Essential Macroglobulinemia
Authors: HAROLD J. WANEBO
Journal: Annals of Internal Medicine (1965)

Case Studies1 May 1965Essential MacroglobulinemiaReport of a Case Including Immunofluorescent and Electron Microscopic StudiesHAROLD J. WANEBO, M.D., BAYARD D. CLARKSON, M.D.HAROLD J. WANEBO, M.D.Search for more papers by this author, BAYARD D. CLARKSON, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-62-5-1025 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptEssential or "Waldenström's" macroglobulinemia was first described by Waldenström (1) in 1944, and since then it has been reported with increasing frequency (2-6). It is a disease characterized by abnormal proliferation of cells that are generally described as atypical lymphoid cells and the presence in the serum of a high molecular weight globulinthat is quite homogeneous on electrophoresis. This paper describes a patient with the characteristic findings of Waldenström's macroglobulinemia in whom macroglobulin was demonstrated in the cytoplasm of certain cells in the spleen by immunofluorescent techniques; these studies were correlated with the morphologic appearance of the cells when...References1. WALDENSTRÖM J: Incipient myelomatosis or "essential" hyperglobulinemia with fibrogenopenia—a new syndrome? Acta Med. Scand. 117: 216, 1944. CrossrefGoogle Scholar2. WALDENSTRÖM J: Diseases associated with abnormal plasma proteins. Proc. Roy. Soc. Med. 53: 789, 1960. CrossrefMedlineGoogle Scholar3. RITZMANNTHURMTRUAXLEVIN SERHWEWC: The syndrome of macroglobulinemia. Arch. Intern. Med. (Chicago) 105: 939, 1960. CrossrefMedlineGoogle Scholar4. MARTIN NH: Macroglobulinaemia: a clinical and pathological study. Quart. J. Med. (new series) 29: 179, 1960. MedlineGoogle Scholar5. FESSEL WJ: Clinical analysis of 142 cases with high molecular weight serum proteins. Acta Med. Scand. (supplement 391) 173: 3, 1962. Google Scholar6. RAPPELERKREBSRIVA RAG: Klinik der makroglobulinämie Waldenström Beschreibung von 21 fällen und ubersicht der literatur. Helv. Med. Acta 25: 54, 1958. MedlineGoogle Scholar7. CEPPELLINIDRAYEDELMANFAHEYFRANĚKFRANKLINGOODMANGRABARGURVICHHEREMANSISLIKERKARUSHPRESSTRNKA RSGJFEHCPAEJFHFEZ: Nomenclature for immunoglobulins. Bull. WHO 30 (3): 447, 1964. MedlineGoogle Scholar8. WALDENSTRÖM J: Studies on conditions associated with disturbed gamma globulin formation (gammopathies). Harvey Lect. 56: 211, 1961. Google Scholar9. WALDENSTRÖM J: Monoclonal and polyclonal gammopathies and the biological system of gamma globulins. Progr. Allerg. 6: 320, 1962. MedlineGoogle Scholar10. MELLORSKORNGOLD RCL: The cellular origin of human immunoglobulins. (γ2, γ1M, γ1A). J. Exp. Med. 118: 387, 1963. CrossrefMedlineGoogle Scholar11. MOESCHLIN S: Spleen Puncture, translated by A. Piney. Grune and Stratton, N. Y., 1951. Google Scholar12. SABATINIBENSCHBARRNETT DDKGRJ: New fixatives for cytological and cytochemical studies, in Proceedings of the Fifth International Congress for Electron Microscopy, Vol. II, Philadelphia, 1962. Academic Press, New York, p. L-3, 1962. CrossrefGoogle Scholar13. MILLONIG G: Further observations on a phosphate buffer for osmium solutions in fixation. Ibid., p. P-8, 1962. Google Scholar14. SPURLOCKKATTINEFREEMAN BOVCJA: Technical modifications in maraglas embedding. J. Cell. Biol. 17: 203, 1963. CrossrefMedlineGoogle Scholar15. WATSON M: Staining of tissue sections for electron microscopy with heavy metals. J. Biophys. Biochem. Cytol. 