancreaticolienal, peripancreatic, splenic
Lesser Curvature of the Stomach:
Lesser curvature, lesser omental, left gastric, cardioesophageal, common hepatic,
celiac, and hepatoduodenal
Distant Nodal Groups:
Retropancreatic, para-aortic, portal, retroperitoneal, mesenteric
Metastatic Sites. The most common metastatic distribution is to the liver,
peritoneal surfaces, and nonregional or distant lymph nodes. Central nervous
system and pulmonary metastases occur but are less frequent. With large, bulky
lesions, direct extension may occur to the liver, transverse colon, pancreas, or
undersurface of the diaphragm.
DEFINITIONS
Primary Tumor (T)
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
Tis Carcinoma  in situ: intraepithelial tumor without invasion of the lamina
propria
T1 Tumor invades lamina propria or submucosa (Figure 10.3)
T2 Tumor invades muscularis propria or subserosa (Figures 10.4A, B)
T2a Tumor invades muscularis propria (Figure 10.3)
T2b Tumor invades subserosa (Figure 10.3)
T3 Tumor penetrates serosa (visceral peritoneum) without invasion of adja-cent structures (Figures 10.5A, B, 10.6)
T4 Tumor invades adjacent structures (Figure 10.6)
Regional Lymph Nodes (N)
NX Regional lymph node(s) cannot be assessed
N0 No regional lymph node metastasis
N1 Metastasis in 1 to 6 regional lymph nodes (Figure 10.7)
N2 Metastasis in 7 to 15 regional lymph nodes (Figure 10.8)
N3 Metastasis in more than 15 regional lymph nodes (Figure 10.9)
Distant Metastasis (M)
MX Distant metastasis cannot be assessed
M0 No distant metastasis
M1 Distant metastasis (Figure 10.10)
American Joint Committee on Cancer • 2006 93
10
T1 T1 T2a T2b
Mucosa
Muscularis mucosae
Lamina propria
Submucosa
Muscularis
propria
Subserosa
Serosa
Mucosa
FIGURE 10.3. Illustrated definitions of T1, T2a, and T2b. Two views of T1 tumor: tumor invading lamina propria (left side of
T1 illustration) and submucosa (right side of T1 illustration). T2a tumor invades muscularis propria whereas T2b tumor
invades subserosa.
94 American Joint Committee on Cancer • 2006
T2
Lesser
omentum
Serosa
Subserosa
Muscularis propria
A
B
T2
Extension
to duodenum
Figure 10.4. A. T2 is defined as tumor that invades muscularis propria or
subserosa. B. T2 is defined as tumor that invades muscularis propria or subserosa.
Distal extension to duodenum does not affect T category.
American Joint Committee on Cancer • 2006 95
10
T3
Lesser
omentum
Serosa
Subserosa
Muscularis propria
A
T3
Extension
to esophagus
B
FIGURE 10.5. A. T3 tumor penetrates serosa (visceral peritoneum) without
invasion of adjacent structures. B. T3 tumor penetrates serosa (visceral
peritoneum) without invasion of adjacent structures. Proximal extension to
esophagus does not affect T category.
96 American Joint Committee on Cancer • 2006
T4T3
Lamina propria
Subserosa
Serosa
Muscularis mucosae
Submucosa
Muscularis propria
Adjacent structures
e.g. pancreas
Mucosa Mucosa
Figure 10.6. T3 tumor penetrates serosa (visceral peritoneum) without invasion of adjacent structures
whereas T4 tumor radially invades adjacent structures, here the pancreas.
American Joint Committee on Cancer • 2006 97
10
N1
FIGURE 10.7. N1 is defined as metastasis in 1 to 6 regional lymph nodes.
N2
FIGURE 10.8. N2 is defined as metastasis in 7 to 15 regional lymph nodes.
98 American Joint Committee on Cancer • 2006
N3
FIGURE 10.9. N3 is defined as metastasis in more than 15 regional lymph nodes.
Distant (M)
Regional (N)
M1
Diaphragm
FIGURE 10.10. Involvement of nodes above the diaphragm is defined as distant
metastasis or M1.
American Joint Committee on Cancer • 2006 99
STAGE GROUPING
0 Tis N0 M0
IA T1 N0 M0
IB T1 N1 M0
T2a/b N0 M0
II T1 N2 M0
T2a/b N1 M0
T3 N0 M0
IIIA T2a/b N2 M0
T3 N1 M0
T4 N0 M0
IIIB T3 N2 M0
IV T4 N1–3 M0
T1–3 N3 M0
Any T Any N M1
10
American Joint Committee on Cancer • 2006 101
11
Small Intestine
(Lymphomas, carcinoid tumors, and visceral sarcomas are not included.)
11
INTRODUCTION
Although the small intestine accounts for one of the largest surface areas in the
human body, less than 2% of all malignant tumors of the gastrointestinal tract
actually occur in the small bowel. Most cancers occur in the first or second
portion of the duodenum and are adenocarcinomas. A variety of other tumor
types occur in the small intestine, but approximately 50% of the primary malig-nant tumors are adenocarcinomas. An increased incidence of second malig-nancies has been noted in patients with primary small bowel adenocarcinoma.
At the beginning of the twenty-first century, approximately 5,000 new cases of
cancer involving the small intestine are seen annually in the United States. The
1,200 deaths predicted to occur from small intestinal cancer are divided equally
between men and women. The patterns of local, regional, and metastatic spread
for adenocarcinomas of the small intestine are comparable to those of similar
histologic malignancies in other areas of the gastrointestinal tract. The classifi-cation and stage groupings described in this chapter are used for both clinical
and pathologic staging of carcinomas of the small bowel and do not apply to
other types of malignant small bowel tumors. Although small bowel carcinoid
tumors are not traditionally staged using the TNM system, reports from the
United States and throughout the world attempt to stage these neuroendocrine
tumors using the TNM system.
ANATOMY
Primary Site. This classification applies to carcinomas arising in the duode-num, jejunum, and ileum. These anatomical sites are illustrated in Figure 11.1.
It does not apply to carcinomas arising in the ileocecal valve or to carcinomas
that may arise in Meckel’s diverticulum. Carcinomas arising in the ampulla of
Vater are staged according to the system described in Chapter 17.
Duodenum. About 25 cm in length, the duodenum extends from the pyloric
sphincter of the stomach to the jejunum. It is usually divided anatomically into
four parts, with the common bile duct and pancreatic duct opening into the
second part at the ampulla of Vater.
C17.0 Duodenum
C17.1 Jejunum
C17.2 Ileum
C17.8 Overlapping lesion of
small intestine
C17.9 Small intestine,
NOS
SUMMARY OF CHANGES
• The definitions of TNM and the Stage Grouping for this chapter have not
changed from the Fifth Edition.
102 American Joint Committee on Cancer • 2006
Jejunum and Ileum. The jejunum (8 feet in length) and ileum (12 feet in
length) extend from the junction with the duodenum proximally to the ileoce-cal valve distally. The division point between the jejunum and the ileum is arbi-trary. As a general rule, the jejunum includes the proximal 40% and the ileum
includes the distal 60% of the small intestine, exclusive of the duodenum.
General. The jejunal and ileal portions of the small intestine are supported by
the mesentery, which is a fold of the peritoneum containing the blood supply
and the regional lymph nodes. The shortest segment, the duodenum, has no real
mesentery and is covered by peritoneum only over its anterior surface. The wall
of all parts of the small intestine has five layers: mucosal, submucosal, muscu-lar, subserosal, and serosal. A very thin layer of smooth muscle cells, the mus-cularis mucosae, separates the mucosa from the submucosal. The small intestine
is entirely ensheathed by peritoneum, except for a narrow strip of bowel that
is attached to the mesentery and that part of the duodenum that is located
retroperitoneally.
Regional Lymph Nodes. For pN, histologic examination of a regional lym-phadenectomy specimen will ordinarily include a representative number of
lymph nodes distributed along the mesenteric vessels extending to the base of
the mesentery.
Duodenum:
Duodenal
Hepatic
Pancreaticoduodenal
Infrapyloric
Gastroduodenal
Pyloric
Superior mesenteric
Duodenum
(C17.0)
Ileum
(C17.2)
Jejunum
(C17.1)
FIGURE 11.1. Anatomical sites of the small intestine.
American Joint Committee on Cancer • 2006 103
Pericholedochal
Regional lymph nodes, NOS
Ileum and Jejunum:
Posterior cecal (terminal ileum only)
Ileocolic (terminal ileum only)
Superior mesenteric
Mesenteric, NOS
Regional lymph nodes, NOS
Metastatic Sites. Cancers of the small intestine can metastasize to most
organs, especially the liver, or to the peritoneal surfaces. Involvement of regional
lymph nodes and invasion of adjacent structures are most common. Involve-ment of the celiac nodes is considered M1 disease for carcinomas of the duo-denum, jejunum, and ileum. The presence of distant metastases and the presence
of residual disease (R) have the most influence on survival.
DEFINITIONS
Primary Tumor (T)
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
Tis Carcinoma in situ
T1 Tumor invades lamina propria or submucosal (Figure 11.2)
T2 Tumor invades muscularis propria (Figure 11.3)
T3 Tumor invades through the muscularis propria into the subserosa (Figure
11.4, top) or into the nonperitonealized perimuscular tissue (mesentery
or retroperitoneum) with extension 2 cm or less(1)
(Figures 11.5, top)
T4 Tumor perforates the visceral peritoneum (Figure 11.4, bottom) or
directly invades other organs or structures (includes mesentery, or
retroperitoneum more than 2 cm [Figure 11.5, bottom], other loops of
small intestine [Figure 11.6], and abdominal wall by way of serosa; for
duodenum only, invasion of pancreas [Figure 11.7])
11
T1
Mucosa
Muscularis mucosae
Lamina propria
Submucosa
Muscularis propria
Perimuscular
tissue (mesentery,
retroperitoneal
adventitia)
Subserosa
Serosa
FIGURE 11.2. Two views of T1: tumor invading lamina propria (left side of figure)
or submucosa (right side of figure).
104 American Joint Committee on Cancer • 2006
T2
Muscularis mucosae
Lamina propria
Submucosa
Muscularis propria
Subserosa
Serosa
Adventitia
Mucosa
FIGURE 11.3. T2 is defined as tumor invading muscularis propria.
T4
T3
Serosa
Subserosa
Subserosa
Serosa
Adventitia
FIGURE 11.4. T3 is defined as tumor invading through the muscularis propria
into the subserosa whereas T4 is defined as tumor that perforates (penetrates) the
visceral peritoneum.
American Joint Committee on Cancer • 2006 105
11
T3
T4
1 Mucosa
2 Submucosa
3 Muscularis propria
4 Perimuscular tissue (mesentery, retroperitoneal
adventitia, or subserosa)
£2 cm
>2 cm
3
2
1
4
3
2
1
4
Adventitia
FIGURE 11.5. T3 is defined as tumor invading into the nonperitonealized
perimuscular tissue (mesentery or retroperitoneum) with extension 2 cm or less
whereas T4 directly invades other organs or structures (includes, mesentery, or
retroperitoneum) more than 2 cm.
T4
FIGURE 11.6. T4 directly invades other organs or structures, including other loops
of small intestine.
106 American Joint Committee on Cancer • 2006
Regional Lymph Nodes (N)
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Regional lymph node metastasis
Distant Metastasis (M)
MX Distant metastasis cannot be assessed
M0 No distant metastasis
M1 Distant metastasis
STAGE GROUPING
0 Tis N0 M0
IT1N0M0
T2 N0 M0
II T3 N0 M0
T4 N0 M0
III Any T N1 M0
IV Any T Any N M1
NOTE
1. The nonperitonealized perimuscular tissue is, for jejunum and ileum, part of the
mesentery and, for duodenum in areas where serosa is lacking, part of the
retroperitoneum.
T4
FIGURE 11.7. T4 (duodenum only) tumor invades the pancreas.
American Joint Committee on Cancer • 2006 107
12
Colon and Rectum
(Sarcomas, lymphomas, and carcinoid tumors of the large intestine or appendix are not included.)
12
INTRODUCTION
The TNM classification for carcinomas of the colon and rectum provides more
detail than other staging systems. Compatible with the Dukes’ system, the TNM
adds greater precision in the identification of prognostic subgroups. TNM
staging is based on the depth of tumor invasion into the wall of the intestine
(T), extension to adjacent structures (T), the number of regional lymph nodes
involved (N), and the presence or absence of distant metastasis (M). The TNM
classification applies to both clinical and pathologic staging. However, most
cancers of the colon or rectum are staged after pathologic examination of the
surgical resection specimen. This staging system applies to all carcinomas arising
in the colon or rectum. Adenocarcinomas of the vermiform appendix may be
classified according to the TNM staging system but should be recorded sepa-rately. Since stage-specific outcomes may differ from colorectal carcinomas.
Cancers that occur in the anal canal are staged according to the classification
used for the anus (see Chapter 13).
C18.0 Cecum
C18.1 Appendix
C18.2 Ascending colon
C18.3 Hepatic flexure of
colon
C18.4 Transverse colon
C18.5 Splenic flexure of
colon
C18.6 Descending colon
C18.7 Sigmoid colon
C18.8 Overlapping lesion of
colon
C18.9 Colon, NOS
C19.9 Rectosigmoid
junction
C20.9 Rectum, NOS
SUMMARY OF CHANGES
• A revised description of the anatomy of the colon and rectum better delineates
the data concerning the boundaries between colon, rectum, and anal canal. Ade-nocarcinomas of the vermiform appendix are classified according to the TNM
staging system but should be recorded separately, whereas cancers that occur in
the anal canal are staged according to the classification used for the anus.
• Smooth extramural nodules of any size in the pericolic or perirectal fat are con-sidered lymph node metastases and will be counted in the N staging. In contrast,
irregularly contoured nodules in the peritumoral fat are considered vascular
invasion and will be coded as transmural extension in the T category and further
denoted as either a V1 (microscopic vascular invasion) if only microscopically
visible or a V2 (macroscopic vascular invasion) if grossly visible.
• Stage Group II is subdivided into IIA and IIB on the basis of whether the primary
tumor is T3 or T4 respectively.
• Stage Group III is subdivided into IIIA (T1-2N1M0), IIIB (T3-4N1M0), or IIIC
(any TN2M0).
108 American Joint Committee on Cancer • 2006
ANATOMY
The anatomical subsites of the colon and rectum are illustrated in Figures 12.1
and 12.2, respectively. The divisions of the colon and rectum are as follows:
Cecum
Ascending colon
Hepatic flexure
Transverse colon
Splenic flexure
Descending colon
Sigmoid colon
Hepatic
flexure
C18.3
Transverse
colon
C18.4 Splenic
flexure
C18.5
Descending
colon
C18.6
Sigmoid
colon
C18.7
Ascending
colon
C18.2
Cecum
C18.0
FIGURE 12.1. Anatomic subsites of the colon.
Rectosigmoid junction
C19.9
Rectum
C20.9
FIGURE 12.2. Anatomic subsites of the rectum.
American Joint Committee on Cancer • 2006 109
Rectosigmoid colon
Rectum
Primary Site. The large intestine (colorectum) extends from the terminal
ileum to the anal canal. Excluding the rectum and vermiform appendix,
the colon is divided into four parts: the right or ascending colon, the middle
or transverse colon, the left or descending colon, and the sigmoid colon.
The sigmoid is continuous with the rectum, which terminates at the anal
canal.
The cecum is a large, blind pouch that arises from the proximal segment of
the right colon. It measures 6 cm by 9 cm and is covered with peritoneum. The
ascending colon measures 15–20 cm in length. The posterior surface of the
ascending (and descending) colon lacks peritoneum and thus is in direct contact
with the retroperitoneum. In contrast, the anterior and lateral surfaces of the
ascending (and descending) colon have serosa and are intraperitoneal. The
hepatic flexure connects the ascending colon with the transverse colon, passing
just inferior to the liver and anterior to the duodenum.
The transverse colon is entirely intraperitoneal, supported on a long
mesentery that is attached to the pancreas. Anteriorly, its serosa is continuous
with the gastrocolic ligament. The splenic flexure connects the transverse
colon to the descending colon, passing inferior to the spleen and anterior to the
tail of the pancreas. As noted above, the posterior aspect of the descending
colon lacks serosa and is in direct contact with the retroperitoneum, whereas
the lateral and anterior surfaces have serosa and are intraperitoneal. The
descending colon measures 10–15 cm in length. The colon becomes com-pletely intraperitoneal once again at the sigmoid colon, where the mesentery
develops at the medial border of the left posterior major psoas muscle and
extends to the rectum. The transition from sigmoid colon to rectum is marked
by the fusion of the tenia of the sigmoid colon to form the circumferential
longitudinal muscle of the rectum. This occurs roughly 12–15 cm from the
dentate line.
Approximately 12 cm in length, the rectum extends proximally from the
fusion of the tenia to the puborectalis ring distally. The rectum is covered by
peritoneum in front and on both sides in its upper third and only on the ante-rior wall in its middle third. The peritoneum is reflected laterally from the
rectum to form the perirectal fossa and, anteriorly, the uterine or rectovesical
fold. There is no peritoneal covering in the lower third, which is often known
as the rectal ampulla. The anal canal, which measures 3–5 cm in length, extends
from the puborectalis sling to the anal verge.
Regional Lymph Nodes. Regional nodes are located (1) along the course of
the major vessels supplying the colon and rectum, (2) along the vascular arcades
of the marginal artery, and (3) adjacent to the colon—that is, located along the
mesocolic border of the colon. Specifically, the regional lymph nodes are the
pericoloic and perirectal nodes and those found along the ileocolic, right colic,
middle colic, left colic, inferior mesenteric artery, superior rectal (hemor-rhoidal), and internal iliac arteries (Figure 12.3).
For pN, the number of lymph nodes sampled should be recorded. The
number of nodes examined from an operative specimen has been reported to
be associated with improved survival, possibly because of increased accuracy in
12
110 American Joint Committee on Cancer • 2006
staging. It is important to obtain at least 12–14 lymph nodes in radical colon
and rectum resections; however, in cases in which tumor is resected for pallia-tion or in patients who have received preoperative radiation, only a few lymph
nodes may be present. A pN0 determination may be assessed when these nodes
are histologically negative, even though fewer than the recommended number
of nodes have been analyzed.
The regional lymph nodes for each segment of the large bowel are desig-nated as follows:
Segment Regional Lymph Nodes
Cecum Pericolic, anterior cecal, posterior cecal, ileocolic, right colic
Ascending colon Pericolic, ileocolic, right colic, middle colic
Hepatic flexure Pericolic, middle colic, right colic
Transverse colon Pericolic, middle colic
Splenic flexure Pericolic, middle colic, left colic, inferior mesenteric
Descending colon Pericolic, left colic, inferior mesenteric, sigmoid
Sigmoid colon Pericolic, inferior mesenteric, superior rectal (hemor-rhoidal), sigmoidal, sigmoid mesenteric
Rectosigmoid Pericolic, perirectal, left colic, sigmoid mesenteric, sig-moidal, inferior mesenteric, superior rectal (hemor-rhoidal), middle rectal (hemorrhoidal)
Rectum Perirectal, sigmoid mesenteric, inferior mesenteric, lateral
sacral presacral, internal iliac, sacral promontory (Gerota’s),
superior rectal (hemorrhoidal), middle rectal (hemor-rhoidal), inferior rectal (hemorrhoidal)
Right colic
artery
Ileocolic
artery
Left colicartery
Superior
rectal artery
Internal iliac
arteries
Inferior mesenteric
artery
Superior mesenteric
artery
Middle colic
artery
FIGURE 12.3. The regional lymph nodes of the colon and rectum.
American Joint Committee on Cancer • 2006 111
Metastatic Sites. Although carcinomas of the colon and rectum can
metastasize to almost any organ, the liver and lungs are the most common sites.
Seeding of other segments of the colon, small intestine, or peritoneum can also
occur.
DEFINITIONS
Primary Tumor (T)
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
Tis Carcinoma in situ: intraepithelial or invasion of lamina propria(1)
T1 Tumor invades submucosa (Figure 12.4)
T2 Tumor invades muscularis propria (Figure 12.5)
T3 Tumor invades through the muscularis propria into the subserosa, or into
nonperitonealized pericolic or perirectal tissues (Figure 12.6)
T4 Tumor directly invades other organs or structures (Figures 12.7A–C),
and/or perforates visceral peritoneum(2,3)
(Figures 12.7C, D)
12
T1
Pericolic
perirectal
tissue
Mucosa
Lamina propria
Submucosa
Muscularis propria
Muscularis mucosae
Subserosa
Serosa
Adventitia
FIGURE 12.4. T1 tumor invades submucosal.
T2
Serosa
Adventitia
FIGURE 12.5. T2 tumor invades muscularis propria.
112 American Joint Committee on Cancer • 2006
T3
Serosa
Adventitia
FIGURE 12.6. T3 tumor invades through the muscularis propria into the subserosa
or into nonperitonealized pericolic, or perirectal tissues (adventitia).
T4
A
T4
B
FIGURE 12.7. A. T4 tumor directly invades other organs or structures (such as the
coccyx shown here), and/or perforates visceral peritoneum. B. T4 tumor directly
invades other organs or structures, and/or perforates visceral peritoneum, as
illustrated here with radial extension into an adjacent loop of small bowel.
American Joint Committee on Cancer • 2006 113
Regional Lymph Nodes (N)
NX Regional lymph nodes cannot be assessed(4)
N0 No regional lymph node metastasis
N1 Metastasis in 1 to 3 regional lymph nodes (Figure 12.8)
N2 Metastasis in 4 or more regional lymph nodes (Figures 12.9A–C)
Distant Metastasis (M)
MX Distant metastasis cannot be assessed
M0 No distant metastasis
M1 Distant metastasis (Figure 12.10)
Residual Tumor (R)
R0 Complete resection, margins histologically negative, no residual tumor
left after resection
R1 Incomplete resection, margins histologically involved, microscopic tumor
remains after resection of gross disease.
R2 Incomplete resection, margins involved or gross disease remains after
resection (Figure 12.11)
12
T4
C
T4
Serosa
D
FIGURE 12.7. C. T4 tumor directly invades other organs or structures (such as
adjacent bowel, shown right), and/or perforates visceral peritoneum (shown left
with gross bowel perforation through the tumor). D. T4 tumor directly invades
other organs or structures, and/or perforates (penetrates) visceral peritoneum, as
illustrated here.
114 American Joint Committee on Cancer • 2006
N1 N1
FIGURE 12.8. Two views of N1, which is defined as metastasis in 1 to 3 regional
lymph nodes.
N2 N2
A
FIGURE 12.9. A. Two views of N2, which is defined as metastasis in 4 or more
regional lymph nodes.
American Joint Committee on Cancer • 2006 115
12
N2 N2
B
N2
C
FIGURE 12.9. B. Two views of N2 which is defined as metastasis in 4 or more
regional lymph nodes. C. N2 showing nodal masses in more than 4 regional lymph
nodes.
116 American Joint Committee on Cancer • 2006
M1
Right colic
artery
Ileocolic
artery
Left colicartery
Superior
rectal artery
Internal iliac
arteries
Inferior mesenteric
artery
Superior mesenteric
artery
Middle colic
artery
FIGURE 12.10. M1 disease is defined as distant metastasis, in this case outside the
regional nodes of the primary tumor.
T4 T3; R2
Circumferential
resection margin
Peritoneum
(serosa)
Adventitia
(Macroscopic involvement
of margin by tumor)
Serosalized area
of colorectum
Non-serosalized area
of colorectum
FIGURE 12.11. T4 (left side) has perforated the visceral peritoneum in a segment
of the colorectum with a serosal covering. In contrast, T3; R2 (right side)
shows macroscopic involvement of the circumferential resection margin of a
nonperitonealized surface of the colorectum by tumor corresponds to  gross
disease remaining after surgical excision).
American Joint Committee on Cancer • 2006 117
STAGE GROUPING
Stage T N M D ukes MAC
0 Tis N0 M0 — —
IT1 N0 M0 A A
T2 N0 M0 A Bl
IIA T3 N0 M0 B B2
IIB T4 N0 M0 B B3
IIIA T1–T3 N1 M0 C Cl
IIIB T3–T4 N1 M0 C C2/C3
IIIC Any T N2 M0 C C1/C2/C3
IV Any T Any N M1 — D
NOTES
1. Tis includes cancer cells confined within the glandular basement membrane
(intraepithelial) or lamina propria (intramucosal) with no extension through the
muscularis mucosae into the submucosa.
2. Direct invasion in T4 includes invasion of other segments of the colorectum by
way of the serosa, for example, invasion of the sigmoid colon by a carcinoma of
the cecum.
3. Tumor that is adherent to other organs or structures, macroscopically, is classified
T4. However, if no tumor is present in the adhesion, microscopically, the classifi-cation should be pT3. The V and L substaging should be used to identify the pres-ence or absence of vascular or lymphatic invasion.
4. A tumor nodule in the pericolorectal adipose tissue of a primary carcinoma
without histologic evidence of residual lymph node in the nodule is classified in
the pN category as a regional lymph node metastasis if the nodule has the form
and smooth contour of a lymph node. If the nodule has an irregular contour, it
should be classified in the T category and also coded as V1 (microscopic venous
invasion) or as V2 (if it was grossly evident), because there is a strong likelihood
that it represents venous invasion.
12
American Joint Committee on Cancer • 2006 119
13
Anal Canal
(The classification applies to carcinomas only; melanomas, carcinoid tumors,
and sarcomas are not included.)
13
SUMMARY OF CHANGES
• The definitions of TNM and the Stage Groupings for this chapter have not
changed from the Fifth Edition.
C21.0 Anus, NOS
C21.1 Anal canal
C21.2 Cloacogenic zone
C21.8 Ovelapping lesion of
rectum, anus, and
anal canal
INTRODUCTION
The proximal region of the anus encompasses true mucosa of three different
histologic types: glandular, transitional, and squamous (proximal to distal,
respectively). Distally, the squamous mucosa merges with the perianal skin (true
epidermis). This mucocutaneous junction historically has been called the anal
verge or margin. Thus, two distinct categories of tumors arise in the anal region.
Tumors that develop from mucosa (of any of the three types) are termed anal
canal cancers, whereas those that arise within skin at or distal to the squamous
mucocutaneous junction are termed anal margin tumors. The proximal bound-ary of the anal margin is indistinct on macroscopic examination and, anatom-ically, may vary with the patient’s body habitus. A proximal boundary located
5–6 cm from the squamous mucocutaneous junction applies in the majority of
adults.
Anal canal tumors are staged using the classification system described and
illustrated herein. Anal margin tumors are biologically comparable to other skin
tumors and therefore are classified by the schema presented in Chapter 23,
Carcinoma of the Skin. However, the regional nodal drainage (relevant to the N
category) of the skin of the anal margin is uniquely specific to this anatomic
site, as outlined in this section.
Because the primary management of carcinomas of the anal canal has
shifted from surgical resection to nonsurgical treatment, they are typically staged
clinically according to the size and extent of the primary tumor. Thus, patients
with cancer of the anal canal may be staged at the time of presentation by inspec-tion, palpation and biopsy of the mass, palpation (and biopsy as needed) of
regional lymph nodes, and radiologic imaging of the chest, abdomen, and
pelvis.
ANATOMY
Primary Site. The anatomic subsites of the anal canal are illustrated in Figure
13.1. The anal canal begins where the rectum enters the puborectalis sling at the
apex of the anal sphincter complex (palpable as the anorectal ring on digital
120 American Joint Committee on Cancer • 2006
exam) and ends at the squamous mucocutaneous junction with the perianal
skin. The most proximal aspect of the anal canal is lined by colorectal mucosa,
and at the dentate line, a narrow zone of transitional mucosa that is similar to
urothelium is variably present. The proximal zone (from the top of the pub-orectalis to the dentate line, including the transitional zone) measures approxi-mately 1–2 cm. In the region of the dentate line, anal glands may be found
subadjacent to the mucosa, often extending across the internal sphincter to the
intersphincteric plane. A proximal boundary located distal to the dentate line
and extending to the mucocutaneous junction is a nonkeratinizing squamous
epithelium devoid of skin appendages (hair follicles, apocrine glands, and sweat
glands).
Carcinomas that overlap the anorectal junction may be problematic. They
should be staged as rectal tumors if their epicenter is located more than 2 cm
proximal to the dentate line and as anal tumors if their epicenter is 2 cm or less
from the dentate line. However, extension of low rectal tumors beyond the
dentate line implies risk of metastatic spread to the superficial inguinal lymph
nodes.
Regional Lymph Nodes. Lymphatic drainage and nodal involvement of anal
cancers depend on the location of the primary tumor. Tumors above the dentate
line spread primarily to the anorectal, perirectal, and paravertebral nodes,
whereas tumors below the dentate line spread to the superficial inguinal
nodes.
The regional lymph nodes are as follows (Figure 13.2):
Perirectal
Anorectal
Perirectal
Lateral sacral
Internal iliac (hypogastric)
Levator ani m.
Internal sphincter m.
Dentate line
External sphincter m.
Anal canal
C21.1
Anal margin
(skin) C44.5
1. Transitional epithelium
2. Squamous epithelium devoid of hair and glands (not skin)
1
2
FIGURE 13.1. Anatomic subsites of the anal canal.
American Joint Committee on Cancer • 2006 121
Inguinal
Superficial
Deep femoral
All other nodal groups represent sites of distant metastasis.
Metastatic Sites. Cancers of the anus may metastasize to any organs, but the
liver and lungs are the distal organs that are most frequently involved. Involve-ment of the abdominal cavity is not unusual.
DEFINITIONS
Primary Tumor (T)
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
Tis Carcinoma in situ
T1 Tumor 2 cm or less in greatest dimension (Figure 13.3)
T2 Tumor more than 2 cm but not more than 5 cm in greatest dimension
(Figure 13.4)
T3 Tumor more than 5 cm in greatest dimension (Figure 13.5)
T4 Tumor of any size invades adjacent organ(s), e.g., vagina, urethra,
bladder(1)
(Figure 13.6)
Regional Lymph Nodes (N)
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Metastasis in perirectal lymph node(s) (Figure 13.7)
N2 Metastasis in unilateral internal iliac and/or inguinal lymph node(s)
(Figures 13.8A, B)
N3 Metastasis in perirectal and inguinal lymph nodes and/or bilateral inter-nal iliac and/or inguinal lymph nodes (Figures 13.9A–C)
13
Inguinal lymph
nodes
Internal iliac
nodes
Perirectal
nodes
FIGURE 13.2. Regional lymph nodes of the anal canal.
122 American Joint Committee on Cancer • 2006
£2 cm
T1
FIGURE 13.4. Two views of T2 showing tumor more than 2 cm but not more than
5 cm in greatest dimension. On the right side of the diagram, the tumor extends
above the dentate line.
>2-5 cm
>2-5 cm
T2 T2
FIGURE 13.3. T1 is defined as tumor 2 cm or less in greatest dimension.
13
>5 cm
T3
FIGURE 13.5. T3 is defined as tumor more than 5 cm in greatest dimension.
T4
FIGURE 13.6. T4 is defined as tumor of any
size invading adjacent organ(s), e.g., vagina
(as illustrated), urethra, bladder.(1)
Inguinal lymph
nodes
Internal iliac
nodes
Perirectal
nodes
N1
FIGURE 13.7. N1 is defined as metastasis in perirectal lymph node(s).
124 American Joint Committee on Cancer • 2006
Inguinal lymph
nodes
Internal iliac
nodes
Perirectal
nodes
N2 N2
A
Inguinal lymph
nodes
Internal iliac
nodes
Perirectal
nodes
N2
B
FIGURE 13.8. A. Two views of N2, which is defined as metastasis in unilateral
internal iliac (left) and/or inguinal lymph node(s) (right). B. N2: metastases in
unilateral internal iliac and inguinal lymph node(s).
