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Chapter 93 – Eyelid Malignancies

Chapter 93 – Eyelid Malignancies

 

GREGORY J. VAUGHN

RICHARD K. DORTZBACH

GREGG S. GAYRE

 

 

 

 

 

DEFINITION

• Cutaneous cancers that arise from the epidermis, dermis, or adnexal structures of the eyelid. Rarely they may be metastatic from distant sites. They include a number of histologically distinct tumors from diverse skin cell types.

 

KEY FEATURES

• Flat, eroded, or elevated lesion on the eyelid margin, eyelid skin, or brow.

• Nodular and well circumscribed or irregular with indistinct borders.

• Ulcerated with a central crater or benign in appearance with some telangiectatic vessels.

• Slow, generally painless, growth.

 

ASSOCIATED FEATURES

• Dilated blood vessels.

• Ectropion from skin contracture.

• Firm induration.

• Loss of eyelashes.

• Palpable preauricular nodes.

• Proptosis.

• Ptosis.

• Restricted ocular motility.

• Thickened eyelid margin.

 

 

 

Malignant lesions are common around the eyes, partly because many are induced by sun exposure or develop from sun-related benign lesions. Most of these are small and grow slowly, which results in minimal concern for the patient and a low index of suspicion for the physician. Although most eyelid malignancies rarely metastasize, they can be very destructive locally. Any periocular lesion that shows some growth, especially when associated with chronic irritation or bleeding, should undergo biopsy for diagnosis. Confirmation of histopathology is also mandatory before committing the patient to a major resection or reconstructive procedure.

BASAL CELL CARCINOMA

INTRODUCTION

Basal cell carcinoma (BCC) is a malignant tumor derived from cells of the basal layer of the epidermis. The etiology of BCC is linked to excessive ultraviolet light exposure in fair-skinned individuals. Other predisposing factors include ionizing radiation, arsenic exposure, and scars. Although metastases are rare, local invasion is common and can be very destructive.

EPIDEMIOLOGY AND PATHOGENESIS

BCC is the most common malignant tumor of the eyelids and constitutes 85–90% of all malignant epithelial eyelid tumors at this site.[1] Over 99% of BCCs occur in whites; about 95% of these lesions occur between the ages of 40 and 79 years, with an average age at diagnosis of 60 years. [2] BCC arises from a pleuripotential stem cell in the epidermis that proliferates, amplifies, and eventually terminally differentiates.[3] [4] Ultraviolet light exposure is one of the most important risk factors, especially in light-skinned individuals. Proposed mechanisms for BCC invasion include enhanced tumor cell motility and collagenase content.[1] Having had one BCC is a prognostic factor for the development of additional lesions.

OCULAR MANIFESTATIONS

Up to 50–60% of BCCs affect the lower eyelid. The medial canthus is involved 25–30% of the time. The upper eyelid is involved nearly 15% of the time and the lateral canthus is only rarely involved (5%). [5] On the basis of their histopathological presentation, BCCs may be classified into five basic types:

• Nodular-ulcerative

• Pigmented

• Morphea or sclerosing

• Superficial

• Fibroepithelioma

Two additional, although very rare, types are the linear basal cell nevus and generalized follicular basal cell nevus.[6]

The nodular type of BCC, the most common lesion, has the classical appearance of a pink or pearly papule or nodule with overlying telangiectatic vessels. As the nodule grows in size, central ulceration may occur surrounded by a rolled border ( Fig. 93-1 ). This appearance is often described as a “rodent ulcer.”

The pigmented BCC is similar to the noduloulcerative type in morphology but with brown or black pigmentation. These lesions represent the most common pigmented malignancy on the eyelids and may resemble malignant melanoma.

The morphea or sclerosing type of BCC appears as a flat, indurated, yellow-pink plaque with ill-defined borders. It may simulate a blepharitis or dermatitis. As it has a flat appearance, it may not be as clinically noticeable as others. However, this form of BCC is aggressive and may invade the dermis deeply. It characteristically occurs in the medial canthal region and may invade into the paranasal sinuses and orbit.

Superficial BCC appears as an erythematous, scaling patch with a raised pearly border. Fibroepithelioma BCC presents as a pedunculated or sessile smooth, pink nodule. Both the superficial and fibroepithelioma types typically arise on the trunk rather than the eyelid.[7]

 

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Figure 93-1 Nodular basal cell carcinoma of the eyelid. A firm, pink-colored left upper eyelid BCC is seen with raised border, superficial telangiectatic vessels, and characteristic central ulceration. These lesions are more commonly seen on the lower eyelid. (Courtesy of Dr Morton Smith.)

