Williams Hematology



Definition and History
Etiology and Pathogenesis
Clinical Features
Laboratory Features

Plasma and Urinary Immunoglobulins

Oligoclonal and Monoclonal Immunoglobulins

Lymphocyte and Plasma Cell Phenotypes
Course, Prognosis, and Therapy
Chapter References

Essential monoclonal gammopathy is defined by two key features: the presence of a monoclonal immunoglobulin G, A, or M in the serum or of monoclonal light chains in the urine and the absence of evidence for an overt or progressive malignancy of B lymphocytes or plasma cells (e.g., lymphoma, myeloma, or amyloidosis). Since the latter diseases may be about to emerge at the time the monoclonal immunoglobulin is first detected, follow-up of the patient over several months is required to ascertain if essential monoclonal gammopathy is the appropriate diagnosis. Long-term follow-up at appropriate intervals is prudent to detect conversion from a stable, benign condition to a progressive lymphoma or myeloma, which occurs in about 1 percent of cases per year. Essential monoclonal gammopathy increases in prevalence from about 1 percent in 30-year-old individuals to 10 percent in those 80 years of age or older. The condition has been reported in association with a large variety of disorders, especially nonlymphocytic cancers, but these coincidences are thought to be the chance concurrence of conditions that have a high prevalence in older populations. Some cases of essential monoclonal gammopathy are symptomatic because the immunoglobulin can interact with plasma proteins or neural tissue and cause serious dysfunction. In such cases, disability may be so great that attempts to remove the immunoglobulin by apheresis and to suppress its production using cytotoxic therapy can be warranted. In the absence of such findings, careful periodic follow-up is all that is required.

Acronyms and abbreviations that appear in this chapter include: Ig, immunoglobulin; IL, interleukin.

The syndrome of essential monoclonal gammopathy has two important characteristics. The first characteristic is a plasma immunoglobulin or urinary immunoglobulin light chain that has the molecular features of the product of a single clone of B lymphocytes or plasma cells: homogeneous electrophoretic migration and a single light-chain type. The second feature is the absence of evidence of an overt neoplastic disorder of B lymphocytes or plasma cells, such as lymphoma or multiple myeloma.
The observations that Bence Jones proteinuria can precede by many years the clinical signs of multiple myeloma1 and that hyperglobulinemia without evidence of multiple myeloma can occur in some patients2 antedated the concept of monoclonal gammopathy as a syndrome. With the more frequent clinical application of zonal electrophoresis of plasma proteins during the 1950s and 1960s, patients were discovered who had a monoclonal immunoglobulin either without an associated disease or with diseases such as nonlymphoid cancers, infections, and inflammatory disorders, which are not typically associated with a monoclonal proliferation of B lymphocytes.3,4,5,6,7,8,9 and 10 The presence of a monoclonal protein in plasma or urine is referred to as essential monoclonal gammopathy if it is not associated with a disease. Over 30 synonyms for the syndrome have been used, particularly essential monoclonal gammopathy and benign monoclonal gammopathy.6 Monoclonal gammopathy of unknown significance (MGUS) has been proposed as a designation preferable to benign monoclonal gammopathy because about one-third of patients were noted to progress to myeloma, macroglobulinemia, amyloidosis, or a B-cell lymphoma in over 25 years of observation.10 The term essential monoclonal gammopathy seems best, since it neither highlights a benign process nor indicates that the risks of subsequent lymphoma or myeloma are unknown. A classification of monoclonal gammopathies is presented in Table 105-1.


Monoclonal gammopathy can occur at any age, but it is unusual before puberty, and its frequency increases with age.11 The frequency of a serum paraprotein using zonal electrophoresis is about 1 percent in persons over age 25 years,4 about 3 percent in those over age 70 years,4,9 and about 10 percent in those over age 80 years.3 A much higher prevalence of monoclonal gammopathy has been reported using more sensitive screening methods, such as isoelectric focusing or immunoblotting.12,13 The prevalence rate among Americans of African descent is significantly greater than among those of European descent in each age group over 50 years.14,15 Familial occurrence also has been described.16,17 An increased incidence of monoclonal gammopathy has been associated with several occupation groups, including farmers and industrial workers.18
Monoclonal gammopathy can be compared with any benign tumor, such as a colonic polyp, that can stay the same size indefinitely or undergo malignant transformation at an unpredictable future time.
Monoclonal gammopathy is caused by the proliferation of a single B lymphocyte, a plasma cell progenitor, leading to a clonal population that reaches a steady state at or below about 1 × 1011 cells. At this cell population density, marrow plasma cell prevalence is indistinguishable from that of normal marrow. The expanded clone secretes monoclonal immunoglobulin at a rate per cell sufficient to be detected by standard tests. The clonal expansion, however, does not cause osteolysis, inhibit hematopoietic proliferation and maturation, or impair differentiation of polyclonal B lymphocytes to plasma cells. As such, immunoglobulin synthesis is normal, and patients do not necessarily incur an increased risk of infection. The cells in the benign clone do not accumulate further and do not elaborate significant amounts of osteoclast-activating factors [i.e., interleukin (IL)-1 b, IL-6, soluble IL-6 receptor a, and macrophage colony stimulating factor (M-CSF)] that are responsible for bone destruction. Remarkably, despite these significant differences from myeloma in the behavior of the neoplastic B cells, cytogenetic abnormalities akin to those seen in myeloma involving chromosomes 3, 7, 11, and 18 are present in plasma cells derived from the clone.19,20 and 21
The C57BL mouse provides a model of benign monoclonal gammopathy. The frequency of monoclonal gammopathy increases with mouse age.22 The disease can be transferred to either irradiated or nonirradiated mice by marrow or spleen cells.23 The transfer can only be accomplished during the first four consecutive transplantations, and there is no effect on the survival of the recipient compared with that of appropriate control subjects. In contrast, if mouse B-cell lymphoma or myeloma cells are transplanted into normal mice, the engraftment frequency is higher than that of B cells from mice with benign gammopathy, and passage from the original recipient to a new recipient is unlimited; progressive disease develops, and survival of recipients is decreased. Thus, there is an intrinsic difference in the growth potential (degree of malignancy) of these two B-cell clones.23 The frequency of monoclonal gammopathy increases with age, but the progression to multiple myeloma in the C57BL mouse is a rare event.24 Studies in transgenic mice and their litter mates replicate the increased incidence of B-cell clones and gammopathy with aging.25
Occasionally, monoclonal gammopathy may occur from the exaggerated production of natural antibody by a B-lymphocyte clone.26 For example, patients with cold agglutinins may have monoclonal IgM for years. A few monoclonal IgMs act as rheumatoid factors and may form cryoglobulins through complex formation with IgG molecules.
Characteristically, individuals are detected by the unexpected identification of a monoclonal protein in plasma or urine in the absence of symptoms or signs caused by diseases associated with monoclonal proteins (e.g., anemia, marrow plasmacytosis, lymph node enlargement, plasmacytoma, bone lesions, or amyloid deposits).6,7,8,9 and 10,26,27,28,29,30,31,32,33 and 34
Some patients may have monoclonal proteins with antibody specificity directed against plasma or cell proteins, resulting in symptomatic pathophysiologic effects, such as immune hemolytic anemia,35 acquired von Willebrand disease,36,37 immune neutropenia,38 or other functional manifestations listed in Table 105-2.