13
Inguinal lymph
nodes
Internal iliac
nodes
Perirectal
nodes
N3
A
FIGURE 13.9. A. N3
is defined as
metastasis in
perirectal and
inguinal lymph
nodes (as illustrated)
and/or bilateral
internal iliac and/or
inguinal lymph
nodes. B. N3:
metastases in
bilateral internal iliac
lymph nodes. C. N3:
metastases in
bilateral internal iliac
and inguinal lymph
nodes.
Inguinal lymph
nodes
Internal iliac
nodes
Perirectal
nodes
N3
B
Inguinal lymph
nodes
Internal iliac
nodes
Perirectal
nodes
N3
C
Distant Metastasis (M)
MX Distant metastasis cannot be assessed
M0 No distant metastasis
M1 Distant metastasis
STAGE GROUPING
0 Tis N0 M0
IT1N0M0
II T2 N0 M0
T3 N0 M0
IIIA T1 N1 M0
T2 N1 M0
T3 N1 M0
T4 N0 M0
IIIB T4 N1 M0
Any T N2 M0
Any T N3 M0
IV Any T Any N M1
NOTE
1. Direct invasion of the rectal wall, perirectal skin, subcutaneous tissue, or the
sphincter muscle(s) is not classified as T4.
126 American Joint Committee on Cancer • 2006
American Joint Committee on Cancer • 2006 127
14
Liver (Including Intrahepatic Bile Ducts)
(Sarcomas and tumors metastatic to the liver are not included.)
14
SUMMARY OF CHANGES
• The T categories in this edition have been redefined and simplified.
• All solitary tumors without vascular invasion, regardless of size, are classified as
T1 because of similar prognosis.
• All solitary tumors with vascular invasion (again regardless of size) are combined
with multiple tumors £5 cm and classified as T2 because of similar prognosis.
• Multiple tumors >5 cm and tumors with evidence of major vascular invasion are
combined and classified as T3 because of similarly poor prognosis.
• Tumor(s) with direct invasion of adjacent organs other than the gallbladder or
with perforation of visceral peritoneum are classified separately as T4.
• The separate subcategory for multiple bilobar tumors has been eliminated
because of a lack of distinct prognostic value.
• T3 N0 tumors and tumors with lymph node involvement are combined into
Stage III because of similar prognosis.
• Stage IV defines metastatic disease only. The subcategories IVA and IVB have
been eliminated.
C22.0 Liver C22.1 Intrahepatic bile duct
INTRODUCTION
Primary malignancies of the liver include tumors arising from the hepatocytes
(hepatocellular carcinoma), intrahepatic bile ducts (intrahepatic cholangiocar-cinoma and cystadenocarcinoma), and mesenchymal elements (primary sarco-mas, not covered in this chapter). Hepatocellular carcinoma is the most common
primary cancer of the liver and is a leading cause of death from cancer world-wide. Although it is uncommon in the United States, its incidence is rising. The
majority of hepatocellular carcinomas arise in a background of chronic liver
disease due to viral hepatitis (B or C) or ethanol abuse. Cirrhosis may dominate
the clinical picture and determine the prognosis. Other important indicators
of the outcome of hepatocellular carcinoma are resectability for cure and the
extent of vascular invasion.
ANATOMY
Primary Site. The liver has a dual blood supply: the hepatic artery, which
branches from the celiac artery, and the portal vein, which drains the intestine.
Blood from the liver passes through the hepatic vein and enters the inferior
vena cava. The liver is divided into right and left lobes by a plane (Cantlie’s line)
projecting between the gallbladder fossa and the vena cava and defined by the
128 American Joint Committee on Cancer • 2006
middle hepatic vein (Figure 14.1). Couinaud refined knowledge about the func-tional anatomy of the liver and proposed division of the liver into four sectors
(formerly called segments) and eight segments. In this nomenclature, the liver
is divided by vertical and oblique planes or scissurae defined by the three main
hepatic veins and a transverse plane or scissura that follows a line drawn through
the right and left portal branches. Thus, the four traditional segments (right
anterior, right posterior, left medial, and left lateral) are replaced by sectors (right
anterior, right posterior, left anterior, and left posterior), and these sectors are
divided into segments by the transverse scissura (Figure 14.2). The eight seg-ments are numbered clockwise in a frontal plane. Recent advances in hepatic
Right lobe
Cantlie’s line
Hepatoduodenal
ligament
Left lobe
FIGURE 14.1. Division of the liver into right and left lobes by the plane of
Cantlie’s line.
Right
scissura
Middle
scissura
Left
scissura
Cantlie’s line
I
II
III
IV
VVI
VII
VIII
Transverse
scissura
FIGURE 14.2. Anatomy of the liver.
American Joint Committee on Cancer • 2006 129
surgery have made possible anatomic (also called typical) resections along these
planes.
Histologically, the liver is divided into lobules with central veins draining
each lobule. The portal spaces between the lobules contain the intrahepatic bile
ducts and the blood supply, which consists of small branches of the hepatic
artery and portal vein (portal triads).
Regional Lymph Nodes. The regional lymph nodes are the hilar, hepatoduo-denal ligament lymph nodes, and caval lymph nodes, among which the most
prominent are the hepatic artery and portal vein lymph nodes. Histologic ex-amination of a regional lymphadenectomy specimen will ordinarily include a
minimum of three lymph nodes.
Nodal involvement beyond these lymph nodes is considered distant metas-tasis and should be coded as M1. Involvement of the inferior phrenic lymph
nodes should also be considered M1.
Metastatic Sites. The main mode of dissemination of liver carcinomas is via
the portal veins (intrahepatic) and hepatic veins. Intrahepatic venous dissemi-nation cannot be differentiated from satellitosis or multifocal tumors and is
classified as multiple tumors. The most common sites of extrahepatic dissemi-nation are the lungs and bones. Tumors may extend through the liver capsule
to adjacent organs (adrenal, diaphragm, and colon) or may rupture, causing
acute hemorrhage and peritoneal carcinomatosis.
DEFINITIONS
Primary Tumor (T)
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
T1 Solitary tumor without vascular invasion (Figure 14.3)
T2 Solitary tumor with vascular invasion or multiple tumors, none more than
5 cm (Figures 14.4A, B)
14
T1
FIGURE 14.3. T1 is defined as a solid tumor without vascular invasion, regardless
of size.
130 American Joint Committee on Cancer • 2006
Vascular
invasion
T2
A
T2
£5 cm
£5 cm
£5 cm
B
FIGURE 14.4. A. All solitary tumors with vascular invasion, regardless of size, are
classified T2. B. Multiple tumors, with none more than 5 cm, are classified T2.
T3 Multiple tumors more than 5 cm or tumor involving a major branch of the
portal or hepatic vein(s) (Figures 14.5A, B)
T4 Tumor(s) with direct invasion of adjacent organs other than the gallblad-der or with perforation of visceral peritoneum (Figure 14.6)
Regional Lymph Nodes (N)
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Regional lymph node metastasis (Figure 14.7)
Distant Metastasis (M)
MX Distant metastasis cannot be assessed
M0 No distant metastasis
M1 Distant metastasis
American Joint Committee on Cancer • 2006 131
14
T3
>5 cm
>5 cm>5 cm
A
T3
>5 cm
B
FIGURE 14.5. A. Multiple tumors more than 5 cm are classified T3. B. A tumor
involving a major branch of the portal or hepatic vein(s) is classified T3.
T4 T4
Perforated visceral
peritoneum
Stomach
FIGURE 14.6. Two views of T4: tumor with perforation of the visceral
peritoneum(left of dotted line); tumor directly invading adjacent organs other than
the gallbladder (right of dotted line, tumor invades stomach).
132 American Joint Committee on Cancer • 2006
STAGE GROUPING
IT1N0M0
II T2 N0 M0
IIIA T3 N0 M0
IIIB T4 N0 M0
IIIC Any T N1 M0
IV Any T Any N M1
Hepatoduodenal
ligament
N1
FIGURE 14.7. N1 is defined as metastasis to regional lymph nodes.
American Joint Committee on Cancer • 2006 133
15
Gallbladder
(Carcinoid tumors and sarcomas are not included.)
15
SUMMARY OF CHANGES
• The T and N classifications have been simplified in an effort to separate locally
invasive tumors into potentially resectable (T3) and unresectable (T4).
• There is no longer a distinction between T3 and T4 based on the depth of liver
invasion.
• Lymph node metastasis is now classified as Stage IIB, and Stage IIA is reserved
for large, invasive tumors (resectable), without lymph node metastasis.
• Stage grouping has been changed to allow Stage III to signify locally unresectable
disease and Stage IV to indicate metastatic disease.
C23.9 Gallbladder
INTRODUCTION
Cancers of the gallbladder are staged according to their depth of penetra-tion and extent of spread. These cancers frequently spread to the liver, which is
involved in 70% of patients at the time of surgical evaluation. Malignant tumors
of the gallbladder can also directly invade other adjacent organs, particularly the
common bile duct, the duodenum, and the transverse colon. Gallbladder cancers
are insidious in their growth, often metastasizing early, before a diagnosis is
made. Tumors can also perforate the wall of the gallbladder, eventually causing
intra-abdominal metastases, carcinomatosis, and ascites. Because gallbladder
cancer is uncommon and is usually diagnosed late, physicians have tended to
ignore anatomic staging, even though its importance for survival, management,
and prognosis has been emphasized. Many cases are not suspected clinically and
first discovered at laparoscopy or incidentally by the pathologist. More than 75%
of carcinomas of the gallbladder are associated with cholelithiasis. Survival cor-relates with the stage of disease.
ANATOMY
Primary Site. The gallbladder is a pear-shaped saccular organ located under
the liver in the gallbladder fossa. It has three parts: a fundus, a body, and a neck
that tapers into the cystic duct. The wall of the gallbladder is much thinner than
that of the intestine and lacks a circular and transverse muscle layer. The wall
has a mucosa (that is, an epithelial lining and lamina propria), a smooth muscle
layer analogous to the muscularis propria of the small intestine, perimuscular
connective tissue, and serosa. In contrast to the intestine, there is no submucosa.
Along the attachment to the liver, no serosa exists, and the perimuscular con-nective tissue is continuous with the interlobular connective tissue of the liver.
Tumors that arise in the cystic duct are classified according to the scheme for
the extrahepatic bile ducts.
134 American Joint Committee on Cancer • 2006
Regional Lymph Nodes. Accurate tumor staging requires that all lymph
nodes that are removed be analyzed. Optimal histologic examination of a re-gional lymphadenectomy specimen should include analysis of a minimum of
three lymph nodes. The regional lymph nodes include the following: hilar, celiac,
periduodenal, peripancreatic, and superior mesenteric. The hilar nodes include
the lymph nodes along the common bile duct, hepatic artery, portal vein, and
cystic duct (Figure 15.1).
Metastatic Sites. Cancers of the gallbladder usually metastasize to the peri-toneum and liver and occasionally to the lungs and pleura.
DEFINITIONS
Primary Tumor (T)
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
Tis Carcinoma in situ
T1 Tumor invades lamina propria or muscle layer
T1a Tumor invades lamina propria (Figure 15.2)
T1b Tumor invades muscle layer (Figure 15.2)
T2 Tumor invades perimuscular connective tissue; no extension beyond
serosa or into liver (Figure 15.3)
T3 Tumor perforates the serosa (visceral peritoneum) and/or directly in-vades the liver and/or one other adjacent organ or structure, such as the
stomach, duodenum, colon, pancreas, omentum, or extrahepatic bile
ducts (Figures 15.4A, B)
T4 Tumor invades main portal vein or hepatic artery or invades two or more
extrahepatic organs or structures (Figures 15.5A, B)
FIGURE 15.1. Regional lymph nodes of the gallbladder.
American Joint Committee on Cancer • 2006 135
15
T1a T1b
Subserosa
Serosa
Lamina propria
Muscle layer
FIGURE 15.2. T1a is defined as tumor invading lamina propria; T1b is defined as
tumor invading muscle layer.
Lamina propria
Muscle layer
T2
T2
Subserosa
Serosa
FIGURE 15.3. Two views of T2: tumor invading perimuscular connective tissue
(illustration and inset below dotted line) and tumor with no extension beyond
serosa into the liver (illustration above dotted line).
136 American Joint Committee on Cancer • 2006
T3
T3
A
T3
B
FIGURE 15.4. A. Two views of T3: tumor perforating the serosa (visceral
peritoneum) (below the dotted line) and/or directly invading the liver (above the
dotted line). B. T3 may also be defined as tumor invading one other adjacent organ
or structure, such as the duodenum (as illustrated), or the stomach, colon,
pancreas, omentum, or extrahepatic bile ducts.
Regional Lymph Nodes (N)
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Regional lymph node metastasis (Figure 15.6)
Distant Metastasis (M)
MX Distant metastasis cannot be assessed
M0 No distant metastasis
M1 Distant metastasis
American Joint Committee on Cancer • 2006 137
15
T4
Main portal vein
Hepatic artery
A
T4
Hepatic
flexure of colon
Duodenum
B
FIGURE 15.5. A. T4 is defined as tumor invading main portal vein or hepatic
artery (as illustrated), or invading two or more extrahepatic organs or structures.
B. T4 invading two or more extrahepatic organs or structures (here, colon and
duodenum).
138 American Joint Committee on Cancer • 2006
N1
FIGURE 15.6. N1 is defined as metastasis to regional lymph nodes.
STAGE GROUPING
0 Tis N0 M0
IA T1 N0 M0
IB T2 N0 M0
IIA T3 N0 M0
IIB T1 N1 M0
T2 N1 M0
T3 N1 M0
III T4 Any N M0
IV Any T Any N M1
American Joint Committee on Cancer • 2006 139
16
Extrahepatic Bile Ducts
(Sarcomas and carcinoid tumors are not included.)
16
SUMMARY OF CHANGES
• The T and N classifications have been redefined and simplified.
• Invasion of the subepithelial fibro (muscular) connective tissue is classified as T1
irrespective of muscular invasion, which cannot always be noted because of the
scarcity of muscle fibers in some bile duct segments.
• T2 is defined as invasion beyond the wall of the bile duct.
• The T classification allows one to separate locally invasive tumors into resectable
(T3) and unresectable (T4).
• Invasion of branches of the portal vein (right or left), hepatic artery, or liver is
classified as T3.
• Invasion of the main portal vein, common hepatic artery, and/or regional organs
is classified as T4.
• The stage grouping has been changed to allow Stage III to signify locally unre-sectable disease and Stage IV to indicate metastatic disease.
C24.0 Extrahepatic bile
duct
C24.8 Overlapping lesion of
the biliary tract
C24.9 Biliary tract,
NOS
INTRODUCTION
Malignant tumors can develop anywhere along the extrahepatic bile ducts
(Figure 16.1). Of these tumors, 70–80% involve the confluence of the right and
left hepatic ducts (hilar carcinomas), and about 20–30% arise more distally.
Diffuse involvement of the ducts is rare, occurring in only about 2% of cases.
All malignant tumors of the extrahepatic bile ducts inevitably cause partial or
complete ductal obstruction. Because the bile ducts have a small diameter, the
signs and symptoms of obstruction usually occur while tumors are relatively
small. Because of their invasion of major vascular structures and direct exten-sion to the liver, hilar carcinomas are more difficult to resect than those that
arise distally and are associated with a worse prognosis (because of the low rate
of resectability).
This TNM classification applies only to cancers arising in the extrahepatic
bile ducts above the ampulla of Vater. This includes malignant tumors that
develop in congenital choledochal cysts and tumors that arise in the intrapan-creatic portion of the common bile duct. Patients with advanced (metastatic)
disease and a primary tumor in the intrapancreatic portion of the common bile
duct may be misclassified as having pancreatic cancer if surgical resection is not
performed. In such cases, it is often impossible to determine (from radiographic
images or endoscopy) whether a tumor arises from the intrapancreatic portion
of the bile duct, the ampulla of Vater, or the pancreas. Tumors of the pancreas
and ampulla of Vater are classified separately.
140 American Joint Committee on Cancer • 2006
ANATOMY
Primary Site. Emerging from the transverse scissura of the liver are the right
and left hepatic bile ducts, which join to form the common hepatic duct. The
cystic duct, which connects to the gallbladder, joins the common hepatic duct
to form the common bile duct, which passes posterior to the first part of the
duodenum, traverses the head of the pancreas, and then enters the second part
of the duodenum through the ampulla of Vater. Histologically, the bile ducts are
lined by a single layer of tall, uniform columnar cells. The mucosa usually forms
irregular pleats or small longitudinal folds. The walls of the bile ducts have a
layer of subepithelial connective tissue and muscle fibers. It should be noted that
the muscle fibers are most prominent in the distal segment of the common bile
duct. More proximally, the muscle fibers are sparse or absent, and the walls of
the bile ducts consist largely of fibrous tissue.
Regional Lymph Nodes. Accurate tumor staging requires that all lymph
nodes that are removed be analyzed. Optimal histologic examination of a
regional lymphadenectomy specimen should include analysis of a minimum of
three lymph nodes. The regional lymph nodes are the same as those listed for
gallbladder cancer and include the following: hilar, celiac, periduodenal, peri-pancreatic, and superior mesenteric. The hilar nodes include the lymph nodes
along the common bile duct, hepatic artery, portal vein, and cystic duct.
Metastatic Sites. Extrahepatic bile duct carcinomas can extend to the liver,
pancreas, ampulla of Vater, duodenum, colon, omentum, stomach, or gallblad-der. Tumors arising in the right or left hepatic ducts usually extend proximally
Left hepatic duct
Right hepatic duct
Common hepatic duct
Cystic duct
Common bile duct
(Choledochus)
Ampulla of Vater C24.1
C24.0
FIGURE 16.1. Anatomic sites of the extrahepatic bile ducts.
American Joint Committee on Cancer • 2006 141
into the liver or distally to the common hepatic duct. Neoplasms from the cystic
duct invade the gallbladder, common bile duct, or both. Carcinomas that arise
in the distal segment of the common bile duct can spread to the pancreas, duo-denum, stomach, colon, or omentum. Distant metastases usually occur late in
the course of the disease and are most often found in the liver, lungs, and
peritoneum.
DEFINITIONS
Primary Tumor (T)
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
Tis Carcinoma in situ
T1 Tumor confined to the bile duct histologically (Figure 16.2)
T2 Tumor invades beyond the wall of the bile duct (Figure 16.3)
16
T1
T1
or
Perifibromuscular
connective tissue
Subepithelial connective tissue
(Lamina propria)
Fibromuscular wall
FIGURE 16.2. Two views of T1: both
tumors are confined to the bile duct
histologically.
T2
FIGURE 16.3. T2 is defined as tumor that
invades beyond the wall of the bile duct.
142 American Joint Committee on Cancer • 2006
T3
A
FIGURE 16.4. A. T3 is defined as tumor invading the liver (as illustrated),
gallbladder, pancreas, and/or ipsilateral branches of the portal vein (right or left) or
hepatic artery (right or left).
T3 Tumor invades the liver, gallbladder, pancreas, and/or ipsilateral branches
of the portal vein (right or left) or hepatic artery (right or left) (Figures
16.4A–C)
T4 Tumor invades any of the following: main portal vein or its branches bilat-erally, common hepatic artery, or other adjacent structures, such as the
colon, stomach, duodenum, or abdominal wall (Figures 16.5A, B)
Regional Lymph Nodes (N)
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Regional lymph node metastasis
Distant Metastasis (M)
MX Distant metastasis cannot be assessed
M0 No distant metastasis
M1 Distant metastasis
American Joint Committee on Cancer • 2006 143
16
T3
B
C
T3
Cystic duct
Main
portal vein
Common
bile duct
FIGURE 16.4. B. T3 tumor invading the pancreas. C. T3 tumor with ipsilateral
invasion of the right portal vein and gallbladder.
T4
Common
hepatic artery
Cystic duct
Main
portal vein
Common
bile duct
Right and left portal vein
A
T4
Cystic duct
Duodenum
B
FIGURE 16.5. A. T4 is defined as tumor that invades any of the following: main
portal vein or its branches bilaterally, common hepatic artery, or other adjacent
structures, such as the colon, stomach, duodenum, or abdominal wall. Here, tumor
invades the common hepatic artery and bilateral branches of the portal vein. B. T4
tumor invading the stomach.
American Joint Committee on Cancer • 2006 145
16
STAGE GROUPING
0 Tis N0 M0
IA T1 N0 M0
IB T2 N0 M0
IIA T3 N0 M0
IIB T1 N1 M0
T2 N1 M0
T3 N1 M0
III T4 Any N M0
IV Any T Any N M1
American Joint Committee on Cancer • 2006 147
17
Ampulla of Vater
(Carcinoid tumors and other neuroendocrine tumors are not included.)
17
SUMMARY OF CHANGES
• There is no longer a distinction between T3 and T4 on the basis of the depth of
pancreatic invasion.
• The stage grouping has been revised.
• Stage I has been replaced with Stage IA and Stage IB.
• Stage II has been replaced with Stage IIA and Stage IIB.
• Node positive disease has been moved to Stage IIB to retain consistency with the
staging of tumors of the bile duct and of the pancreas.
C24.1 Ampulla of Vater
INTRODUCTION
The ampulla of Vater is strategically located at the confluence of the pancreatic
and common bile ducts. Most tumors that arise in this small structure obstruct
the common bile duct, causing jaundice, abdominal pain, and occasionally
pancreatitis. Clinically and pathologically, carcinomas of the ampulla may be
difficult to differentiate from those arising in the head of the pancreas or in the
distal segment of the common bile duct. Primary cancers of the ampulla are not
common, although they constitute a high proportion of the malignant tumors
occurring in the duodenum. Tumors of the ampulla must be differentiated from
those arising in the second part of the duodenum and invading the ampulla,
which are staged as small bowel tumors. Carcinomas of the ampulla and peri-ampullary region are often associated with the familial adenomatous polyposis
syndrome.
ANATOMY
Primary Site. The ampulla is a small dilated duct less than 1.5 cm long, formed
in most individuals by the union of the terminal segments of the pancreatic and
common bile ducts (Figure 17.1). In 42% of individuals, however, the ampulla
is the termination of the common duct only, the pancreatic duct having its
own entrance into the duodenum adjacent to ampulla. In these individuals, the
ampulla may be difficult to locate or even nonexistent. The ampulla opens into
the duodenum, usually on the posterior-medial wall, through a small mucosal
elevation, the duodenal papilla, which is also called the ampulla of Vater.
Although carcinomas can arise in the mucosa of either the lining of the ampulla
or the duodenal surface of the duodenal papilla, they most commonly arise near
the junction of the two types of mucosa at the ampullary orifice. Nearly all
cancers that arise in this area are well-differentiated adenocarcinomas. They have
a variety of designations, including carcinoma of the ampulla of Vater, carci-
148 American Joint Committee on Cancer • 2006
noma of the periampullary portion of the duodenum, and carcinoma of the
peripapillary portion of the duodenum. It may not be possible to determine the
exact site of origin for large tumors.
Regional Lymph Nodes. A rich lymphatic network surrounds the pancreas
and periampullary region, and accurate tumor staging requires that all lymph
nodes that are removed by analyzed. Optimal histologic examination of a pan-creaticoduodenectomy specimen should include analysis of a minimum of
10 lymph nodes. The regional lymph nodes are the peripancreatic lymph nodes,
which also include the lymph nodes along the hepatic artery, celiac axis, and
pyloric regions (Figures 17.2, 17.3). Anatomic division of regional lymph nodes
is not necessary; however, separately submitted lymph nodes should be reported
as submitted.
Ampulla of Vater
C24.1
Extrahepatic
bile ducts
C24.0
FIGURE 17.1. Anatomic site of the ampulla of Vater.
Superior to head
Cystic duct node
Pyloric
Hepatic nodes
Splenic nodes
Superior
to body
Inferior
to head
Inferior
to body
Inferior to tail
Superior
pancreaticoduodenal nodes
(Anterior and posterior)
Inferior
pancreaticoduodenal nodes
(Anterior and posterior)
Inferior pancreatic nodes
Superior pancreatic nodes
Hilum
of spleen
Superior
to tail
FIGURE 17.2. Regional lymph nodes of the ampulla of Vater.
American Joint Committee on Cancer • 2006 149
Metastatic Sites. Tumors of the ampulla may infiltrate adjacent structures,
such as the wall of the duodenum, the head of the pancreas, and extrahepatic
bile ducts. Metastatic disease is most commonly found in the liver and peri-toneum and is less commonly seen in the lungs and pleura.
DEFINITIONS
Primary Tumor (T)
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
Tis Carcinoma in situ
T1 Tumor limited to ampulla of Vater or sphincter of Oddi (Figure 17.4)
T2 Tumor invades duodenal wall (Figure 17.5)
T3 Tumor invades pancreas (Figure 17.6)
T4 Tumor invades peripancreatic soft tissues or other adjacent organs or
structures (Figure 17.7)
Regional Lymph Nodes (N)
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Regional lymph node metastasis (Figures 17.8A–C for tumors located in
the head of the pancreas)
Distant Metastasis (M)
MX Distant metastasis cannot be assessed
M0 No distant metastasis
M1 Distant metastasis (Figures 17.9A, B)
17Superior mesenteric nodes
Hepatic
nodes
Celiac
nodes
Splenic
nodes
Superior
pancreatic
nodes
FIGURE 17.3. Regional lymph nodes to the ampulla of Vater, namely the proximal
mesenteric and common bile duct nodes. View shows the pancreatic body cut away
to reveal the proximal mesenteric lymph nodes.
150 American Joint Committee on Cancer • 2006
T1 T1
FIGURE 17.4. Two views of T1: tumor limited to ampulla of Vater (below dotted
line) or sphincter of Oddi (tumor shown above dotted line).
T2
FIGURE 17.5. T2 tumor invading duodenal wall.
T3
FIGURE 17.6. T3 tumor invading pancreas.
American Joint Committee on Cancer • 2006 151
17
T4
FIGURE 17.7. T4 tumor invading peripancreatic soft tissues or other adjacent
organs or structures.
N1
Common
bile duct
Portal
vein Aorta
A
FIGURE 17.8. A. N1 is defined as regional lymph node metastasis.
152 American Joint Committee on Cancer • 2006
N1
Not regional
lymph nodes
B
N1
Not regional
lymph nodes
Portal vein
Pancreatico-duodenal artery
Superior
mesenteric artery
Splenic vein
Splenic
artery
Left gastric artery
Common
hepatic artery
Superior
mesenteric vein
C
FIGURE 17.8. B, C. N1 is defined as regional lymph node metastasis.
American Joint Committee on Cancer • 2006 153
17
M1
Not regional
lymph nodes
A
M1
Not regional
lymph nodes
B
FIGURE 17.9. A. M1 is defined as distant metastasis, here to those of the tail of the
pancreas. B. M1 is defined as distant metastasis, here to the splenic lymph nodes.
STAGE GROUPING
0 Tis N0 M0
IA T1 N0 M0
IB T2 N0 M0
IIA T3 N0 M0
IIB T1 N1 M0
T2 N1 M0
T3 N1 M0
III T4 Any N M0
IV Any T Any N M1
American Joint Committee on Cancer • 2006 155
18
Exocrine Pancreas
(Endocrine tumors arising from the islets of Langerhans and carcinoid tumors are not included.)
18
SUMMARY OF CHANGES
• The T classification reflects the distinction between potentially resectable (T3)
and locally advanced (T4) primary pancreatic tumors.
• Stage grouping has been changed to allow Stage III to signify unresectable, locally
advanced pancreatic cancer, while Stage IV is reserved for patients with metasta-tic disease.
C25.0 Head of pancreas
C25.1 Body of pancreas
C25.2 Tail of pancreas
C25.3 Pancreatic duct
C25.7 Other specified parts
of pancreas
C25.8 Overlapping lesion of
pancreas
C25.9 Pancreas, NOS
INTRODUCTION
In the United States, pancreatic cancer is the second most common tumor of
the gastrointestinal tract and the fifth leading cause of cancer-related death in
adults. The disease is difficult to diagnose, especially in its early stages. Most pan-creatic cancers arise in the head of the pancreas, often causing bile duct obstruc-tion that results in clinically evident jaundice. Cancers that arise in either the
body or the tail of the pancreas are insidious in their development and often far
advanced when first detected. Most pancreatic cancers are adenocarcinomas,
which usually originate from the pancreatic duct cells. Surgical resection
remains the only potentially curative approach, although multimodality therapy
that includes innovative systemic agents and often radiation therapy is available.
Staging of exocrine pancreas cancers depends on the size and extent of the
primary tumor. This TNM classification does not apply to endocrine tumors.
ANATOMY
Primary Site. The pancreas is a long, coarsely lobulated gland that lies trans-versely across the posterior abdomen and extends from the duodenum to the
splenic hilum. The organ is divided into a head with a small uncinate process,
a neck, a body, and a tail. The anatomic subsites of the pancreas are illustrated
in Figure 18.1. The anterior aspect of the body of the pancreas is in direct contact
with the posterior wall of the stomach; posteriorly, the pancreas extends to the
aorta, splenic vein, and left kidney.
Tumors on the head of the pancreas are those arising to the right of the
superior mesenteric-portal vein confluence (Figure 18.2, posterior view of pan-creatic head). The uncinate process is part of the pancreatic head. Tumors of the
body of the pancreas are roughly defined as those arising between the superior
mesenteric-portal vein confluence and the aorta. Tumors of the tail of the pan-creas are those arising between the aorta and the hilum of the spleen.
156 American Joint Committee on Cancer • 2006
Portal vein
Aorta
Tail
C25.2
Body
C25.1
Head
C25.0
Superior
mesenteric
vein
Superior
mesenteric
artery
Celiac axis
Common
bile duct
FIGURE 18.1. Anatomic subsites of the pancreas.
FIGURE 18.2. Posterior view of pancreatic head with dotted line indicating the
location of the confluence of the portal and superior mesenteric veins. The hatched
area shows the uncinate process margin.
American Joint Committee on Cancer • 2006 157
Regional Lymph Nodes. A rich lymphatic network surrounds the pancreas
and accurate tumor staging requires that all lymph nodes that are removed be
analyzed. Optimal histologic examination of a pancreaticoduodenectomy spec-imen should include analysis of a minimum of 10 lymph nodes, although patho-logic analysis of fewer than 10 lymph nodes may still result in a pN0 designation.
The nomenclature for the regional lymph nodes of the pancreas is not stan-dardized, but the main classification systems currently in use are descriptive and
based on the anatomic location of the nodes. Accordingly, the pancreas has two
broad groups of regional nodes: those that form a ring around the organ and
those surrounding the adjacent large vessels (the abdominal aorta and its major
branches including the celiac axis, the superior mesenteric artery, and the renal
arteries). The specific nodal groups include: the anterior pancreaticoduodenal
nodes (superior and inferior), the posterior pancreaticoduodenal nodes (supe-rior and inferior), the pyloric nodes (adjacent to the pylorus), the gastroduode-nal nodes (adjacent to the gastroduodenal artery), the hepatic nodes (adjacent
to the common bile duct and the hepatic artery), the cystic node (adjacent to
the choledochal cystic duct), the superior mesenteric nodes, the celiac nodes, the
supra- and infrapancreatic nodes (located along the superior and inferior
borders of the pancreas, respectively), the mesocolic nodes, the splenic nodes,
and the gastrosplenic nodes. Some anatomic studies have shown primary lym-phatic drainage into the renal nodes as well. Although the nodes located closest
to the regional subdivisions of the pancreas (head, body, and tail) are the
primary lymphatic drainage stations for those zones, all of the specific nodal
groups named above are included in the N category for the pancreas (Figures
18.3, 18.4). Anatomic division of the regional lymph nodes is not necessary;
however, separately submitted lymph nodes should be reported as submitted.
