Dysimmunoglobulinemia in the absence of clinical features of multiple myeloma and macroglobulinemia

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      The protein abnormalities characterizing multiple myeloma and primary macroglobulinemia also occur in the absence of the distinctive clinical features of these disorders, and often of other laboratory features as well. Since many of these cases are discovered accidentally, usually in the absence of any symptoms referable to the underlying disorder, it is suggested that they represent examples of “lanthanic” disease. The term “dysimmunoglobulinemia” is proposed as a designation of the disorder of protein synthesis since it is inconclusive and noncommital, yet pinpoints the area of protein abnormality somewhat better than previously suggested terms.
      Eighteen cases with dysimmunoglobulinemia have been studied and reported in detail. In four cases there were morphologic changes of the bone marrow supportive of the diagnosis of plasma cell myeloma; in nine cases only dysimmunoglobulinemia was found; three patients presented with isolated Bence Jones proteinuria; one patient presented with dysimmunogobulinemia and immunoglobulin deficiency; and there was one case of lanthanic macroglobulinemia.
      These cases were marked by lack of progression over periods of observation for as long as six years. Mild anemia and susceptibility to infection were the principal clinical features. Peripheral neuropathy, myopathy, secondary gout and herpes zoster were less commonly noted.
      The combination of serum electrophoresis and immunoelectrophoresis appears to be a valuable and sensitive screening method. It is possible that the early detection of dysimmunoglobulinemia may shed light on the natural history of the lymphoplasmacytic disorders.
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        • Feinstein A.R.
        Boolean algebra and clinical taxonomy. I. Analytic synthesis of the general spectrum of a human disease.
        New England J. Med. 1963; 269: 929
        • Gitlin D.
        The hypogammaglobulinemias.
        Dis. Month. May 1962; : 1
        • Marchal G.
        • Adida J.
        • Fine J.M.
        Dysglobulinémies au coures des leucoses.
        Nouv. rev. Franç. d'hémat. 1964; 4: 365
        • Apitz K.
        Die Paraproteinosen. Über die Störung des Eiwess-stoffwechsels bei Plasmacytom.
        Virchow Arch. path. Anat. 1940; 306: 631
        • Waldenström J.
        Incipient myelomatosis or “essential” hyperglobulinemia with fibrinogenopenia —a new syndrome?.
        Acta med. scandinav. 1944; 117: 216
        • Waldenström J.
        The occurrence of benign, essential monoclonal (M type), non-macromolecular hyperglobulinemia and its differential diagnosis. IV. Studies in the gammopathies.
        Acta med. scandinav. 1964; 176: 345
        • Waldenström J.
        Studies on conditions associated with disturbed gamma globulin formation (gammopathies).
        Harvey Lect. 1961; 56: 211
        • Burnet M.
        The Clonal Selection Theory of Antibody Production.
        Oxford University Press, New York1959
        • Hammack W.J.
        • Bolding F.E.
        • Frommeyer Jr., W.B.
        The dysgammaglobulinemic syndrome.
        Ann. Int. Med. 1959; 50: 288
        • Rádl J.
        • Masopust J.
        Idiopatische Paraproteinämie.
        Schweiz. Med. Wchnschr. 1964; 94: 961
        • Bergsagel D.E.
        Proposed Guidelines for Protocol Studies of Multiple Myeloma. Prepared at the direction of the clinical studies panel by the protocol committee of chronic leukemia-multiple myeloma task force.
        National Cancer Institute, April, 1965
        • Heremans J.F.
        Immunochemical studies on protein pathology. The immunoglobulin concept.
        Clin. chim. acta. 1959; 4: 639
        • Rowe D.S.
        • Fahey J.L.
        A new class of human immunoglobulins. I. A unique myeloma protein.
        J. Exper. Med. 1965; 121: 171
        • Rowe D.S.
        • Fahey J.L.
        A new class of human immunoglobulins. II. Normal serum IgD.
        J. Exper. Med. 1965; 121: 185
      1. Nomenclature for human immunoglobulins.
        Bull. World Health Organ. 1964; 30: 447
        • Edelman G.M.
        • Gally J.A.
        A model for the 7S antibody molecule.
        in: Proc. Nat. Ac. Sc.51. 1964: 846
        • Franklin E.C.
        The immune globulins—their structure and function and some techniques for their isolation.
        Progr. Allergy. 1964; 8: 58
        • Fahey J.L.