DIAGNOSIS

The diagnosis of BCC is initially made from its clinical appearance, especially with the noduloulcerative type with its raised pearly borders and central ulcerated crater. Definitive diagnosis, however, can be made only on histopathological examination of biopsy specimens.

DIFFERENTIAL DIAGNOSIS

The differential diagnosis of BCC and of other periocular malignant lesions may be divided into several categories: other malignant lesions, premalignant lesions, benign adnexal tumors and cysts, and inflammatory and infectious conditions ( Table 93-1 ; see Chapter 92 ).[8] In many cases the diagnosis depends upon histopathology.

SYSTEMIC ASSOCIATIONS

Basal cell nevus syndrome (Gorlin-Goltz syndrome) is inherited as an autosomal dominant disorder with high penetrance and variable expressivity. Basal cell nevus syndrome is rare, occurring in less than 1% of individuals with BCC.[9] The group of clinical findings described in 1960 as a syndrome by Gorlin and Goltz[10] includes:

• Multiple BCCs affecting the face, trunk, and extremities

• Cysts of the jaw (odontogenic keratocysts)

• Skeletal abnormalities (e.g., bifid ribs)

• Neurological abnormalities (e.g., mental retardation, ectopic calcification, cerebellar medulloblastoma)

• Endocrine disorders (e.g., ovarian cysts and testicular disorders)[7]

Palmar and plantar pits also develop in young adulthood. The BCCs in this syndrome typically develop at puberty and have a predilection for the periorbital region and face.[2] Multiple lesions occur with a high rate of recurrence. Other rare BCC syndromes include Bazex’s syndrome, linear unilateral basal cell nevus, and Rombo syndrome.

Also, BCC may be associated with albinism, xeroderma pigmentosum, and nevus sebaceus.

PATHOLOGY

The BCCs may be grouped as either undifferentiated or differentiated by their histopathological appearance.[6] The typical histopathology of an undifferentiated BCC consists of nests, lobules, and cords of tumor cells with peripheral palisading of cells and stromal retraction ( Fig. 93-2 ). Undifferentiated BCCs include the solid noduloulcerative, morphea or sclerosing, pigmented,

 

TABLE 93-1 — DIFFERENTIAL DIAGNOSIS OF PERIOCULAR MALIGNANCIES

Simulating Lesion

BCC

SCC

SGC

MM

KS

MCT

OTHER MALIGNANT LESIONS

Amelanotic melanoma

 

 

 

 

 

X

Basal cell carcinoma

 

X

X

 

 

 

Glomus tumor

 

 

 

 

 

X

Lymphoma

 

 

 

 

X

X

Malignant melanoma

X

 

 

 

X

 

Metastatic oat cell carcinoma

 

 

 

 

 

X

Sebaceous cell carcinoma

X

X

 

 

 

X

Squamous cell carcinoma

X

 

X

 

 

 

Squamous cell carcinoma in situ

X

X

 

 

 

 

PREMALIGNANT LESIONS

Actinic keratosis

X

X

 

 

 

 

Radiation dermatitis

X

 

 

 

 

 

Keratoacanthoma

X

X

 

 

 

 

ADNEXAL TUMORS AND CYSTS

Cavernous hemangioma

 

 

 

X

 

 

Cutaneous horns

X

 

 

 

 

 

Dermoid and sebaceous cysts

X

 

 

 

 

 

Eccrine and apocrine cysts

X

 

 

 

 

 

Inverted follicular keratosis

 

X

 

 

 

 

Nevus cell and nevocellular nevi, pigmented lesions of epidermal and dermal melanocyte origin

 

 

 

X

 

 

Papillomatous lesions

X

X

X

 

 

 

Pseudoepitheliomatous hyperplasia

 

X

 

 

 

 

Seborrheic keratosis nevus

X

X

 

 

 

 

Trichilemomma

 

X

 

 

 

 

INFLAMMATORY/INFECTIOUS CONDITIONS

Blepharitis

X

 

X

 

 

 

Chalazion

X

 

X

 

X

 

Eczema

X

 

 

 

 

 

Foreign body granuloma

 

 

 

 

X

 

Fungal infections

 

X

 

 

 

X

Hordeolum

X

 

 

 

 

 

Psoriasis

X

 

 

 

 

 

Pyogenic granuloma

 

 

 

 

X

 

Seborrheic dermatitis

X

 

 

 

 

 

Superior limbic keratoconjunctivitis

 

 

X

 

 

 

Verruca vulgaris

 

X

 

 

 

 

OTHER

Conjunctival hemorrhage

 

 

 

X

X

 

BCC, Basal cell carcinoma; SCC, squamous cell carcinoma; SGC, sebaceous gland carcinoma; MM, malignant melanoma; KS, Kaposi’s sarcoma; MCT, Merkel cell tumor.