Rare patients with essential urinary light-chain excretion and renal disease have been described.43,44 and 45
There is a significant association between the occurrence of neuropathies and essential monoclonal gammopathy.46,47,48,49,50,51,52,53,54,55 and 56 About 10 percent of patients with idiopathic neuropathy have a monoclonal immunoglobulin, a frequency about eight times that of healthy comparison groups.46,47,50 Monoclonal antibodies can react with peripheral nerve myelin, specifically with myelin-associated glycoprotein, glycolipids, or sulfitides.48,52,56,57,58 and 59 Neuropathy in the absence of such reactivity implies that other mechanisms also may operate to cause nerve damage.49,52
Patients with essential IgM gammopathy and neuropathy can have dysesthesia of the hands and feet, loss of vibration and position sense, atrophy of distal muscles, ataxia, and intention tremor.56,57,58,59 and 60 In contrast, patients with essential IgG or IgA gammopathy usually have a chronic axonal sensorimotor neuropathy, sometimes with limb paralysis and occasionally with a remitting-relapsing course.61,62,63 and 64 Essential IgA gammopathy has been associated with dysautonomia.49 The presence or absence of antibody to myelin-associated glycoprotein may have an effect on the specific nature of the neuropathic manifestations.52,56,57,58,59 and 60
Demyelinization is reflected in a marked decrease in conduction velocity. Axonal loss is reflected in decreased sensory potentials.50,52,55,56,61,62,63 and 64 Electromyography shows denervation of muscles.50,52,65,66 and 67 Immunofluorescence studies of sural nerve or of skin biopsies may uncover immunoglobulin binding to nerve.52,56,58
Four treatment approaches may result in improvement in the neuropathies: (1) intravenous gamma globulin administration, (2) immunoadsorption of perfused blood with staphylococcal protein A, (3) plasmapheresis, or (4) immunosuppressive chemotherapy, such as cyclophosphamide or chlorambucil with or without glucocorticoids.52,55,59,60,65,67,68,69 and 70 In some cases use of plasmapheresis has been followed by cytotoxic therapy in an effort to produce a sustained effect. Response rates to each form of therapy are low and duration of response is variable,52,60,65,66,67,68,69 and 70 but some patients appear to obtain significant improvement for prolonged periods.
Monoclonal gammopathy unrelated to a clinically evident proliferation of B lymphocytes or plasma cells has been observed in association with a wide variety of conditions, shown in Table 105-3.71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,
91,92,93,94,95,96,97,98,99,100 and 101 Although they are grouped under the designation monoclonal gammopathy with an associated disease, few such reports have examined whether the coincidence is greater than would be expected in a control group matched for age and ethnicity, the two variables that have the greatest impact on incidence of monoclonal gammopathy. Non-B-cell malignancies, including solid tumors,3,5,6,102,103 and 104 myeloproliferative disorders,105,106,107,108,109,110 and 111 and non-B-cell lymphomas,112,113,114 and 115 have been associated with paraproteinemia. These relationships could be the result of (1) patients with an M component having an increased risk of developing cancer, (2) the M component being an antibody against some antigen associated with the cancer, (3) the globulin being the product of cancer cells, or (4) coincidence. The last possibility is favored by one epidemiologic study that found the same frequency of monoclonal gammopathy in a matched control group as in cancer patients.9 Furthermore, where the monoclonal immunoglobulin is associated with a cancer, it usually persists after surgical excision of the tumor.