Metastatic Sites. Distant spread occurs commonly to the liver, peritoneal
cavity, and lungs. Metastases to other sites are uncommon (or rarely detected),
18
Superior to head
Cystic duct node
Pyloric
Hepatic nodes
Splenic nodes
Superior
to body
Inferior
to head
Inferior
to body
Inferior to tail
Superior
pancreaticoduodenal nodes
(Anterior and posterior)
Inferior
pancreaticoduodenal nodes
(Anterior and posterior)
Inferior pancreatic nodes
Superior pancreatic nodes
Hilum
of spleen
Superior
to tail
FIGURE 18.3. Regional lymph nodes of the pancreas (anterior view).
158 American Joint Committee on Cancer • 2006
possibly because of the short interval from diagnosis of distant metastasis to
death.
DEFINITIONS
Primary Tumor (T)
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
Tis Carcinoma in situ
T1 Tumor limited to the pancreas 2 cm or less in greatest dimension (Figure
18.5)
T2 Tumor limited to the pancreas more than 2 cm in greatest dimension
(Figure 18.5)
T3 Tumor extends beyond the pancreas but without involvement of the celiac
axis or the superior mesenteric artery (Figures 18.6A–C)
T4 Tumor involves the celiac axis or the superior mesenteric artery (unre-sectable primary tumor) (Figure 18.7)
Regional Lymph Nodes (N)
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Regional lymph node metastasis (Figures 18.8A–D)
Distant Metastasis (M)
MX Distant metastasis cannot be assessed
M0 No distant metastasis
M1 Distant metastasis
Superior mesenteric nodes
Hepatic
nodes
Celiac
nodes
Splenic
nodes
Superior
pancreatic
nodes
FIGURE 18.4. Regional lymph nodes of the pancreas (anterior view with
pancreatic body removed to reveal retroperitoneal vessels and lymph nodes).
American Joint Committee on Cancer • 2006 159
18
T1 T2
>2 cm
£2 cm
Portal vein
Aorta
Superior
mesenteric
artery
Celiac axis
Common
bile duct
Superior
mesenteric
vein
FIGURE 18.5. T1 (left of dotted line) is defined as tumor limited to the pancreas
2 cm or less in greatest dimension. T2 (right of dotted line) is defined as tumor
limited to the pancreas more than 2 cm in greatest dimension.
T3 T3
Peripancreatic
Portal vein Celiac axis
Common
bile duct
Superior
mesenteric
vein
Superior
mesenteric
artery
A
FIGURE 18.6. A. Two views of T3, which is defined as tumor that extends beyond
the pancreas but without involvement of the celiac axis or the superior mesenteric
artery. Left of the dotted line: tumor invades the common bile duct without
involving the superior mesenteric artery. Right of the dotted line: tumor invades
peripancreatic tissues without involving the celiac axis.
160 American Joint Committee on Cancer • 2006
T3
Duodenum
Portal vein Celiac axis
Superior
mesenteric
vein
Superior
mesenteric
artery
B
T3
Duodenum
Spleen
Portal vein
Aorta
Superior
mesenteric
vein
Superior
mesenteric
artery
Celiac axis
Common
bile duct
C
FIGURE 18.6. B. T3: tumor invades duodenum without involvement of the
superior mesenteric artery. C. T3: tumor invades spleen without involvement of
celiac axis or superior mesenteric artery.
American Joint Committee on Cancer • 2006 161
18
T4
T4
Duodenum
Portal vein
Aorta
Superior
mesenteric
vein
Superior
mesenteric
artery
Celiac axis
Common
bile duct
FIGURE 18.7. Two views of T4, which is defined as tumor involving the celiac axis
(above dotted line) or (below dotted line) the superior mesenteric artery
(unresectable primary tumor).
N1
Portal vein
Aorta
Superior
mesenteric
vein
Celiac axis
Common
bile duct
Body of
of pancreas
Tail of
of pancreas
Uncinate process
Head of pancreas
Superior
mesenteric
artery
A
FIGURE 18.8. A. N1 is defined as regional lymph node metastasis. Here, the
primary tumor and single nodal metastasis are located within the head of pancreas.
162 American Joint Committee on Cancer • 2006
N1
Portal vein
Aorta
Superior
mesenteric
vein
Celiac axis
Common
bile duct
Body of
of pancreas
Tail of
of pancreas
Uncinate process
Head of pancreas
Superior
mesenteric
artery
B
N1
Portal vein
Aorta
Superior
mesenteric
vein
Common
bile duct
Body of
of pancreas
Tail of
of pancreas
Uncinate process
Head of pancreas
C
FIGURE 18.8. N1 is defined as regional lymph node metastasis. B. Here, the
primary tumor and multiple nodal metastases are located in the head of pancreas.
C. Here, the primary tumor is located in the body of pancreas with multiple nodal
metastases in the head and body of pancreas.
American Joint Committee on Cancer • 2006 163
STAGE GROUPING
0 Tis N0 M0
IA T1 N0 M0
IB T2 N0 M0
IIA T3 N0 M0
IIB T1 N1 M0
T2 N1 M0
T3 N1 M0
III T4 Any N M0
IV Any T Any N M1
18
N1
Portal vein
Aorta
Superior
mesenteric
vein
Common
bile duct
Body of
of pancreas
Tail of
of pancreas
Uncinate process
Head of pancreas
D
FIGURE 18.8. D. N1 is defined as regional lymph node metastasis. Here, the
primary tumor is located in the tail of pancreas with multiple nodal metastases in
the tail of pancreas and hilum of spleen.
American Joint Committee on Cancer • 2006 167
19
Lung
(Sarcomas and other rare tumors are not included.)
19
SUMMARY OF CHANGES
• The definitions of TNM and the Stage Grouping for this chapter have not
changed from the Fifth Edition.
INTRODUCTION
Lung cancer is among the most common malignancies in the Western world and
is the leading cause of cancer deaths in both men and women. It is one of the
few tumors with a known carcinogen, namely tobacco, contributing to its etiol-ogy. In recent years we have come to appreciate that the initiation of lung cancer
is a complex process that also involves certain biologic factors, such as the body’s
ability to process carcinogens. This disease is usually not diagnosed early, and
therefore the overall 5-year survival rate is approximately 15%. The treatment
of lung cancer depends on the extent of disease, the location of the primary
tumor, and the presence or absence of medical comorbidities. The assessment
of extrapulmonary intrathoracic and extrathoracic metastasis is important for
staging and patient evaluation.
ANATOMY
Primary Site. Carcinomas of the lung arise either from the alveolar lining cells
of the pulmonary parenchyma or from the mucosa of the tracheobronchial tree.
The trachea, which lies in the middle mediastinum, divides into the right and
left main bronchi, which extend into the right and left lungs, respectively. The
bronchi then subdivide into the lobar bronchi for the upper, middle, and lower
lobes on the right and the upper and lower lobes on the left. The lungs are
encased in membranes called the visceral pleura. The inside of the chest cavity
is lined by a similar membrane called the parietal pleura. The potential space
between these two membranes is called the pleural space. The mediastinum con-tains the heart, thymus, great vessels, and other structures between the lungs.
The great vessels include:
Aorta
Superior vena cava
Inferior vena cava
Main pulmonary artery
Intrapericardial segments of the trunk of the right and left pulmonary artery
Intrapericardial segments of the superior and inferior right and left pulmonary
veins
C34.0 Main bronchus
C34.1 Upper lobe, lung
C34.2 Middle lobe, lung
C34.3 Lower lobe, lung
C34.8 Overlapping lesion of
lung
C34.9 Lung, NOS
168 American Joint Committee on Cancer • 2006
The main anatomical subsites are shown in Figure 19.1:
C34.0: Main bronchus
C34.1: Upper lobe
C34.2: Middle lobe
C34.3: Lower lobe
Regional Lymph Nodes. All regional lymph nodes are above the diaphragm.
They include the intrathoracic, scalene, and supraclavicular nodes. For purposes
of staging, the intrathoracic nodes include the following:
Mediastinal:
Paratracheal (including those that may be designated tracheobronchial—that is,
lower paratracheal, including azygous)
Pre- and retrotracheal (includes precarinal)
Aortic (includes aortopulmonary window, periaortic, ascending aortic, and
phrenic)
Subcarinal
Periesophageal
Inferior pulmonary ligament
Intrapulmonary:
Hilar (proximal lobar)
Peribronchial
Intrapulmonary (includes interlobar, lobar, and segmental)
Figure 19.2 illustrates lymph node maps of the lungs. All N1 nodes lie distal to
the mediastinal pleural reflection and within the visceral pleura. All N2 nodes lie
within the mediastinal pleural envelope on the ipsilateral side.
C34.1
C34.3
C34.1
C34.3
C34.3
C34.0
FIGURE 19.1. Anatomic subsites of the lung.
American Joint Committee on Cancer • 2006 169
Distant Metastatic Sites. The most common metastatic sites are the brain,
bones, adrenal glands, contralateral lung, liver, pericardium, and kidneys.
However, virtually any organ can be a site of metastases.
DEFINITIONS OF TNM
Primary Tumor (T)
TX Primary tumor cannot be assessed, or tumor proven by the presence of
malignant cells in sputum or bronchial washings but not visualized by
imaging or bronchoscopy
T0 No evidence of primary tumor
Tis Carcinoma in situ
T1 Tumor 3 cm or less in greatest dimension, surrounded by lung or visceral
pleura, without bronchoscopic evidence of invasion more proximal than
the lobar bronchus(1)
(i.e., not in the main bronchus) (Figure 19.3)
T2 Tumor with any of the following features of size or extent (Figure 19.4):
• More than 3 cm in greatest dimension
• Involves main bronchus, 2 cm or more distal to the carina
• Invades the visceral pleura
• Associated with atelectasis or obstructive pneumonitis that extends to
the hilar region but does not involve the entire lung
T3 Tumor of any size that directly invades any of the following: chest wall
(including superior sulcus tumors), diaphragm, mediastinal pleura, pari-etal pericardium; or tumor in the main bronchus less than 2 cm distal to
19
1 Highest medistinal
2 Upper paratracheal
3 Prevascular and retrotracheal
4 Lower paratracheal
N1 nodes:
10 Hilar
11 Interlobar
12 Lobar nodes bronchi
13 Segmental
14 Subsegmental
A
Azygus
v.
Inferior
pulmonary ligament
Ligamentum
arteriosum
PA
PA
Ao
B
3a
6
5
3p
1R
2R
4R
10
10
11
11
12
11
11
1213
13 13
1314
14
14
14
14
4L
7
8
9 9
2L
1L
5 Subaortic
6 Para-aortic
7 Subcarinal
8 Paraesophageal
9 Pulmonary ligament
N2 nodes:
Ao
Brachiocephalic
(innominate) a.
FIGURE 19.2. Lymph node maps of the lung.
170 American Joint Committee on Cancer • 2006
T1 T1
£3 cm
£3 cm
FIGURE 19.3. Two views of T1 showing tumor 3 cm or less in greatest dimension.
T2 T2
T2 T2
Atelectasis or
obstructive
pneumonia
>3 cm
≥2 cm
≥2 cm
FIGURE 19.4. T2 is defined as a tumor with any of the following features of size or
extent: more than 3 cm in greatest dimension; involving main bronchus, 2 cm or
more distal to the carina; invades the visceral pleura; associated with atelectasis or
obstructive pneumonitis that extends to the hilar region but does not involve the
entire lung.
American Joint Committee on Cancer • 2006 171
the carina, but without involvement of the carina; or associated atelecta-sis or obstructive pneumonitis of the entire lung (Figure 19.5)
T4 Tumor of any size that invades any of the following: mediastinum, heart,
great vessels, trachea, esophagus, vertebral body, carina; or separate tumor
nodules in the same lobe; or tumor with malignant pleural effusion(2)
(Figures 19.6A–E)
19
T3
T3
T3 T3
£2 cm
Atelectasis or
obstructive
pneumonia of
the entire lung
Pleural effusion
with negative
cytology
FIGURE 19.5. T3 is defined as a tumor of any size that directly invades any of the
following: chest wall (including superior sulcus tumors), diaphragm, mediastinal
pleura, parietal pericardium; or tumor in the main bronchus less than 2 cm distal
to the carina, but without involvement of the carina; or associated atelectasis or
obstructive pneumonitis of the entire lung.
T4
Great
vessels
Heart
A
FIGURE 19.6. A. Tumor invasion of the heart and great vessels.
172 American Joint Committee on Cancer • 2006
Regional Lymph Nodes (N)
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Metastasis to ipsilateral peribronchial and/or ipsilateral hilar lymph nodes,
and intrapulmonary nodes including involvement by direct extension of
the primary tumor (Figure 19.7)
N2 Metastasis to ipsilateral mediastinal and/or subcarinal lymph nodes(s)
(Figure 19.8)
N3 Metastasis to contralateral mediastinal, contralateral hilar, ipsilateral or
contralateral scalene, or supraclavicular lymph node(s) (Figure 19.9)
T4
Heart
Superior
vena cava
B
T4
Aorta
Esophagus
Vertebral body
C
FIGURE 19.6. B. Tumor invasion of the superior vena cava and heart. C. Tumor
invasion of the aorta, esophagus, and vertebral body.
American Joint Committee on Cancer • 2006 173
19
T4 M1
Tumor nodule
Primary tumor
Primary tumor
Separate tumor
nodule
D
T4
Malignant
pleural effusion
E
FIGURE 19.6. D. N1 is defined as a separate tumor nodule(s) in the same lobe. M1
is defined as a separate tumor nodule(s) in a different lobe (ipsilateral or
contralateral). E. Tumor with malignant pleural effusion (see note 2).
Distant Metastasis (M)
MX Distant metastasis cannot be assessed
M0 No distant metastasis
M1 Distant metastasis present(3)
(Figure 19.9)
174 American Joint Committee on Cancer • 2006
N1
Peribronchial
N1
Hilar
FIGURE 19.7. N1 is defined as metastasis to ipsilateral peribronchial (left side of
diagram) and/or ipsilateral hilar lymph nodes (right side of diagram), and
intrapulmonary nodes including involvement by direct extension of the primary
tumor.
N2
Ipsilateral mediastinal
N2
Subcarinal
FIGURE 19.8. N2 is defined as metastasis to ipsilateral mediastinal (right side of
diagram) and/or subcarinal lymph nodes(s) (left side of diagram).
American Joint Committee on Cancer • 2006 175
19
M1
N3
N3
FIGURE 19.9. N3 is defined as metastasis to contralateral mediastinal, contralateral
hilar, ipsilateral or contralateral scalene, or supraclavicular lymph node(s) whereas
M1 is defined as distant metastasis.
STAGE GROUPING
Occult carcinoma TX N0 M0
0 Tis N0 M0
IA T1 N0 M0
IB T2 N0 M0
IIA T1 N1 M0
IIB T2 N1 M0
T3 N0 M0
IIIA T1 N2 M0
T2 N2 M0
T3 N1 M0
T3 N2 M0
IIIB Any T N3 M0
T4 Any N M0
IV Any T Any N M1
NOTES
1. The uncommon superficial tumor of any size with its invasive component limited
to the bronchial wall, which may extend proximal to the main bronchus, is also
classified T1.
2. Most pleural effusions associated with lung cancer are due to tumor. However,
there are a few patients in whom multiple cytopathologic examinations of pleural
fluid are negative for tumor. In these cases, fluid is non-bloody and is not an
176 American Joint Committee on Cancer • 2006
exudate. Such patients may be further evaluated by videothoracoscopy (VATS) and
direct pleural biopsies. When these elements and clinical judgment dictate that the
effusion is not related to the tumor, the effusion should be excluded as a staging
element and the patient should be staged T1, T2, or T3.
3. M1 includes separate tumor nodule(s) in a different lobe (ipsilateral or
contralateral).
American Joint Committee on Cancer • 2006 177
20
Pleural Mesothelioma
(Tumors metastatic to the pleura and lung tumors that have extended to the pleural surfaces
are not included.)
20
SUMMARY OF CHANGES
• The AJCC has adopted the staging system proposed by the International
Mesothelioma Working Group (IMIG) in 1995. It is based on updated informa-tion about the relationships between tumor (T) and N status and overall sur-vival. This staging system applies only to tumors arising in the pleura.
• T categories have been redefined
• T1 lesions have been divided into T1a and T1b, leading to the division of Stage
I into Stage IA and Stage IB.
• T3 is defined as locally advanced but potentially resectable tumor.
• T4 is defined as locally advanced, technically unresectable tumor.
• Stage II no longer involves tumors with nodal metastasis; all nodal metastasis is
categorized in Stage III or Stage IV.
C38.4 Pleura NOS
INTRODUCTION
Malignant mesotheliomas are relatively rare tumors that arise from the mesothe-lium lining the pleural, pericardial, and peritoneal cavities. They represent less
than 2% of all malignant tumors. The most common risk factor for malignant
mesotheliomas is previous exposure to asbestos. The latency period between
asbestos exposure and the development of malignant mesothelioma is generally
20 years or more. Although peritoneal mesotheliomas are thought to occur in
individuals who have had heavier exposure than those with pleural mesothe-lioma, there is no clearly documented relationship between the amount of
asbestos exposure and the subsequent development of this neoplasm. Malignant
mesotheliomas were previously thought to be virulent tumors. However, this
impression was probably related to the fact that most mesotheliomas are diag-nosed when they are already at an advanced stage. Recent data indicate that the
clinical and biological behavior of mesotheliomas is variable and that most
mesotheliomas grow relatively slowly.
All mesotheliomas are fundamentally epithelial tumors. However, their
morphology ranges from a pure epithelial appearance to an entirely sarco-matoid or even desmoplastic appearance. Distinguishing the pleiomorphic his-tology of mesotheliomas from that of other neoplasms can be difficult, especially
for the pure epithelial mesotheliomas, which may closely resemble metastatic
adenocarcinoma. Therefore, confirmation of the histologic diagnosis by
immunohistochemistry and/or electron microscopy is essential.
During the past 30 years, many staging systems have been proposed for
malignant pleural mesothelioma. The first staging system for this disease
178 American Joint Committee on Cancer • 2006
published by the American Joint Committee on Cancer (AJCC), and simulta-neously accepted by the International Union Against Cancer, appeared in the
fifth edition of the AJCC Cancer Staging Manual. The staging system described
here represents adoption of the one proposed in 1995 by the International
Mesothelioma Interest Group (IMIG), which is based on updated information
about the relationships between tumor (T) and N status and overall survival.
Although this system has been validated by several surgical reports, it will prob-ably require revision in the future as further data in larger numbers of patients
become available. This staging system applies only to tumors arising in the
pleura. Peritoneal and pericardial mesotheliomas are rare and do not lend them-selves easily to a TNM staging system.
ANATOMY
Primary Site. The mesothelium covers the external surface of the lungs and
the inside of the chest wall. It is usually composed of flat, tightly connected cells
no more than one layer thick.
Regional Lymph Nodes. The regional lymph nodes include internal
mammary, intrathoracic, scalene, and supraclavicular. The regional lymph node
map and nomenclature adopted for the mesothelioma staging system is identi-cal to that used for lung cancer. See Chapter 19 and Figure 19.2 for a detailed
list and diagram of intrathoracic lymph nodes. For pN, histologic examination
of a mediastinal lymphadenectomy or lymph node sampling specimen will
ordinarily include regional nodes taken from the ipsilateral N1 and N2 nodal
stations. Contralateral and supraclavicular nodes may be available if a
mediastinoscopy or node biopsy is also performed.
Distant Metastatic Sites. Advanced malignant pleural mesotheliomas often
metastasize widely to uncommon sites, including retroperitoneal lymph nodes,
the brain and spine, or even organs such as the thyroid or prostate. However,
the most frequent sites of metastatic disease are the peritoneum, contralateral
pleura, and lung.
DEFINITIONS OF TNM
IMIG Staging System for Diffuse Malignant Pleural Mesothelioma
Primary Tumor (T)
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
T1 Tumor involves ipsilateral parietal pleura, with or without focal involve-ment of visceral pleura
T1a Tumor involves ipsilateral parietal (mediastinal, diaphragmatic) pleura;
no involvement of the visceral pleura (Figure 20.1)
T1b Tumor involves ipsilateral parietal (mediastinal, diaphragmatic) pleura,
with focal involvement of the visceral pleura (Figure 20.1)
T2 Tumor involves any of the ipsilateral pleural surfaces with at least one of
the following (Figure 20.2):
American Joint Committee on Cancer • 2006 179
20
T1a T1b
Visceral pleura
Parietal pleura
FIGURE 20.1. T1a (left) shows no involvement of the visceral pleura. T1b (right)
involves ipsilateral parietal pleura, with focal involvement of the visceral pleura.
T2
Lung
parenchyma
Diaphragm
FIGURE 20.2. T2 involves any of the ipsilateral pleural surfaces with at least one of
the following: confluent visceral pleural tumor (including fissure); invasion of
diaphragmatic muscle (as illustrated); and/or invasion of lung parenchyma (as
illustrated).
180 American Joint Committee on Cancer • 2006
• Confluent visceral pleural tumor (including fissure)
• Invasion of diaphragmatic muscle
• Invasion of lung parenchyma
T3(1)
Tumor involves any of the ipsilateral pleural surfaces, with at least one of
the following (Figure 20.3):
• Invasion of the endothoracic fascia
• Invasion into mediastinal fat
• Solitary focus of tumor invading the soft tissues of the chest wall
• Non-transmural involvement of the pericardium
T4(2)
Tumor involves any of the ipsilateral pleural surfaces, with at least one of
the following (Figure 20.4):
• Diffuse or multifocal invasion of soft tissues of the chest wall
• Any involvement of rib
• Invasion through the diaphragm to the peritoneum
• Invasion of any mediastinal organ(s)
• Direct extension to the contralateral pleura
• Invasion into the spine
• Extension to the internal surface of the pericardium
• Pericardial effusion with positive cytology
• Invasion of the myocardium
• Invasion of the brachial plexus
T3
Chest wall
FIGURE 20.3. T3 involves any of the ipsilateral pleural surfaces, with at least one
of the following: invasion of the endothoracic fascia; invasion into mediastinal fat;
solitary focus of tumor invading the soft tissues of the chest wall (as illustrated);
and/or non-transmural involvement of the pericardium.
American Joint Committee on Cancer • 2006 181
Regional Lymph Nodes (N)
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastases
N1 Metastases in the ipsilateral bronchopulmonary and/or hilar lymph
node(s)
N2 Metastases in the subcarinal lymph node(s) and/or the ipsilateral internal
mammary or mediastinal lymph node(s)
N3 Metastases in the contralateral mediastinal, internal mammary, or hilar
lymph node(s), and/or the ipsilateral or contralateral supraclavicular or
scalene lymph node(s)
Distant Metastasis (M)
MX Distant metastasis cannot be assessed
M0 No distant metastasis
M1 Distant metastasis
STAGE GROUPING
IT1N0M0
IA T1a N0 M0
IB T1b N0 M0
II T2 N0 M0
20
T4
Aorta
FIGURE 20.4. T4 involves any of the ipsilateral pleural surfaces with at least one
additional parameter, such as extension to the internal surface of the pericardium
as illustrated here. (The full list of additional parameters is provided under
Definitions of TNM.)
182 American Joint Committee on Cancer • 2006
III T1, T2 N1 M0
T1, T2 N2 M0
T3 N0, N1, N2 M0
IV T4 Any N M0
Any T N3 M0
Any T Any N M1
NOTES
1. T3 describes locally advanced but potentially resectable tumor.
2. T4 describes locally advanced, technically unresectable tumor.
American Joint Committee on Cancer • 2006 185
21
Bone
(Primary malignant lymphoma and multiple myeloma are not included.)
21
SUMMARY OF CHANGES
• T1 has changed from “Tumor confined within the cortex” to “Tumor 8 cm or less
in greatest dimension.”
• T2 has changed from “Tumor invades beyond the cortex” to “Tumor more than
8 cm in greatest dimension.”
• T3 designation of skip metastasis is defined as “Discontinuous tumors in the
primary bone site.” This designation is a Stage III tumor that was not previously
defined.
• M1 lesions have been divided into M1a and M1b.
• M1a is lung-only metastases.
• M1b is metastases to other distant sites, including lymph nodes.
• In the Stage Grouping, Stage IVA is M1a, and Stage IVB is M1b.
INTRODUCTION
This classification is used for all primary malignant tumors of bone except
primary malignant lymphoma and multiple myeloma. Cases are categorized by
histological type (e.g., osteosarcoma, chondrosacrcoma) and by histologic grade
of differentiation.
ANATOMY
Primary Site. All bones of the skeleton.
Regional Lymph Nodes. Regional lymph node metastasis from bone tumors
is extremely rare.
Metastatic Sites. A metastatic site includes any site beyond the regional lymph
nodes of the primary site. Spread to the lungs is frequent.
C40.0 Long bones of upper
limb, scapula, and
associated joints
C40.1 Short bones of upper
limb and associated
joints
C40.2 Long bones of lower
limb and associated
joints
C40.3 Short bones of lower
limb and associated
joints
C40.8 Overlapping lesion of
bones, joints, and
articular cartilage of
limbs
C40.9 Bone of limb, NOS
C41.0 Bones of skull and
face and associated
joints
C41.1 Mandible
C41.2 Vertebral column
C41.3 Rib, sternum, clavicle,
and associated joints
C41.4 Pelvic bones, sacrum,
coccyx, and associated
joints
C41.8 Overlapping lesion of
bones, joints, and
articular cartilage
C41.9 Bone, NOS
186 American Joint Committee on Cancer • 2006
DEFINITIONS
Primary Tumor (T)
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
T1 Tumor 8 cm or less in greatest dimension (Figure 21.1)
T2 Tumor more than 8 cm in greatest dimension (Figure 21.2A, B)
T3 Discontinuous tumors in the primary bone site (Figure 21.3)
T1 T1
<8 cm
Cortex
<8 cm
FIGURE 21.1. T1 is defined as tumor less than 8 cm in greatest dimension whether
the tumor is confined within the cortex or invades beyond the cortex.
T2
>8 cm
Cortex
A
Cortex
T2
>8 cm
B
FIGURE 21.2. A. T2 is defined as tumor more than 8 cm in greatest dimension
whether the tumor is confined within the cortex or invades beyond the cortex.
B. T2 is defined as tumor more than 8 cm in greatest dimension whether the tumor
is confined within the cortex or invades beyond the cortex.
American Joint Committee on Cancer • 2006 187
Regional Lymph Nodes (N)
NX Regional lymph nodes cannot be assessed(1)
N0 No regional lymph node metastasis
N1 Regional lymph node metastasis
Distant Metastasis (M)
MX Distant metastasis cannot be assessed
M0 No distant metastasis
M1 Distant metastasis
M1a Lung (Figure 21.4)
M1b Other distant sites (Figure 21.5)
Histologic Grade (G)
GX Grade cannot be assessed
G1 Well differentiated—Low grade
G2 Moderately differentiated—Low grade
G3 Poorly differentiated—High grade
G4 Undifferentiated—High grade(2)
STAGE GROUPING
IA T1 N0 M0 G1,2 Low grade
IB T2 N0 M0 G1,2 Low grade
IIA T1 N0 M0 G3,4 High grade
IIB T2 N0 M0 G3,4 High grade
III T3 N0 M0 Any G
IVA Any T N0 M1a Any G
IVB Any T N1 Any M Any G
Any T Any N M1b Any G
21
T3
Cortex
Discontinuous
tumors
FIGURE 21.3. T3 is defined as discontinuous tumors in the primary bone site.
188 American Joint Committee on Cancer • 2006
FIGURE 21.5. M1b is
defined as metastases to
other distant sites,
including lymph nodes.
FIGURE 21.4. M1a is defined as lung-only metastases.
Primary
tumor
Metastasis (node)
Metastasis (node)
Metastasis (node)
Metastasis (bone)
Primary
tumor
Metastasis
American Joint Committee on Cancer • 2006 189
21
NOTES
1. Because of the rarity of lymph node involvement in sarcomas, the designation NX
may not be appropriate and could be considered N0 if no clinical involvement is
evident.
2. Ewing’s sarcoma is classified as G4.
American Joint Committee on Cancer • 2006 191
22
Soft Tissue Sarcoma
(Kaposi’s sarcoma, dermatofibrosarcoma protuberans, fibromatosis [desmoid tumor], and sarcoma
arising from the dura mater, brain, parenchymatous organs, or hollow viscera are not included.)
22
SUMMARY OF CHANGES
• Angiosarcoma and malignant mesenchymoma are no longer included in the list
of histologic types for this site.
• Gastrointestinal stromal tumor and Ewing’s sarcoma/primitive neuroectodermal
tumor have been added to the list of histologic types for this site.
• Fibrosarcoma grade I has been replaced by fibromatosis (desmoid tumor) in the
list of histologic types not included in this site.
• G 1–2, T2b, N0, M0 tumors have been reclassified as Stage I rather than Stage II
disease.
C38.0 Heart
C38.1 Anterior
mediastinum
C38.1 Posterior
mediastinum
C38.3 Mediastinum, NOS
C38.8 Overlapping lesion of
heart, mediastinum,
and pleura
C47.0 Peripheral nerves and
autonomic nervous
system of head, face,
and neck
C47.1 Peripheral nerves and
autonomic nervous
system of upper limb
and shoulder
C47.2 Peripheral nerves and
autonomic nervous
system of lower limb
and hip
C47.3 Peripheral nerves and
autonomic nervous
system of thorax
C47.4 Peripheral nerves and
autonomic nervous
system of abdomen
C47.5 Peripheral nerves and
autonomic nervous
system of pelvis
C47.6 Peripheral nerves and
autonomic nervous
system of trunk, NOS
C47.8 Overlapping lesion of
peripheral nerves and
autonomic nervous
system
C47.9 Autonomic nervous
system, NOS
C48.0 Retroperitoneum
C48.1 Specified parts of
peritoneum
C48.2 Peritoneum, NOS
C48.8 Overlapping lesion of
retroperitoneum and
peritoneum
C49.0 Connective, subcuta-neous, and other soft
tissues of head, face,
and neck
C49.1 Connective, subcuta-neous, and other soft
tissues of upper limb
and shoulder
C49.2 Connective, subcuta-neous, and other soft
tissues of lower limb
and hip
C49.3 Connective, subcuta-neous, and other soft
tissues of thorax
C49.4 Connective, subcuta-neous, and other soft
tissues of abdomen
C49.5 Connective, subcuta-neous, and other soft
tissues of pelvis
C49.6 Connective, subcuta-neous, and other soft
tissues of trunk, NOS
C49.7 Overlapping lesion of
connective, subcuta-neous, and other soft
tissues
C49.9 Connective, subcuta-neous, and other soft
tissues, NOS
INTRODUCTION
The staging system applies to all soft tissue sarcomas except Kaposi’s sarcoma,
dermatofibrosarcoma, infantile fibrosarcoma, and angiosarcoma. In addition,
sarcomas arising within the confines of the dura mater, including the brain, and
sarcomas arising in parenchymatous organs and from hollow viscera are not
optimally staged by this system.
192 American Joint Committee on Cancer • 2006
Data to support this staging system are based on current analyses from mul-tiple institutions and represent the recommendations of an AJCC task force on
soft tissue sarcoma. In the era of cytoreductive neoadjuvant treatments, clinical
and pathologic staging may be altered in the future. Because pathologic staging
drives adjuvant therapy decisions, patients should be restaged after neoadjuvant
therapies have been administered.
Histologic type, grade, and tumor size and depth are essential for staging.
Histologic grade of sarcoma is one of the most important parameters of the
staging system. Grade is based on analysis of various pathologic features of a
tumor, such as histologic subtype, degree of differentiation, mitotic activity, and
necrosis. Accurate grading requires an adequate sample of well-fixed tissue
for evaluation. Accurate grading is not always possible on the basis of needle
biopsies or in tumors that have been previously irradiated or treated with
chemotherapy.