 

 

superficial, and fibroepithelioma forms. The morphea or sclerosing form is characterized by strands of proliferating, malignant basal cells in a fibrous stroma ( Fig. 93-3 ).

The adenoid and metatypical or basosquamous are the most common differentiated forms. These tumors differentiate toward

 

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Figure 93-2 Nodular basal cell carcinoma of the eyelid. Basophilic nests of proliferating epithelial tumor cells are shown with characteristic peripheral, palisading nuclei and stromal reaction. (Courtesy of Dr Morton Smith.)

 

 

Figure 93-3 Morphea or sclerosing type of basal cell carcinoma of the eyelid. Strands and islands of basaloid cells are shown within a dense connective tissue matrix. (Courtesy of Dr Morton Smith.)

glandular structures with mucinous stroma. They exhibit morphological features between those of basal cell and squamous cell carcinoma. The metatypical BCCs are more aggressive and invasive with a higher recurrence rate and potential for metastasis.[11]

TREATMENT

The goal of therapy is the complete removal of tumor cells with preservation of unaffected eyelid and periorbital tissues. Although nonsurgical treatments such as cryotherapy, electrodesiccation, and laser ablation are advocated by some, surgical therapy is generally accepted as the treatment of choice for removal of BCCs. Some BCCs, especially the morphea and multicentric types, may extend far beyond the area that is apparent clinically. Therefore, histological monitoring of tumor margins is essential. Mohs’ micrographic surgery and excisional biopsy with frozen section control are the two basic techniques available. An incisional biopsy may be performed prior to definitive treatment to confirm the clinical suspicion of BCC.[12]

Surgery

Mohs’ micrographic surgery provides the highest cure rate with the most effective preservation of normal tissue. Tissue is excised in layers that provide a three-dimensional mapping of the excised tumor. These layers are processed as frozen sections and viewed under the microscope. Any areas of residual tumor are identified, and the map is used to direct additional tumor excision.[13] [14] This technique is particularly useful for morphea and multicentric-type BCCs in the medial canthal region, which may exhibit subclinical extension to orbital bone or sinuses. Mohs’ micrographic surgery technique is somewhat limited if the tumor has extended to the plane of orbital fat. In addition, it requires the collaboration of a trained Mohs’ surgeon and dermatopathologist.

Excisional biopsy with frozen section control is also an effective way to remove BCCs and can be performed by the ophthalmologist. Several studies have reported no recurrences after excision of BCCs with frozen section monitoring.[5] [15] [16] However, following simple excisional biopsy without frozen section control, recurrence rates up to 50% have been reported.[17]

Eyelid reconstruction should be performed within 2–3 days after tumor excision. Various reconstructive surgical techniques may be used depending upon the location and size of the residual defect (see Chapter 94 ).

Radiation Therapy

Radiation therapy is generally not recommended in the initial treatment of periocular BCCs. However, it may be useful in the treatment of advanced or recurrent lesions in the medial canthal region or elsewhere. Doses are in the range 4000–7000?cGy.[18] Radiation therapy is less effective in treating morphea BCCs, with the likelihood of BCC recurrence following radiotherapy being higher than that for previously described surgical techniques.[19] A recurrence rate of 12% was noted in one series following radiation therapy. [20] Surgical management is very difficult after radiation treatment of an affected area. Radiotherapy complications include skin atrophy and necrosis, madarosis, cicatricial entropion and ectropion, dry eye syndrome, cataract, and corneal ulceration.[21] Radiation therapy is contraindicated in basal cell nevus syndrome and is associated with significant complications in patients who have scleroderma or acquired immunodeficiency syndrome (AIDS).[22]

Cryotherapy

Cryotherapy is often used to treat BCCs outside the periorbital area. Around the eyelids it may be used to treat eyelid notching and malpositions, symblepharon formation with fornix foreshortening, and pigmentary changes. It is associated with a higher recurrence rate than the surgical approaches. Cryotherapy is contraindicated in lesions greater than 1?cm in diameter, medial canthal lesions, morphea-like lesions, and recurrent BCC.[23]

Chemotherapy and Photodynamic Therapy

Topical, intralesional, and systemic chemotherapeutic agents, including 5-fluorouracil, cisplatinum, doxorubicin, bleomycin, and interferon, have been used to treat BCCs. However, these agents are generally not recommended for tumors in the periorbital region.[2]

Photodynamic therapy may be considered as an alternative treatment for large numbers of cutaneous BCCs (e.g., basal cell nevus syndrome). However, long-term follow-up of patients treated with this modality is not yet available.[24]

COURSE AND OUTCOME

Complete surgical excision of BCC is almost always curative because these lesions rarely metastasize. The incidence of metastasis ranges from 0.028–0.55%. [7] Tumor-related death is exceedingly rare, but when it does occur, it is usually caused by direct orbital and intracranial extension.