Chemotherapy, radiotherapy, and organ or marrow transplantation have been associated with a transient or persistent monoclonal immunoglobulin,116,117,118,119,120 and 121 as have other miscellaneous disorders (Table 105-3).5,7,10,15,16,78,79
The high prevalence of monoclonal proteins and associated diseases, especially after age 50 years, indicates that some of these associations may be coincidental. Thus, although surgical correction of hyperparathyroidism has been associated with disappearance of the plasma monoclonal protein,88 statistical studies of this disorder suggest a coincidental relationship in most patients.89 In hematopoietic stem cell diseases, some observers have proposed that the paraprotein reflects subtle B-cell lineage involvement. In inflammatory, autoimmune, and infectious diseases, the association has been viewed as an unusual expansion of a restricted population of B lymphocytes. Following marrow transplantation, the presence of oligoclonal blood B-lymphocyte populations may reflect the effect of a reconstitution of the B-cell population.
The monoclonal protein is usually IgG; however, IgM, IgA, IgD, and IgE urinary light chains, double gammopathy involving IgA and IgG or IgM and IgA, and triple gammopathy can occur (Table 105-1).103,104,105,106 and 107,129 By definition, no findings other than a plasma or urinary M component are present that would permit a diagnosis of a B-lymphocyte or plasma cell malignancy.
In monoclonal gammopathy of the IgG type, the concentration of monoclonal immunoglobulin is usually less than 3.0 g/dl, and in the IgA or IgM type, it is usually below 2.5 g/dl.10,129 However, there are dramatic exceptions to this rule, with occasional patients with essential monoclonal gammopathy having concentrations as high as 6.0 g/dl. Some patients have Bence Jones proteinuria as the sole manifestation of monoclonal gammopathy.1,10 The amount of urinary light chains excreted may occasionally be large (>1.0 g/day), and renal dysfunction can develop.43
Most patients with myeloma or macroglobulinemia have a significant depression in the nonmonoclonal immunoglobulin levels. For example, patients with IgG myeloma usually have very low IgA and IgM concentrations as well as a reduction in polyclonal IgG level. Patients with monoclonal gammopathy usually have normal polyclonal immunoglobulin levels, and depression of their polyclonal immunoglobulin levels, when it occurs, is usually not as severe as in myeloma.10,129,130
Oligoclonal or monoclonal serum immunoglobulins have been detected with high-resolution agarose gel electrophoresis in hospitalized patients with acute phase reactions or polyclonal hyperglobulinemia.127 Oligoclonal immunoglobulin bands are frequently seen in the cerebrospinal fluid and serum of patients with a variety of neurological conditions, especially in patients with multiple sclerosis when the fluids are analyzed by isoelectric focusing.131 Patients with acquired immunodeficiency syndrome (AIDS) have B-cell activation and aberrancies of B-cell regulation. High-resolution electrophoresis has indicated that most AIDS patients with advanced disease have monoclonal or oligoclonal serum immunoglobulin bands. Subjects with AIDS, lymphadenopathy syndrome, or antibody to the human immunodeficiency virus also have oligoclonal or monoclonal immunoglobulin bands by standard zonal electrophoresis.94,96 These monoclonal proteins are IgG.
The concentration of plasma cells in the marrow is less than 5 percent, and the incorporation of tritiated thymidine into marrow plasma cells is negligible (<1 percent) in essential monoclonal gammopathy. Blood T-lymphocyte subset levels are normal in monoclonal gammopathy, whereas CD4+ T cell levels are lower and CD8+ T cell levels higher in myeloma and macroglobulinemia.132,133,134 and 135 Blood B-cell concentration is normal in monoclonal gammopathy but is often decreased in myeloma patients. Clonally restricted, idiotype-positive blood B cells are characteristic of myeloma but not of monoclonal gammopathy.136
b2 microglobulin is the light chain of cell surface HLA molecules, and normally it is present at low concentrations in serum. Its concentration in serum frequently is elevated in myeloma, and the magnitude of the elevation is positively correlated with tumor mass. b2 microglobulin concentration is not elevated in essential monoclonal gammopathy.137,138
The distinction between stable essential monoclonal gammopathy and emerging (so-called larval myeloma) with a very low tumor burden is blurred at the margins. This has not kept investigators from looking for a distinguishing test. Over 20 variables have been studied as an index for discriminating benignity from malignancy (Table 105-4). No single test is sufficiently sensitive and specific to be useful in an individual patient. Periodic examination of the patient is the best method of detecting the emergence of myeloma or a related disease. Measurement of the concentration of the serum monoclonal protein, urinary light chains, serum b2-microglobulin, and hemoglobin concentration at appropriate intervals is required. Practical methods of measuring serum IL-6 and bone density may become additional useful measures of stability or progression.


Longitudinal studies have reported three major patterns of outcome for patients with essential monoclonal gammopathy.10,129,130,139,170,171 and 172 About 25 percent of patients do not progress. In this group, occasional patients may experience increases in monoclonal protein concentration of up to 50 percent of their initial diagnostic value. However, these patients restabilize and do not develop signs of myeloma, macroglobulinemia, amyloidosis, or lymphoproliferative disease. About one-half of patients die of an unrelated cause. The remaining one-quarter of the patients develop myeloma, amyloidosis, macroglobulinemia, or lymphoma over two decades of observation. The latter group of patients continues to increase slowly without reaching a plateau, and evolution to myeloma has been observed more than 20 years after the diagnosis of monoclonal gammopathy. The actuarial risk of progressing to lymphoma or myeloma is about 1percent per year.139,141,170,171,172 and 173 In rare patients, the monoclonal protein may appear transiently in relation to a disease (e.g., infection)125,126 and 127 or may disappear spontaneously even when not associated with a disease.3
Generally, the diagnosis of essential monoclonal gammopathy cannot be made with certainty at the time of the initial evaluation. Periodic reexamination is required to document a stable clinical course. Therapy usually is not required unless there is a confirmed diagnosis of myeloma, macroglobulinemia, amyloidosis, or lymphoma with evidence of progressive disease. Therapy may also be indicated in the uncommon circumstance that the monoclonal protein interferes with the vital function of a normal plasma or tissue constituent.

Prentiss RG Jr: Multiple myeloma with diffuse skeletal involvement: case report. Mil Surg 80:294, 1937.

Waldenstrom JG: Incipient myelomatosis or essential hyperglobulinemia with fibrinogenopenia: a new syndrome? Acta Med Scand 117:216, 1944.

Hallen J: Frequency of “abnormal serum globulins” (M-components) in the aged. Acta Med Scand 173:737, 1963.

Axelsson U, Bachmann R, Hallen J: Frequency of pathological proteins (M-components) in 6995 sera from an adult population. Acta Med Scand 179:235, 1966.

Migliore PJ, Alexanian R: Monoclonal gammopathy in human neoplasia. Cancer 21:1127, 1968.

Ritzmann SE, Loukes D, Sakai H, et al: Idiopathic (asymptomatic) monoclonal gammopathies. Arch Intern Med 135:95, 1975.

Amies A, Ko HS, Pruzanski W: M-components: a review of 1242 cases. Can Med Assoc J 114:889, 1976.

Lindstrom FD, Dahlstrom V: Multiple myeloma or benign monoclonal gammopathy? A study of differential diagnostic criteria in 44 cases. Clin Immunol Immunopathol 10:168, 1978.

Salerin JP, Vicariot M, Deroff P, et al: Monoclonal gammopathies in the adult population of Finistère, France. J Clin Pathol 35:63, 1982.

Kyle RA: Monoclonal gammopathy of undetermined significance and solitary myeloma. Hematol Oncol Clin North Am 11:71, 1997.

Ligthart GL, Radl J, Corberand JX, et al: Monoclonal gammopathies in human aging: increased occurrence with age and correlation with health status. Mech Ageing Dev 52:235, 1990.

Sinclair D, Sheehan T, Parrott DMV, Stott DI: The incidence of monoclonal gammopathy in a population over 45 years old determined by isoelectric focusing. Br J Haematol 67:745, 1986.