        Antibodies and immunoglobulins. I. Structure and function.
        J.A.M.A. 1965; 194: 71
        • Fahey J.L.
        Antibodies and immunoglobulins. II. Normal development and changes in disease.
        J.A.M.A. 1965; 194: 255
        • Slater R.J.
        • Kunkel H.G.
        Filter paper electrophoresis with special reference to urinary proteins.
        J. Lab. & Clin. Med. 1953; 41: 619
        • Zinneman H.H.
        • Glenchur H.
        • Gleason D.F.
        The significance of urine electrophoresis in patients with multiple myeloma.
        Arch. Int. Med. 1960; 106: 172
        • Grabar P.
        • Williams C.A.
        Méthode permettant l'étude conjugée des propriétés électrophorétiques et immunochimiques d'un mélange de protéines. Application au sérum sanguin.
        Biochim. & biophys. acta. 1953; : 10
        • Grabar P.
        • Williams C.A.
        Méthode permettant l'étude conjugée des propriétés électrophorétiques et immunochimiques d'un mélange de protéines. Application au sérum sanguin.
        Biochim. & biophys. acta. 1953; : 193
        • Scheidegger J.J.
        Une micro-méthode de l'immuno-électrophorèse.
        Int. Arch. Allergy. 1955; 7: 103
        • Snapper I.
        • Ores R.O.
        Determination of Bence Jones protein in the urine.
        J.A.M.A. 1960; 173: 1137
        • Cohen E.
        • Raducha J.J.
        Detection of urinary Bence Jones protein by means of p-toluene sulfonic acid.
        Am. J. Clin. Path. 1962; 37: 660
        • Fahey J.L.
        Serum protein disorders causing clinical symptoms in malignant neoplastic disease.
        J. Chron. Dis. 1963; 16: 703
        • Stefanini M.
        • Dameshek W.
        The Hemorrhagic Disorders. A Clinical and Therapeutic Approach.
        in: Grune & Stratton, Inc, New York1962: 403
        • Wallenius G.
        • Trautman R.
        • Kunkel H.G.
        • Franklin E.C.
        Ultracentrifugal studies of major non-lipide electrophoretic components of normal human serum.
        J. Biol. Chem. 1957; 225: 253
        • Kyle R.A.
        • Bayrd E.D.
        • McKenzie B.F.
        • Heck F.J.
        Diagnostic criteria for electrophoretic patterns of serum and urinary proteins in multiple myeloma.
        J.A.M.A. 1960; 174: 245
        • Grabar P.
        • Burtin P.
        Immuno-electrophoretic Analysis. Applications to Human Biological Fluids.
        Elsevier Publishing Co, New York1964
        • Heremans J.
        Les Globulines Sériques du Système Gamma: Eeur Nature et Leur Pathologie.
        Editions Arscia, S.A, Brussels1960
        • Clausen J.
        Immunoelectrophoresis—a survey of its application in clinical chemistry.
        Science Tools. 1963; 10: 29
        • Korngold L.
        Abnormal plasma components and their significance in disease.
        Ann. New York Acad. Sc. 1961; 94: 110
        • Osserman E.F.
        • Lawlor D.
        Iminunoelectrophoretic characterization of the serum and urinary proteins in plasma cell myeloma and Waldenström's macroglobulinemia.
        Ann. New York Acad. Sc. 1961; 94: 93
        • Osserman E.F.
        • Takatuski K.
        • Talal N.
        Multiple myeloma. I. The pathogenesis of “amyloidosis.” Studies of the role of abnormal gamma globulins and gamma globulin fragments of the Bence Jones (L-polypeptide) type in the pathogenesis of “primary” and “secondary amyloidosis.” and the “amyloidosis” associated with plasma cell myeloma.
        in: 7th ed. Seminars Hemat.1. 1964: 3
        • Snapper I.
        • Turner L.B.
        • Moscovitz H.L.
        Multiple myeloma.
        Grune & Stratton, Inc, New York1953
        • Osserman E.F.
        • Takatuski K.
        Plasma cell myeloma: gamma globulin synthesis and structure.
        Medicine. 1963; 42: 357
        • Snapper I.
        • Kahn A.
        Multiple myeloma.
        in: 7th ed. Seminars Hemat.1. 1964: 87
        • Heremans J.F.
        • Heremans M.-Th.
        • Laurrel A.H.F.
        • Laurell C.-B.
        • Sjöquist J.