 

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SQUAMOUS CELL CARCINOMA

INTRODUCTION

Squamous cell carcinoma (SCC) is a malignant tumor of the squamous layer of cells of the epidermis. It is much less common than BCC on the eyelids and carries a greater potential for metastatic spread.

EPIDEMIOLOGY AND PATHOGENESIS

Typically, SCC affects elderly, fair-skinned individuals. In the region of the eye it is usually found on the lower eyelid. Although SCC is 40 times less common than BCC of the eyelid, it is more common than BCC on the upper eyelid and lateral canthus.[25] [26]

The exact mechanism of the pathogenesis of SCC is not known. However, environmental and intrinsic stimuli initiate a process in which cell growth and regulation are lost. Most periorbital SCCs arise from actinic lesions, but they may also arise de novo. Environmental factors may contribute to the development of SCC, including cumulative ultraviolet radiation (sun exposure), ionizing radiation, arsenic ingestion, psoralen plus ultraviolet A (PUVA) therapy for psoriasis, and the human papilloma virus.[27]

Intrinsic factors that contribute to the development of SCC include the autosomal recessive conditions xeroderma pigmentosum and oculocutaneous albinism. Chronic skin dermatoses, ulceration, and scarring are also associated with the development of this tumor. In fact, scarring of the skin is the most common intrinsic factor leading to SCC in black patients.[28]

OCULAR MANIFESTATIONS

Typically, SCC presents as an erythematous, indurated, hyperkeratotic plaque or nodule with irregular margins. These lesions have a high tendency toward ulceration and tend to affect the eyelid margin and medial canthus. Lymphatic spread and perineural invasion are possible.

DIAGNOSIS

The diagnosis of SCC is often suspected from the clinical appearance. However, because so many other malignant and benign processes can be confused with SCC, the diagnosis requires biopsy for histological confirmation.

DIFFERENTIAL DIAGNOSIS

A number of lesions can be mistaken for SCC (see Table 93-1 ). These include both other malignant tumors and benign lesions.[27]

PATHOLOGY

Well-differentiated SCC exhibits polygonal cells with abundant eosinophilic cytoplasm and hyperchromatic nuclei ( Fig. 93-4 ). Dyskeratosis, keratin pearls, intercellular bridges, and abnormal mitotic figures are prominent. Poorly differentiated lesions show little keratinization and fewer intercellular bridges.[7]

TREATMENT

Before planning any therapy, the clinical diagnosis of SCC should be confirmed by incisional biopsy. Compared with BCC, SCC is a more aggressive and invasive tumor, but early SCC lesions of the eyelid rarely metastasize. Surgery, irradiation, and cryotherapy management options are similar to those described previously for BCC.

 

 

Figure 93-4 Squamous cell carcinoma of the eyelid. Anaplastic squamous cells with hyperchromatic nuclei, abundant eosinophilic cytoplasm, and intercellular bridges. (Courtesy of Dr Morton Smith.)

COURSE AND OUTCOME

Wide local surgical excision, either with the Mohs’ technique or under frozen section control, is usually curative. Advanced cases may be associated with metastasis to the preauricular and submandibular lymph nodes, which heralds a more guarded prognosis. Invasion of the deep orbital tissues may sometimes be seen and frequently requires orbital exenteration for cure.

SEBACEOUS GLAND CARCINOMA

INTRODUCTION

Sebaceous gland carcinoma (SGC) is a highly malignant neoplasm that arises from the meibomian glands, the glands of Zeis, and the sebaceous glands of the caruncle and eyebrow. It is an aggressive tumor with a high recurrence rate, a significant metastatic potential, and a notable mortality rate.