The current staging system does not take into account anatomic site.
However, anatomic site is known to influence outcome, and therefore outcome
data should be reported specifying site. Generic grouping of site is accepted. The
following site groups can be used in reports that include sarcomas arising in
tissues other than soft tissues (such as parenchymal organs). Extremity and
superficial trunk can be combined; viscera, including all the intra-abdominal
viscera, can also be combined. Where enough numbers exist, these can be
reported by subdivision into the various components of the gastrointestinal
tract. Lung, gastrointestinal, genitourinary, and gynecologic sarcomas should be
grouped separately.
Site Groups for Soft Tissue Sarcomas
Head and neck
Extremity and superficial trunk
Gastrointestinal
Genitourinary
Visceral
Retroperitoneal
Gynecologic
Breast
Lung, pleura, mediastinum
Other
STAGING OF SOFT TISSUE SARCOMA
Inclusions. The present staging system applies to soft tissue sarcomas. Primary
sarcomas can arise from a variety of soft tissues. These tissues include fibrous
connective tissue, fat, smooth or striated muscle, vascular tissue, peripheral
neural tissue, and visceral tissue.
Regional Lymph Nodes. Involvement of regional lymph nodes by soft tissue
sarcomas is uncommon in adults. When present, regional nodal disease has
prognostic significance similar to that of visceral metastatic disease.
Metastatic Sites. Metastatic sites for soft tissue sarcoma are often dependent
on the original site of the primary lesion. For example, the most common site
American Joint Committee on Cancer • 2006 193
of metastatic disease for patients with extremity sarcomas is the lung, whereas
retroperitoneal and gastrointestinal sarcomas often have liver as the first site of
metastasis.
DEFINITIONS
Primary Tumor (T)
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
T1 Tumor 5 cm or less in greatest dimension
T1a Superficial tumor(1)
(Figure 22.1)
T1b Deep tumor (Figure 22.2)
T2 Tumor more than 5 cm in greatest dimension
T2a Superficial tumor(1)
(Figure 22.1)
T2b Deep tumor (Figure 22.3)
22
T1a T2a
£5 cm >5 cm
FIGURE 22.1. T1a is defined as a superficial tumor 5 cm or less in greatest
dimension and T2a is defined as a superficial tumor more than 5 cm in greatest
dimension.
T1b
£5 cm
FIGURE 22.2. T1b is a deep tumor 5 cm or
less in greatest dimension.
194 American Joint Committee on Cancer • 2006
Regional Lymph Nodes (N)
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Regional lymph node metastasis
Distant Metastasis (M)
MX Distant metastasis cannot be assessed
M0 No distant metastasis
M1 Distant metastasis
Histologic Grade (G)
GX Grade cannot be assessed
G1 Well differentiated
G2 Moderately differentiated
G3 Poorly differentiated
G4 Poorly differentiated or undifferentiated (four-tiered systems only)(2)
STAGE GROUPING
IA T1a N0 NX M0 G1–2 G1 Low
T1b N0 NX M0 G1–2 G1 Low
IB T2a N0 NX M0 G1–2 G1 Low
T2b N0 NX M0 G1–2 G1 Low
IIA T1a N0 NX M0 G3–4 G2–3 High
T1b N0 NX M0 G3–4 G2–3 High
IIB T2a N0 NX M0 G3–4 G2–3 High
III T2b N0 NX M0 G3–4 G2–3 High
IV Any T N1 M0 Any G Any G High or Low
Any T Any N M1 Any G Any G High or Low
NOTES
1. Superficial tumor is located exclusively above the superficial fascia without inva-sion of the fascia; deep tumor is located either exclusively beneath the superficial
fascia, superficial to the fascia with invasion of or through the fascia, or both super-ficial yet beneath the fascia. Retroperitoneal, mediastinal, and pelvic sarcomas are
classified as deep tumors.
2. Ewing’s sarcoma is classified as G4.
T2b
>5 cm
FIGURE 22.3. T2b is a deep tumor more
than 5 cm in greatest dimension.
American Joint Committee on Cancer • 2006 197
23
Carcinoma of the Skin
(Excluding Eyelid, Vulva, and Penis)
23
SUMMARY OF CHANGES
• The definitions of TNM and the Stage Groupings for this chapter have not
changed from the Fifth Edition.
INTRODUCTION
This chapter applies to non-melanomatous cancers of the skin, which are pre-dominantly basal cell carcinomas and squamous cell carcinomas. Skin cancers
are largely related to solar exposure and are relatively common, although their
frequency varies with geographical latitude and population at risk. For example,
they occur in 729 individuals per 100,000 population in Hawaii but in only 195
per 100,000 in the northern United States. Higher rates are found in Australia
and New Zealand, and the incidence generally is rising rapidly. Basal cell carci-nomas are the most common cancer in humans, and are four to five times more
common than squamous cell carcinomas of the skin. For the most part, non-melanomatous skin cancers have a good prognosis and nearly always can be
treated with curative intent.
ANATOMY
Primary Site. The skin is made up of three layers: an outermost epidermis, a
middle dermis, and an inner subcutis. The epidermis consists predominantly of
stratified squamous epithelium, the outermost layer of which is keratinized. The
innermost layer consists primarily of germinative cells and melanocytes. The
dermis is made up of connective tissue and elastic fibers immersed in an amor-phous matrix of mucoproteins and mucopolysaccharides. The subcutis is pre-dominantly adipose tissue. The sebaceous and other glands of the skin, as well as
the hair follicles—collectively called adnexal structures—are found in the dermis
and subjacent subcutis. All of the components of the skin (epidermis, dermis, and
adnexal structures within the subcutis) can give rise to malignant neoplasms.
Cancers of the skin most commonly arise on those surfaces exposed to sun-light (including the face, ears, hands, and scalp, especially in balding men) and
the role of sunlight in the induction of cutaneous cancer has been well described.
Approximately four-fifths of all cutaneous squamous cell cancers and approxi-mately two-thirds of all basal cell cancers occur in unprotected sun-exposed skin
of lightly pigmented persons. Squamous cell carcinoma can also arise in skin
C44.0 Skin of lip, NOS
C44.2 External ear
C44.3 Skin of other and
unspecified parts of
face
C44.4 Skin of scalp and neck
C44.5 Skin of trunk
C44.6 Skin of upper limb
and shoulder
C44.7 Skin of lower limb
and hip
C44.8 Overlapping lesion of
skin
C44.9 Skin, NOS
C63.2 Scrotum, NOS
198 American Joint Committee on Cancer • 2006
that was previously scarred or ulcerated—that is, at sites of burns and chronic
ulcers. Radiation in other than ultraviolet forms, chemicals, and genetic syn-dromes are also proven causes of cutaneous carcinomas.
Skin cancers rarely cause symptoms. Signs vary depending on the local site
of origin and whether the precursor lesion is an actinic keratosis or a cutaneous
ulcer. Squamous cell tumors developing at the site of actinic keratoses usually
begin as hyperkeratotic papules or plaques or as ulcers. Induration, which is
usually absent in actinic keratoses, may develop early in squamous cell cancer.
Further progression is associated with thickening of the plaque, ulceration, and
bleeding. Tumors that arise in cutaneous ulcers or burn scars present as an
expanding mass at the site. High-risk tumors (higher local recurrence rate or
high risk for metastasis) are found on the lip, scalp, ears, eyelids, and nose.
Basal cell carcinomas initially appear clinically as firm, translucent papules
coursed by telangiectatic blood vessels. Central areas of crusting and depression,
associated with ulceration, usually occur late. Bleeding, however, may be
described in early as well as late lesions. Pigmentation occurs uncommonly and
may lead clinically to confusion with cutaneous melanoma. Morpheaform basal
cell carcinoma (basal cell carcinoma with a fibrotic component) may look and
feel like patches of scleroderma, or a scar, and is generally without telangiecta-sia or measurable elevation.
Primary Growth. Local extension is the predominant mode of growth of non-melanomatous skin cancers. Basal cell carcinomas that remain untreated for
long periods will eventually erode adjacent structures, such as bone, and into
local vasculature. Perineural invasion in morpheaform basal cell cancers is often
observed, and it is associated with a high rate of incomplete excision and recur-rence. Squamous cell carcinoma may also penetrate into other local structures,
including muscle, bone, and vasculature.
Regional Lymph Nodes. Skin cancers characteristically spread by local exten-sion. Involvement of regional lymph nodes infrequently occurs and is usually
associated with large size and invasiveness into the dermis and subcutaneous fat.
Which specific lymph node chains are involved depends on the location of the
primary lesion, because tumor cells are passively borne along with the “drain-ing” lymphatic fluid, usually to the geographically closest node(s). Regional
lymph node chains are illustrated in Figures 23.1, 23.2, and 23.3. In this context,
Parotid, preauricular
and facial
Submandibular (submaxillary)
Lymph nodes overlying
thyroid cartilage
Inferior deep jugular,
prelaryngeal and
paratracheal
Auricular
and occipital
Superior
deep jugular
Spinal accessory
Supraclavicular
Retropharyngeal
C77.0
FIGURE 23.1. C77.0, regional lymph nodes of the head and neck.
American Joint Committee on Cancer • 2006 199
23
Axillary
(C77.3)
Inguinal
(C77.4)
Epitrochlear
(C77.3)
FIGURE 23.2. C77.3, axillary and epitrochlear lymph nodes, and C77.4, inguinal
lymph nodes.
Popliteal
(C77.4)
FIGURE 23.3. C77.4, popliteal lymph nodes.
200 American Joint Committee on Cancer • 2006
Tis
Epidermis
Papillary dermis
Reticular dermis
Subcutaneous tissue
T1
£2 cm
FIGURE 23.4. Carcinoma in situ.
FIGURE 23.5. T1 is defined as a tumor 2 cm or
less in greatest dimension.
for tumors of the lower torso or lower extremities, the inguinal nodes are con-sidered the regional basin and should be designated N1. For pN (pathologic
staging), histologic examination of a regional lymphadenectomy specimen
should include careful examination of all resected nodes.
Hematogenously Borne Metastases. Basal cell and squamous cell cancers
that arise in actinically damaged skin are relatively slow growing and rarely
metastasize. Metastases are more likely to arise from squamous cell tumors that
originate in scars or ulcers. Tumors that metastasize have often been present for
a long time before metastases are observed. The most common visceral metasta-tic site is the lung, especially for squamous cell carcinomas. Other sites of distant
spread are unusual. Non-melanoma skin cancers arising in transplant patients
may be more aggressive and may metastasize more readily and more widely.
DEFINITIONS
Primary Tumor (T)
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
Tis Carcinoma in situ (Figure 23.4)
T1 Tumor 2 cm or less in greatest dimension (Figure 23.5)
T2 Tumor more than 2 cm, but not more than 5 cm, in greatest dimension
(Figure 23.6)
American Joint Committee on Cancer • 2006 201
23
T2
>2-5 cm
FIGURE 23.6. T2 is defined as a tumor more
than 2 cm, but not more than 5 cm, in greatest
dimension.
T3
>5 cm
FIGURE 23.7. T3 is defined as a tumor more
than 5 cm in greatest dimension.
T4
Epidermis
Papillary dermis
Reticular dermis
Subcutaneous tissue
Cartilage, skeletal
muscle, bone
FIGURE 23.8. T4 is defined as tumor invading deep extradermal structures such as
cartilage, skeletal muscle, or bone.
T3 Tumor more than 5 cm in greatest dimension (Figure 23.7)
T4 Tumor invades deep extradermal structures (i.e., cartilage, skeletal muscle,
or bone) (Figure 23.8)
Note: In case of multiple simultaneous tumors, the tumor with the highest T
category will be classified and the number of separate tumors will be indicated
in parentheses, e.g., T2 (5) (Figure 23.9).
202 American Joint Committee on Cancer • 2006
Regional Lymph Nodes (N)
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Regional lymph node metastasis
Distant Metastasis (M)
MX Distant metastasis cannot be assessed
M0 No distant metastasis
M1 Distant metastasis
Figure 23.10 illustrates the designation of N1 (Stage III disease) based upon
metastasis to regional lymph nodes vs. the designation of M1 (Stage IV disease)
defined by distant metastasis, in this case to lymph nodes outside the region of
the primary tumor. Figures 23.11, 23.12, 23.13, and 23.14 illustrate N1 (Stage
T2(5)
>2-5 cm
FIGURE 23.9. In the case of multiple
simultaneous tumors, the tumor with the
highest T category will be classified and the
number of separate tumors indicated in
parentheses.
Stage III Stage IV
N1
Primary
tumor
M1(LYM)
FIGURE 23.10. N1 disease is defined as
regional lymph node metastasis while M1
disease involves distant metastasis (here to
lymph nodes beyond the region of the
primary tumor).
American Joint Committee on Cancer • 2006 203
23
Stage IV
Stage IV
Stage IV Stage III
Primary
tumor
M1(LYM)
M1(LYM) N1
M1(LYM)
FIGURE 23.11.
Stage of disease as
determined by
lymph node
involvement
relative to the
location of the
primary tumor.
The shaded areas
indicate
involvement of
regional lymph
nodes or N1
disease (Stage III).
Nonshaded areas
indicate distant
metastasis to
lymph nodes
outside the
primary tumor or
M1 disease (Stage
IV).
Stage IV Stage III
Stage IV
Stage III
N1
M1(LYM)
N1
M1(LYM)
Primary
tumor
FIGURE 23.12.
Stage of disease as
determined by
lymph node
involvement
relative to the
location of the
primary tumor.
The shaded areas
indicate
involvement of
regional lymph
nodes or N1
disease (Stage III).
Nonshaded areas
indicate distant
metastasis to
lymph nodes
outside the
primary tumor or
M1 disease (Stage
IV).
204 American Joint Committee on Cancer • 2006
Stage IV Stage IV
Stage III Stage III
Primary
tumor
M1(LYM)
N1 N1
M1(LYM)
FIGURE 23.13.
Stage of disease as
determined by
lymph node
involvement
relative to the
location of the
primary tumor.
The shaded areas
indicate
involvement of
regional lymph
nodes or N1
disease (Stage III).
Nonshaded areas
indicate distant
metastasis to
lymph nodes
outside the
primary tumor or
M1 disease (Stage
IV).
Stage III Stage III
Stage III Stage III
N1
N1 N1
N1
Primary
tumor
FIGURE 23.14.
Stage of disease as
determined by
lymph node
involvement
relative to the
location of the
primary tumor.
The shaded areas
indicate
involvement of
regional lymph
nodes or N1
disease (Stage III).
Metastasis to either
the axillary or
inguinal lymph
nodes are both
considered N1
(Stage III) disease
due to the location
of the primary
tumor directly in
the center of the
torso.
American Joint Committee on Cancer • 2006 205
III) or M1 (Stage IV) disease based upon whether affected lymph nodes fall
within or beyond the regional nodal chain of the primary tumor. The shaded
areas in the figures indicate disease spread to regional lymph nodes for a classi-fication of N1 (Stage III).
STAGE GROUPING
0 Tis N0 M0
IT1N0M0
II T2 N0 M0
T3 N0 M0
III T4 N0 M0
Any T N1 M0
IV Any T Any N M1
23
American Joint Committee on Cancer • 2006 207
24
Melanoma of the Skin
24
SUMMARY OF CHANGES
• Melanoma thickness and ulceration, but not level of invasion, are used in the T
category (except for T1 melanomas).
• The number of metastatic lymph nodes, rather than their gross dimensions, and
the delineation of clinically occult (i.e., microscopic) vs. clinically apparent (i.e.,
macroscopic) nodal metastases are used in the N category.
• The site of distant metastases and the presence of elevated serum lactic dehy-drogenase (LDH) are used in the M category.
• All patients with Stage I, II, or III disease are upstaged when a primary melanoma
is ulcerated.
• Satellite metastases around a primary lesion and in-transit metastases have been
merged into a single staging entity that is grouped Stage IIIc disease.
• A new convention for defining clinical and pathologic staging has been devel-oped that takes into account the new staging information gained from intra-operative lymphatic mapping and sentinel node excision.
C44.0 Skin of lip, NOS
C44.1 Eyelid
C44.2 External ear
C44.3 Skin of other and
unspecified parts of
face
C44.4 Skin of scalp and
neck
C44.5 Skin of trunk
C44.6 Skin of upper limb
and shoulder
C44.7 Skin of lower limb
and hip
C44.8 Overlapping lesion of
skin
C44.9 Skin, NOS
C51 Vulva
C51.0 Labium majus
C51.1 Labium minus
C51.2 Clitoris
C51.8 Overlapping lesion of
vulva
C51.9 Vulva, NOS
C60 Penis
C60.0 Prepuce
C60.1 Glans penis
C60.2 Body of penis
C60.8 Overlapping lesion of
penis
C60.9 Penis, NOS
C63.2 Scrotum, NOS
INTRODUCTION
Melanoma of the skin continues to increase in frequency, with 47,700 new cases
and 9,200 deaths expected in 2005 (1). Melanoma can arise from skin anywhere
on the body. It occurs most commonly in fair-skinned persons, especially those
with a history of significant sun exposure.
A completely revised melanoma staging system is provided herein, along
with operational definitions. In addition, a major database analysis of prognos-tic factors involving 17,600 cancer patients from 13 cancer centers and organi-zations was performed to validate the staging categories and groupings (2).
Within each stage grouping and its subgroups, there is a uniform risk for distant
metastases and a uniform survival probability. This revised version of melanoma
staging more accurately reflects the prognosis and natural history of melanoma
and will therefore be more applicable to treatment planning and clinical trials
involving melanoma.
208 American Joint Committee on Cancer • 2006
ANATOMY
Primary Sites. Cutaneous melanoma can occur anywhere on the skin. It occurs
most commonly on the extremities in females and on the trunk in males. Mela-nomas located on the palms, soles, and nailbeds (acral lentiginous melanoma),
although they occur infrequently, are distinctive because they can occur in
individuals of any ethnic origin and in persons with no history of significant
sun exposure.
Regional Lymph Nodes. The regional lymph nodes are the most common site
of metastases. The widespread use of cutaneous lymphoscintigraphy, lymphatic
mapping, and sentinel lymph node biopsies has greatly enhanced the ability to
identify the presence or absence of, and to stage, nodal metastases. Intralym-phatic regional metastases may also become clinically manifest either as satellite
metastases (defined arbitrarily as intralymphatic metastases occurring within 2
cm of the primary melanoma) or as in-transit metastases (defined arbitrarily
as intralymphatic metastases occurring more than 2 cm from the primary
melanoma but before the first echelon of regional lymph nodes). By convention,
the term regional nodal metastases refers to disease confined to one nodal basin
or two contiguous nodal basins, as in patients with nodal disease in combina-tions of femoral/iliac, axillary/supraclavicular, cervical/supraclavicular, axil-lary/femoral, or bilateral axillary or femoral metastases.
Metastatic Sites. Melanoma can metastasize to virtually any organ site. Metas-tases most commonly occur in the skin or soft tissues, the lung, and the liver.
DEFINITIONS
Primary Tumor (T)
TX Primary tumor cannot be assessed (e.g., shave biopsy or regressed
melanoma)
T0 No evidence of primary tumor
Tis Melanoma in situ
T1 Melanoma £1.0 mm with or without ulceration (Figures 24.1A–D)
T1a Melanoma £1.0 mm in thickness and level II or III, no ulceration (Figure
24.2)
T1b Melanoma  £1.0 mm in thickness and level IV or V or with ulceration
(Figures 24.3A, B)
T2 Melanoma 1.01–2.0 mm in thickness with or without ulceration
T2a Melanoma 1.01–2.0 mm in thickness, no ulceration (Figure 24.4)
T2b Melanoma 1.01–2.0 mm in thickness, with ulceration (Figure 24.5)
T3 Melanoma 2.01–4.0 mm in thickness with or without ulceration
T3a Melanoma 2.01–4.0 mm in thickness, no ulceration (Figure 24.6)
T3b Melanoma 2.01–4.0 mm in thickness, with ulceration (Figure 24.7)
T4 Melanoma greater than 4.0 mm in thickness with or without ulceration
T4a Melanoma >4.0 mm in thickness, no ulceration (Figure 24.8)
T4b Melanoma >4.0 mm in thickness, with ulceration (Figure 24.9)
Regional Lymph Nodes (N)
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
American Joint Committee on Cancer • 2006 209
24
Clark level II Clark level III
Epidermis
A B
CD
Papillary dermis
Reticular dermis
Subcutaneous tissue
Clark level IV Clark level V
Epidermis
Papillary dermis
Reticular dermis
Subcutaneous tissue
FIGURE 24.1. A–D. The level of invasion, as defined by Dr. Wallace Clark, is used
to define subcategories of T1 melanomas but not for thicker melanomas (i.e., T2,
T3, or T4). A–D illustrate Clark levels II, III, IV, and V, respectively.
T1a
£1 mm
Epidermis
Papillary dermis
Reticular dermis
Subcutaneous tissue
FIGURE 24.2. T1a is defined as melanoma £1.0 mm in thickness, level II or III,
with no ulceration.
Epidermis
Papillary dermis
Reticular dermis
Subcutaneous tissue
T1b
£1 mm
A
FIGURE 24.3. A. T1b is defined as melanoma £1.0 mm in thickness, level IV or V,
or with ulceration. This figure illustrates T1b with level V invasion and no
ulceration.
210 American Joint Committee on Cancer • 2006
Epidermis
Papillary dermis
Reticular dermis
Subcutaneous tissue
T1b
£1 mm
Ulceration
B
FIGURE 24.3. B. T1b is illustrated here as melanoma £1.0 mm in thickness with
level II invasion and ulceration.
T2a
>1–2 mm
Epidermis
Papillary dermis
Reticular dermis
Subcutaneous tissue
FIGURE 24.4. T2a is defined as melanoma greater than 1.0 mm but not more than
2.0 mm in thickness without ulceration.
T2b
>1–2 mm
Ulceration
Epidermis
Papillary dermis
Reticular dermis
Subcutaneous tissue
T3a
>2–4 mm
Epidermis
Papillary dermis
Reticular dermis
Subcutaneous tissue
FIGURE 24.5. T2b is defined as melanoma greater than 1.0 mm but not more than
2.0 mm in thickness with ulceration.
FIGURE 24.6. T3a is defined as melanoma greater than 2.0 mm but not more than
4.0 mm in thickness without ulceration.
American Joint Committee on Cancer • 2006 211
N1 Metastasis in one lymph node
N1a Clinically occult (microscopic) metastasis (Figure 24.10)
N1b Clinically apparent (macroscopic) metastasis (Figure 24.11)
N2 Metastasis in 2 to 3 regional nodes or intralymphatic regional metastasis
without nodal metastasis
N2a Clinically occult (microscopic) metastasis (Figure 24.12)
N2b Clinically apparent (macroscopic) metastasis (Figure 24.13)
N2c Satellite or in-transit metastasis without nodal metastasis (Figure 24.14)
N3 Metastasis in four or more regional nodes, or matted metastatic nodes, or
in-transit metastasis or satellite(s) with metastasis in regional node(s)
(Figure 24.15)
24
T3b
>2–4 mm
Ulceration
Epidermis
Papillary dermis
Reticular dermis
Subcutaneous tissue
FIGURE 24.7. T3b is defined as melanoma greater than 2.0 mm but not more than
4.0 mm in thickness with ulceration.
T4a
>4 mm
Epidermis
Papillary dermis
Reticular dermis
Subcutaneous tissue
FIGURE 24.8. T4a is defined as melanoma >4.0 mm in thickness without
ulceration.
T4b
>4 mm
Ulceration
Epidermis
Papillary dermis
Reticular dermis
Subcutaneous tissue
FIGURE 24.9. T4b is defined as melanoma >4.0 mm in thickness with ulceration.
212 American Joint Committee on Cancer • 2006
N1a
Clinically occult
(non-palpable)
involved node
Primary
tumor
FIGURE 24.10. N1a is defined as clinically occult metastasis in one lymph node.
N1b
Clinically apparent
(palpable)
involved node
Primary
tumor
FIGURE 24.11. N1b is defined as clinically apparent metastasis in one lymph
node.
American Joint Committee on Cancer • 2006 213
24
N2a
Clinically occult
(non-palpable)
involved nodes
Primary
tumor
FIGURE 24.12. N2a is defined as clinically occult metastasis in 2–3 regional nodes.
N2b
Clinically apparent
(palpable)
involved nodes
Primary
tumor
FIGURE 24.13. N2b is defined as clinically apparent metastasis in 2–3 regional
lymph nodes.
214 American Joint Committee on Cancer • 2006
N2c
Primary
tumor
In-transit metastasis
without nodal
metastasis
FIGURE 24.14. N2c is defined as satellite or in-transit
metastasis without nodal metastasis. This figure
illustrates an in-transit metastasis, which is defined as
intralymphatic metastasis occurring more than 2 cm
from the primary melanoma but before the first
echelon of regional lymph nodes.
N3
Primary
tumor
Satellite
lesions
In-transit
metastasis
Matted nodes
FIGURE 24.15. N3 may be defined as metastasis in 4
or more regional nodes or matted metastatic nodes
(top) or as in-transit metastasis (middle) or satellite
lesions that occur within 2 cm of the primary tumor
(bottom).
American Joint Committee on Cancer • 2006 215
Distant Metastasis (M)
MX Distant metastasis cannot be assessed
M0 No distant metastasis
M1 Distant metastasis
M1a Metastasis to skin, subcutaneous tissues, or distant lymph nodes
M1b Metastasis to lung
M1c Metastasis to all other visceral sites or distant metastasis at any site asso-ciated with an elevated serum lactic dehydrogenase (LDH)
PATHOLOGIC STAGE GROUPING(1)
0 Tis N0 M0
IA T1a N0 M0
IB T1b N0 M0
T2a N0 M0
IIA T2b N0 M0
T3a N0 M0
IIB T3b N0 M0
T4a N0 M0
IIC T4b N0 M0
IIIA T1-4a N1a M0
T1-4a N2a M0
IIIB T1-4b N1a M0
T1-4b N2a M0
T1-4a N1b M0
T1-4a N2b M0
T1-4a/b N2c M0
IIIC T1-4b N1b M0
T1-4b N2b M0
Any T N3 M0
IV Any T Any N M1
CLINICAL STAGE GROUPING(2)
0 Tis N0 M0
IA T1a N0 M0
IB T1b N0 M0
T2a N0 M0
IIA T2b N0 M0
T3a N0 M0
IIB T3b N0 M0
T4a N0 M0
IIC T4b N0 M0
III Any T N1 M0
Any T N2 M0
Any T N3 M0
IV Any T Any N M1
24
216 American Joint Committee on Cancer • 2006
NOTES
1. Pathologic staging includes microstaging of the primary melanoma and path-ologic information about the regional lymph nodes after partial or complete
lymphadenectomy. Pathologic Stage 0 or Stage IA patients are the exception; they
do not require pathological evaluation of their lymph nodes.
2. Clinical staging includes microstaging of the primary melanoma and clinical/
radiologic evaluation for metastases. By convention, it should be used after com-plete excision.
REFERENCES
1. Jemal A, Taylor M, Ward E, et al. Cancer statistics, 2005. CA Cancer J Clin
55:10–30, 2005.
2. Balch C, Soong SJ, Gershenwald JE, Thompson JF, Reintgen DS, Cascinelli N,
Urist MM, McMasters KM, Ross MI, Kirkwood JM, Atkins MB, Thompson JA,
Coit DG, Byrd D, Desmond R, Zhang Y, Liu PY, Lyman GH, Morabito A. Prog-nostic factors analysis of 17,600 melanoma patients: Validation of the AJCC
melanoma staging system. J Clin Oncol 19:3622–3634, 2001.
American Joint Committee on Cancer • 2006 219
25
Breast
25
SUMMARY OF CHANGES
• Micrometastases are distinguished from isolated tumor cells on the basis of size
and histologic evidence of malignant activity.
• Identifiers have been added to indicate the use of sentinel lymph node dissection
and immunohistochemical or molecular techniques.
• Major classifications of lymph node status are designated according to the
number of involved axillary lymph nodes as determined by routine hematoxylin
and eosin staining (preferred method) or by immunohistochemical staining.
• The classification of metastasis to the infraclavicular lymph nodes has been added
as N3.
• Metastasis to the internal mammary nodes, based on the method of detection and
the presence or absence of axillary nodal involvement, has been reclassified.
Microscopic involvement of the internal mammary nodes detected by sentinel
node dissection using lymphoscintigraphy but not by imaging studies or clinical
examination is classified as N1. Macroscopic involvement of the internal mam-mary nodes as detected by imaging studies (excluding lymphoscintigraphy) or by
clinical examination is classified as N2 if it occurs in the absence of metastases
to the axillary lymph nodes or as N3 if it occurs in the presence of metastases to
the axillary lymph nodes.
• Metastasis to the supraclavicular lymph nodes has been reclassified as N3 rather
than M1.
INTRODUCTION
This staging system for carcinoma of the breast applies to infiltrating (includ-ing microinvasive) and  in situ carcinomas. Microscopic confirmation of the
diagnosis is mandatory, and the histologic type and grade of carcinomas should
be recorded
ANATOMY
Primary Site. The anatomic subsites of the breast are illustrated in Figure 25.1.
The mammary gland, situated on the anterior chest wall, is composed of glan-dular tissue with a dense fibrous stroma. The glandular tissue consists of lobules
that group together into 15–25 lobes arranged approximately in a spoke-like
pattern. Multiple major and minor ducts connect the milk-secreting lobular
C50.0 Nipple
C50.1 Central portion of the
breast
C50.2 Upper inner quadrant
of breast
C50.3 Lower inner quadrant
of breast
C50.4 Upper outer quadrant
of breast
C50.5 Lower outer quadrant
of breast
C50.6 Axillary tail of breast
C50.8 Overlapping lesion of
breast
C50.9 Breast, NOS
220 American Joint Committee on Cancer • 2006
units to the nipple. Small milk ducts course throughout the breast, converging
into larger collecting ducts that open into the lactiferous sinus at the base of
the nipple. Most cancers form initially in the terminal duct lobular units of the
breast. Glandular tissue is more abundant in the upper outer portion of the
breast; as a result, half of all breast cancers occur in this area.
Chest Wall. The chest wall includes ribs, intercostal muscles and serratus
anterior muscle, but not the pectoral muscles.
Regional Lymph Nodes. The regional lymph nodes of the breast are illus-trated in Figure 25.2. The breast lymphatics drain by way of three major routes:
axillary, transpectoral, and internal mammary. Intramammary lymph nodes are
coded as axillary lymph nodes for staging purposes. Supraclavicular lymph
nodes are classified as regional lymph nodes for staging purposes. Metastasis to
any other lymph node, including cervical or contralateral internal mammary
lymph nodes, is classified as distant (M1).
The regional lymph nodes are as follows:
1. Axillary (ipsilateral): interpectoral (Rotter’s) nodes and lymph nodes along
the axillary vein and its tributaries that may be (but are not required to be)
divided into the following levels:
a. Level I (low-axilla): lymph nodes lateral to the lateral border of pectoralis
minor muscle.
b. Level II (mid-axilla): lymph nodes between the medial and lateral
borders of the pectoralis minor muscle and the interpectoral (Rotter’s)
lymph nodes.
c. Level III (apical axilla): lymph nodes medial to the medial margin of the
pectoralis minor muscle, including those designated as apical.
2. Internal mammary (ipsilateral): lymph nodes in the intercostal spaces along
the edge of the sternum in the endothoracic fascia.
3. Supraclavicular: lymph nodes in the supraclavicular fossa, a triangle defined
by the omohyoid muscle and tendon (lateral and superior border), the
C50.6
C50.2
C50.0
C50.1
C50.3
C50.4
C50.5
C50.8
FIGURE 25.1. Anatomic sites and subsites of the breast.