        • Waldenström J.
        Studies on “abnormal” serum globulins (M-components) in myeloma, macroglobulinemia and related diseases.
        Acta med. scandinav. 1961; 170: 7
        • Waldenström J.
        Monoclonal and polyclonal gammopathies and the biological system of gamma globulins.
        Progr. Allergy. 1962; 6: 320
        • Owen J.A.
        • Pitney W.R.
        • O'Dea J.F.
        “Myeloma” serum electrophoretic patterns in conditions other than myelomatosis.
        J. Clin. Path. 1959; 12: 344
        • Owen J.A.
        • Got C.
        The biological significance of the anomalous serum and urinary proteins of myelomatosis, lymphoma and other conditions.
        J. Clin. Path. 1960; 13: 58
        • Schubothe H.
        • Baumgartner W.
        • Yoshimura H.
        Makroglobulin-vermehrung und lymphoide Zellenproliferation bei der chronischen Kaelteagglutininkrankheit.
        Schweiz. Med. Wchnschr. 1961; 39: 1154
        • Teitelbaum J.I.
        • Wiener J.
        • Desforges J.F.
        A serologic and electrophoretic study of the malignant and proliferative disorders of the hematopoietic and reticuloendothelial systems.
        J. Lab. & Clin. Med. 1959; 53: 535
        • Osserman E.F.
        Natural history of multiple myeloma before radiological evidence of disease.
        Radiology. 1958; 71: 157
        • Solomon A.
        • Fahey J.L.
        Bence Jones proteinemia.
        Am. J. Med. 1964; 37: 206
        • Cone L.
        • Uhr J.W.
        Immunological deficiency disorders associated with chronic lymphocytic leukemia and multiple myeloma.
        J. Clin. Invest. 1964; 43: 2241
        • Fahey J.L.
        • Scoggins R.
        • Utz J.P.
        • Szwed C.F.
        Infection antibody response and gamma globulin components in multiple myeloma and macroglobulinemia.
        Am. J. Med. 1963; 35: 698
        • Scharff M.D.
        • Uhr J.W.
        Immunologic deficiency disorders associated with lymphoproliferative disease.
        in: 7th ed. Seminars Hemat.2. 1965: 47
        • Fudenberg H.H.
        • Hirschhorn K.
        Agammaglobulinemia: some current concepts.
        M. Clin. North America. 1965; 49: 1533
        • Gleich G.F.
        • Condemi J.J.
        • Vaugman J.H.
        Dysgammaglobulinemia in the presence of plasma cells.
        New England J. Med. 1965; 272: 331
        • Osserman E.F.
        • Takatsuki K.
        Considerations regarding the pathogenesis of the plasmacytic dyscrasias.
        Series Haematologica. 1965; 4: 28
        • Imhof J.W.
        • Baars H.
        • Verloop M.C.
        Clinical and haematological aspects of macroglobulinaemia Waldenström.
        Acta med. scandinav. 1959; 163: 349
        • Kappeler R.
        • Krebs A.
        • Riva G.
        Klinik der Macroglobulinaemia Waldenström. Beschreibung von 21 Fällen und Übersicht der Literatur.
        Helvet. med. acta. 1958; 25: 54
        • Ritzman S.E.
        • Thurm R.H.
        • Truax W.E.
        • Levin W.C.
        The syndrome of macroglobulinemia: Review of the literature and report of two cases of macrocryogelglobulinemia.
        Arch. Int. Med. 1960; 105: 939
        • Strisover E.H.
        • Galleto A.T.
        Waldenström's macroglobulinemia.
        Am. J. Med. 1962; 32: 304
        • Martin N.H.
        Quart. J. Med. 1960; 29: 179
        • Fahey J.L.
        • Barth W.F.
        • Solomon A.
        Serum hyperviscosity syndrome.
        J.A.M.A. 1965; 192: 464
        • Undritz E.
        Der Knochenmarkbefund bei der Makroglobulinaemie Waldenström.
        Schweiz. med Wchnschr. 1957; 87: 1431
        • Tishendorf W.
        • Hartmann F.
        Makroglobulinaemie (Waldenström) mit gleichzeitiger Hyperplasie der Gewebsmastzellen.
        Acta Haemat. 1950; 4: 374
        • Zucker-Franklin D.
        • Franklin E.C.
        • Cooper N.S.
        Production of macroglobulins in vitro and a study of their cellular origin.