EPIDEMIOLOGY AND PATHOGENESIS

Although it is relatively rare, SGC is the third most common eyelid malignancy, accounting for 1–5.5% of all eyelid cancers. It affects all races, occurs in women more often than men, and usually presents in the sixth to seventh decades, but cases in younger patients have been reported. [29] [30] [31]

The cause of SGC is unclear. However, there are reported associations that link SGC with prior radiation therapy[32] and with the production of nitrosamines and photosensitization from prior diuretic use.[33]

OCULAR MANIFESTATIONS

The upper eyelid is the site of origin in about two thirds of all cases, but SGC may arise from any of the periocular structures previously mentioned [7] and may have a variety of clinical appearances. It often presents as a firm, yellow nodule that resembles a chalazion. It may present as a plaque-like thickening of the tarsal plate with destruction of meibomian gland orifices and tumor invasion of eyelash follicles leading to madarosis, or loss of lashes ( Fig. 93-5 ). Also, SGC may mimic a chronic blepharoconjunctivitis, meibomianitis, or chalazion that does not respond to standard therapies, thus the term “masquerade syndrome.”

SGC tends to invade overlying epithelium, which may form nests of malignant cells (pagetoid spread), or it may result in diffuse spread that replaces the entire thickness of the conjunctiva (intraepithelial carcinoma). The carcinoma may exhibit multicentric

 

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Figure 93-5 Sebaceous cell carcinoma of the eyelid. A large, firm, irregular nodule with yellowish coloration of the left upper eyelid is shown. Associated inflammation, telangiectatic vessels, and loss of cilia are observed. (Courtesy of Dr Morton Smith.)

spread to the other eyelid, conjunctiva, or corneal epithelium.[7] This neoplasm may spread through the canaliculus to the lacrimal excretory system and even to the nasal cavity.[33]

DIAGNOSIS

The clinical appearance of SGC must be confirmed by a full-thickness wedge biopsy of the affected eyelid. Because of potential multicentric spread, multiple biopsy specimens should also be taken from the adjacent bulbar and palpebral conjunctiva and the other ipsilateral eyelid. The pathologist should be alerted to the clinical suspicion of SGC, and fresh tissue should be submitted to pathology so that special lipid stains may be performed on the specimen to confirm the diagnosis.

DIFFERENTIAL DIAGNOSIS

Unfortunately, SGC is frequently confused with a large number of other lesions, especially benign inflammatory and infectious diseases (see Table 93-1 ). As this tumor is so rare, it is usually not considered by the physician, but its potential consequences demand a high index of suspicion. This is especially true for any benign-appearing lesion that does not respond to the usual medical management.

PATHOLOGY

Dysplasia and anaplasia of the sebaceous lobules in the meibomian glands are exhibited by SGC, with associated destruction of tarsal and adnexal tissues. Intraepithelial (pagetoid) spread to conjunctiva distant from the primary tumor may be observed. The intraepithelial spread may resemble SCC in situ.

Typically, SGC shows highly pleomorphic cells arranged in lobules or nests with hyperchromatic nuclei and vacuolated (foamy or frothy) cytoplasm due to a high lipid content ( Fig. 93-6 ). Histologically, SGC may resemble the appearance of SCC. However, the cytoplasm in SGC tends to be more basophilic compared with the eosinophilic appearance of SCC. Also, SCC cells tend not to exhibit a regular, lobular arrangement. Four histological patterns have been described: lobular, comedocarcinoma, papillary, and mixed. Special stains for lipid (e.g., oil red O) on fresh tissue may assist in the histopathological diagnosis of SGC ( Fig. 93-7 ). [7] [34]

TREATMENT

Successful treatment of SGC depends largely upon heightened clinical suspicion and awareness of the possible masquerade

 

 

Figure 93-6 Sebaceous cell carcinoma of the eyelid. Large, hyperchromatic neoplastic cells with vacuolated (frothy), basophilic cytoplasm are observed. (Courtesy of Dr Morton Smith.)

 

 

Figure 93-7 Lipid stain (oil red O) of sebaceous gland carcinoma. Tumor cells stain strongly positive (red) for lipid. (Courtesy of Dr Morton Smith.)

syndrome followed by early confirmatory biopsy. Wide surgical excision with microscopic monitoring of the margins is the procedure of choice. Mohs’ micrographic surgical excision may be used, but it may not be as successful as in BCC or SCC because of the possibility of multicentric and pagetoid spread. If the tumor is very large or recurrent with demonstrated spread to bulbar conjunctiva, to the other eyelid, or to orbital tissues, a subtotal or complete exenteration may be necessary.[2] [30] [31] [33] [35] If evidence of spread to regional lymph nodes is present, the patient should be referred to a head and neck surgeon for possible lymph node or radical neck dissection.[34]

Radiation therapy may be considered as an adjunct to local surgery. However, primary treatment of the tumor with irradiation alone is inadequate. Recurrence of tumor usually occurs within 3 years following radiotherapy alone.[36]