American Joint Committee on Cancer • 2006 221
internal jugular vein (medial border), and the clavicle and subclavian vein
(lower border). Adjacent lymph nodes outside of this triangle are consid-ered to be lower cervical nodes (M1).
Metastatic Sites. Tumor cells may be disseminated by either the lymphatic or
the blood vascular system. The four major sites of involvement are bone, lung,
brain, and liver, but tumor cells are also capable of metastasizing to many other
sites.
DEFINITIONS
Primary Tumor (T)
Definitions for classifying the primary tumor (T) are the same for clinical and
for pathologic classification. If the measurement is made by physical examina-tion, the examiner will use the major headings (T1, T2, or T3). If other meas-urements, such as mammographic or pathologic measurements, are used, the
subsets of T1 can be used. Tumors should be measured to the nearest 0.1 cm
increment.
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
Tis Carcinoma in situ
Tis (DCIS) Ductal carcinoma in situ
Tis (LCIS) Lobular carcinoma in situ
Tis (Paget’s) Paget’s disease of the nipple with no tumor (Figure 25.3)
25
Low axillary,
level I Mid-axillary,
level II
High axillary, apical,
level III
Supraclavicular
Pectoralis minor
muscle
Internal
mammary
FIGURE 25.2. Schematic diagram of the breast and regional lymph nodes.
222 American Joint Committee on Cancer • 2006
Note:  Paget’s disease associated with a tumor is classified according to the size
of the tumor.
T1 Tumor 2 cm or less in greatest dimension
T1mic Microinvasion 0.1 cm or less in greatest dimension (Figure 25.4)
T1a Tumor more than 0.1 cm but not more than 0.5 cm in greatest dimen-sion (Figure 25.5)
T1b Tumor more than 0.5 cm but not more than 1 cm in greatest dimen-sion (Figure 25.5)
T1c Tumor more than 1 cm but not more than 2 cm in greatest dimension
(Figure 25.5)
T2 Tumor more than 2 cm but not more than 5 cm in greatest dimension
(Figure 25.6)
Non-invasive Paget’s diseaseTis
FIGURE 25.3. Tis (Paget’s) is defined as Paget’s disease of the nipple with no
tumor.
T1mic(m) or T1mic(3)
T1mic
£0.1 cm
£0.1 cm
£0.1 cm
£0.1 cm
FIGURE 25.4. T1mic is defined as microinvasion 0.1 cm or less in greatest
dimension. The presence of multiple tumor foci of microinvasion (top of diagram)
should be noted in parentheses.
American Joint Committee on Cancer • 2006 223
T3 Tumor more than 5 cm in greatest dimension (Figure 25.6)
T4 Tumor of any size with direct extension to
a. Chest wall or
b. Skin, only as described below
T4a Extension to chest wall, not including pectoralis muscle (Figure 25.7)
T4b Edema (including peau d’orange) or ulceration of the skin of the
breast, or satellite skin nodules confined to the same breast (Figures
25.8A, B)
T4c Both T4a and T4b (Figure 25.9)
T4d Inflammatory carcinoma (Figure 25.10)
25
T1
>1-2 cm=T1c
>0.5-1 cm=T1b
>0.1-0.5 cm=T1a
FIGURE 25.5. T1 is defined as a tumor 2 cm or less in greatest dimension.
T1a is defined as tumor more than 0.1 cm but not more than 0.5 cm in greatest
dimension; T1b is defined as tumor more than 0.5 cm but not more than 1 cm in
greatest dimension; T1c is defined as tumor more than 1 cm but not more than 2
cm in greatest dimension.
T2
T3
>2-5 cm
>5 cm
FIGURE 25.6. T2 (above dotted line) is defined as tumor more than 2 cm but not
more than 5 cm in greatest dimension and T3 (below dotted line) is defined as
tumor more than 5 cm in greatest dimension.
224 American Joint Committee on Cancer • 2006
T4a
FIGURE 25.7. T4 is defined as a tumor of any size with direct extension to chest
wall, not including pectoralis muscle.
T4b
Satellite
nodule
A
B
T4b
FIGURE 25.8. A. T4b, illustrated here as satellite skin nodules, is defined as edema
(including peau d’orange) or ulceration of the skin of the breast, or satellite skin
nodules confined to the same breast. B. T4b illustrated here as edema (including
peau d’orange).
T4c
FIGURE 25.9. T4c is defined as both T4a and T4b.
American Joint Committee on Cancer • 2006 225
Regional Lymph Nodes (N)
NX Regional lymph nodes cannot be assessed (e.g., previously removed)
N0 No regional lymph node metastasis
N1 Metastasis in movable ipsilateral axillary lymph node(s) (Figure 25.11)
N2 Metastases in ipsilateral axillary lymph nodes fixed or matted, or in
clinically apparent(1)
ipsilateral internal mammary nodes in the absence of
clinically evident axillary lymph node metastasis
N2a Metastasis in ipsilateral axillary lymph nodes fixed to one another
(matted) or to other structures (Figure 25.12)
N2b Metastasis only in clinically apparent(1)
ipsilateral internal mammary
nodes and in the absence of clinically evident axillary lymph node metas-tasis (Figure 25.13)
N3 Metastasis in ipsilateral infraclavicular lymph node(s) with or without
axillary lymph node involvement, or in clinically apparent(1)
ipsilateral
25
T4d
Inflammatory
carcinoma
FIGURE 25.10. T4d, inflammatory carcinoma.
N1
FIGURE 25.11. N1 is defined as metastasis in movable ipsilateral axillary lymph
node(s).
226 American Joint Committee on Cancer • 2006
internal mammary lymph node(s) and in the presence of clinically evident
axillary lymph node metastasis; or metastasis in ipsilateral supraclavicu-lar lymph node(s) with or without axillary or internal mammary lymph
node involvement
N3a Metastasis in ipsilateral infraclavicular lymph node(s) (Figure 25.14)
N3b Metastasis in ipsilateral internal mammary lymph node(s) and axillary
lymph node(s) (Figure 25.15)
N3c Metastasis in ipsilateral supraclavicular lymph node(s) (Figure 25.16)
N2a
FIGURE 25.12. N2a is defined as metastasis in ipsilateral axillary lymph nodes
fixed to one another (matted) or to other structures.
N2b
FIGURE 25.13. N2b is defined as metastasis only in clinically apparent(1)
ipsilateral
internal mammary nodes and in the absence of clinically evident axillary lymph
node metastasis.
American Joint Committee on Cancer • 2006 227
25
N3aFIGURE 25.14. N3a metastasis in ipsilateral
infraclavicular lymph node(s) without
axillary or internal mammary lymph node
involvement.
N3b
pN3c
FIGURE 25.15. N3b metastasis in
ipsilateral internal mammary lymph
node(s) and axillary lymph node(s).
FIGURE 25.16. N3c is defined as metastasis
in ipsilateral supraclavicular lymph node(s).
228 American Joint Committee on Cancer • 2006
Regional Lymph Nodes (pN)(2)
pNX Regional lymph nodes cannot be assessed (e.g., previously
removed, or not removed for pathologic study)
pN0 No regional lymph node metastasis histologically, no additional
examination for isolated tumor cells (ITC)(3)
pN0(i-) No regional lymph node metastasis histologically, negative IHC
pN0(i+
) No regional lymph node metastasis histologically, positive IHC, no
IHC cluster greater than 0.2 mm (Figure 25.17)
pN0(mol–
) No regional lymph node metastasis histologically, negative molec-ular findings (RT-PCR)(4)
pN0(mol+
) No regional lymph node metastasis histologically, positive molec-ular findings (RT-PCR)(4)
pN1 Metastasis in 1 to 3 axillary lymph nodes, and/or in internal
mammary nodes with microscopic disease detected by sentinel
lymph node dissection but not clinically apparent(5)
pN1mi Micrometastasis (greater than 0.2 mm, none greater than 2.0 mm)
(Figure 25.18)
pN1a Metastasis in 1 to 3 axillary lymph nodes (Figure 25.18)
pN1b Metastasis in internal mammary nodes with microscopic disease
detected by sentinel lymph node dissection but not clinically
apparent(5)
(Figure 25.19)
pN1c Metastasis in 1 to 3 axillary lymph nodes and in internal mammary
lymph nodes with microscopic disease detected by sentinel lymph
node dissection but not clinically apparent(5,6)
(Figure 25.20)
pN2 Metastasis in 4 to 9 axillary lymph nodes, or in clinically appar-ent(1)
internal mammary lymph nodes in the  absence  of axillary
lymph node metastasis
£0.2 mm
pN0(i+)
FIGURE 25.17. pN0(i+
) is defined as regional lymph node metastasis histologically,
positive IHC, no IHC cluster greater than 0.2 mm.
American Joint Committee on Cancer • 2006 229
pN2a Metastasis in 4 to 9 axillary lymph nodes (at least one tumor
deposit greater than 2.0 mm) (Figure 25.18)
pN2b Metastasis in clinically apparent(1)
internal mammary lymph nodes
in the absence of axillary lymph node metastasis (Figure 25.21)
pN3 Metastasis in 10 or more axillary lymph nodes, or in infraclavicu-lar lymph nodes, or in clinically apparent(1)
ipsilateral internal
mammary lymph nodes in the presence of 1 or more positive axil-lary lymph nodes; or in more than 3 axillary lymph nodes with
clinically negative microscopic metastasis in internal mammary
lymph nodes; or in ipsilateral supraclavicular lymph nodes
25
>0.2-2 mm
pN1mi
pN1a: 1-3 nodes
pN2a: 4-9 nodes (at least
one tumor deposit >2.0 mm)
pN3a: ≥10 nodes (at least
one tumor deposit >2.0 mm)
FIGURE 25.18. Illustrated definition of pN1mi, defined as micrometastasis greater
than 0.2 mm with none greater than 2.0 mm, as well as pN1a, pN2a, and pN3a.
pN1b
SNB+
FIGURE 25.19. pN1b with isolated tumor cells in a single internal mammary
node, sentinel lymph node positive.
230 American Joint Committee on Cancer • 2006
pN3a Metastasis in 10 or more axillary lymph nodes (at least one tumor
deposit greater than 2.0 mm), or metastasis to the infraclavicular
lymph nodes (Figure 25.18)
pN3b Metastasis in clinically apparent(1)
ipsilateral internal mammary
lymph nodes in the presence of 1 or more positive axillary lymph
nodes; or in more than 3 axillary lymph nodes and in internal
mammary lymph nodes with microscopic disease detected by
SNB+
pN1c
FIGURE 25.20. pN1c illustrating 3 positive axillary lymph nodes with isolated
tumor cells in a single internal mammary lymph node, sentinel lymph node
positive.
American Joint Committee on Cancer • 2006 231
sentinel lymph node dissection but not clinically apparent(5)
(Figure 25.22A, B)
pN3c Metastasis in ipsilateral supraclavicular lymph nodes (Figure
25.16)
Distant Metastasis (M)
MX Distant metastasis cannot be assessed
M0 No distant metastasis
M1 Distant metastasis
25
pN2b
FIGURE 25.21. pN2b illustrating clinically apparent metastasis in 2 positive
internal mammary nodes with no axillary lymph node involvement.
pN3b
A
FIGURE 25.22. A. pN3b illustrated as clinically apparent metastasis in 2 positive
internal mammary nodes in the presence of 3 positive axillary lymph nodes.
232 American Joint Committee on Cancer • 2006
STAGE GROUPING
0 Tis N0 M0
IT1(7)
N0 M0
IIA T0 N1 M0
T1(7)
N1 M0
T2 N0 M0
IIB T2 N1 M0
T3 N0 M0
IIIA T0 N2 M0
T1(7)
N2 M0
T2 N2 M0
T3 N1 M0
T3 N2 M0
IIIB T4 N0 M0
T4 N1 M0
T4 N2 M0
IIIC Any T N3 M0
IV Any T Any N M1
Note: Stage designation may be changed if post-surgical imaging studies reveal
the presence of distant metastases, provided that the studies are carried out
within 4 months of diagnosis in the absence of disease progression and provided
that the patient has not received neoadjuvant therapy.
NOTES
1. Clinically apparent  is defined as detected by imaging studies (excluding lym-phoscintigraphy) or by clinical examination or grossly visible pathologically.
SNB+
pN3b
B
FIGURE 25.22. B. pN3b illustrated as clinically apparent metastasis in 6 positive
axillary lymph nodes with isolated tumor cells in one internal mammary lymph
node, sentinel lymph node positive.
American Joint Committee on Cancer • 2006 233
2. Classification is based on axillary lymph node dissection with or without sentinel
lymph node dissection. Classification based solely on sentinel lymph node dissec-tion without subsequent axillary lymph node dissection is designated (sn) for
“sentinel node,” e.g., pNO(i+)(sn).
3. Isolated tumor cells (ITC) are defined as single tumor cells or small cell clusters
not greater than 0.2 mm, usually detected only by immunohistochemical (IHC) or
molecular methods but which may be verified on H&E stains. ITCs do not usually
show evidence of metastatic activity (e.g., proliferation or stromal reaction).
4. RT-PCR: reverse transcriptase/polymerase chain reaction.
5. Not clinically apparent is defined as not detected by imaging studies (excluding lym-phoscintigraphy) or by clinical examination.
6. If associated with greater than 3 positive axillary lymph nodes, the internal
mammary nodes are classified as pN3b to reflect increased tumor burden.
7. T1 includes T1mic.
25
American Joint Committee on Cancer • 2006 237
26
Vu l v a
(Mucosal malignant melanoma is not included.)
26
SUMMARY OF CHANGES
• The definitions of TNM and the Stage Grouping for this chapter have not
changed from the Fifth Edition.
ANATOMY
Primary Site. The vulva is the anatomic site immediately external to the
vagina. It includes the labia and the perineum. The tumor may extend to involve
the vagina, urethra, or anus. It may be fixed to the pubic bone (Figure 26.1).
Regional Lymph Nodes. (See Chapter 27, Figure 27.3.) The femoral and
inguinal nodes are the sites of regional spread. For pN, histologic examination
of an inguinal lymphadenectomy specimen will ordinarily include six or more
lymph nodes. Negative pathologic examination of a lesser number of nodes still
mandates a pN0 designation. The concept of sentinel lymph node mapping
where only one or two key nodes are removed is currently being investigated.
Metastatic Sites. The metastatic sites include any site beyond the area of the
regional lymph nodes. Tumor involvement of pelvic lymph nodes, including
internal iliac, external iliac, and common iliac lymph nodes, is considered distant
metastasis.
DEFINITIONS
The definitions of the T categories correspond to the stages accepted by the Fed-eration Internationale de Gynecologie et d’Obstetrique (FIGO). Both systems
are included for comparison.
Primary Tumor (T)
TNM FIGO Definitions
Categories Stages
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
Tis 0 Carcinoma in situ (preinvasive carcinoma)
T1 I Tumor confined to the vulva or vulva and perineum, 2 cm
or less in greatest dimension (Figure 26.2)
C51.0 Labium majus
C51.1 Labium minus
C51.2 Clitoris
C51.8 Overlapping lesion of
vulva
C51.9 Vulva, NOS
238 American Joint Committee on Cancer • 2006
T1a IA Tumor confined to the vulva or vulva and perineum, 2 cm
or less in greatest dimension, and with stromal invasion no
greater than 1 mm(1)
(Figure 26.3A)
T1b IB Tumor confined to the vulva or vulva and perineum, 2 cm
or less in greatest dimension, and with stromal invasion
greater than 1 mm(1)
(Figure 26.3B)
T2 II Tumor confined to the vulva or vulva and perineum, more
than 2 cm in greatest dimension (Figure 26.4)
T3 III Tumor of any size with contiguous spread to the lower
urethra and/or vagina or anus (Figures 26.5A, B)
C51.9
C51.2
Urethra
Vagina
C51.1
C51.0
FIGURE 26.1. Anatomic sites and subsites of the vulva.
T1
T1
£2 cm
TNM:
FIGO: I
TNM:
FIGO: I
£2 cm
FIGURE 26.2. T1 tumor confined to the vulva (top of figure, above dotted line) or
vulva and perineum (bottom of figure, below dotted line), 2 cm or less in greatest
dimension.
26
T1a T1b
AB
£1 mm
£2 cm
>1 mm
£2 cm
FIGURE 26.3. T1a A is tumor confined to the vulva or vulva and perineum, 2 cm
or less in greatest dimension, and with stromal invasion no greater than 1 mm.(1)
T1b B is tumor confined to the vulva or vulva and perineum, 2 cm or less in
greatest dimension, and with stromal invasion greater than 1 mm.(1)
T2
T2
>2 cm
TNM:
FIGO: II
TNM:
FIGO: II
>2 cm
FIGURE 26.4. T2 tumor confined to the vulva (top of figure, above dotted line)
or vulva and perineum (bottom of figure, below dotted line) more than 2 cm in
greatest dimension.
T3
T3
TNM:
FIGO: III
TNM:
FIGO: III
A
FIGURE 26.5. A. T3 is a tumor of any size with contiguous spread to the lower
urethra (top of figure, above dotted line) or vagina and/or anus (bottom of figure,
below dotted line).
240 American Joint Committee on Cancer • 2006
T4 IVA Tumor invades any of the following: upper urethra, bladder
mucosa, rectal mucosa, or is fixed to the pubic bone (Figure
26.6)
Regional Lymph Nodes (N)
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
T3TNM:
FIGO: III
B
FIGURE 26.5. B. Cross-sectional diagram showing spread of tumor into anus and
lower urethra.
T4TNM:
FIGO: IVA
FIGURE 26.6. T4 is defined as tumor invading any of the following: upper urethra,
bladder mucosa, rectal mucosa, or is fixed to the pubic bone.
American Joint Committee on Cancer • 2006 241
N1 III Unilateral regional lymph node metastasis (Figure 26.7)
N2 IVA Bilateral regional lymph node metastasis (Figure 26.8)
Every effort should be made to determine the site and laterality of lymph node
metastases. However, if “regional lymph node metastases, NOS” is the final diag-nosis, then the patient should be staged as N1.
Distant Metastasis (M)
MX Distant metastasis cannot be assessed
M0 No distant metastasis
M1 IVB Distant metastasis (including pelvic lymph node metastasis)
26
N1
FIGO: III
C77.4
FIGURE 26.7. N1: unilateral regional lymph node metastasis.
N2
FIGO: IVA
FIGURE 26.8. N2: bilateral regional lymph node metastasis.
242 American Joint Committee on Cancer • 2006
STAGE GROUPING (AJCC/UICC/FIGO)
0 Tis N0 M0
IT1N0M0
IA T1a N0 M0
IB T1b N0 M0
II T2 N0 M0
III T1 N1 M0
T2 N1 M0
T3 N0 M0
T3 N1 M0
IVA T1 N2 M0
T2 N2 M0
T3 N2 M0
T4 Any N M0
IVB Any T Any N M1
NOTE
1. The depth of invasion is defined as the measurement of the tumor from the
epithelial-stromal junction of the adjacent most superficial dermal papilla to the
deepest point of invasion.
American Joint Committee on Cancer • 2006 243
27
Vagina
27
SUMMARY OF CHANGES
• The definitions of TNM and the Stage Grouping for this chapter have not
changed from the Fifth Edition.
C52.9 Vagina, NOS
ANATOMY
Primary Site. The vagina extends from the vulva upward to the uterine cervix.
It is lined by squamous epithelium with only rare glandular structures. The
vagina (Figure 27.1) is drained by lymphatics toward the pelvic nodes (Figure
27.2) in its upper two-thirds and toward the inguinal nodes (Figure 27.3) in its
lower third.
Regional Lymph Nodes. The upper two-thirds of the vagina is drained by
lymphatics to the pelvic nodes, including:
Obturator
Internal iliac (hypogastric)
External iliac
Pelvic, NOS
The lower third of the vagina is drained to the groin nodes, including:
Inguinal
Femoral
Metastatic Sites. The most common sites of distant spread include the aortic
lymph nodes, lungs, and skeleton.
DEFINITIONS
The definitions of the T categories correspond to the stages accepted by the Fed-eration Internationale de Gynecologie et d’Obstetrique (FIGO). Both systems
are included for comparison.
Primary Tumor (T)
TNM FIGO Definitions
Categories Stages
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
Tis 0 Carcinoma in situ
T1 I Tumor confined to vagina (Figure 27.4)
T2 II Tumor invades paravaginal tissues but not to pelvic wall
(Figure 27.5)
C53.0
C52.9
Lower
third
Upper
two-thirds
C51
FIGURE 27.1. Anatomical sites and subsites of the vagina.
C77.5
FIGURE 27.2. Regional pelvic lymph nodes draining the upper two-thirds of the
vagina.
C77.4
FIGURE 27.3. Regional lymph nodes in the groin draining the lower third of the
vagina.
American Joint Committee on Cancer • 2006 245
27
T1TNM:
FIGO: I
T1TNM:
FIGO: I
T1TNM:
FIGO: I
FIGURE 27.4. Three views of T1, each showing tumor confined to the vagina.
T2TNM:
FIGO: II
FIGURE 27.5. T2 tumor invading paravaginal tissues but not to pelvic wall.
T3 III Tumor extends to pelvic wall(1)
(Figure 27.6)
T4 IVA Tumor invades mucosa of the bladder or rectum and/or
extends beyond the true pelvis (bullous edema is not suffi-cient evidence to classify a tumor as T4) (Figure 27.7)
Regional Lymph Nodes (N)
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Pelvic or inguinal lymph node metastasis (Figures 27.8A–C)
246 American Joint Committee on Cancer • 2006
T3TNM:
FIGO: III
FIGURE 27.6. T3 tumor extending to pelvic wall.
T4TNM:
FIGO: IVA
T4TNM:
FIGO: IVA
FIGURE 27.7. Two views of T4 showing tumor invading rectum (left side of dotted
line) or extending beyond true pelvis or invading bladder (right side of dotted
line).
FIGURE 27.8. A–C. N1: pelvic (27.8A) or unilateral inguinal (27.8B) or bilateral
inguinal (27.8C) lymph node metastasis.

27
N1
FIGO: IVB
A
N1
FIGO: IVB
B
N1
FIGO: IVB
C
Distant Metastasis (M)
MX Distant metastasis cannot be assessed
M0 No distant metastasis
M1 IVB Distant metastasis
STAGE GROUPING (AJCC/UICC/FIGO)
0 Tis N0 M0
IT1 N0 M0
II T2 N0 M0
III T1–T3 N1 M0
T3 N0 M0
IVA T4 Any N M0
IVB Any T Any N M1
NOTE
1. Pelvic wall is defined as the muscle, fascia, associated neurovascular structures, or
skeletal portions of the bony pelvis.
248 American Joint Committee on Cancer • 2006
American Joint Committee on Cancer • 2006 249
28
Cervix Uteri
28
SUMMARY OF CHANGES
• The definitions of TNM and the Stage Grouping for this chapter have not
changed from the Fifth Edition.
C53.0 Endocervix
C53.1 Exocervix
C53.8 Overlapping lesion of
cervix uteri
C53.9 Cervix uteri
ANATOMY
Primary Site. The cervix is in the lower third of the uterus. It is roughly cylin-drical in shape and projects into the upper vagina. Through the cervix runs the
endocervical canal, which is the passageway connecting the vagina with the
uterine cavity. The endocervical canal is lined by glandular or columnar epithe-lium. The vaginal portion of the cervix, known as the exocervix, is covered by
squamous epithelium. The squamocolumnar junction is usually located at the
external cervical os, where the endocervical canal begins. Cancer of the cervix
may originate from the squamous epithelium of the exocervix or the glandular
epithelium of the canal (Figure 28.1).
Regional Lymph Nodes. The cervix is drained by parametrial, cardinal, and
uterosacral ligament routes into the following regional lymph nodes (Figure
28.2):
Parametrial
Paracervical
Obturator
Internal iliac (hypogastric)
External iliac
Common iliac
Sacral
Presacral
Metastatic Sites. The most common sites of distant spread include the aortic
and mediastinal nodes, lungs, and skeleton. Para-aortic node involvement is
considered distant metastasis and is coded M1.
DEFINITIONS
The definitions of the T categories correspond to the stages accepted by the
Federation Internationale de Gynecologie et d’Obstetrique (FIGO). Both
systems are included for comparison.
250 American Joint Committee on Cancer • 2006
Primary Tumor (T)
TNM FIGO Definitions
Categories Stages
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
Tis 0 Carcinoma in situ
C52.9
C53.1
C53.0
C54.0
C56.9
C57.2
C54.1
C57.0
C54.3
C54
C53
C54.2
FIGURE 28.1. Anatomic sites and subsites of the cervix uteri.
5
4
2
1
3
3
C77.5
6
FIGURE 28.2. Regional lymph nodes of the cervix: (1) paracervical; (2)
parametrial; (3) hypogastric (internal iliac) including obturator; (4) external iliac;
(5) common iliac; (6) presacral.
American Joint Committee on Cancer • 2006 251
T1 I Cervical carcinoma confined to uterus (extension to corpus
should be disregarded)
T1a IA Invasive carcinoma diagnosed only by microscopy.(1)
All
macroscopically visible lesions—even with superficial inva-sion— are T1b/IB. Stromal invasion with a maximal depth
of 5.0 mm measured from the base of the epithelium and a
horizontal spread of 7.0 mm or less. Vascular space involve-ment, venous or lymphatic, does not affect classification.
(Figure 28.3)
T1a1 IA1 Measured stromal invasion 3.0 mm or less in depth and 7.0
mm or less in horizontal spread (Figure 28.4)
T1a2 IA2 Measured stromal invasion more than 3.0 mm and not more
than 5.0 mm with a horizontal spread 7.0 mm or less (Figure
28.5)
T1b IB Clinically visible lesion confined to the cervix or micro-scopic lesion greater than Tla2/IA2 (Figure 28.6)
T1b1 IB1 Clinically visible lesion 4.0 cm or less in greatest dimension
(Figure 28.7)
T1b2 IB2 Clinically visible lesion more than 4.0 cm in greatest dimen-sion (Figure 28.8)
T2 II Cervical carcinoma invades beyond uterus but not to pelvic
wall or to lower third of vagina (Figure 28.9)
T2a IIA Tumor without parametrial invasion (Figure 28.9)
T2b IIB Tumor with parametrial invasion (Figure 28.9)
T3 III Tumor extends to pelvic wall and/or involves lower third of
vagina and/or causes hydronephrosis or nonfunctioning
kidney (Figure 28.10)
T3a IIIA Tumor involves lower third of vagina, no extension to pelvic
wall (Figure 28.10)
28
Invasive carcinoma diagnosed only by microscopy
A
BC
T1aTNM:
FIGO: IA
FIGURE 28.3. T1a is defined as invasive carcinoma diagnosed only by
microscopy(1)
with stromal invasion to a maximal depth of 5.0 mm measured from
the base of the epithelium and a horizontal spread of 7.0 mm or less.
252 American Joint Committee on Cancer • 2006
£3 mm
£7 mm
Invasive carcinoma diagnosed only by microscopy
A
B
T1a1TNM:
FIGO: IA1
>3-5 mm
£7 mm
A
B
Invasive carcinoma diagnosed only by microscopy
T1a2TNM:
FIGO: IA2
FIGURE 28.5. T1a2 is defined as invasive
carcinoma diagnosed only by microscopy
with measured stromal invasion more
than 3.0 mm and not more than 5.0 mm
with horizontal spread 7.0 mm or less B.
FIGURE 28.4. T1a1 is defined as invasive
carcinoma diagnosed only by microscopy
with measured stromal invasion 3.0 mm
or less in depth and 7.0 mm or less in
horizontal spread B.
American Joint Committee on Cancer • 2006 253
28
£5 mm
>7 mm
>5 mm
A
CB
£7 mm
Microscopic lesion >T1a/IA2
T1bTNM:
FIGO: IB
FIGURE 28.6. T1b is defined as a microscopic lesion greater than Tla2/IA2, i.e.,
stromal invasion greater than 5.0 mm and/or horizontal spread greater than
7.0 mm B and C or a clinically visible lesion confined to the cervix.
T1b1TNM:
FIGO: IB1
£4 cm
FIGURE 28.7. T1b1 is defined as a clinically visible lesion 4.0 cm or less in greatest
dimension.
254 American Joint Committee on Cancer • 2006
T1b2TNM:
FIGO: IB2
>4 cm
FIGURE 28.8. T1b2 is defined as a clinically visible lesion more than 4.0 cm in
greatest dimension.
T2aTNM:
FIGO: IIA
T2bTNM:
FIGO: IIB
2/3
1/3
FIGURE 28.9. T2 is defined as a cervical carcinoma that invades beyond uterus but
not to pelvic wall or to lower third of vagina. T2a (left of the vertical dotted line) is
T2 tumor without parametrial invasion. T2b (right of the vertical dotted line) is T2
tumor with parametrial invasion.
American Joint Committee on Cancer • 2006 255
T3b IIIB Tumor extends to pelvic wall and/or causes hydronephrosis
or nonfunctioning kidney (Figure 28.10)
T4 IVA Tumor invades mucosa of bladder or rectum and/or extends
beyond true pelvis (bullous edema is not sufficient evidence
to classify a tumor as T4) (Figure 28.11)
Regional Lymph Nodes (N)
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Regional lymph mode metastasis (Figure 28.12)
Distant Metastasis (M)
MX Distant metastasis cannot be assessed
M0 No distant metastasis
M1 IVB Distant metastasis
28
T3aTNM:
FIGO: IIIA
T3bTNM:
FIGO: IIIB
2/3
1/3
FIGURE 28.10. T3 tumor extends to pelvic wall and/or involves lower third of
vagina and/or causes hydronephrosis or nonfunctioning kidney. T3a (left of
vertical dotted line) involves lower third of vagina with no extension to pelvic wall.
T3b (right of vertical dotted line) extends to pelvic wall and/or causes
hydronephrosis or nonfunctioning kidney.
256 American Joint Committee on Cancer • 2006
T4TNM:
FIGO: IVA
T4TNM:
FIGO: IVA
FIGURE 28.11. Two views of T4. Bottom of illustration (below dotted line), tumor
invades mucosa of bladder or rectum. Top of illustration (above dotted line),
tumor extends beyond true pelvis.
N1
FIGURE 28.12. N1 is defined as regional lymph node metastasis.
American Joint Committee on Cancer • 2006 257
STAGE GROUPING (AJCC/UICC/FIGO)
0 Tis N0 M0
IT1 N0 M0
IA T1a N0 M0
IA1 T1a1 N0 M0
IA2 T1a2 N0 M0
IB T1b N0 M0
IB1 T1b1 N0 M0
IB2 T1b2 N0 M0
II T2 N0 M0
IIA T2a N0 M0
IIB T2b N0 M0
III T3 N0 M0
IIIA T3a N0 M0
IIIB T1 N1 M0
T2 N1 M0
T3a N1 M0
T3b Any N M0
IVA T4 Any N M0
IVB Any T Any N M1
NOTE
1. The depth of invasion is defined as the measurement of the tumor from the
epithelial-stromal junction of the adjacent most superficial dermal papilla to the
deepest point of invasion.
28
American Joint Committee on Cancer • 2006 259
29
Corpus Uteri
29
SUMMARY OF CHANGES
• The definitions of TNM and the Stage Grouping for this chapter have not
changed from the Fifth Edition.
C54.0 Isthmus uteri
C54.1 Endometrium
C54.2 Myometrium
C45.3 Fundus uteri
C54.8 Overlapping lesion of
corpus uteri
C54.9 Corpus uteri
C55.9 Uterus, NOS
ANATOMY
Primary Site. The upper two-thirds of the uterus above the level of the inter-nal cervical os is referred to as the uterine corpus (see Figure 28.1). The oviducts
(fallopian tubes) and the round ligaments enter the uterus at the upper and
outer corners (cornu) of the pear-shaped organ. The portion of the uterus that
is above a line connecting the tubo-uterine orifices is referred to as the uterine
fundus. The lower third of the uterus is called the cervix and lower uterine
segment. Tumor involvement of the endocervical mucosa and/or the stroma of
the endocervix is prognostically important and affects staging (T2). The loca-tion of the tumor must be carefully evaluated and recorded by the pathologist.