        Blood. 1962; 20: 56
        • Wanebo H.J.
        • Clarkson B.D.
        Essential macroglobulinemia. Report of a case including immunofluorescent and electron microscopic studies.
        Ann. Int. Med. 1965; 62: 1025
        • Smith E.W.
        Non-myelomatous paraproteinemia.
        in: 7th ed. Clin. Res. Proc.5. 1957: 158
        • Schobel B.
        • Wewalka F.
        Paraproteinaemia ohne klinisch nachweisbarem Plasmocytom oder Morbus Waldenström.
        Deutsch. Arch. Klin. Med. 1961; 207: 85
        • Hällén J.
        Frequency of “abnormal” serum globulins (M-components) in the aged.
        Acta med. scandinav. 1963; 173: 737
        • Fine J.M.
        • Derycke C.
        • Bilski-Pasquier
        • Marchal G.
        Dysglobulinémies atypiques et dysglobulinémies essentielles.
        in: Abstracts of Xth Congress of International Society of Haematology, Stockholm7th ed. Abstract D: 12. 1964
        • Danon F.
        • Seligmann M.
        Etudes sur les “para-proteinémies” de type gamma and beta 2A sans evidence de myelomes multiples.
        in: Abstracts of Xth Congress of International Society of Haematology, Stockholm7th ed. Abstract D: 11. 1964
        • Glenchur H.
        • Zinneman H.H.
        • Hall W.H.
        A review of fifty-one cases of multiple myeloma. Emphasis on pneumonia and other infections as complications.
        Arch. Int. Med. 1959; 103: 173
        • Cline M.J.
        • Berlin N.I.
        Studies of the anemia of multiple myeloma.
        Am. J. Med. 1962; 33: 510
        • Victor M.
        • Banker B.Q.
        • Adams R.D.
        The neuropathy of multiple myeloma.
        J. Neurol. Neurosurg. Psychiat. 1958; 21: 73
        • Waldenström J.
        Metabolism of proteins and amino acids: Clinical Section.
        in: 7th ed. Thannhauser's Textbook of Metabolism and Metabolic Disorders. Grune & Stratton, Inc, New York1962
        • Osgood E.E.
        The survival time of patients with plasmocytic myeloma.
        Cancer Chem. Rep. 1960; 9: 1
      2. Multiple Myeloma. General aspects of diagnosis, course and survival. Study committee of the mid-west cooperative chemotherapy group.
        J.A.M.A. 1964; 188: 741
        • Norgaard O.
        Recherches sur l'évolution préclinique du myélome multiple.
        Acta med. scandinav. 1964; 176: 137
        • Bloom M.L.
        • Schulman S.
        • Witebsky E.
        Anticomplementary activity of multiple myeloma.
        Clin. Res. 1958; 6: 206
        • Prentiss Jr., R.G.
        Multiple myeloma with diffuse skeletal involvement; case report.
        Mil. Surgeon. 1937; 80: 294
        • Porter D.D.
        • Dixon F.J.
        • Larsen A.E.
        The development of a myeloma-like condition in mink with Aleutian disease.
        Blood. 1965; 25: 736
        • Bottura C.
        Chromosome abnormalities in multiple myeloma.
        Acta Haemat. 1963; 30: 274
        • Ferguson J.
        • Mackay I.R.
        Macroglobulinemia with chromosomal anomaly.
        Australasian Ann. Med. 1963; 12: 197
        • Nadeau L.A.
        • Magalini S.I.
        • Stefanini M.
        Familial multiple myeloma.
        Arch. Path. 1956; 61: 101
        • Seligmann M.
        • Danon F.
        • Mihaesco C.
        Family studies in Waldenström's macroglobulinaemia.
        Series Haematologica. 1965; 4: 50
        • Dunn T.B.
        Plasma cell neoplasms beginning in the ileocecal area in the strain C3H mice.
        J. Nat. Cancer Inst. 1957; 19: 371
        • Schaub F.
        Gleichzeitiges Vorkommen von Makroglobulinämie Waldenström and von malignen Tumoren.
        Schweiz. Med. Wchnschr. 1953; 83: 1256
        • Siegel M.
        • Lee S.L.
        • Ginsberg V.
        • Schultz F.
        • Wong W.
        Racial differences in serum gamma globulin levels: comparative data for Negroes, Puerto Ricans, and other Caucasians.
        J. Lab. & Clin. Med. 1965; 66: 715