Radl J, Wels J, Hoogeven CM: Immunoblotting with (sub)class specific antibodies reveals a high frequency of monoclonal antibodies in persons thought to be immunodeficient. Clin Chem 34:1839, 1988.

Schecter GP, Shoff N, Chan C, et al: The frequency of monoclonal gammopathy in black and white veterans in a hospital population, in Obrams GI, Potter M (eds): Epidemiology and Biology of Multiple Myeloma. New York, Springer-Verlag, pp 83–85.

Singh J, Dudley AW, Kulig KA: Increased incidence of monoclonal gammopathy of undetermined significance in blacks and its age-related differences with whites on the basis of a study of 397 men and one woman in a hospital setting. J Lab Clin Med 116:785, 1990.

Bizzaro N, Pasini P: Familial occurrence of multiple myeloma and monoclonal gammopathy of undetermined significance in siblings. Haematologica 75:58, 1990.

Jensen TS, Schroeder HD, Jonsson V, et al: IgM monoclonal gammopathy and neuropathy in two siblings. J Neurol Neurosurg Psychiatry 51:1308, 1988.

Pasqualetti P, Collacciani A, Casole R: Risk of monoclonal gammopathy of undetermined significance. Am J Hematol 52:217, 1996.

Drach J, Angerler J, Schuster J, et al: Interphase fluorescence in situ hybridization identifies chromosomal abnormalities in plasma cells from patients with monoclonal gammopathy of undetermined significance. Blood 86:3915, 1995.

Zandecki M, Lai JL, Genevieve F, et al: Several cytogenetic subclones may be identified within plasma cells from patients with monoclonal gammopathy of undetermined significance both at diagnosis and during the indolent course of the disease. Blood 90:3682, 1997.

Zandecki M, Obein V, Bernardi F, et al: Monoclonal gammopathy of undetermined significance: chromosome changes as a common finding within bone marrow plasma cells. Br J Haematol 90:693, 1995.

Radl J, Hollander CF: Homogeneous immunoglobulins in sera of mice during aging. J Immunol 112:2271, 1974.

Radl J, DeGlopper E, Schuit HRE, Zurcher C: Idiopathic paraproteinemia: II. Transplantation of the paraprotein-producing clone from old to young 57B1/KaLwRij mice. J Immunol 122:609, 1979.

Radl J: Age-related monoclonal gammopathies: clinical lessons from the aging C57BL mouse. Immunol Today 11:234, 1990.

van Arkel C, Hopstaken CM, Zurcher C, et al: Monoclonal gammopathies in aging m,x-transgenic mice: involvement of the B-1 cell lineage. Eur J Immunol 27:2436, 1997.

George G, Gilburd B, Schoenfeld Y: The emerging concept of pathogenic natural antibodies. Hum Antibod 8:70, 1997.

Ludwig H, Vormittag W: “Benign” monoclonal Ig E gammopathy. Br Med J 281:539, 1980.

O’Connor ML, Rice DT, Buss DH, Muss HB: Immunoglobulin D benign monoclonal gammopathy. Cancer 68:611, 1991.

Kinoshita K, Nagai H, Murate T, et al: Ig D monoclonal gammopathy of undetermined significance. Int J Hematol 65:169, 1997.

Imhof JW, Balliux RE, Mul NAJ, Poen H: Monoclonal and diclonal gammopathies. Acta Med Scand 179(suppl 455):102, 1966.

Jensen K, Jensen B, Olesen H: Three M-components in serum from an apparently healthy person. Scand J Haematol 4:485, 1967.

Kyle RA, Robinson RA, Katzmann JA: The clinical aspects of biclonal gammopathies: review of 57 cases. Am J Med 71:999, 1981.

Riddell S, Traczyk Z, Paraskevas F, Israels LG: The double gammopathies: clinical and immunological studies. Medicine (Baltimore) 65:135, 1986.

Kyle RA, Greipp PR: “Idiopathic” Bence-Jones proteinuria. N Engl J Med 306:564, 1982.

Kay NE, Gordon LI, Douglas SD: Autoimmune hemolytic anemia in association with monoclonal IgM(k) with anti-i-activity. Am J Med 64:845, 1978.

Federici AB, Stabile F, Castaman G, et al: Treatment of acquired von Willebrand syndrome in patients with monoclonal gammopathy of uncertain significance: comparison of three different therapeutic approaches. Blood 92:2707, 1998.

Lopez-Fernandez MF, Lopez-Berges C, Martin R, et al: Unique multimeric pattern of von Willebrand factor in a patient with a benign monoclonal gammopathy. Scand J Haematol 36:302, 1986.

Carrington PA, Walsh SE, Houghton JB: Benign paraproteinemia and immune neutropenia. Clin Lab Haematol 2:407, 1989.

Gabriel DA, Carr ME, Cook L, Roberts HR: Spontaneous antithrombin in a patient with benign paraprotein. Am J Hematol 25:85, 1987.

Sluiter WJ, Marrink J, Houwen B: Monoclonal gammopathy with an insulin binding IgG(K) M-component, associated with severe hypoglycaemia. Br J Haematol 62:679, 1986.

Wasada T, Egueli Y, Takayama S, Yoo K, et al: Insulin autoimmune syndrome associated with benign monoclonal gammopathy. Diabetes Care 12:147, 1989.

Ahlberg RE, Lefvert AK: Monoclonal gammopathy and antibody activity against the acetylcholine receptor. Am J Hematol 29:49, 1988.

Maldonado JE, Velosa JA, Kyle RA, et al: Fanconi syndrome in adults: a manifestation of a latent form of myeloma. Am J Med 58:354, 1975.

Gavarotti P, Fortina F, Costa D, et al: Benign monoclonal gammopathy presenting with severe renal failure. Scand J Haematol 36:115, 1986.

Kebler R, Kithier K, McDonald FD, Cadnapaphornchai P: Rapidly progressive glomerulonephritis and monoclonal gammopathy. Am J Med 78:133, 1985.

Kahn SN, Riches PG, Kohn J: Paraproteinemia in neurologic disease: incidence, associations, and classification of monoclonal immunoglobulins. J Clin Pathol 33:617, 1980.

Kelly JJ Jr, Kyle RA, O’Brien PC, Dyck PJ: Prevalence of monoclonal protein in peripheral neuropathy. Neurology 31:1480, 1981.