COURSE AND OUTCOME

An invasive, potentially lethal tumor, SGC may cause extensive local destruction of eyelid tissues. It carries a risk of metastasis to preauricular and submandibular lymph nodes or may spread hematogenously to distant sites. It may invade locally into the globe, the orbit, the sinuses, or the brain. Early reports demonstrated a high (30%) tumor-related mortality rate.[32] More recent reviews show a much lower mortality rate, attributed to heightened clinical suspicion and early diagnosis of the tumor.[30] Nonmetastatic disease has a 0–15% mortality rate. However, the presence of distant metastases carries a very poor prognosis with a 50–67% 5-year mortality.[29] [32]

 

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MALIGNANT MELANOMA

INTRODUCTION

Cutaneous malignant melanoma is an invasive proliferation of malignant melanocytes. Melanoma may also arise from the conjunctiva, where it constitutes a distinct entity (see Chapter 56 ). Cutaneous malignant melanoma may be classified into four different types[7] :

• Lentigo maligna melanoma (5%)

• Superficial spreading melanoma (70%)

• Nodular melanoma (16%)

• “Other,” including acral lentiginous melanoma (9%)

Nodular melanoma is the most common type to affect the eyelids. [37]

EPIDEMIOLOGY AND PATHOGENESIS

Cutaneous malignant melanoma of the eyelid accounts for about 1% of all eyelid malignancies. The incidence of malignant melanoma has been increasing, and it causes about two thirds of all tumor-related deaths from cutaneous cancers. The incidence increases with age but remains relatively stable from the fifth to the seventh decades.[38]

Risk factors for the development of malignant melanoma include congenital and dysplastic nevi, changing cutaneous moles, excessive sun exposure and sun sensitivity, family history (genetic factors), age greater than 20 years, and Caucasian race. Malignant melanoma is 12 times more common in whites than in blacks and 7 times more common in whites than in Hispanics.[39] In contrast to BCC, a history of severe sunburns rather than cumulative actinic exposure is thought to be a major risk factor for developing malignant melanoma.[38]

Cutaneous malignant melanoma arises from the neoplastic transformation of intraepidermal melanocytes derived from the neural crest. Initially, a noninvasive horizontal growth phase occurs, which is followed by an invasive vertical growth phase.

OCULAR MANIFESTATIONS

Lentigo maligna melanoma and its precursor, lentigo maligna (melanotic freckle of Hutchinson), present as a flat macule with irregular borders and variable pigmentation. It may have a long in situ (horizontal growth) phase, in which the pigmentation extends for up to several centimeters in diameter and lasts many years. This phase is associated with variable growth and spontaneous regression of the lesion with alteration in pigmentation. It typically occurs in sun-exposed areas and commonly involves

 

 

Figure 93-8 Lentigo maligna melanoma (Hutchinson freckle). Clinical appearance of acquired pigmented lesion of the left lower lid.

the lower eyelid and canthi ( Fig. 93-8 ). Superficial spreading melanoma is typically a smaller pigmented lesion with mild elevation and irregular borders. It tends to have a more rapid progression to the invasive phase, characterized by development of nodules and induration. Nodular melanoma may present as a markedly pigmented or amelanotic nodule that rapidly increases in size with associated ulceration and bleeding. Acral lentiginous melanoma occurs on the palms, soles, and distal phalanges as well as on the mucous membranes.[7] [38]

DIAGNOSIS

The diagnosis of cutaneous malignant melanoma is made by clinical suspicion and confirmed with excisional biopsy and histopathological examination.

DIFFERENTIAL DIAGNOSIS

The differential diagnosis of malignant melanoma of the eyelid primarily comprises nonmalignant pigmented nevi that affect the eyelids (see Table 93-1 ).[7]

SYSTEMIC ASSOCIATIONS

The dysplastic nevus syndrome (also known as B-K mole syndrome) is an autosomal dominantly inherited condition characterized by multiple, large, atypical cutaneous nevi. The moles appear in childhood and continue to grow through adulthood. Patients with this syndrome have a high risk of developing malignant melanoma. [40]

PATHOLOGY

Lentigo maligna is hyperpigmentation in the epidermis characterized by a diffuse hyperplasia of atypical melanocytes throughout the basal cell layer. The entity is regarded as lentigo malignant melanoma when dermal invasion occurs during the transition to the vertical growth phase ( Fig. 93-9 ). Superficial spreading melanoma is typified by atypical melanocytes that occur in nests or singly throughout all levels of the epidermis. Pagetoid spread into the epidermis is characteristic. A mixture of epithelioid, spindle, and nevus-like cells may be present. In nodular melanoma dermal invasion is always present; it exhibits large, anaplastic epithelioid cells.