The depth of tumor invasion into the myometrium is also of prognostic signif-icance and should be included in the pathology report. Extension of the tumor
through the myometrial wall of the uterus into the parametrium occurs on occa-sion and constitutes regional extension (T3a). Involvement of the ovaries (T3a)
by direct extension or metastases or extension to the vagina (T3b) occurs rela-tively infrequently.
Regional Lymph Nodes. The regional lymph nodes are paired and each of the
paired sites should be examined. The regional nodes are illustrated in Figure
28.2 (see labels 2, 3, 4, 5, and 6) plus the para-aortic lymph nodes and regional
lymph nodes, NOS.
Obturator
Internal iliac (hypogastric)
External iliac
Common iliac
Para-aortic
Presacral
Parametrial
Pelvic lymph nodes, NOS
For adequate evaluation of the regional lymph nodes, sampling of para-aortic and bilateral obturator nodes and at least one other regional node group
should be documented in either or both of the operative and surgical pathol-ogy reports.
260 American Joint Committee on Cancer • 2006
Parametrial nodes are not commonly detected unless a radical hysterectomy
is performed for cases with gross cervical stromal invasion.
Metastatic Sites. The vagina and lung are the common metastatic sites. Intra-abdominal metastases occur frequently in advanced disease.
DEFINITIONS
Primary Tumor (T)
The definitions of the T categories correspond to the stages accepted by FIGO.
FIGO stages are further subdivided by histologic grade of tumor—for example,
Stage IC G2. Both systems are included for comparison.
FIGO recommends surgical/pathologic staging. Clinical staging is done with 1971
FIGO as follows:
TNM FIGO Definitions
cTis 0 Carcinoma  in situ; histologic findings suspicious of
malignancy
cT1 I Carcinoma is confined to the corpus including the isthmus
cT1a IA Length of the uterine cavity is 8 cm or less
cT1b IB Length of the uterine cavity is more than 8 cm
Stage I cases should be subgrouped with regard to the histologic type of the adeno-carcinoma as follows:
G1 Highly differentiated adenomatous carcinoma
G2 Moderately differentiated adenomatous carcinoma with
partly solid areas
G3 Predominately solid or entirely undifferentiated carcinoma
cT2 II Carcinoma has involved the corpus and the cervix, but has
not extended outside the uterus
cT3 III Carcinoma has extended outside the uterus, but not outside
the true pelvis
cT4 IV Carcinoma has extended outside the true pelvis or has obvi-ously involved the mucosa of the bladder or rectum (bullous
edema as such does not permit a case to be allotted to stage
IV)
cT4a IVA Spread of the growth to adjacent organs as urinary bladder,
rectum, sigmoid colon, or small bowel
Stage 0 cases should not be included in any therapeutic statistics.
Primary Tumor (T)
TNM FIGO Definitions
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
Tis 0 Carcinoma in situ
T1 I Tumor confined to corpus uteri
T1a IA Tumor limited to endometrium (Figure 29.1)
T1b IB Tumor invades less than one-half of the myometrium
(Figure 29.1)
American Joint Committee on Cancer • 2006 261
T1c IC Tumor invades one-half or more of the myometrium
(Figure 29.1)
T2 II Tumor invades cervix but does not extend beyond uterus
(Figure 29.2)
T2a IIA Tumor limited to the glandular epithelium of the endo-cervix, with no evidence of connective tissue stromal inva-sion (Figure 29.2)
T2b IIB Invasion of the stromal connective tissue of the cervix
(Figure 29.2)
29
T1aTNM:
FIGO: IA
T1bTNM:
FIGO: IB
T1cTNM:
FIGO: IC
Figure 29.1. T1 tumor confined to corpus
uteri. T1a tumor is limited to
endometrium (left); T1b tumor invades
less than one-half of the myometrium
(upper right); T1c tumor invades one-half
or more of the myometrium (lower right)
indicated by the tumor traversing the
dotted horizontal line marking the halfway
plane of the myometrium.
T2aTNM:
FIGO: IIA
T2bTNM:
FIGO: IIB
Figure 29.2. T2 tumor invades cervix but
does not extend beyond uterus.T2a (left) is
T2 tumor limited to the glandular epithelium
of the endocervix with no evidence of
connective tissue stromal invasion. T2b
(right) is T2 tumor that has invaded the
stromal connective tissue of the cervix.
262 American Joint Committee on Cancer • 2006
T3bTNM:
FIGO: IIIB
T3aTNM:
FIGO: IIIA
Figure 29.3. T3a (right) is a tumor involving serosa and/or adnexa (by direct
extension or metastasis) and/or cancer cells in ascites or peritoneal washings. T3b
(left) is a tumor with vaginal involvement (by direct extension or metastasis).
T4TNM:
FIGO: IVA
Figure 29.4. T4 tumor that invades bladder mucosa and/or bowel mucosa.
T3 III Local and/or regional spread as defined below
T3a IIIA Tumor involves serosa and/or adnexa (direct extension or
metastasis) and/or cancer cells in ascites or peritoneal wash-ings (Figure 29.3)
T3b IIIB Vaginal involvement (direct extension or metastasis) (Figure
29.3)
T4 IVA Tumor invades bladder mucosa and/or bowel mucosa
(bullous edema is not sufficient evidence to classify a tumor
as T4) (Figure 29.4)
American Joint Committee on Cancer • 2006 263
Regional Lymph Nodes (N)
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 IIIC Regional lymph node metastasis to pelvic and/or para-aortic
lymph nodes (Figure 29.5)
Distant Metastasis (M)
MX Distant metastasis cannot be assessed
M0 No distant metastasis
M1 IVB Distant metastasis includes metastasis to intra-abdominal lymph
nodes other than para-aortic, and/or inguinal lymph nodes;
excludes metastasis to vagina, pelvic serosa, or adnexa
STAGE GROUPING(AJCC/UICC/FIGO)
0 Tis N0 M0
IT1N0M0
IA T1a N0 M0
IB T1b N0 M0
IC T1c N0 M0
II T2 N0 M0
IIA T2a N0 M0
IIB T2b N0 M0
III T3 N0 M0
IIIA T3a N M0
IIIB T3b N0 M0
29
N1
FIGO: IIIC
Figure 29.5. N1 is defined as regional lymph node metastasis to pelvic and/or
para-aortic lymph nodes.
264 American Joint Committee on Cancer • 2006
IIIC T1 N1 M0
T2 N1 M0
T3 N1 M0
IVA T4 Any N M0
IVB Any T Any N M1
American Joint Committee on Cancer • 2006 265
30
Ovary
30
SUMMARY OF CHANGES
• The definitions of TNM and the Stage Grouping for this chapter have not
changed from the Fifth Edition.
C56.9 Ovary
ANATOMY
Primary Site. The ovaries are a pair of solid, flattened ovoids, 2 to 4 cm in
diameter that are connected by a peritoneal fold to the broad ligament and by
the infundibulopelvic ligament to the lateral wall of the pelvis. They are attached
medially to the uterus by the utero-ovarian ligament. (See Figure 28.1.)
In some cases, an adenocarcinoma is primary in the peritoneum. The
ovaries are not involved or are only involved with minimal surface implants. The
clinical presentation, surgical therapy, chemotherapy, and prognosis of these
peritoneal tumors mirror those of papillary serous carcinoma of the ovary.
Patients who undergo prophylactic oophorectomy for a familial history of
ovarian cancer appear to retain a 1 to 2% chance of developing peritoneal ade-nocarcinoma, which is histopathologically and clinically similar to primary
ovarian cancer.
Regional Lymph Nodes. The lymphatic drainage occurs by the utero-ovarian
and round ligament trunks and an external iliac accessory route into the fol-lowing regional nodes:
External iliac
Internal iliac (hypogastric)
Obturator
Sacral
Common iliac
Para-aortic
Inguinal
Pelvic, NOS
Retroperitoneal, NOS
For pN0, histologic examination should include both pelvic and para-aortic
lymph nodes. Figure 30.1 illustrates the regional lymph nodes.
Metastatic Sites. The peritoneum, including the omentum and the pelvic and
abdominal visceral and parietal peritoneum, comprises common sites for
seeding. Diaphragmatic and liver surface involvement are also common.
However, to be consistent with FIGO staging, these implants within the
abdominal cavity (T3) are not considered distant metastases. Primary peritoneal
adenocarcinoma is always metastatic at diagnosis (M1). Extraperitoneal sites,
266 American Joint Committee on Cancer • 2006
including parenchymal liver, lung, skeletal metastases, and supraclavicular and
axillary nodes, are M1.
DEFINITIONS
Primary Tumor (T)
TNM FIGO
Categories Stages Definitions
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
T1 I Tumor limited to ovaries (one or both)
T1a IA Tumor limited to one ovary; capsule intact, no tumor on
ovarian surface; no malignant cells in ascites or peritoneal
washings(1)
(Figure 30.2)
T1b IB Tumor limited to both ovaries; capsule intact, no tumor on
ovarian surface; no malignant cells in ascites or peritoneal
washings(1)
(Figure 30.3)
T1c IC Tumor limited to one or both ovaries with any of the fol-lowing: capsule ruptured, tumor on ovarian surface, malig-nant cells in ascites or peritoneal washings (Figure 30.4)
T2 II Tumor involves one or both ovaries with pelvic extension
T2a IIA Extension and/or implants on uterus and/or tube(s); no
malignant cells in ascites or peritoneal washings (Figure
30.5)
T2b IIB Extension to and/or implants on other pelvic tissues; no
malignant cells in ascites or peritoneal washings (Figure
30.6)
5
1
6
7
2
4
3
7
6
C77.2
C77.5
C77.4
FIGURE 30.1. Regional lymph nodes: (1) hypogastric; (2) common iliac; (3)
external iliac; (4) lateral sacral; (5) para-aortic; (6) inguinal; (7) obturator.
American Joint Committee on Cancer • 2006 267
30
T1aTNM:
FIGO: IA
FIGURE 30.2. T1a is tumor limited to one ovary; capsule intact, no tumor on
ovarian surface, and no malignant cells in ascites or peritoneal washings.(1)
T1bTNM:
FIGO: IB
FIGURE 30.3. T1b is tumor limited to both ovaries; capsule intact, no tumor on
ovarian surface. No malignant cells in ascites or peritoneal washings.(1)
268 American Joint Committee on Cancer • 2006
T1cTNM:
FIGO: IC
T1cTNM:
FIGO: IC
Ascites,
peritoneal
washing
FIGURE 30.4. Two views of T1c, defined as tumor limited to one or both ovaries
with any of the following: capsule ruptured, tumor on ovarian surface (left side of
dotted line), malignant cells in ascites or peritoneal washings (right side of
dotted line).
T2aTNM:
FIGO: IIA
FIGURE 30.5. T2 is tumor involving one or both ovaries with pelvic extension.
T2a involves extension and/or implants on uterus (shown) and/or tube(s) without
any malignant cells in ascites or peritoneal washings.
American Joint Committee on Cancer • 2006 269
30
T2bTNM:
FIGO: IIB
FIGURE 30.6. T2b is defined as tumor extension to and/or implants on other
pelvic tissues. No malignant cells in ascites or peritoneal washings.
T2cTNM:
FIGO: IIC
Ascites,
peritoneal
washing
FIGURE 30.7. T2c is defined as tumor with pelvic extension and/or implants (T2a
or T2b) and with malignant cells in ascites or peritoneal washings.
T2c IIC Pelvic extension and/or implants (T2a or T2b) with malig-nant cells in ascites or peritoneal washings (Figure 30.7)
T3 III Tumor involves one or both ovaries with microscopically
confirmed peritoneal metastasis outside the pelvis(2)
(Figures
30.8, 30.9)
270 American Joint Committee on Cancer • 2006
T3a IIIA Microscopic peritoneal metastasis beyond pelvis (no macro-scopic tumor)(2)
(Figure 30.8)
T3b IIIB Macroscopic peritoneal metastasis beyond pelvis 2 cm or less
in greatest dimension(2)
(Figure 30.8)
T3TNM:
FIGO: III
3c/IIIC:
Peritoneal
metastasis
>2 cm
3b/IIIB:
Macroscopic
peritoneal
metastasis
£2 cm
3a/IIIA:
Microscopic
peritoneal
metastasis
only
T3TNM:
FIGO: III
FIGURE 30.8. Three views of T3: T3a (top right) is defined as microscopic
peritoneal metastasis beyond pelvis (no macroscopic tumor)(2)
; T3b (bottom right)
is defined as macroscopic peritoneal metastasis beyond pelvis 2 cm or less in
greatest dimension(2)
; T3c (left side) is defined as peritoneal metastasis beyond
pelvis more than 2 cm in greatest dimension and/or regional lymph node
metastasis.
M1T3TNM:
FIGO: III
TNM:
FIGO: IV
Parenchymal
Liver capsule
FIGURE 30.9. Liver capsule metastasis classified as T3/Stage III. Liver parenchymal
metastasis classified as M1/Stage IV.
American Joint Committee on Cancer • 2006 271
T3c IIIC Peritoneal metastasis beyond pelvis more than 2 cm in great-est dimension and/or regional lymph node metastasis(2)
(Figure 30.8)
Regional Lymph Nodes (N)
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 IIIC Regional lymph node metastasis (Figure 30.10)
Distant Metastasis (M)
MX Distant metastasis cannot be assessed
M0 No distant metastasis
M1 IV Distant metastasis (excludes peritoneal metastasis)(2)
(Figure 30.9)
STAGE GROUPING (AJCC/UICC/FIGO)
IT1N0M0
IA T1a N0 M0
IB T1b N0 M0
IC T1c N0 M0
II T2 N0 M0
IIA T2a N0 M0
IIB T2b N0 M0
IIC T2c N0 M0
III T3 N0 M0
IIIA T3a N0 M0
30
N1
FIGO: IIIC
FIGURE 30.10. N1: regional lymph node metastasis.
272 American Joint Committee on Cancer • 2006
IIIB T3b N0 M0
IIIC T3c N0 M0
Any T N1 M0
IV Any T Any N M1
NOTES
1. The presence of nonmalignant ascites is not classified. The presence of ascites does
not affect staging unless malignant cells are present.
2. Liver capsule metastasis T3/III, liver parenchymal metastasis M1/Stage IV. Pleural
effusion must have positive cytology for M1/Stage IV.
American Joint Committee on Cancer • 2006 273
31
Fallopian Tube
31
SUMMARY OF CHANGES
• The definitions of TNM and Stage Grouping for this chapter have not changed
from the Fifth Edition.
C57.0 Fallopian tube
ANATOMY
Primary Site. The fallopian tube extends from the posterior superior aspect of
the uterine fundus laterally and anteriorly to the ovary. Its length is approxi-mately 10 cm. The medial end arises in the cornual portion of the uterine cavity,
and the lateral end opens to the peritoneal cavity.
Carcinoma of the fallopian tube is almost always an adenocarcinoma arising
from an in situ lesion of the tubal mucosa. It invades locally into the muscular
wall of the tube and then into the peritubal soft tissue or adjacent organs such
as the uterus or ovary, or through the serosa of the tube into the peritoneal
cavity. Metastatic tumor implants can be found throughout the peritoneal cavity.
The tumor may obstruct the tubal lumen and present as a ruptured or unrup-tured hydrosalpinx or hematosalpinx.
Regional Nodes. Carcinoma of the fallopian tube can also metastasize to the
regional lymph nodes (see Figure 30.1), which include:
Common iliac
Internal iliac (hypogastric)
Obturator
Presacral
Para-aortic
Inguinal
Pelvic lymph nodes, NOS
Adequate evaluation of the regional lymph nodes usually includes aortic
and pelvic nodes.
Distant Metastases. Surface implants within the pelvic cavity and the
abdominal cavity are common, but these are classified as T2 and T3 disease,
respectively. Parenchymal liver metastases and extraperitoneal sites, including
lung and skeletal metastases, are M1 (see Figure 30.9).
DEFINITIONS
Primary Tumor (T)
TNM FIGO
Categories Stages
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
274 American Joint Committee on Cancer • 2006
Tis 0 Carcinoma in situ (limited to tubal mucosa)
T1 I Tumor limited to the fallopian tube(s)
T1a IA Tumor limited to one tube, without penetrating the serosal
surface; no ascites (Figure 31.1)
T1b IB Tumor limited to both tubes, without penetrating the serosal
surface; no ascites (Figure 31.2)
T1aTNM:
FIGO: IA
FIGURE 31.1. T1a is tumor
limited to one fallopian tube,
without penetrating the serosal
surface; no ascites.
T1bTNM:
FIGO: IB
FIGURE 31.2. T1b is tumor
limited to both tubes, without
penetrating the serosal surface;
no ascites.
American Joint Committee on Cancer • 2006 275
31
T1c T1cTNM:
FIGO: IC
TNM:
FIGO: IC
Ascites,
peritoneal
washing
FIGURE 31.3. Two views of T1c: tumor limited to one (left of dotted line) or both
tubes with extension onto or through the tubal serosa, or with malignant cells in
ascites or peritoneal washings (right of the dotted line).
T1c IC Tumor limited to one or both tubes with extension onto or
through the tubal serosa, or with malignant cells in ascites
or peritoneal washings (Figure 31.3)
T2 II Tumor involves one or both fallopian tubes with pelvic
extension
T2a IIA Extension and/or metastasis to the uterus and/or ovaries
(Figure 31.4)
T2b IIB Extension to other pelvic structures (Figure 31.5)
T2c IIC Pelvic extension with malignant cells in ascites or peritoneal
washings (Figure 31.6)
T3 III Tumor involves one or both fallopian tubes, with peritoneal
implants outside the pelvis
T3a IIIA Microscopic peritoneal metastasis outside the pelvis
T3b IIIB Macroscopic peritoneal metastasis outside the pelvis 2 cm or
less in greatest dimension
T3c IIIC Peritoneal metastasis more than 2 cm in diameter
Regional Lymph Nodes (N)
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 IIIC Regional lymph node metastasis
Distant Metastasis (M)
MX Distant metastasis cannot be assessed
M0 No distant metastasis
M1 IV Distant metastasis (excludes metastasis within the peritoneal
cavity)
276 American Joint Committee on Cancer • 2006
T2aTNM:
FIGO: IIA
FIGURE 31.4. T2a is tumor involving one or both fallopian tubes with pelvic
extension and/or metastasis to the uterus (shown) and/or ovaries.
T2bTNM:
FIGO: IIB
FIGURE 31.5. T2b is tumor with extension to other pelvic structures.
American Joint Committee on Cancer • 2006 277
STAGE GROUPING (AJCC/UICC/FIGO)
0 Tis N0 M0
IT1N0M0
IA T1a N0 M0
IB T1b N0 M0
IC T1c N0 M0
II T2 N0 M0
IIA T2a N0 M0
IIB T2b N0 M0
IIC T2c N0 M0
III T3 N0 M0
IIIA T3a N0 M0
IIIB T3b N0 M0
IIIC T3c N0 M0
Any T N1 M0
IV Any T Any N M1
31
T2cTNM:
FIGO: IIC
Ascites,
peritoneal
washing
FIGURE 31.6. T2c is pelvic extension with malignant cells in ascites or peritoneal
washings.
American Joint Committee on Cancer • 2006 279
32
Gestational Trophoblastic Tumors
32
SUMMARY OF CHANGES
• Gestational trophoblastic tumors are effectively treated with chemotherapy even
when widely metastatic so that traditional anatomic staging parameters do not
adequately provide different diagnostic categories. For this reason, although
the anatomic categories are preserved, a scoring system of other nonanatomic
risk factors has been added. This risk factor score provides the basis for substag-ing patients into A (low risk, score of 7 or less) or B (high risk, score of 8 or
greater).
• The “Risk Factors” portion of the stage grouping has been revised to reflect the
new scoring system.
C58.9 Placenta
INTRODUCTION
Gestational trophoblastic tumors are uncommon (1 in 1,000 pregnancies)
malignancies that arise from the placenta. Usually as a result of a genetic acci-dent in the developing egg, the maternal chromosomes are lost, and the pater-nal chromosomes duplicate (46xxx). The resulting tumor is known as a complete
hydatidiform mole: there are no fetal parts; the tumor is composed of dilated,
avascular, “grape-like” vesicles that may grow as large as, or larger than, the
normal pregnancy it replaces. There is obviously no heartbeat detected, and the
patient may have vaginal bleeding similar to a miscarriage. Many times, the diag-nosis is not made until a dilatation and curettage is done and the tissue is exam-ined pathologically. In some patients, fetal parts will be found in association with
mild proliferative trophoblastic (placental) tissues. Such patients have a partial
hydatidiform mole, which has a 69xxx or 69xxy chromosomal complement
resulting from twice the normal number of paternal chromosomes. Both of
these tumors usually follow a benign course, resolving completely after evacua-tion by the dilatation and suction or curettage, but approximately 20% of com-plete moles and 5% of partial moles persist locally or metastasize and thus
require chemotherapy.
Much less frequently (about 1 in 20,000 pregnancies in the United States),
a highly malignant, rapidly growing metastatic form of gestational tropho-blastic disease called choriocarcinoma is encountered. This solid, anaplastic,
avascular, and aggressively proliferative tumor is easily recognized microscopi-cally and may present with symptoms of vaginal bleeding (as with a hydatidi-form mole). However, metastatic lesions may be the first sign of this lesion,
which can follow any pregnancy event, including an incomplete abortion or a
full-term pregnancy.
The trophoblastic tissue that makes up these tumors produces a serum
tumor marker, beta-human chorionic gonadotrophin (b-hCG), which is very
helpful in the diagnosis and monitoring of therapy in these patients. Gestational
280 American Joint Committee on Cancer • 2006
trophoblastic tumors are very responsive to chemotherapy, with cure rates
approaching 100%.
ANATOMY
Because of the responsiveness of this tumor to treatment and the accuracy of
the serum marker hCG in reflecting the status of disease, the traditional
anatomic staging system used in most solid tumors has little prognostic signif-icance. Trophoblastic tumors not associated with pregnancy (ovarian teratomas)
are not included in this classification.
Primary Site. By definition, gestational trophoblastic tumors arise from
placental tissue in the uterus. Although most of these tumors are noninvasive
and are removed by dilatation and suction evacuation, local invasion of the
myometrium can occur. When this is diagnosed on a hysterectomy specimen
(rarely done these days), it may be reported as an invasive hydatidiform mole.
Regional Lymph Nodes. Nodal involvement in gestational trophoblastic
tumors is rare but has a very poor prognosis when diagnosed. There is no
regional designation in the staging of these tumors. Nodal metastases should be
classified as metastatic (M1) disease.
Metastatic Sites. This is a highly vascular tumor that results in frequent, wide-spread metastases when these lesions become malignant. The cervix and vagina
are common pelvic sites of metastases (T2), and the lungs are often involved by
distant metastases (M1a). Other, less frequently encountered metastatic sites
include kidney, gastrointestinal tract, and spleen (M1b). The liver and brain are
occasionally involved and may harbor metastatic sites that are difficult to treat
with chemotherapy.
DEFINITIONS
Primary Tumor (T)(1)
TNM* FIGO
Categories Stages
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
T1 I Disease limited to uterus (Figure 32.1)
T2 II Disease outside of uterus but limited to genital structures
(ovary, tube, vagina, broad ligaments) (Figure 32.2)
Distant Metastasis (M)
MX Metastasis cannot be assessed
M0 No distant metastasis
M1 Distant metastasis
M1a III Lung metastasis (Figure 32.3)
M1b IV All other distant metastasis (Figure 32.4)
*Note: There is no regional nodal staging for this tumor.
American Joint Committee on Cancer • 2006 281
32
T1TNM:
FIGO: I
T1TNM:
FIGO: I
FIGURE 32.1. Two views of T1 (disease confined to the uterus): tumor confined to
endometrium (left side of dotted line) and tumor with invasion of myometrium
and cervix (right side of dotted line).
T2TNM:
FIGO: II
T2TNM:
FIGO: II
Ascites,
peritoneal
washing
FIGURE 32.2. Two views of T2 (disease outside of the uterus but limited to genital
structures): involvement of the vagina (left side of the dotted line), fallopian tube
and ovary as well as the presence of malignant ascites (right side of the dotted
line).
STAGE GROUPING(2)
Stage T M Risk Factors
I T1 M0 Unknown
IA T1 M0 Low risk
IB T1 M0 High risk
II T2 M0 Unknown
IIA T2 M0 Low risk
IIB T2 M0 High risk
III Any T M1a Unknown
IIIA Any T M1a Low risk
IIIB Any T M1a High risk
IV Any T M1b Unknown
IVA Any T M1b Low risk
IVB Any T M1b High risk
282 American Joint Committee on Cancer • 2006
M1a
FIGO: III
Primary
tumor
Metastasis
FIGURE 32.3. M1a is defined as metastatic disease to the lung.
American Joint Committee on Cancer • 2006 283
32
M1b
FIGO: IV
Metastasis (node)
Metastasis (node)
Metastasis (node)
Metastasis (bone)
Primary
tumor
FIGURE 32.4. M1b disease is metastases to all other distant sites.
TABLE 32.1 Prognostic Indicators Scoring Index
Risk Score
Prognostic Factor 01 2 4
Age <40 >40
Antecedent pregnancy H. mole Abortion Term pregnancy
Interval months from <44–<7 7–12 >12
index pregnancy
Pretreatment hCG <103
≥103
–<104
104
–<105
≥105
(IU/ml)
Largest tumor size <3cm 3–<5cm ≥5cm
including uterus
Site of metastases Lung Spleen, Gastrointestinal  Brain, liver
kidney tract
Number of metastases 1–4 5–8 >8
identified
Previous failed  Single drug Two or more
chemotherapy drugs
Total Score
Low risk is a score of 7 or less. High risk is a score of 8 or greater.
NOTES
1. See Table 32.1, prognostic indicator section for substage definitions.
2. See Table 32.1, prognostic indicators for substage grouping.
American Joint Committee on Cancer • 2006 287
33
Penis
(Melanomas are not included.)
33
SUMMARY OF CHANGES
• The definitions of TNM and the Stage Grouping for this chapter have not
changed from the Fifth Edition.
INTRODUCTION
Cancers of the penis are rare in the United States, although the incidence varies
in different countries of the world. Most are squamous cell carcinomas that arise
in the skin or on the glans penis. Prognosis is favorable provided that the lymph
nodes are not involved. Melanomas can also occur. The staging classification,
however, applies to carcinomas. Melanomas are staged in Chapter 24. Some
cancers of the penis may be described as verrucous. Similarly, basaloid tumors
are recognized as a subtype of squamous carcinoma. An  in situ lesion is also
included and by definition should be coded as an in situ carcinoma of the penis.
ANATOMY
Primary Site. The penis is composed of three cylindrical masses of cavernous
tissue bound together by fibrous tissue. Two masses are lateral and are known
as the corpora cavernosa penis. The corpus spongiosum penis is a median mass
and contains the greater part of the urethra. The penis is attached to the front
and the sides of the pubic arch. The skin covering the penis is thin and loosely
connected with the deeper parts of the organ. The skin at the root of the penis
is continuous with that over the scrotum and perineum. Distally, the skin
becomes folded upon itself to form the prepuce, or foreskin. Anatomical sites
are illustrated in Figure 33.1. Circumcision has been associated with a decreased
incidence of cancer of the penis.
Regional Lymph Nodes. The regional lymph nodes are:
Single superficial inguinal (femoral)
Multiple or bilateral superficial inguinal (femoral)
Deep inguinal: Rosenmuller’s or Cloquet’s node
External iliac
Internal iliac (hypogastric)
Pelvic nodes, NOS
Metastatic Sites. Lung, liver, and bone are most often involved.
C60.0 Prepuce
C60.1 Glans penis
C60.2 Body of penis
C60.8 Overlapping lesion of
penis
C60.9 Penis, NOS
288 American Joint Committee on Cancer • 2006
DEFINITIONS
Primary Tumor (T)
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
Tis Carcinoma in situ
Ta Noninvasive verrucous carcinoma (Figure 33.2)
T1 Tumor invades subepithelial connective tissue (Figure 33.3)
T2 Tumor invades corpus spongiosum or cavernosum (Figure 33.4)
T3 Tumor invades urethra or prostate (Figures 33.5A, B)
T4 Tumor invades other adjacent structures (Figures 33.6, 33.7)
C60.1
C60.0
C60.2
FIGURE 33.1. Anatomic sites and subsites of the penis.
Epithelium
Subepithelial
connective tissueNon-invasive
Ta Ta
FIGURE 33.2. Ta: Noninvasive verrucous carcinoma.
Epithelium
Subepithelial
connective tissueInvasive
T1
T1
T1
FIGURE 33.3. T1: Two views of tumor invading subepithelial connective tissue.
American Joint Committee on Cancer • 2006 289
33
T2 T2
FIGURE 33.4. T2: Two views of tumor invading corpus spongiosum or
cavernosum.
T3 T3
A
T3
B
FIGURE 33.5. A. T3: Two views of tumor invading urethra. B. T3: Tumor invades
prostate.
T4
FIGURE 33.6. T4: Tumor invades other adjacent structures.
290 American Joint Committee on Cancer • 2006
Regional Lymph Nodes (N)
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Metastasis in a single superficial inguinal lymph node (Figure 33.8)
N2 Metastasis in multiple or bilateral superficial inguinal lymph nodes
(Figures 33.9A, B)
N3 Metastasis in deep inguinal or pelvic lymph node(s), unilateral or bilat-eral (Figures 33.10A–C)
Distant Metastasis (M)
MX Distant metastasis cannot be assessed
M0 No distant metastasis
M1 Distant metastasis
FIGURE 33.7. T4: Tumor invades other adjacent structures.
T4
N1
FIGURE 33.8. N1: Metastasis in a single superficial inguinal lymph node.
American Joint Committee on Cancer • 2006 291
33
N2
A
N2
B
FIGURE 33.9. A. N2: Metastasis in multiple, as shown above, or bilateral
superficial inguinal lymph nodes. B. N2: Metastasis in bilateral superficial inguinal
nodes.
N3
Deep
inguinal
A
N3
B
N3
C
FIGURE 33.10. A. N3: Metastasis in deep inguinal, as shown above, or pelvic
lymph node(s), unilateral or bilateral. B. N3: Metastasis in unilateral pelvic lymph
node(s). C. N3: Metastasis in bilateral pelvic lymph node(s).
292 American Joint Committee on Cancer • 2006
STAGE GROUPING
0 Tis N0 M0
Ta N 0 M 0
IT1 N0 M0
II T1 N1 M0
T2 N0 M0
T2 N1 M0
III T1 N2 M0
T2 N2 M0
T3 N0 M0
T3 N1 M0
T3 N2 M0
IV T4 Any N M0
Any T N3 M0
Any T Any N M1
American Joint Committee on Cancer • 2006 293
34
Prostate
(Sarcomas and transitional cell carcinomas are not included.)
34
SUMMARY OF CHANGES
• T2 lesions have been divided to include T2a, T2b, and T2c once again. These are
the same subcategories found in the Fourth Edition of the AJCC Manual.
• Gleason score is emphasized as the grading system of choice and using the terms
well differentiated, moderately differentiated, and poorly differentiated for grading
is not recommended.
C61.9 Prostate gland
INTRODUCTION
Prostate cancer is the most common cancer in men, with increasing incidence
in older age groups. Prostate cancer has a tendency to metastasize to bone.
Earlier detection is possible with a blood test, prostate-specific antigen (PSA),
and diagnosis is generally made using transrectal ultrasound (TRUS) guided
biopsy.