Lee KW, Inghirami G, Spatz L, et al: The B-cells that express anti-MAG antibodies in neuropathy and non-malignant IgM monoclonal gammopathy belong to the CD5 subpopulation. J Neuroimmunol 31:83, 1991.

Bailey RO, Ritaccio AL, Bishop MB, Wu AY: Benign monoclonal IgAk gammopathy associated with polyneuropathy and dysautonomia. Acta Neurol Scand 73:574, 1986.

Simmons Z, Albers JW, Bromberg MB, Feldman EL: Presentation and initial clinical course in patients with chronic inflammatory demyelinating polyradiculoneuropathy: comparison of patients without and with monoclonal gammopathy. Neurology 43:2202, 1993.

Vallatt JM, Jauberteau MO, Bordessoule D, et al: Link between peripheral neuropathy and monoclonal dysglobulinemia: a study of 66 cases. J Neurol Sci 137:124, 1996.

Ropper AH, Gorsin KC: Neuropathies associated with paraproteinemia. N Engl J Med 338:1601, 1998.

Kissel JT, Mendell JR: Neuropathies associated with monoclonal gammopathies. Neuromuscular Disord 6:3, 1996.

Lavrnic D, Vidakovic A, Miletic V, et al: Motor neuron disease and monoclonal gammopathy. Eur Neurol 35:104, 1995.

Gorsin KC, Allan G, Ropper AH: Chronic inflammatory demyelinating polyneuropathy: clinical features and response to treatment in 67 consecutive patients with and without a monoclonal gammopathy. Neurology 48:321, 1997.

Chassande B, Léger J-M, Younes-Chennoufi AB, et al: Peripheral neuropathy associated with IgM monoclonal gammopathy: correlation between M-protein antibody activity and clinical/electrophysicological features in 40 cases. Muscle Nerve 21:55, 1998.

Pestronk A, Li F, Bieser BS, et al: Anti-MAG antibodies. Neurology 44:1131, 1994.

Johnsson V, Jensen TS, Früs ML, et al: Immunoglobulin deposits in peripheral nerve endings detected by skin biopsy in patients with IgM M proteins and neuropathy. Neurology 37:303, 1987.

Ellie E, Vital A, Steck A, et al: Neuropathy associated with “benign” anti-myelin-associated glycoprotein IgM gammopathy: clinical, immunological, neurophysiological pathological findings and response to treatment in 33 cases. J Neurol 243:34, 1996.

Notermans NC: Monoclonal gammopathy and neuropathy. Curr Opin Neurol 9:334, 1996.

Barbieri S, Sandroni P, Orazio-Noble E, et al: Small fiber involvement in neuropathy associated with IgG, IgA and IgM monoclonal gammopathy. Electromyogr Clin Neurophysiol 35:39, 1995.

Notermans NC, Wokke JHJ, vanden Berg LH, et al: Chronic idiopathic axonal polyneuropathy. Brain 119:421, 1996.

Jonsson V, Schroder HD, Trojaborg W, et al: Autoimmune reactions in patients with M-component and peripheral neuropathy. J Intern Med 232:185, 1992.

Gorsin KC, Ropper AH: Axonal neuropathy associated with monoclonal gammopathy of undertermined significance. J Neurol Neurosurg Psychiatry 63:163, 1997.

Latov N: Pathogensis and therapy of neuropathies associated with monoclonal gammopathies. Ann Neruol 37( suppl 1):532, 1995.

Frayne J, Stark RJ: Peripheral neuropathy with gammopathy responding to plasmapheresis. Clin Exp Neurol 21:195, 1985.

Kiprov DD, Miller RG: Paraproteinemia associated with demyelinating polyneuropathy or myositis: treatment with plasmapheresis and immunosuppressive drugs. Artif Organs 9:47, 1985.

Dyck PJ, Low PA, Windeback AJ, et al: Plasma exchange in polyneuropathy associated with monoclonal gammopathy in undetermined significance. N Engl J Med 325:1482, 1991.

Blume G, Pestronk A, Goodnough LT: Anti-MAG antibody-associated polyneuropathies: improvement following immunotherapy with monthly plasma exchange and IV cyclophosphamide. Neurology 45:1577, 1995.

Oksenhendler E, Chevret S, Léger JM, et al: Plasma exchange and chlorambucil in polyneuropathy associated with monoclonal IgM gammopathy. J Neurol Neurosurg Psychiatry 59:243, 1995.

Burner E, Swahlen A, Cruchaud A: Nonmalignant monoclonal immunoglobulinemia, pernicious anemia, and gastric carcinoma: a model of immunologic dysfunction. Am J Med 60:1019, 1976.

Rowland LP, Osserman EF, Scharfman WB, et al: Myasthenia gravis with a myeloma-type gamma-G (IgG) immunoglobulin abnormality. Am J Med 46:599, 1969.

Ilfeld D, Barzilay J, Vana D, et al: IgG monoclonal gammopathy in four patients with polymyalgia rheumatica (letter). Ann Rheum Dis 44:501, 1985.

Nanji AA: Monoclonal gammopathy associated with Crohn’s disease during treatment with total parenteral nutrition. J Parenteral Nutr 9:621, 1985.

Wallach D, Carado Y, Foldes C, Cottennot F: Dermatomyositis and monoclonal gammopathy. Ann Dermatol Venereol 112:783, 1985.

McFadden N, Ree K, Syland E, Larse TE: Scleredema adultorum associated with a monoclonal gammopathy and generalized hyperpigmentation. Arch Dermatol 123:629, 1987.

Oikarinen A, Ala-Kokko L, Palatsi R, et al: Scleroderma and paraproteinemia. Arch Dermatol 123:226, 1987.

Johnsson V, Svendsen B, Vostrup S, et al: Multiple autoimmune manifestations in monoclonal gammopathy of undetermined significance and chronic lymphocytic leukemia. Leukemia 10:327, 1996.

Kyle RA: Monoclonal gammopathy of unknown significance (MGUS). Ballière’s Clin Haematol 8:761, 1995.

Probst LE, Hoffman E, Cherian MG, et al: Ocular copper deposition associated with benign monoclonal gammopathy and hypercupremia. Cornea 15: 94, 1996.

Secundo W, Seifert P: Monoclonal corneal gammopathy: topographic considerations. Ger J Ophthalmol 5:262, 1996.