TREATMENT

Wide surgical excision, with 1?cm of skin margins (when possible) confirmed by histological monitoring, is the procedure of choice for treatment of cutaneous malignant melanoma of the eyelid.

 

 

Figure 93-9 Malignant melanoma. Subepithelial pigmented, spindle-shaped melanoma cells invade the dermis. (Courtesy of Dr Morton Smith.)

 

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Regional lymph node dissection should be performed for tumors greater than 1.5?mm in depth and/or for tumors that show evidence of vascular or lymphatic spread. A metastatic evaluation is also recommended for patients who have such tumors. Cryotherapy may be useful in treating some conjunctival malignant melanomas, but it is not an effective treatment option for cutaneous malignant melanoma of the eyelid.[37]

COURSE AND OUTCOME

Prognosis and metastatic potential are linked to the depth of invasion and thickness of the tumor. Clark and associates[41] correlated prognosis with depth of invasion, characterized at five levels:

• Level 1: tumor confined to the epidermis with an intact basement membrane.

• Level 2: tumor extension beyond the basement membrane with early invasion of the papillary dermis.

• Level 3: tumor fills the papillary dermis and reaches the interface between the papillary and reticular dermis.

• Level 4: tumor penetrates the reticular dermis.

• Level 5: tumor invasion of the subcutaneous tissues.

For lentigo maligna melanoma in levels 1 and 2 there is a 100% survival rate after therapy, whereas for nodular melanoma extending to level 4 there is a 65% survival rate following treatment. The survival drops dramatically to only 15% with extension of any type to level 5.[42]

Breslow[43] related prognosis to tumor thickness—malignant melanomas less than 0.76?mm thick are associated with a 100% 5-year survival rate after excision; tumors greater than 1.5?mm in thickness are associated with a less than 50% 5-year survival rate. Therefore, nodular melanoma has the worst prognosis and lentigo maligna melanoma has the most favorable prognosis of all tumor types. The Clark and Breslow systems may be used in conjunction to predict the prognosis for patients with malignant melanoma.

In a review by Tahery et al., [44] malignant melanoma involving the eyelid margin was found to have a poorer prognosis than eyelid malignant melanoma that did not affect the margin. This worse prognosis was attributed to conjunctival involvement in the eyelid margin tumors.

KAPOSI’S SARCOMA

INTRODUCTION

Kaposi’s sarcoma is a rare neoplasm that may affect the cutaneous or mucosal surfaces of the eyelids. Prior to the advent of AIDS, this tumor was exceedingly rare, but it is now seen more commonly in those with AIDS.

 

 

Figure 93-10 Kaposi’s sarcoma of the eyelid margin. A solitary, vascular reddish purple nodule of the left upper eyelid. (Courtesy of Dr Morton Smith.)

EPIDEMIOLOGY AND PATHOGENESIS

Ophthalmic involvement with Kaposi’s sarcoma occurs in 24–30% of AIDS patients. Generally, Kaposi’s sarcoma is associated with slowly progressive disease, but the condition may resolve spontaneously.[45] A rare form of systemic Kaposi’s sarcoma is seen in elderly men of southern Mediterranean origin. Studies suggest that the endothelial cells characteristic of this tumor may be of lymphatic or viral origin.[46] [47]

OCULAR MANIFESTATIONS

Usually Kaposi’s sarcoma presents as highly vascular, purple or red nodules on the cutaneous aspect of the eyelids and caruncle or on the conjunctiva ( Fig. 93-10 ), but it may also involve the lacrimal sac and, rarely, the orbit. Intraocular involvement has not been described.[48] [49]

DIFFERENTIAL DIAGNOSIS

A number of lesions can be confused with Kaposi’s sarcoma (see Table 93-1 ),[50] but in the setting of an immunocompromised host the diagnosis is usually not difficult to make.

SYSTEMIC ASSOCIATION

The most important systemic association is AIDS.

PATHOLOGY

Kaposi’s sarcoma is composed of slit-like vascular channels lined by endothelial cells and surrounded by spindle-shaped mesenchymal cells and collagen ( Fig. 93-11 ).

TREATMENT, COURSE, AND OUTCOME

The goal of therapy is to relieve ocular irritation, mass effect, and disfigurement. Cryotherapy, irradiation, surgical excision, and intralesional chemotherapy have been described.[49] [50] Therapy may reduce or clear the visible lesions, but it is not curative.

MERKEL CELL TUMOR (CUTANEOUS NEUROENDOCRINE CARCINOMA)

INTRODUCTION

Merkel cell tumor is a rare neoplasm composed of nondendritic and nonkeratinocytic epithelial clear cells of neural crest origin.[51] It is characterized by frequent local recurrences following excision and by lymphatic spread.[52]

 

 

Figure 93-11 Kaposi’s sarcoma. A network of plump endothelial cells line slit-like vascular channels. (Courtesy of Dr Morton Smith.)