ANATOMY
Primary Site. Anatomy of the prostate is illustrated in Figure 34.1. Adenocar-cinoma of the prostate frequently arises within the peripheral zone of the gland,
where it may be amenable to detection by digital rectal examination (DRE). A
less common site of origin is the anteromedial prostate, the transition zone,
which is remote from the rectal surface and is the site of origin of benign nodular
hyperplasia. The central zone, which makes up most of the base of the prostate,
seldom gives rise to cancer but is often invaded by the spread of large cancers.
Pathologically, cancers of the prostate are often multifocal.
There is agreement that the incidence of both clinical and latent carcinoma
increases with age. However, this cancer is rarely diagnosed clinically in men
under 40 years of age. There are substantial limitations in the ability of both
DRE and TRUS to define precisely the size or local extent of disease; DRE is cur-rently the most common modality used to define the local stage. Heterogeneity
within the T1c category resulting from inherent limitations of either DRE or
imaging to quantify the cancer may be balanced by the inclusion of other prog-nostic factors, such as histologic grade, PSA level, and possibly extent of cancer
on needle biopsies that contain cancer. Diagnosis of clinically suspicious areas
of the prostate can be confirmed histologically by needle biopsy. Less commonly,
prostate cancer may be diagnosed by inspection of the resected tissue from
a transurethral resection of the prostate (TURP) for obstructive voiding
symptoms.
The histologic grade of the prostate cancer is important for prognosis. The
histopathologic grading of these tumors can be complex because of the
294 American Joint Committee on Cancer • 2006
morphologic heterogeneity so often encountered in surgical specimens. Either
a histologic or a pattern type of grading method can be used. The Gleason score
for assessing the histologic pattern of prostate cancer is preferred.
Regional Lymph Nodes. The regional lymph nodes are the nodes of the true
pelvis, which essentially are the pelvic nodes below the bifurcation of the
common iliac arteries (Figure 34.2). They include the following groups:
Pelvic NOS
Hypogastric
Obturator
Iliac (internal, external, or NOS)
Sacral (lateral, presacral, promontory [Gerota’s], or NOS)
Laterality does not affect the “N” classification.
C61.9
FIGURE 34.1. Anatomy of the prostate.
C77.5
FIGURE 34.2. Shaded area represents regional distribution of lymph nodes.
Nonshaded area indicates nodes outside of regional distribution.
American Joint Committee on Cancer • 2006 295
Distant Lymph Nodes. Distant lymph nodes lie outside the confines of the
true pelvis. They can be imaged using ultrasound, computed tomography, mag-netic resonance imaging, or lymphangiography. Although enlarged lymph nodes
can occasionally be visualized, because of a stage migration associated with PSA
screening, very few patients will be found to have nodal disease, so false-positive and false-negative results are common when imaging tests are
employed. In lieu of imaging, risk tables are generally used to determine indi-vidual patient risk of nodal involvement. Involvement of distant lymph nodes
is classified as M1a. The distant lymph nodes include:
Aortic (para-aortic lumbar)
Common iliac
Inguinal, deep
Superficial inguinal (femoral)
Supraclavicular
Cervical
Scalene
Retroperitoneal, NOS
The significance of regional lymph node metastasis, pN, in staging prostate
cancer lies in the presence of metastatic foci within the lymph nodes.
Metastatic Sites. Osteoblastic metastases are the most common non-nodal
site of prostate cancer metastasis. In addition, this tumor frequently spreads to
distant lymph nodes. Lung and liver metastases are usually identified late in the
course of the disease.
DEFINITIONS
Primary Tumor (T)
Clinical
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
T1 Clinically inapparent tumor neither palpable nor visible by imaging
T1a Tumor incidental histologic finding in 5% or less of tissue resected
(Figure 34.3)
34
T1a T1b
£5% >5%
FIGURE 34.3. T1a (left) shows tumor incidental histologic finding in 5% or less of
tissue resected. T1b (right) shows tumor incidental histologic finding in more than
5% of tissue resected.
296 American Joint Committee on Cancer • 2006
T1b Tumor incidental histologic finding in more than 5% of tissue resected
(Figure 34.3)
T1c Tumor identified by needle biopsy (e.g., because of elevated PSA)
T2 Tumor confined within prostate(1)
T2a Tumor involves one-half of one lobe or less (Figure 34.4)
T2b Tumor involves more than one-half of one lobe but not both lobes (Figure
34.4)
T2c Tumor involves both lobes (Figure 34.5)
T3 Tumor extends through the prostate capsule(2)
T3a Extracapsular extension (unilateral or bilateral) (Figures 34.6A, B)
T3b Tumor invades seminal vesicle(s) (Figure 34.7)
T2a T2b
FIGURE 34.4. T2a (left) shows tumor involving one-half of one lobe or less
whereas T2b (right) shows tumor involving more than one-half of one lobe but
not both lobes.
T2c
FIGURE 34.5. T2c tumor involving both lobes
American Joint Committee on Cancer • 2006 297
T4 Tumor is fixed or invades adjacent structures other than seminal vesicles:
bladder neck, external sphincter, rectum, levator muscles, and/or pelvic
wall (Figures 34.8A, B)
Pathologic (pT)(3)
pT2 Organ confined
pT2a Unilateral, one-half of one lobe or less
pT2b Unilateral, involving more than one-half of lobe but not both lobes
pT2c Bilateral disease
pT3 Extraprostatic extension
pT3a Extraprostatic extension(4)
pT3b Seminal vesicle invasion
pT4 Invasion of bladder, rectum
34
T3a
A
T3a
B
FIGURE 34.6. A,B. T3a is defined as a tumor with unilateral extracapsular
extension, as shown in A, or with bilateral extracapsular extension, as shown in B.
T3b
FIGURE 34.7. T3b tumor invading seminal vesicle(s).
298 American Joint Committee on Cancer • 2006
T4
A
T4
Tumor is fixed
B
FIGURE 34.8. A. T4 tumor invading adjacent structures other than seminal vesicles
such as bladder neck, as shown here, external sphincter, rectum, levator muscles,
and/or pelvic wall or tumor is fixed. B. T4 showing tumor fixed to adjacent
structures.
American Joint Committee on Cancer • 2006 299
34
N1
A
N1
B
FIGURE 34.9. A. N1 metastasis in regional lymph nodes, here shown unilaterally.
B. N1 metastasis in regional lymph nodes, here shown bilaterally.
Regional Lymph Nodes (N)
Clinical
NX Regional lymph nodes were not assessed
N0 No regional lymph node metastasis
N1 Metastasis in regional lymph node(s) (Figures 34.9A, B)
300 American Joint Committee on Cancer • 2006
Regional Lymph Nodes (N)
Pathologic
pNX Regional nodes not sampled
pN0 No positive regional nodes
pN1 Metastases in regional node(s)
Distant Metastasis (M)(5)
MX Distant metastasis cannot be assessed (not evaluated by any modality)
M0 No distant metastasis
M1 Distant metastasis
M1a Nonregional lymph node(s)
M1b Bone(s)
M1c Other site(s) with or without bone disease
STAGE GROUPING
I T1a N0 M0 G1
II T1a N0 M0 G2,3–4
T1b N0 M0 Any G
T1c N0 M0 Any G
T1 N0 M0 Any G
T2 N0 M0 Any G
III T3 N0 M0 Any G
IV T4 N0 M0 Any G
Any T N1 M0 Any G
Any T Any N M1 Any G
HISTOLOGIC GRADE (G)
Gleason score is considered to be the optimal method of grading, because this
method takes into account the inherent heterogeneity of prostate cancer, and
because it has been clearly shown that this method is of great prognostic value.
A primary and secondary pattern (the range of each is 1–5) are assigned and
then summed to yield a total score. Scores of 2–10 are thus possible. (If a single
focus of disease is seen, it should be reported as both scores. For example, if a
single focus of Gleason 3 disease is seen, it is reported as 3 + 3).
GX Grade cannot be assessed
G1 Well differentiated (slight anaplasia) (Gleason 2–4)
G2 Moderately differentiated (moderate anaplasia) (Gleason 5–6)
G3–4 Poorly differentiated/undifferentiated (marked anaplasia) (Gleason
7–10)
NOTES
1. Tumor found in one or both lobes by needle biopsy, but not palpable or reliably
visible by imaging, is classified as T1c.
2. Invasion into the prostatic apex or into (but not beyond) the prostatic capsule is
classified not as T3, but as T2.
3. There is no pathologic T1 classification.
American Joint Committee on Cancer • 2006 301
4. Positive surgical margin should be indicated by an R1 descriptor (residual micro-scopic disease).
5. When more than one site of metastasis is present, the most advanced category is
used. pM1c is most advanced.
34
American Joint Committee on Cancer • 2006 303
35
Testis
35
SUMMARY OF CHANGES
• The definitions of TNM and the Stage Grouping for this chapter have not
changed from the Fifth Edition.
C62.0 Undescended testis C62.1 Descended testis C62.9 Testis, NOS
INTRODUCTION
Cancers of the testis are usually found in young adults and account for less than
1% of all malignancies in males. However, during the twentieth century, the inci-dence has more than doubled. Cryptorchidism is a predisposing condition, and
other associations include atypical germ cells and multiple atypical nevi. Germ
cell tumors of the testis are categorized into two main histologic types: semino-mas and non-seminomas. The latter group is composed of either individual or
combinations of histologic subtypes, including embryonal carcinoma, teratoma,
choriocarcinoma, and yolk sac tumor. The presence of serum markers, includ-ing alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG), and lactate
dehydrogenase (LDH), is frequent in this disease. Staging and prognostication
are based on the determination of the extent of disease and assessment of serum
tumor markers. Cancer of the testis is highly curable, even in cases with
advanced, metastatic disease.
ANATOMY
Primary Site. The anatomy of the testes is illustrated in Figure 35.1. The testes
are composed of convoluted seminiferous tubules with a stroma containing
functional endocrine interstitial cells. Both are encased in a dense capsule, the
tunica albuginea, with fibrous septa extending into the testes and separating
them into lobules. The tubules converge and exit at the mediastinum of the testis
into the rete testis and efferent ducts, which join a single duct. This duct—the
epididymis—coils outside the upper and lower poles of the testicle and then
joins the vas deferens, a muscular conduit that accompanies the vessels and lym-phatic channels of the spermatic cord. The major route for local extension of
cancer is through the lymphatic channels. The tumor emerges from the medi-astinum of the testis and courses through the spermatic cord. Occasionally, the
epididymis is invaded early, and then the external iliac nodes may become
involved. If there has been previous scrotal or inguinal surgery or if invasion of
the scrotal wall is found (though this is rare), then the lymphatic spread may be
to inguinal nodes.
Regional Lymph Nodes. The following nodes are considered regional (Figure
35.2):
Interaortocaval
Para-aortic (periaortic)
304 American Joint Committee on Cancer • 2006
Paracaval
Preaortic
Precaval
Retroaortic
Retrocaval
The intrapelvic, external iliac, and inguinal nodes are considered regional
only after scrotal or inguinal surgery prior to the presentation of the testis tumor.
C62.1
FIGURE 35.1. Anatomy of the testis.
C77.2
C77.5
C77.4
C77.4 and 5 only
after scrotal or
inguinal surgery
FIGURE 35.2. Regional lymph nodes of the testis.
American Joint Committee on Cancer • 2006 305
All nodes outside the regional nodes are distant. Nodes along the spermatic vein
are considered regional.
Metastatic Site. Distant spread of testicular tumors occurs most commonly
to the lymph nodes, followed by metastases to the lung, liver, bone, and
other visceral sites. Stage is dependent on the extent of disease and on the
determination of serum tumor markers. Extent of disease includes assessment
for involvement and size of regional lymph nodes, evidence of disease in
nonregional lymph nodes, and metastases to pulmonary and non-pulmonary
visceral sites. The stage is subdivided on the basis of the presence and degree of
elevation of serum tumor markers. Serum tumor markers are measured
immediately after orchiectomy and, if elevated, should be measured serially after
orchiectomy to determine whether normal decay curves are followed. The
physiological half-life of AFP is 5–7 days, and the half-life of HCG is 24–
48 hours. The presence of prolonged half-life times implies the presence of
residual disease after orchiectomy. It should be noted that in some cases,
tumor marker release may occur (for example, in response to chemotherapy or
handling of a primary tumor intraoperatively) and may cause artificial eleva-tion of circulating tumor marker levels. The serum level of lactate dehydroge-nase (LDH) has prognostic value in patients with metastatic disease and is
included for staging.
DEFINITIONS
Primary Tumor (T)(1)
The extent of primary tumor is usually classified after radical orchiectomy, and
for this reason, a pathologic stage is assigned.
pTX Primary tumor cannot be assessed (if no radical orchiectomy has been
performed, TX is used)
pT0 No evidence of primary tumor (e.g., histologic scar in testis)
pTis Intratubular germ cell neoplasia (carcinoma in situ)
pT1 Tumor limited to the testis and epididymis without vascular/lymphatic
invasion; tumor may invade into the tunica albuginea but not the tunica
vaginalis (Figure 35.3A)
pT2 Tumor limited to the testis and epididymis with vascular/lymphatic inva-sion, or tumor extending through the tunica albuginea with involvement
of the tunica vaginalis (Figures 35.3A, B)
pT3 Tumor invades the spermatic cord with or without vascular/lymphatic
invasion (Figure 35.4)
pT4 Tumor invades the scrotum with or without vascular/lymphatic invasion
(Figure 35.5)
Regional Lymph Nodes (N)
Clinical
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Metastasis with a lymph node mass 2 cm or less in greatest dimension; or
multiple lymph nodes, none more than 2 cm in greatest dimension
(Figures 35.6A–F)
35
T. vaginalis
pT1= without vascular/
lymphatic invasion
pT2= with vascular/
lymphatic invasion
T. albuginea
A
T. vaginalis
T. albuginea
pT2
B
FIGURE 35.3. A. Illustration of
pT1 and pT2 showing tumor
without and with vascular/
lymphatic invasion. B. pT2
tumor extending through
the tunica albuginea with
involvement of the tunica
vaginalis.
pT3
FIGURE 35.4. pT3 tumor invades the
spermatic cord.
pT4
FIGURE 35.5. pT4 tumor invades the
scrotum.
American Joint Committee on Cancer • 2006 307
35
FIGURE 35.6. A. N1 is defined
as metastasis with a lymph node
mass 2 cm or less in greatest
dimension. B. N1: metastasis in
multiple lymph nodes, none
more than 2 cm in greatest
dimension. C. N1: metastasis
with a lymph node mass 2 cm or
less in greatest dimension,
following scrotal or inguinal
surgery.
N1
£2 cm
A
N1
£2 cm
B
After scrotal or
inguinal surgery
£2 cm
N1
C
308 American Joint Committee on Cancer • 2006
After scrotal or
inguinal surgery
£2 cm
N1
D
N1 pN2
>2-<5 cm£2 cm
E
FIGURE 35.6. D. N1: metastasis in
multiple lymph nodes, none more
than 2 cm in greatest dimension,
following scrotal or inguinal
surgery. E. N1 (left) is defined as
metastasis in multiple lymph nodes,
none more than 2 cm in greatest
dimension. pN2 (right) is defined
as more than 5 nodes positive,
more than 2 cm but none larger
than 5 cm in greatest dimension.
American Joint Committee on Cancer • 2006 309
35
N1 pN2
£2 cm
Extranodal
extension
£2 cm
F
FIGURE 35.6. F. N1 (left) defined as metastasis with a lymph node mass 2 cm or
less in greatest dimension. pN2 (right) defined as of extranodal extension of
tumor.
N2 Metastasis with a lymph node mass more than 2 cm but not more than
5 cm in greatest dimension; or multiple lymph nodes, any one mass greater
than 2 cm but not more than 5 cm in greatest dimension (Figures 35.7A–C)
N3 Metastasis with a lymph node mass more than 5 cm in greatest dimension
(Figures 35.8A–D)
Regional Lymph Nodes (N)
Pathologic
pNX Regional lymph nodes cannot be assessed
pN0 No regional lymph node metastasis
pN1 Metastasis with a lymph node mass 2 cm or less in greatest dimension
and less than or equal to 5 nodes positive, none more than 2 cm in great-est dimension
pN2 Metastasis with a lymph node mass more than 2 cm but not more than
5 cm in greatest dimension; or more than 5 nodes positive, none more
than 5 cm; or evidence of extranodal extension of tumor (Figures 35.6E,
F; Figures 35.7A–C)
310 American Joint Committee on Cancer • 2006
N2 pN2
>2-5 cm
A
N2 pN2
>2-5 cm
B
After scrotal or
inguinal surgery
>2-5 cm
N2 pN2
C
FIGURE 35.7. A. N2/pN2:
metastasis with a lymph
node mass more than
2 cm but not more than
5 cm in greatest dimension.
B. N2/pN2: metastasis in
multiple lymph nodes, any
one mass greater than 2 cm
but not more than 5 cm in
greatest dimension. C.
N2/pN2: metastasis with a
lymph node mass more
than 2 cm but not more
than 5 cm in greatest
dimension, following scrotal
or inguinal surgery.
American Joint Committee on Cancer • 2006 311
35
>5 cm
N3 pN3
A
After scrotal or
inguinal surgery
>5 cm
N3 pN3
B
FIGURE 35.8. A. N3/pN3:
metastasis with a lymph node mass
more than 5 cm in greatest
dimension. B. N3/pN3 metastasis
with a lymph node mass more than
5 cm in greatest dimension,
following scrotal or inguinal
surgery.
312 American Joint Committee on Cancer • 2006
FIGURE 35.8. C. N3/pN3:
metastasis with a lymph node mass
more than 5 cm in greatest
dimension. As illustrated here,
multiple nodes are involved with
one nodal mass exceeding 5 cm. D.
N3/pN3: metastasis with a lymph
node mass more than 5 cm in
greatest dimension. As illustrated
here following scrotal or inguinal
surgery, multiple nodes are
involved with one nodal mass
exceeding 5 cm.
>5 cm
N3 pN3
C
After scrotal or
inguinal surgery
>5 cm
N3 pN3
D
American Joint Committee on Cancer • 2006 313
35
pN3 Metastasis with a lymph node mass more than 5 cm in greatest dimen-sion (Figures 35.8A–D)
Distant Metastasis (M)
MX Distant metastasis cannot be assessed
M0 No distant metastasis
M1 Distant metastasis
M1a Nonregional nodal or pulmonary metastasis
M1b Distant metastasis other than to nonregional lymph nodes and lungs
Serum Tumor Markers (S)
(N indicates the upper limit of normal for the LDH assay.)
SX Marker studies not available or not performed
S0 Marker study levels within normal limits
S1 LDH <1.5 ¥ N AND
hCG (mIu/ml) <5,000 AND
AFP (ng/ml) <1,000
S2 LDH 1.5–10 ¥ N OR
hCG (mIu/ml) 5,000–50,000 OR
AFP (ng/ml) 1,000–10,000
S3 LDH >10 ¥ N OR
hCG (mIu/ml) >50,000 OR
AFP (ng/ml) >10,000
STAGE GROUPING
0pTisN0M0S0
I pT1–4 N0 M0 SX
IA pT1 N0 M0 S0
IB pT2 N0 M0 S0
pT3 N0 M0 S0
pT4 N0 M0 S0
IS Any pT/Tx N0 M0 S1–3
II Any pT/Tx N1–3 M0 SX
IIA Any pT/Tx N1 M0 S0
Any pT/Tx N1 M0 S1
IIB Any pT/Tx N2 M0 S0
Any pT/Tx N2 M0 S1
IIC Any pT/Tx N3 M0 S0
Any pT/Tx N3 M0 S1
III Any pT/Tx Any N M1 SX
IIIA Any pT/Tx Any N M1a S0
Any pT/Tx Any N M1a SI
IIIB Any pT/Tx N1–3 M0 S2
Any pT/Tx Any N M1a S2
IIIC Any pT/Tx N1–3 M0 S3
Any pT/Tx Any N M1a S3
Any pT/Tx Any N M1b Any S
314 American Joint Committee on Cancer • 2006
NOTE
1. Except for pTis and pT4, extent of primary tumor is classified by radical
orchiectomy. TX may be used for other categories in the absence of radical
orchiectomy.
American Joint Committee on Cancer • 2006 315
36
Kidney
36
SUMMARY OF CHANGES
• T1 lesions have been divided into T1a and T1b.
• T1a is defined as tumors 4 cm or less in greatest dimension, limited to the kidney.
• T1b is defined as tumors greater than 4 cm but not more than 7 cm in greatest
dimension, limited to the kidney.
C64.9 Kidney
INTRODUCTION
Cancers of the kidney are relatively rare, accounting for less than 3% of all malig-nancies. Nearly all malignant tumors are carcinomas arising from the renal
tubular epithelium or, less frequently, from the renal pelvis (see Chapter 37).
These tumors are more common in males. Pain and hematuria are usually the
presenting features, but a majority of kidney tumors are not being detected inci-dentally in asymptomatic individuals. These carcinomas have a tendency to
extend into the renal vein and even into the vena cava. Staging depends on the
size of the primary tumor, invasion of the adjacent structures, and vascular
extension.
Since publication of the Fifth Edition of the AJCC Cancer Staging Manual,
the evidence has become compelling that the T1 category should be subdivided
into stages T1a and T1b, the former being tumors of 4 cm or less and the latter
being tumors greater than 4 cm to 7 cm. The rationale is twofold: (1) the recur-rence of survival difference between the two and (2) the current practice of
applying partial nephrectomy for solitary tumors 4 cm or less in diameter. In the
case of partial nephrectomy for tumors <4 cm in diameter, evidence suggests that
survival outcomes are equivalent to outcomes with radical nephrectomy.
ANATOMY
Primary Site. Encased by a fibrous capsule and surrounded by perirenal fat,
the kidney consists of the cortex (glomeruli, convoluted tubules) and the
medulla (Henle’s loops, pyramids of converging tubules). Each papilla opens
into the minor calices; these in turn unite in the major calices and drain into
the renal pelvis. At the hilus are the pelvis, ureter, and renal artery and vein.
Gerota’s fascia overlies the psoas and quadratus lumborum. The anatomic sites
and subsites of the kidney are illustrated in Figure 36.1.
Regional Lymph Nodes. The regional lymph nodes, illustrated in Figure 36.2,
are:
Renal hilar
Paracaval
316 American Joint Committee on Cancer • 2006
C74
C65.9
C66.9
Perinephric
fat
Gerota
fascia
C64.9
FIGURE 36.1. Anatomical sites and subsites of the kidney.
C77.2
FIGURE 36.2. Regional lymph nodes of the kidney.
Aortic (para-aortic, periaortic, lateral aortic)
Retroperitoneal, NOS
Metastatic Sites. Common metastatic sites include bone, liver, lung, brain,
and distant lymph nodes.
American Joint Committee on Cancer • 2006 317
DEFINITIONS
Primary Tumor (T)
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
T1 Tumor 7 cm or less in greatest dimension, limited to the kidney
T1a Tumor 4 cm or less in greatest dimension, limited to the kidney (Figure
36.3)
T1b Tumor more than 4 cm but not more than 7 cm in greatest dimension,
limited to the kidney (Figure 36.4)
36
£4 cm
T1a
FIGURE 36.3. T1a: tumor 4 cm or less in greatest dimension, limited to the kidney.
>4–£7 cm
T1b
FIGURE 36.4. T1b: tumor more than 4 cm but not more than 7 cm in greatest
dimension, limited to the kidney.
318 American Joint Committee on Cancer • 2006
T2 Tumor more than 7 cm in greatest dimension, limited to the kidney
(Figure 36.5)
T3 Tumor extends into major veins or invades adrenal gland or perinephric
tissues but not beyond Gerota’s fascia
T3a Tumor directly invades adrenal gland or perirenal and/or renal sinus fat
but not beyond Gerota’s fascia (Figure 36.6)
>7 cm
T2
FIGURE 36.5. T2: tumor more than 7 cm in greatest dimension, limited to the
kidney.
T3a T3a
Perinephric fat
Gerota fascia Adrenal gland
FIGURE 36.6. Two views of T3a, defined as tumor directly invades adrenal gland
(right) or perirenal and/or renal sinus fat (left) but not beyond Gerota’s fascia.
American Joint Committee on Cancer • 2006 319
T3b Tumor grossly extends into the renal vein or its segmental (muscle-containing) branches, or vena cava below the diaphragm (Figure 36.7)
T3c Tumor grossly extends into vena cava above diaphragm or invades the
wall of the vena cava (Figure 36.8)
T4 Tumor invades beyond Gerota’s fascia (Figure 36.9)
Regional Lymph Nodes (N)
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastases
N1 Metastasis in a single regional lymph node (Figure 36.10)
N2 Metastasis in more than one regional lymph node (Figures 36.10, 36.11)
Distant Metastasis (M)
MX Distant metastasis cannot be assessed
M0 No distant metastasis
M1 Distant metastasis
36
T3b
FIGURE 36.7. T3b: tumor grossly extends into the renal vein or its segmental
(muscle-containing) branches, or vena cava below the diaphragm.
T3c
FIGURE 36.8. T3c: tumor grossly extends into vena cava above diaphragm or
invades the wall of the vena cava.
320 American Joint Committee on Cancer • 2006
T4
Perinephric fat
Gerota fascia
FIGURE 36.9. T4: tumor invades
beyond Gerota’s fascia.
N1 N2
FIGURE 36.10. N1, on the left, is defined as
metastasis in a single regional lymph node. N2, on
the right, is defined as metastasis in more than one
regional lymph node.
N2
FIGURE 36.11. N2: Metastasis in more than one
regional lymph node.
American Joint Committee on Cancer • 2006 321
STAGE GROUPING
IT1N0M0
II T2 N0 M0
III T1 N1 M0
T2 N1 M0
T3 N0 M0
T3 N1 M0
T3a N0 M0
T3a N1 M0
T3b N0 M0
T3b N1 M0
T3c N0 M0
T3c N1 M0
IV T4 N0 M0
T4 N1 M0
Any T N2 M0
Any T Any N M1
36
American Joint Committee on Cancer • 2006 323
37
Renal Pelvis and Ureter
37
SUMMARY OF CHANGES
• The definitions of TNM and the Stage Grouping for this chapter have not
changed from the Fifth Edition.
C65.9 Renal pelvis C66.9 Ureter
INTRODUCTION
Urothelial (transitional cell) carcinoma may occur at any site within the upper
urinary collecting system from the renal calyx to the ureterovesical junction. The
tumors occur most commonly in adults and are rare before 40 years of age.
There is a two- to threefold increase in incidence in men compared with women.
The lesions are often multiple and are more common in patients with a history
of urothelial carcinoma of the bladder. A number of analgesics (such as
phenacetin) have also been associated with this disease. Local staging depends
on the depth of invasion. A common staging system is used regardless of tumor
location within the upper urinary collecting system, except for category T3,
which differs between the pelvis or calyceal system and the ureter.
ANATOMY
Primary Site. The renal pelvis and the ureter form a single unit that is con-tinuous with the collecting ducts of the renal pyramids and comprises the minor
and major calyces, which are continuous with the renal pelvis. The ureteropelvic
junction is variable in position and location but serves as a “landmark” that sep-arates the renal pelvis and the ureter, which continues caudad and traverses the
wall of the urinary bladder as the intramural ureter opening in the trigone of
the bladder at the ureteral orifice. The renal pelvis and the ureter are composed
of the following layers: epithelium, subepithelial connective tissue, and muscu-laris, which is continuous with a connective tissue adventitial layer. It is in this
outer layer that the major blood supply and lymphatics are found.
The intrarenal portion of the renal pelvis is surrounded by renal
parenchyma, and the extrarenal pelvis by perihilar fat. The ureter courses
through the retroperitoneum adjacent to the parietal peritoneum and rests on
the retroperitoneal musculature above the pelvic vessels. As it crosses the vessels
and enters the deep pelvis, the ureter is surrounded by pelvic fat until it trav-erses the bladder wall.
Regional Lymph Nodes. The regional lymph nodes for the renal pelvis are:
Renal hilar
Paracaval
Aortic
Retroperitoneal, NOS
324 American Joint Committee on Cancer • 2006
The regional lymph nodes for the ureter are:
Renal hilar
Iliac (common, internal [hypogastric], external)
Paracaval
Periureteral
Pelvic, NOS
Any amount of regional lymph node metastasis is a poor prognostic finding and
outcome is minimally influenced by the number, size, or location of the regional
nodes that are involved.
Metastatic Sites. Distant spread is most commonly to the lung, bone, or liver.
DEFINITIONS
Primary Tumor (T)
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
Ta Papillary noninvasive carcinoma (Figure 37.1)
Tis Carcinoma in situ
T1 Tumor invades subepithelial connective tissue (Figure 37.1)
T2 Tumor invades the muscularis (Figure 37.2)
T3 (For renal pelvis only) Tumor invades beyond muscularis into peripelvic
fat or the renal parenchyma (Figure 37.2)
T3 (For ureter only) Tumor invades beyond muscularis into periureteric fat
T4 Tumor invades adjacent organs, or through the kidney into the perinephric
fat (Figures 37.3A–C)
Ta T1 T2
Epthelium
Subepithelial
connective tissue
Muscularis
Periureteric fat
Peripelvic fat
FIGURE 37.1. Ta is defined as papillary noninvasive carcinoma; T1 is defined as
tumor invading subepithelial connective tissue; T2 is defined as tumor invading the
muscularis.
American Joint Committee on Cancer • 2006 325
37
T3
T3
FIGURE 37.2. T3 (for renal pelvis only, top of diagram): tumor invades beyond
muscularis into peripelvic fat or the renal parenchyma. T3 (for ureter only, bottom
of diagram): tumor invades beyond muscularis into periureteric fat.
T4
Vertebral
body
A
FIGURE 37.3. A. T4 tumor invades adjacent organs, or through the kidney into the
perinephric fat. Here, the tumor invades the vertebral body.
326 American Joint Committee on Cancer • 2006
T4 T4
B
T4
Perinephric fat
Gerota fascia
C
FIGURE 37.3. B. T4 tumor (ureter) invades adjacent organs. On the left, tumor
invades the iliac vessels. On the right, tumor invades the bladder. C. T4 tumor
invades through the kidney into the perinephric fat.
N1
£2 cm
FIGURE 37.4. N1 is defined as metastasis in a single lymph node, 2 cm or less in
greatest dimension.
Regional Lymph Nodes (N)
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Metastasis in a single lymph node, 2 cm or less in greatest dimension
(Figure 37.4)
N2 Metastasis in a single lymph node, more than 2 cm but not more than 5
cm in greatest dimension; or multiple lymph nodes, none more than 5 cm
in greatest dimension (Figures 37.5A, B)
American Joint Committee on Cancer • 2006 327
N3 Metastasis in a lymph node, more than 5 cm in greatest dimension (Figures
37.6A, B)
Distant Metastasis (M)
MX Distant metastasis cannot be assessed
M0 No distant metastasis
M1 Distant metastasis
37
N2
>2-5 cm
A
N2
£5 cm
B
FIGURE 37.5. A. N2 nodal metastasis in a single lymph node, more than 2 cm but
not more than 5 cm in greatest dimension, as illustrated; or multiple lymph nodes,
none more than 5 cm in greatest dimension B. N2 nodal metastasis in a single
lymph node, more than 2 cm but not more than 5 cm in greatest dimension; or
multiple lymph nodes, none more than 5 cm in greatest dimension, as illustrated.
N3
>5 cm
A
N3
>5 cm
B
FIGURE 37.6. A. N3 is defined as metastasis in a lymph node, more than 5 cm in
greatest dimension. B. N3 nodal metastasis in a lymph node, more than 5 cm in
greatest dimension. As illustrated here, multiple lymph nodes are involved with one
nodal mass exceeding 5 cm.