Doutre MS, Beylot C, Bioulac P, Bezian JH: Monoclonal IgM and chronic urticaria: two cases. Ann Allergy 58:413, 1987.

Samochocki Z, Szudzinski A: Gangrenous pyoderma in monoclonal IgA gammopathy and functional disorders of T lymphocytes. Przegl Dermatol 73:409, 1986.

Abraham Z, Feuerman EJ: IgA benign monoclonal gammopathy with recurrent self-healing skin tumors. J Am Acad Dermatol 21:1303, 1989.

Puddu P, Cianchini G, Giardelli CR, et al: Schnitzler’s syndrome: report of a new case and review of the literature. Clin Exper Rheumatol 15:91, 1997.

Wayte JA, Rogers S, Powell FC: Pyoderma gangrenosum, erythema elevatum diutinum and Ig A monoclonal gammopathy. Australas J Dermatol 36:21, 1995.

Paul C, Fermaud J-P, Flageul B, et al: Hyperkeratotic spicules and monoclonal gammopathy. J Am Acad Dermatol 33:346, 1995.

Schnur MJ, Appel GB, Bilezikian JP: Primary hyperparathyroidism and benign monoclonal gammopathy. Arch Intern Med 137:1201, 1977.

Rao DS, Antonelli R, Kane KR, et al: Primary hyperparathyroidism and monoclonal gammopathy. Henry Ford Hosp Med J 39:41, 1991.

Schoenfeld Y, Berliner S, Pinkhas J, Beutler E: The association of Gaucher’s disease and dysproteinemias. Acta Haematol (Basel) 64:241, 1980.

Brady K, Corash L, Bhargava E: Multiple myeloma arising from monoclonal gammopathy of unknown significance in a patient with Gaucher’s disease. Arch Pathol Lab Med 121:1108, 1997.

Schafer AL, Miller JB, Lester EP, et al: Monoclonal gammopathy in hereditary spherocytosis: a possible pathogenetic relation. Ann Intern Med 88:45, 1978.

Danon F, Bussel A, Perol Y: Immunoglobulines monoclonales infections a cytomegalovirus et hémopathies malignes. Ann Immunol 128A:83, 1977.

Papadopoulos NM, Lane HC, Costello R, et al: Oligoclonal immunoglobulins in patients with the acquired immunodeficiency syndrome. Clin Immunol Immunopathol 35:43, 1985.

Heriot K, Hallquist AE, Tomar RH: Paraproteinemia in patients with acquired immunodeficiency syndrome (AIDS) or lymphadenopathy syndrome (LAS). Clin Chem 31:1224, 1985.

Kouns DM, Marty AM, Sharpe RW: Oligoclonal bands in serum protein electrophoretograms of individuals with human immunodeficiency virus antibodies. JAMA 256:2343, 1986.

Ong F, Hermans J, Noordik EM, et al: A population-based registry on paraproteinaemia in the Netherlands. Br J Haematol 99:914, 1997.

Johnston JD, Lumb PJ, Wierzbicki AS: Hyperlipidaemia in association with benign paraproteinemia. Ann Clin Bichem 34:697, 1997.

Buonocore E, Solmon A, Kerley HE: Pseudomyeloma. Radiology 95:41, 1970.

Maldonado JE, Riggs L, Bayrd ED: Pseudomyeloma. Arch Intern Med 135:267, 1975.

Silverman S, Vescio R, Silver D, et al: Silicone gel implants and monoclonal gammopathies. Curr Top Microbiol Immunol 210:367, 1996.

Kyle RA: Monoclonal gammopathy of unknown significance. Curr Top Microbiol Immunol 210:375, 1996.

Solomon A: Homogeneous (monoclonal) immunoglobulins in cancer. Am J Med 63:169, 1977.

Colls BM, Lorier MA: Immunocytoma, cancer, and other associations of monoclonal gammopathy: a review of 224 cases. N Z Med J 82:221, 1975.

Abdul M, Hassein NM: Gammopathy associated with advanced prostate cancer. Urol Res 23:185, 1995.

Thys LG, Hijmans W, Leene W, et al: Blast cell leukemia associated with IgA paraproteinemia and Bence-Jones protein. Br J Haematol 19:485, 1970.

Shoenfeld Y, Berliner S, Ayalone A, et al: Monoclonal gammopathy in patients with chronic and acute myeloid leukemia. Cancer 54:280, 1984.

Berner Y, Berrebi A: Myeloproliferative disorders and nonmyelomatous paraprotein. Isr J Med Sci 22:109, 1986.

Tosato F, Fossaluzza V, Rossi P, et al: Monoclonal gammopathy of undetermined significance in a case of primary thrombocythemia. Haematologica (Pavia) 71:417, 1986.

Economopoulos T, Economidou J, Papageorgiou E, et al: Monoclonal gammopathy in chronic myeloproliferative disorders. Blut 58:7, 1989.

Ito T, Kojima H, Otani K, et al: Chronic neutrophilic leukemia associated with monoclonal gammopathy of unknown significance. Acta Haematol 95:140, 1996.

Offit K, Macris NT, Hellman G, Rotterdam, HZ: Consecutive lymphoma with monoclonal gammopathy in a married couple. Cancer 57:277, 1986.

Venencie PY, Winkelmann RK, Puissant A, Kyle RA: Monoclonal gammopathy in Sézary syndrome: report of three cases and review of the literature. Arch Dermatol 120:605, 1984.

Kamihira S, Taguchi H, Kinoshita K, Ichimaru M: Monoclonal gammopathy in adult T-cell leukemia/lymphoma: a report of three cases. Jpn J Clin Oncol 14:699, 1984.

Chisesi I, Capnist G, Barbui T: Two serum IgG M-components of differing light chain types in a case of Hodgkin’s disease. Acta Haematol (Basel) 55:250, 1976.

VanCamp B, Reynaerts PH, Naets JP, Radl J: Transient IgA1l para-proteinemia during treatment of acute myeloblastic leukemia. Blood 55:21, 1980.

Hammarstrom L, Smith CIE: Frequent occurrence of monoclonal gammopathies with an imbalanced light-chain ratio following bone marrow transplantation. Transplantation 43:447, 1987.