 

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EPIDEMIOLOGY AND PATHOGENESIS

Nearly equal incidences of Merkel cell tumors are seen in men and women, primarily in the elderly, and the tumors have a predilection for the head and neck region. The upper eyelid tends to be involved more than other periocular sites. No tumors have been reported in blacks.[7]

The Merkel cell as the origin for cutaneous neuroendocrine carcinoma was described after electron microscopic ultrastructural analysis demonstrated neurosecretory granules.[53]

OCULAR MANIFESTATIONS

Clinically, Merkel cell tumors of the eyelid present as solitary, vascularized, nontender, red or violaceous nodules ( Fig. 93-12 ). Tumors of the upper eyelid may cause a mechanical blepharoptosis.

DIFFERENTIAL DIAGNOSIS

The most common lesions in the differential diagnosis are given in Table 93-1 .

PATHOLOGY

Light microscopy demonstrates tumor cells with uniformly sized nuclei, scant cytoplasm, and numerous mitotic figures. Tumor cells invade the dermis and are arranged in sheets or in a trabecular pattern ( Fig. 93-13 ). Hair follicles may be involved, but

 

 

Figure 93-12 Merkel cell tumor of the eyelid. A large, firm, reddish nodule that resembles an angiomatous lesion of the left upper eyelid. Telangiectatic vessels appear on the surface of the nodule. These lesions are typically more violaceous in coloration. (Courtesy of Dr Morton Smith.)

 

 

Figure 93-13 Merkel cell tumor. Sheets of densely packed basophilic, round, and ovoid tumor cells with scant cytoplasm are observed. (Courtesy of Dr Morton Smith.)

the epidermis is usually spared. Ultrastructural examination reveals secretory granules, microfilaments, desmosomes, and intranuclear rodlets.[7]

TREATMENT

Wide surgical excision with frozen section control of the margins is the treatment of choice. Patients should be evaluated for evidence of metastasis. The possible roles of chemotherapy and radiotherapy are unclear.

COURSE AND OUTCOME

A high incidence of local, multiple recurrences occurs with Merkel cell tumors, with recurrent disease being more common in men. Tumor-related death is usually attributed to distant metastatic disease. The mean survival period after diagnosis of distant metastasis is 16 months in men and 23 months in women.[54]

OTHER RARE TUMORS OF THE EYELIDS

INTRODUCTION, PATHOLOGY, AND TREATMENT

Mucinous Sweat Gland Adenocarcinoma

Mucinous sweat gland adenocarcinoma is a rare malignancy of the eccrine sweat glands that may present in the skin of the eyelid and typically affects male, middle-aged adults. These tumors occur more frequently in blacks. Although it usually presents as a skin-colored, firm, indurated nodule or lobulated mass, it may occasionally have a red-blue, cystic appearance. The clinical differential diagnosis includes benign cysts, keratoacanthomas, and BCC.[55]

Histopathologically, the tumor exhibits cords and lobules of epithelial cells in a pool of mucin, separated by thin fibrovascular septa. The tumor cells are cuboidal or polygonal in shape with nuclear pleomorphism. The tumor is composed of both light and dark cell populations—the dark cells are generally located closer to the periphery and produce mucin and the light cells are located more centrally. Light cells have a paucity of intracellular organelles.[7]

Wide surgical excision with frozen section control of the margins is the treatment of choice for mucinous adenocarcinomas. As these have a propensity for local recurrence, long-term follow-up is required. However, they have low metastatic potential and a better prognosis than other sweat gland carcinomas.

Adenocarcinoma of the Gland of Moll

Adenocarcinoma of the gland of Moll is an exceedingly rare tumor that arises from apocrine sweat glands. It is characterized by a glandular arrangement of large cells that have eosinophilic cytoplasm with evidence of decapitation secretion. The cells may group together to form irregularly shaped lumina.[56] A racial predilection for this tumor in blacks has been attributed to the more numerous and highly developed apocrine axillary glands found in blacks.[57]

Eyelid Metastases

Eyelid metastases from distant sites are uncommon. The most frequent primary sites are the breast, cutaneous melanoma, lung, and stomach. Other primary sites, including colon, thyroid, parotid, trachea, and kidney, have been reported. [7]

The histopathology of these lesions is consistent with the primary tumor of origin. Treatment of the eyelid tumor is usually palliative, and definitive therapy must be systemic.

 

 

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