328 American Joint Committee on Cancer • 2006
STAGE GROUPING
0a Ta N0 M0
0is Tis N0 M0
IT1N0M0
II T2 N0 M0
III T3 N0 M0
IV T4 N0 M0
Any T Nl M0
Any T N2 M0
Any T N3 M0
Any T Any N M1
American Joint Committee on Cancer • 2006 329
38
Urinary Bladder
38
SUMMARY OF CHANGES
• The definitions of TNM and the Stage Grouping for this chapter have not
changed from the Fifth Edition.
C67.0 Trigone of bladder
C67.1 Dome of bladder
C67.2 Lateral wall of
bladder
C67.3 Anterior wall of
bladder
C67.4 Posterior wall of
bladder
C67.5 Bladder neck
C67.6 Ureteric orifice
C67.7 Urachus
C67.8 Overlapping lesion of
bladder
C67.9 Bladder, NOS
INTRODUCTION
Bladder cancer is one of the most common malignancies in Western society, and
it occurs more commonly in males. Predisposing factors include smoking, expo-sure to chemicals, such as phenacetin and dyes, and schistosomiasis. It has also
been suggested that the incidence of this disease correlates inversely with fluid
intake. Hematuria is the most common presenting feature. Bladder cancer can
present as a low-grade papillary lesion, as an in situ lesion that can occupy large
areas of the mucosal surface, or as an infiltrative cancer that rapidly extends
through the bladder wall and can thereafter metastasize. The papillary and  in
situ lesions may be associated with a malignant course, with sudden invasion of
the bladder wall. The most common histologic variant is urothelial (transitional
cell) carcinomas, although this may exhibit features of glandular or squamous
differentiation. In less than 10% of cases, pure adenocarcinoma or squamous
carcinoma of the bladder may occur, and less frequently, sarcoma, lymphoma,
small cell anaplastic carcinoma, pheochromocytoma, choriocarcinoma. Squa-mous carcinoma is associated with schistosomiasis and smoking.
ANATOMY
Primary Site. The anatomic sites and subsites of the urinary bladder are illus-trated in Figure 38.1. The urinary bladder consists of three layers: the epithe-lium and the subepithelial connective tissue, the muscularis, and the perivesical
fat (peritoneum covering the superior surface and upper part). In the male, the
bladder adjoins the rectum and seminal vesicle posteriorly, the prostate inferi-orly, and the pubis and peritoneum anteriorly. In the female, the vagina is located
posteriorly and the uterus superiorly. The bladder is located extraperitoneally.
Regional Lymph Nodes. The regional lymph nodes are the nodes of the true
pelvis (Figure 38.2), which essentially are the pelvic nodes below the bifurcation
of the common iliac arteries. The significance of regional lymph node metasta-sis in staging bladder cancer lies in the number and size, not in whether metas-tasis is unilateral or contralateral. One of the major prognostic determinants of
330 American Joint Committee on Cancer • 2006
ultimate cure is whether the tumor is confined to the bladder, and a major
adverse prognostic feature is the presence of any lymph nodal metastases.
Regional nodes include:
Hypogastric
Obturator
Urachus (C67.7)
Dome (C67.1)
Lateral wall
(C67.2)
Anterior wall
(C67.3)
Ureteric orifice
(C67.6)
Bladder neck
(C67.5)
Prostate (C61.9)
Posterior
wall (C67.4)
FIGURE 38.1. Anatomical sites and subsites of the urinary bladder.
C77.5
FIGURE 38.2. Regional lymph nodes of the urinary bladder.
American Joint Committee on Cancer • 2006 331
Iliac (internal, external, NOS)
Perivesical
Pelvic, NOS
Sacral (lateral, sacral promontory [Gerota’s])
Presacral
The common iliac nodes are considered sites of distant metastasis and
should be coded as M1.
Metastatic Sites. Distant spread is most commonly to lymph nodes, lung,
bone, and liver.
DEFINITIONS
Primary Tumor (T)
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
Ta Noninvasive papillary carcinoma (Figure 38.3)
Tis Carcinoma in situ: “flat tumor” (Figure 38.3)
T1 Tumor invades subepithelial connective tissue (Figure 38.3)
T2 Tumor invades muscle (Figure 38.3)
38
1 Epithelium
2 Subepithelial connective tissue
3 Muscle
4 Perivesical fat
1
2
3
4
Tis
T1
T2a
1/2
T2b
T3a
T3b
T4aT4b
Ta
FIGURE 38.3. Illustration of the definitions of primary tumor (T) for primary
bladder cancer, ranging from Ta to T4.
332 American Joint Committee on Cancer • 2006
pT2a Tumor invades superficial muscle (inner half)
pT2b Tumor invades deep muscle (outer half)
T3 Tumor invades perivesical tissue (Figure 38.3)
pT3a Microscopically
pT3b Macroscopically (extravesical mass)
T4 Tumor invades any of the following: prostate, uterus, vagina, pelvic wall,
abdominal wall
T4a Tumor invades prostate, uterus, vagina (Figure 38.3)
T4b Tumor invades pelvic wall, abdominal wall (Figure 38.3)
Regional Lymph Nodes (N)
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
Nl Metastasis in a single lymph node, 2 cm or less in greatest dimension
(Figure 38.4)
N2 Metastasis in a single lymph node, more than 2 cm but not more than
5 cm in greatest dimension; or multiple lymph nodes, none more than
5 cm in greatest dimension (Figures 38.5A, B)
N3 Metastasis in a lymph node, more than 5 cm in greatest dimension (Figures
38.6A, B)
Distant Metastasis (M)
MX Distant metastasis cannot be assessed
M0 No distant metastasis
M1 Distant metastasis
£2 cm
N1
FIGURE 38.4. N1 is defined as metastasis in a single lymph node, 2 cm or less in
greatest dimension.
American Joint Committee on Cancer • 2006 333
38
>2-5 cm
N2
A
£5 cm
N2
B
FIGURE 38.5. A. N2 is defined as metastasis in a single lymph node, more than 2
cm but not more than 5 cm in greatest dimension, as illustrated, or multiple lymph
nodes, none more than 5 cm in greatest dimension. B. N2 is defined as metastasis
in a single lymph node, more than 2 cm but not more than 5 cm in greatest
dimension, or multiple lymph nodes, as illustrated, none more than 5 cm in
greatest dimension.
334 American Joint Committee on Cancer • 2006
>5 cm
N3
A
>5 cm
N3
B
FIGURE 38.6. A. N3 is defined as metastasis in a lymph node more than 5 cm in
greatest dimension. Here, multiple lymph nodes are involved with one nodal mass
greater than 5 cm. B. N3 is defined as metastasis in a lymph node more than 5 cm
in greatest dimension.
American Joint Committee on Cancer • 2006 335
STAGE GROUPING
0a Ta N0 M0
0is Tis N0 M0
IT1N0M0
II T2a N0 M0
T2b N0 M0
III T3a N0 M0
T3b N0 M0
T4a N0 M0
IV T4b N0 M0
Any T Nl M0
Any T N2 M0
Any T N3 M0
Any T Any N M1
38
American Joint Committee on Cancer • 2006 337
39
Urethra
39
SUMMARY OF CHANGES
• The definitions of TNM and the Stage Grouping for this chapter have not
changed from the Fifth Edition.
C68.0 Urethra
INTRODUCTION
Cancer of the urethra is a rare neoplasia that is found in both sexes but is more
common in females. The cancer may be associated in males with chronic stric-ture disease and in females with urethral diverticula. Tumors of the urethra may
be of primary origin from the urethral epithelium or ducts, or they may be asso-ciated with multifocal urothelial neoplasia. Histologically, these tumors may rep-resent the spectrum of epithelial neoplasms, including squamous, adenothelial,
or urothelial (transitional cell) carcinoma. Prostatic urethral neoplasms arising
from the prostatic urethral epithelium or from the periurethral portion of the
prostatic ducts are considered urethral neoplasms as distinct from those arising
elsewhere in the prostate (see Chapter 34).
ANATOMY
Primary Site. The male urethra consists of mucosa, submucosal stroma, and
the surrounding corpus spongiosum. Histologically, the meatal and parameatal
urethra are lined with squamous cell epithelium, the penile and bulbomembra-nous urethra with pseudostratified or stratified columnar epithelium, and bul-bomembranithelium, and the prostatic urethra with transitional epithelium.
There are scattered islands of stratified squamous epithelium and glands of
Littré liberally situated throughout the entire urethra distal to the prostate
portion.
The epithelium of the female urethra is supported on subepithelial con-nective tissue. The periurethral glands of Skene are concentrated near the meatus
but extend along the entire urethra. The urethra is surrounded by a longitudi-nal layer of smooth muscle continuous with the bladder. The urethra is con-tiguous to the vaginal wall. The distal two-thirds of the urethra is lined with
squamous epithelium, the proximal one-third with transitional epithelium. The
periurethral glands are lined with pseduostratified and stratified columnar
epithelium.
Regional Lymph Nodes. The regional lymph nodes are:
Inguinal (superficial or deep)
Iliac (common, internal [hypogastric], obturator, external)
Presacral
Sacral, NOS
Pelvic, NOS
338 American Joint Committee on Cancer • 2006
The significance of regional lymph node metastasis in staging urethral
cancer lies in the number and size, not in whether unilateral or bilateral.
Metastatic Sites. Distant spread is most commonly to lung, liver, or bone.
DEFINITIONS
Primary Tumor (T)
(Male and Female)
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
Ta Noninvasive papillary, polypoid, or verrucous carcinoma (Figures 39.1,
39.2)
Tis Carcinoma in situ
T1 Tumor invades subepithelial connective tissue (Figures 39.1, 39.3)
T2 Tumor invades any of the following: corpus spongiosum, prostate,
periurethral muscle (Figures 39.1, 39.4, 39.5)
Ta T1 T2
Epthelium
Subepithelial
connective tissue
Urethral muscle
Urogenital diaphragm
FIGURE 39.1. Illustrated definitions of primary tumor (T) for Ta, T1, and T2 with
depth of invasion ranging from the epithelium to the urogenital diaphragm.
Epithelium
Ta
Corpus cavernosum
Subepithelial connective tissue
Urethral muscle
Corpus spongiosum
FIGURE 39.2. Ta is defined as noninvasive papillary, polypoid, or verrucous
carcinoma.
American Joint Committee on Cancer • 2006 339
39
T1
FIGURE 39.3. T1 tumor invading subepithelial connective tissue.
T2
FIGURE 39.4. T2 tumor invades any of the following: corpus spongiosum,
prostate, periurethral muscle (as illustrated).
Subepithelial connective tissue
Urethral muscle
Corpus spongiosum
Corpus cavernosum
Prostate
T2 T2
FIGURE 39.5. Two views of T2 tumor in the male with invasion of the corpus
spongiosum (left) and the prostate (right).
T3 Tumor invades any of the following: corpus cavernosum, beyond prosta-tic capsule, anterior vagina, bladder neck (Figures 39.6A–C)
T4 Tumor invades other adjacent organs (Figure 39.7)
Urothelial (Transitional Cell) Carcinoma of the Prostate
Tis pu Carcinoma in situ, involvement of the prostatic urethra (Figure 39.8A)
Tis pd Carcinoma in situ, involvement of the prostatic ducts (Figure 39.8B)
T1 Tumor invades subepithelial connective tissue (Figures 39.8A, B)
340 American Joint Committee on Cancer • 2006
Subepithelial connective tissue
Urethral muscle
Corpus spongiosum
Corpus cavernosum
T3 T3
A
T3
Urethra
Vagina
B
FIGURE 39.6. A. Two views of T3 tumor in the male with invasion of the corpus
cavernosum (left) and prostatic capsule (right). B. T3 tumor in the female with
invasion of the anterior vagina.
American Joint Committee on Cancer • 2006 341
39
T3
Bladder
neck
C
FIGURE 39.6. C. T3 tumor in the female with invasion of the bladder neck.
T4
Public
bone
Vulva
FIGURE 39.7. T4 tumor in the female with invasion to other adjacent organs
(here, the pubic bone and vulva).
342 American Joint Committee on Cancer • 2006
Epithelium
Tis pu
T1
Subepithelial
connective tissue
Periurethral muscleA
Epithelium
Tis pd
Subepithelial
connective tissue
Prostatic stroma
Epithelium
T1
Subepithelial
connective tissue
Prostatic stroma
Epithelium
T2
Subepithelial
connective tissue
Prostatic stromaB
FIGURE 39.8. A. The definition of Tis pu for urothelial (transitional cell)
carcinoma of the prostate (above dotted lines) is carcinoma in situ, involvement of
the prostatic urethra. T1 (below dotted lines) is defined as tumor invading
subepithelial connective tissue. B. Definitions of primary tumor (T) for urothelial
(transitional cell) carcinoma of the prostate for Tis pd, T1, and T2 with depth of
invasion ranging from the epithelium to the prostatic stroma.
American Joint Committee on Cancer • 2006 343
39
Urethral epithelium
and subepithelial
connective tissue
Periurethral muscle
T2
Corpus spongiosum
Urethral epithelium
and subepithelial
connective tissue
Periurethral muscle
Corpus spongiosum
FIGURE 39.9. T2 for urothelial (transitional cell) carcinoma is defined as tumor
invading any of the following: prostatic stroma, corpus spongiosum, periurethral
muscle.
T2 Tumor invades any of the following: prostatic stroma, corpus spongio-sum, periurethral muscle (Figures 39.8B, 39.9)
T3 Tumor invades any of the following: corpus cavernosum, beyond pro-static capsule, bladder neck (extraprostatic extension) (Figure 39.10)
T4 Tumor invades other adjacent organs (invasion of the bladder) (Figure
39.11)
Regional Lymph Nodes (N)
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Metastasis in a single lymph node 2 cm or less in greatest dimension
(Figure 39.12)
N2 Metastasis in a single node more than 2 cm in greatest dimension, or in
multiple nodes(Figures 39.13A, B)
Distant Metastasis (M)
MX Distant metastasis cannot be assessed
M0 No distant metastasis
M1 Distant metastasis
344 American Joint Committee on Cancer • 2006
Urethral epithelium
and subepithelial
connective tissue
Periurethral muscle
Corpus spongiosum
Corpus cavernosum
T3
Bladder neck
T3
Beyond prostatic
capsule
Corpus cavernosum
FIGURE 39.10. Two views of T3 for urothelial (transitional cell) carcinoma.
Tumor invades any of the following: corpus cavernosum, as illustrated below
dotted lines; beyond prostatic capsule; bladder neck (extraprostatic extension), as
illustrated above dotted lines.
T4
Urinary bladder
FIGURE 39.11. T4
tumor invades other
adjacent organs
(invasion of the
bladder).
American Joint Committee on Cancer • 2006 345
39
£2 cm
£2 cm
N1 N1
FIGURE 39.12. N1 is defined as metastasis in a single lymph node 2 cm or less in
greatest dimension.
>2 cm
N2
A
FIGURE 39.13. A. N2 is defined as metastasis in a single node more than 2 cm in
greatest dimension, as illustrated, or in multiple nodes.
346 American Joint Committee on Cancer • 2006
STAGE GROUPING
0a Ta N0 M0
0is Tis N0 M0
Tis pu N0 M0
Tis pd N0 M0
IT1N0M0
II T2 N0 M0
III T1 N1 M0
T2 N1 M0
T3 N0 M0
T3 N1 M0
IV T4 N0 M0
T4 N1 M0
Any T N2 M0
Any T Any N M1
N2
B
FIGURE 39.13. B. N2 is defined as metastasis in a single node more than 2 cm in
greatest dimension or in multiple nodes, as illustrated.
American Joint Committee on Cancer • 2006 347
Index
primary site, 219–220
primary tumors (T), 221–225
regional lymph nodes, 220–221
regional lymph nodes (N)
classification, 225–227
regional lymph nodes (pN)
classification, 228–232
stage grouping, 232
Buccal mucosa
features/location, 19
See also Lips and oral cavity
C
Carcinoma of the skin, 197–205
distant metastasis (M), 202
hematogenously borne metastases,
200
primary growth, 198
primary site, 197–198
primary tumor (T), 200–202
regional lymph nodes, 198–200
regional lymph nodes (N)
classification, 202–205
regional lymph nodes and stage of
disease, 203–205
stage grouping, 205
Cervical esophagus
features/location, 79
regional lymph nodes of, 79
See also Esophagus
Cervix uteri, 249–257
distant metastasis (M), 255
metastatic sites, 249
primary site, 249
primary tumor (T), 250–256
regional lymph nodes, 249
regional lymph nodes (N)
classification, 255–256
stage grouping, 257
Choriocarcinoma. diagnosis of,
279–280
See also Gestational trophoblastic
tumors
Classification
systems, titles of, 3
TNM system, 1–2
Clinical classification, elements of,
5
A
Abdominal esophagus
features/location, 41
See also Esophagus
Alveolar ridge
features/location, 19–21
See also Lips and oral cavity
Ampulla of vater, 147–153
distant metastasis (M), 149, 153
metastatic sites, 149
primary site, 147–148
primary tumor (T), 149–151
regional lymph nodes, 148–149
regional lymph nodes (N)
classification, 149, 151–152
stage grouping, 153
Anal canal, 119–126
distant metastasis (M), 126
metastatic sites, 121
primary sites/subsites, 119–120
primary tumor (T), 121–122
regional lymph nodes, 120–121
regional lymph nodes (N)
classification, 121, 123–125
stage grouping, 126
a prefix, meaning of, 8
Atlas of Tumor Pathology,3
Autopsy classification, pathologic
information of, 6
B
Bile ducts. See Extrahepatic bile ducts;
Liver
Bladder. See Urinary bladder
Bone, 185–189
distant metastasis (M), 187–188
histologic grade (G), 187
metastatic sites, 185
primary site, 185
primary tumor (T), 186–187
regional lymph nodes, 185
regional lymph nodes (N)
classification, 187
stage grouping, 187
Breast, 219–233
chest wall, 220
distant metastasis (M), 231
metastatic sites, 221
348 American Joint Committee on Cancer • 2006
Colon and rectum, 107–117
anatomical subsites, 108–109
distant metastasis (M), 113
metastatic sites, 111, 116
primary site, 109
primary tumor (T), 111–113
regional lymph nodes, 109–110
regional lymph nodes (N)
classification, 113–115
residual tumor (R), 113, 116
stage grouping, 117
and TNM system, 107
Corpus uteri, 259–264
distant metastasis (M), 263
metastatic sites, 260
primary site, 259
primary tumor (T), 260–262
regional lymph nodes, 259–260
regional lymph nodes (N)
classification, 263
stage grouping, 263–264
D
Distant metastasis (M)
definitions, 7
notations used, 7
Duodenum
features/location, 101
regional lymph nodes, 102–103
See also Small intestine
E
Epiglottis
features/location, 41
See also Larynx
Esophagus, 77–88
cervical esophagus, 79
distant metastasis (M), 81
early signs, 77
gastroesophageal junction, 79–80
intraabdominal portion of, 79
intrathoracic esophagus, 79
metastatic sites, 81
primary site/subsites, 78–79
primary tumor (T), 81–83
regional lymph nodes, 80–81
regional lymph nodes (N)
classification, 81, 84–87
stage grouping, 88
Ethmoid sinuses
primary tumor (T), 57–58
regions of, 53
See also Nasal cavity and paranasal
sinuses
Exocrine pancreas, 155–163
distant metastasis (M), 158
metastatic sites, 157–158
primary site/subsites, 155–156
primary tumor (T), 158–161
regional lymph nodes, 157
regional lymph nodes (N)
classification, 158, 161–163
stage grouping, 163
Extrahepatic bile ducts, 139–145
distant metastasis (M), 142
metastatic sites, 140–141
primary site, 140
primary tumor (T), 141–144
regional lymph nodes, 140
regional lymph nodes (N)
classification, 142
stage grouping, 145
and TNM classification, 139
F
Fallopian tube, 273–277
distant metastasis (M), 273, 275
primary site, 273
primary tumor (T), 273–277
regional lymph nodes (N)
classification, 275
regional nodes, 273
stage grouping, 277
G
Gallbladder, 133–138
distant metastasis (M), 136
metastatic sites, 134
primary site, 133
primary tumor (T), 134–137
regional lymph nodes, 134
regional lymph nodes (N)
classification, 136, 138
stage grouping, 138
Gastroesophageal junction
features/location of, 79
regional lymph nodes of, 80
See also Esophagus
Gestational trophoblastic tumors, 279–284
distant metastasis (M), 280, 282–283
frequency of, 279
metastatic sites, 280
primary site, 280
primary tumor (T), 280–281
prognostic indicators scoring index,
283
regional lymph nodes, 280
stage grouping, 282
Glottis
features/location, 41–42
American Joint Committee on Cancer • 2006 349
primary tumor (T), 47–49
See also Larynx
H
Head and neck sites, 13–18
diagnostic methods, 13, 16
distant metastasis (M), 18
lymph nodes measurement, 16
metastatic sites, 16
regional lymph nodes, 14–16
regional lymph nodes (N)
classification, 17
Histologic grade (G)
notations used, 8
tissue-based descriptions, 8
Hydatidiform mole. See Gestational
trophoblastic tumors
Hypopharynx
features/location, 28–29
primary tumor (T), 32–36
regional lymph nodes (N)
classification, 38
stage grouping, 39
See also Pharynx
I
Ileum
features/location, 102
regional lymph nodes, 103
See also Small intestine
International Classification of Diseases
for Oncology (ICD-O), 3, 7
International Histological Classification
of Tumours,3
International Union Against Cancer
(UICC), 1, 3
Intraabdominal portion of esophagus
features/location, 79
See also Esophagus
Intrahepatic bile ducts. See Liver
Intrathoracic esophagus
features/location, 79
regional lymph nodes of, 79
See also Esophagus
Isolated tumor cells (ITC), pathologic
classification, 5–6
J
Jejunum
features/location, 102
regional lymph nodes, 103
See also Small intestine
K
Kidney, 315–321
distant metastasis (M), 319
metastatic sites, 316
primary site, 315
primary tumor (T), 317–320
regional lymph node (N)
classification, 319–320
regional lymph nodes, 315–316
stage grouping, 321
L
Larynx, 41–52
distant metastasis (M), 52
epiglottis, 41–42
glottis, 41–42, 47–49
metastatic sites, 43
primary site/subsites, 41–42
primary tumors (T), 41–50
regional lymph nodes, 41–42
regional lymph nodes (N)
classification, 50–51
stage grouping, 52
subglottis, 41–42, 49–51
supraglottis, 41–42, 43–46
Lip and oral cavity, 19–26
distant metastasis (M), 25
metastatic sites, 21–22
primary site/subsites, 19–21
primary tumors (T), 22–25
regional lymph nodes, 21–22
regional lymph nodes (N)
classification, 23–25
stage grouping, 26
Liver, 127–132
distant metastasis (M), 130
metastatic sites, 129
primary site, 127–129
primary tumor (T), 129–131
regional lymph nodes, 129
regional lymph nodes (N)
classification, 130, 132
stage grouping, 132
Lung, 167–176
distant metastasis (M), 169, 173
primary site/subsites, 167–168
primary tumor (T), 169–172
regional lymph nodes, 168–169
regional lymph nodes (N)
classification, 172–175
stage grouping, 175
Lymphatic vessel invasion, notation
used, 8
M
Maxillary sinus
primary tumor (T), 55–57
regions of, 53
350 American Joint Committee on Cancer • 2006
Maxillary sinus (cont.)
See also Nasal cavity and paranasal
sinuses
Melanoma of the skin, 207–216
clinical stage grouping, 215
distant metastasis (M), 215
metastatic sites, 208
pathologic stage grouping, 215
primary sites, 208
primary tumor, 208–211
regional lymph nodes, 208
regional lymph nodes (N)
classification, 208, 212–214
Mesothelioma. See Pleural
mesothelioma
Mouth
floor of, features/location, 21
See also Lips and oral cavity
m suffix, meaning of, 8
Multiple tumors, selection for staging,
6
N
Nasal cavity and paranasal sinuses,
53–60
distant metastasis (M), 60
ethmoid sinuses, 53, 57–58
location and prognosis, 53
maxillary sinus, 53, 55–57
metastatic sites, 55
nasoethmoidal complex, 53
primary site/subsites, 53–54
primary tumor (T), 55–59
regional lymph nodes, 54–55
regional lymph nodes (N)
classification, 58, 60
stage grouping, 60
Nasoethmoidal complex
regions of, 53
See also Nasal cavity and paranasal
sinuses
Nasopharynx
features/location, 27
primary tumor (T), 30–32
regional lymph nodes (N)
classification, 36–38
stage grouping, 39
See also Pharynx
Neck. See Head and neck sites
O
Ohngren’s line, 53
Oral cavity. See Lip and oral cavity
Oropharynx
features/location, 27–28
primary tumor (T), 32
regional lymph nodes (N)
classification, 38
stage grouping, 39
See also Pharynx
Ovary, 265–272
distant metastasis (M), 271
metastatic sites, 265–266
primary site, 265
primary tumor (T), 266–270
regional lymph nodes, 265
regional lymph nodes (N)
classification, 271
stage grouping, 271–272
P
Palate, soft. See Pharynx
Palate, hard
features/location, 21
See also Lips and oral cavity
Pancreas. See Exocrine pancreas
Paranasal sinuses. See Nasal cavity and
paranasal sinuses
Parotid gland. See Salivary glands
Pathologic classification, elements of,
5–6
Penis, 287–292
distant metastasis (M), 290–291
metastatic sites, 287
primary site/subsites, 287–288
primary tumor (T), 288–290
regional lymph nodes, 287
regional lymph nodes (N)
classification, 290
stage grouping, 292
Pharynx, 27–39
distant metastasis (M), 38
hypopharynx, 28–29, 32–36, 38
lymph nodes measurement,
29–30
metastatic sites, 30
nasopharynx, 27–28, 30–32,
36–38
oropharynx, 28–29, 32, 38
primary sites/subsites, 27–29
primary tumor (T), 30–36
regional lymph nodes, 29–30
regional lymph nodes (N)
classification, 36–38
stage grouping, 39
Pleural mesothelioma, 177–182
distant metastasis (M), 178, 181
primary site, 178
primary tumor (T), 178–181
regional lymph nodes, 178
American Joint Committee on Cancer • 2006 351
regional lymph nodes (N)
classification, 181
risk factors, 177
stage grouping, 181–182
staging systems for, 177–178
Prefix descriptors, 8
Pregnancy. See Gestational
trophoblastic tumors
Primary tumor (T)
definitions, 7
notations used, 7
Prostate, 293–301
distant lymph nodes, 295
distant metastasis (M), 300
histologic grade (G), 300
metastatic sites, 295
pathologic (pT), 297
primary site, 293–294
primary tumor (T), 295–298
regional lymph nodes, 294
regional lymph nodes (N)
classification, 299–300
regional lymph nodes (pN)
classification, 300
stage grouping, 300
R
Rectum
anatomical subsites, 108–109
See also Colon and rectum
Regional lymph nodes (N)
definitions, 7
notations used, 7
Renal pelvis and ureter, 323–328
distant metastasis (M), 327
metastatic sites, 324
primary site, 323
primary tumor (T), 324–326
regional lymph nodes, 323–324
regional lymph nodes (N)
classification, 326–327
stage grouping, 328
Residual tumor, notation used, 9
Retreatment classification, elements of,
6
Retromolar gingiva
features/location, 21
See also Lips and oral cavity
r prefix, meaning of, 8
S
Salivary glands, 61–66
distant metastasis (M), 65
metastatic sites, 62
primary site, 61
primary tumor (T), 62–65
regional lymph nodes, 61–62
regional lymph nodes (N)
classification, 65
stage grouping, 66
Sarcomas. See Soft tissue sarcomas
Sinuses, paranasal. See Nasal cavity and
paranasal sinuses
Skin. See Carcinoma of the skin;
Melanoma of the skin
Small intestine, 101–106
distant metastasis (M), 106
duodenum, 101, 102–103
ileum, 102, 103
jejunum, 102, 103
metastatic sites, 103
primary sites, 101–102
primary tumor (T), 103–106
regional lymph nodes, 102–103
regional lymph nodes (N)
classification, 106
stage grouping, 106
Soft tissue sarcoma, 191–194
distant metastasis (M), 194
histologic grade (G), 192, 194
inclusions, 192
metastatic sites, 192–193
primary tumor (T), 193–194
regional lymph nodes, 192
regional lymph nodes (N)
classification, 194
site groups for sarcomas, 192
stage grouping, 194
Stage grouping
functions of, 9
stages, meaning of, 9
Staging, general rules, 3–4
Stomach, 89–99
distant metastasis (M), 92
metastatic sites, 92
primary site, 90–91
primary tumor (T), 92–96
regional lymph nodes, 91–92
regional lymph nodes (N)
classification, 92, 97–98
stage grouping, 99
Subglottis
features/location, 41–42
primary tumor, 49–50
See also Larynx
Sublingual gland. See Salivary
glands
Submandibular gland. See Salivary
glands
Suffix descriptors, 8
352 American Joint Committee on Cancer • 2006
Supraglottis
features/location, 41–42
primary tumor (T), 43–47
See also Larynx
Systematized Nomenclature of Medicine
(SNOMED), 3
T
Testis, 303–314
distant metastasis (M), 313
metastatic site, 305
primary site, 303–304
primary tumor (T), 305–306
regional lymph nodes, 303–305
regional lymph nodes (N)
classification, 305, 307–313
regional lymph nodes (pN)
classification, 309–313
serum tumor markers (S), 303, 313
stage grouping, 313
Thyroid, 67–73
distant metastasis (M), 71
metastatic sites, 68
primary site, 67
primary tumor (T), 68–70
regional lymph nodes, 67–68
regional lymph nodes (N)
classification, 70–72
stage grouping and age, 67, 72–73
stage grouping for anaplastic, 73
stage grouping for medullary, 73
stage grouping for papillary/
follicular, 72–73
TNM system, 4–9
anatomic site considerations, 1–2
autopsy classification, 6
clinical classification, 5
distant metastasis (M), 7
elements of, 1, 4–5
histologic grade (G), 8
lymphatic vessel invasion (L)
descriptors, 8
multiple tumors, selection for
staging, 6
pathologic (pTNM) classification, 1
pathologic classification, 5–6
primary tumor (T), 7
recurrent cancer (rTNM)
classification, 1, 6
regional lymph nodes (N), 7
residual tumor (R) descriptors, 9
retreatment classification, 6
stage grouping, 6, 9
subsets of TNM, 6
suffix/prefix descriptors, 8
unknown primary, 6
venous invasion (V) descriptors, 8
Tongue
oral, features/location, 21
See also Lip and oral cavity; Pharynx
U
Unknown primary, meaning of, 6
Ureter. See Renal pelvis and ureter
Urethra, 337–346
distant metastasis (M), 343
metastatic sites, 338
primary site, 337
primary tumor (T), 338–344
regional lymph nodes, 337
regional lymph nodes (N)
classification, 343, 345–346
stage grouping, 346
urothelial carcinoma of prostate,
339–340, 342–344
Urinary bladder, 329–335
distant metastasis (M), 332
metastatic sites, 331
primary site, 329
primary tumor (T), 331–332
regional lymph nodes, 329–331
regional lymph nodes (N)
classification, 332–334
stage grouping, 335
Urothelial carcinoma of prostate
primary tumor (T), 339, 342–344
See also Urethra
Uterus. See Corpus uteri
Uvula. See Pharynx
V
Vagina, 243–248
distant metastasis (M), 248
metastatic sites, 243
primary site, 243
primary tumor (T), 243–246
regional lymph nodes, 243
regional lymph nodes (N)
classification, 245, 247
stage grouping, 248
Venous invasion, notation used, 8
Vulva, 237–242
metastatic sites, 237
primary site, 237
primary tumor (T), 237–240
regional lymph nodes, 237
regional lymph nodes (N)
classification, 240–241
stage grouping, 242
Y
y prefix, meaning of, 8

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