Mitus AJ, Stein R, Rappeport JM, et al: Monoclonal and oligoclonal gammopathy after bone marrow transplantation. Blood 74:2764, 1989.

Passweg J, Thiel G, Bock HA: Monoclonal gammopathy after intense induction immunosuppression in renal transplant patients. Nephrol Dial Transplant 11:2461, 1996.

Badley AD, Portela DF, Patel R, et al: Development of monoclonal gammopathy precedes the development of Epstein-Barr virus-induced posttransplant lymphoproliferatve disorder. Liver Transpantl Surg 2:375, 1996.

Touchard G, Pasdeloup T, Parpeix J, et al: High prevalence and usual persistence of serum monoclonal immunoglobulins evidenced by sensitive methods in renal transplant recipients. Nephrol Dial Transplant 12:1199, 1997.

Ho JL, Polde PA, McEniry D, et al: Acquired immunodeficiency syndrome with progressive multifocal leukoencephalopathy and monoclonal B-cell proliferation. Ann Intern Med 100:693, 1984.

Nagler A, Ben-Arieh Y, Brenner B, et al: Eosinophilic fibrohistiocytic lesion of bone marrow associated with monoclonal gammopathy and osteolytic lesions. Am J Hematol 23:277, 1986.

Hineman VL, Phyliky RL, Banks PM: Angiofollicular lymph node hyperplasia and peripheral neuropathy: association with monoclonal gammopathy. Mayo Clin Proc 57:379, 1982.

Radl J, VandenBerg A: Transitory appearance of homogeneous immunoglobulins—paraproteins—in children with severe combined immunodeficiency before and after transplantation, in Peeters H (ed): Protides of Biological Fluids, vol 20. Oxford, Pergamon, 1973, p 203–211.

DelCarpio J, Espinoza LR, Lauater S, Osterland CK: Transient monoclonal proteins in drug hypersensitivity reactions. Am J Med 66:1051, 1979.

Keshgegian AA: Prevalence of small monoclonal proteins in the serum of hospitalized patients. Am Soc Clin Pathol 77:436, 1982.

Bakker AJ, Kothman-Tijkotte MJ: Artifactually high concentration of iron determined in serum from a patient with a monoclonal immunoglobulin. Clin Chem 36:1517, 1990.

Malacrida V, De-Francesco D, Banfi G, et al: Laboratory investigation of monoclonal gammopathy during 10 years of screening in a general hospital. J Clin Pathol 40:793, 1987.

Moller-Petersen J, Schmidt EB: Diagnostic value of the concentration of M-component in initial classification of monoclonal gammopathy. Scand J Haematol 26:295, 1986.

Link H, Kostulas V: Utility of isoelectric focusing of cerebrospinal fluid and serum of agarose evaluated for neurological patients. Clin Chem 29:810, 1983.

Greipp PR, Kyle RA: Clinical, morphological and cell kinetic differences among multiple myeloma, monoclonal gammopathy of undetermined significance and smoldering myeloma. Blood 62:166, 1983.

Boccadoro M, Gavarotti P, Fossati G: Low plasma cell 3(H)-thymidine incorporation in MGUS, smoldering myeloma and remission phase myeloma: reliable identification of patients not requiring therapy. Br J Haematol 58:689, 1984.

San Miguel JF, Caballero MD, Gonzalez M: T-cell subpopulations in patients with monoclonal gammopathies: essential monoclonal gammopathy, multiple myeloma and Waldenstrom macroglobulinemia. Am J Hematol 20:267, 1985.

Lindstrom FD, Hardy WR, Eberle BJ, Williams RC Jr: Multiple myeloma and benign monoclonal gammopathy: differentiation by immunofluorescence of lymphocytes. Ann Intern Med 78:837, 1973.

Billadeau D, Greipp P, Ahmann G, et al: Detection of B-cells clonally related to the tumor population in multiple myeloma and MGUS. Curr Top Microbiol Immunol 194:9, 1995.

Morrell A, Riesen W: Serum B2-macroglobulin, serum creatinine and bone marrow plasma cells in benign and malignant monoclonal gammopathy. Acta Haematol (Basel) 64:87, 1980.

Fine JM, Lambin P, Desjobert H: Serum neopterin and B2-microglobulin concentrations in monoclonal gammopathies. Acta Med Scand 224:179, 1988.

Vuckovic J, Ilic A, Knezevic N, et al: Progress in monoclonal gammopathy of undetermined significance. Br J Haematol 97:649, 1997.

Bataille R: New insights in the clinical biology of multiple myeloma. Sem Hematol 34:23, 1997.

Baldini L, Guffanti A, Cesana BM, et al: Role of different hematologic variables in defining the risk of malignant transformation in monoclonal gammopathy. Blood 87:92, 1996.

French M, Fench P, Remy F, et al: Plasma cell proliferation in monoclonal gammopathy: relations with other biologic variables—diagnostic and prognostic significance. Am J Med 98:60, 1995.

Witzig TE, Gonchoroff NJ, Katzmann JA, et al: Peripheral blood B cell labeling indices are a measure of disease activity in patients with monoclonal gammopathies. J Clin Oncol 6:1041, 1988.

Yi Q, Eriksson I, He W, et al: Idiotype-specific T lymphocytes in monoclonal gammopathies: evidence for the presence of CD4+ and CD8+ subsets. Br J Haematol 96:338, 1997.

Yi Q, Osterborg A, Bergenbrant S, et al: Idiotype-reactive T-cell subsets and tumor load in monoclonal gammopathies. Blood 86:3043, 1995.

Halapi E, Werner A, Wahlstrom J, et al: T cell repertoire in patients with multiple myeloma and monoclonal gammopathy of undetermined significance: clonal CD8+ T cell expansions are found preferentially in patients with a low tumor burden. Eur J Immunol 27:2245, 1997.

Corso A, Castelli G, Pagnucco G, et al: Bone marrow T-cell subsets in patients with monoclonal gammopathies: correlation with clinical stage and disease. Haematologia 82:43, 1997.

Miguel-Garcia A, Matutes E, Tarin F, et al: Circulating Ki 67 positive lymphocytes in multiple myeloma and benign monoclonal gammopathy. J Clin Pathol 48:835, 1995.

Billadeau D, Van Ness B, Kimlinger T, et al: Clonal circulation cells are common in plasma cell proliferative disorders: a comparison of monoclonal gammopathy, smoldering myeloma, and active myeloma. Blood 88:289, 1996.

Isaksson E, Bjockholm M, Holm G, et al: Blood clonal B-cell excess in patients with monoclonal gammopathy of undetermined significance (MGUS): association with malignant transformation. Br J Haematol 92:71, 1996.

Sawanoborj M, Suzuki K, Nakagawa Y, et al: Natural killer cell frequency and serum cytokine levels in monoclonal gammopathies: correlation of bone marrow granular lymphocytes to prognosis. Acta Haematol 98:150, 1997.

Leo E, Kropff M, Lindemann A, et al: DNA aneuploidy, increased proliferation and nuclear area of plasma cells in monoclonal gammopathy of undetermined significance and multiple myeloma. Anal Quant Cytol Histol 17:113, 1995.

Turesson I: Nucleolar size in benign and malignant plasma cell proliferation. Acta Med Scand 197:7, 1975.

Dehou MF, Schots R, Lacor P, Arras N, et al: Diagnostic and prognostic value of the MB2 monoclonal antibody in paraffin-embedded bone marrow sections of patients with multiple myeloma and monoclonal gammopathy of undetermined significance. J Clin Pathol 94:287, 1990.

Yasuda N, Kanoh T, Uchino H: J chain synthesis in human myeloma cells: light and electron microscopic studies. Clin Exp Immunol 40:573, 1980.

Cassuto JP, Hammore JC, Pastorelli E, et al: Plasma cell acid phosphatase, a discriminative test for benign and malignant monoclonal gammopathies. Biomed 27:97, 1977.

Sonneveld P, Durie BGM, Lokhorst HM, et al: Analysis of multidrug-resistance (MDR-1) glycoprotein and CD56 expression to separate monoclonal gammopathy from multiple myeloma. Br J Haematol 83:63, 1993.

Zandecki N, Facon T, Bernard F, et al: CD19 and immunophenotype of bone marrow plasma cells in monoclonal gammopathy of undetermined significance. J Clin Pathol 48:548, 1995.

Majumdar G, Heard SE, Singh AK: Use of cytoplasmic 5-prime nucleotidase for differentiating malignant from benign monoclonal gammopathies. J Clin Pathol 43:891, 1990.

Van de Berg BC, Michaux L, Lecouvet FE, et al: Nonmyelomatous monoclonal gammopathy: correlation of bone marrow MR images with laboratory findings and spontaneous clinical outcome. Radiology 202:249, 1997.

Bellaiche L, Laredo J-D, Lioté F, et al: Magnetic resonance appearance of monoclonal gammopathies of unknown significance and mutiple myeloma. Spine 22:2551, 1997.

Laroche M, Attal M, Pouilles JM, et al: Dual-energy x-ray absorption in patients with multiple myeloma and benign gammopathies. Clin Exp Rheumatol 14:108, 1996.

Bataille R, Chappard D, Basle M: Quantifiable excess of bone resorption in monoclonal gammopathy is an early symptom of malignancy: a prospective study of 87 bone biopsies. Blood 87:4762, 1996.

Pecherstorfer M, Seibel MJ, Woitge HW, et al: Bone resorption in multiple myeloma and in monoclonal gammopathy of undetermined significance: quantification by urinary pyridinium cross-links of collagen. Blood 90:3743, 1997.

Ong F, Kaiser U, Seelen PJ, et al: Serum neural cell adhesion molecule differentiates multiple myeloma from paraproteinemias due to other causes. Blood 87:712, 1996.

Greco C, Ameglio F, Alvino S, et al: Selection of patients with monoclonal gammopathy of undetermined significance is mandatory for a reliable use of interleukin-6 and other nonspecific multiple myeloma serum markers. Acta Haematol 92:1, 1994.

Mathiot C, Mary JY, Tartour E, et al: Soluble CD16 (sCD16), a marker of malignancy in individuals with monoclonal gammopathy of undetermined significance (MGUS). Br J Haematol 95:660, 1996.

Gaillard JP, Bataille R, Brailly H, et al: Increased and highly stable levels of functional soluble interleukin-6 receptor levels in sera of patients with monoclonal gammopathy. Eur J Immunol 23:820, 1993.

DuVillard L, Guiguet M, Casasnovas R-O, et al: Diagnostic value of serum IL-6 level in monoclonal gammopathies. Br J Haematol 89:243, 1995.

Pasqualetti P, Festucci V, Collacciani A, Casale R: The natural history of monoclonal gammopathy of undetermined significance. Acta Haematol 97:174, 1997.

Van de Poel MHW, Coebergh JWW, Hillen HFP: Malignant transformation of monoclonal gammopathy of undetermined significance among out-patients of a community hospital in southeastern Netherlands. Br J Haematol 91:121, 1995.

Kyle RA: Monoclonal gammopathy of undetermined significance. Blood Review 8:135, 1994.

Pasqualetti P, Casale R: Risk of malignant transformation in patients with monoclonal gammopathy of undetermined significance. Biomed Pharmacother 51:74, 1997.

Cozzolino F, Torcia M, Aldinucci D, et al: Production of interleukin-1 by bone marrow myeloma cells. Blood 74:380, 1989.

Donovan KA, Lacy MQ, Kline MP, et al: Contrast in cytokine expression between patients with monoclonal gammopathy of undetermined significance or multiple myeloma. Leukemia 12:593, 1998.

Disdier P, Swiader L, Aillaud M-F, et al: Ig M monoclonal gammopathy, lymphoid proliferations and lupus anticoagulant. Am J Med 102:319, 1997.

Chryssikkopoulos A, Dalamaga AL, Hassiakos D: Monoclonal gammopathy of unknown significance in pregnancy. Clin Exp Obstet Gynecol 24:31, 1997.

deKleijn EM, Telgt D, Laan R: Schnitzler’s syndrome presenting as fever of unknown origin (FUO): the role of cytokines in its systemic features. Neth J Med 51:140, 1997.

Andreone P, Zignego AL, Cursaro C, et al: Prevalence of monoclonal gammopathies in patients with hepatitis C virus infection. Ann Intern Med 129:294, 1998.
Copyright © 2001 McGraw-Hill
Ernest Beutler, Marshall A. Lichtman, Barry S. Coller, Thomas J. Kipps, and Uri Seligsohn
Williams Hematology


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