4: 475, 1958. CrossrefMedlineGoogle Scholar16. REYNOLDS ES: The use of lead citrate at high pH as an electron-opaque stain in electron microscopy. J. Cell. Biol. 17: 208, 1963. CrossrefMedlineGoogle Scholar17. SCHEIDEGGER JJ: Une micro-methode de l'immuno-electrophorese. Int. Arch. Allerg. 7: 103, 1955. CrossrefGoogle Scholar18. DUTCHERFAHEY TFJL: Immunocytochemical demonstration of intranuclear localization of 18S gamma macroglobulin in macroglobulinemia of Waldenström. Proc. Soc. Exp. Biol. Med. 103: 452, 1960. CrossrefMedlineGoogle Scholar19. BURTIN P: Etude en immunofluorescence des ganglions da macroglobulinemie de Waldenström. Rev. Franc. Etud. Clin. Biol. 6: 1044, 1961. Google Scholar20. ZUCKER-FRANKLINFRANKLINCOOPER DECNS: Production of macroglobulins in vitro and a study of their cellular origin. Blood 20: 56, 1962. CrossrefGoogle Scholar21. KRITZMANKUNKELMCCARTHYMELLORS JHGJRC: Studies of a Waldenström-type macroglobulin with rheumatoid factor properties. J. Lab. Clin. Med. 57: 905, 1961. MedlineGoogle Scholar22. CURTAIN CC: Localization of 18S gamma-macroglobulin in plasmacytoid cells of bone marrow of a case of macroglobulinemia. Aust. J. Exp. Biol. Med. Sci. 39: 391, 1961. CrossrefMedlineGoogle Scholar23. SOLOMONFAHEYMALMGREN AJLRA: Immunohistologic localization of gamma-1-macroglobulins, beta-2A-myeloma proteins, 6.6 S gamma-myeloma proteins and Bence Jones proteins. Blood 21: 403, 1963. CrossrefMedlineGoogle Scholar24. MELLORSNOWOSLAWSKIKORNGOLDSENGSON RCALBL: Rheumatoid factor and the pathogenesis of rheumatoid arthritis. J. Exp. Med. 113: 475, 1961. CrossrefMedlineGoogle Scholar25. BERHNARDGRANBOULAN WN: Ultrastructure of immunologically competent cells, in CIBA Foundation Symposium on Cellular Aspects of Immunity, edited by Wolstenholme, G. E. W., and O'Connor, M. Little, Brown, and Co., Boston, 1960, p. 92. CrossrefGoogle Scholar26. BESSIS MC: Ultrastructure of lymphoid and plasma cells in relation to globulin and antibody formation. Lab. Invest. 10: 1040, 1961. MedlineGoogle Scholar27. BRECHERTANAKAMALMGRENFAHEY GYRAJ.: Morphology and protein synthesis in multiple myeloma and macroglobulinemia. Ann. NY Acad. Sci. 113: (article 2), 642 (Feb. 28), 1964. CrossrefMedlineGoogle Scholar28. BRAUNSTEINERFELLINGERPAKESCH HKF: Electron microscopic investigations on sections from lymph nodes and bone marrow in malignant blood disease. Blood 12: 278, 1957. CrossrefMedlineGoogle Scholar29. HARRIS TN: Discussion: ultrastructure of antibody-producing cells, in CIBA Foundation Symposium on Cellular Aspects of Immunity, edited by Wolstenholme, G. E. W., and O'Connor, M., Little Brown and Co., Boston, 1960, p. 120. Google Scholar30. BERMAN L: The immunologically competent cell ("Immunocyte") system—an attempt at a delineation of cellular relationships (editorial). Blood 21: 246, 1963. CrossrefMedlineGoogle Scholar31. PEARMAINLYCETTEFITZGERALD GRRPH: Tuberculin-induced mitosis in peripheral blood leukocytes. Lancet 1: 637, 1963. CrossrefMedlineGoogle Scholar32. HIRSCHHORNKOLODNYHASHEMBACH KRLNF: Mitogenic action of phytohaemagglutinin (letter to the editor). Lancet 2: 305, 1963. CrossrefMedlineGoogle Scholar33. ELVESROATHISRAËLS MWSMC: The response of lymphocytes to antigen challenge in vitro. Lancet 1: 806, 1963. CrossrefGoogle Scholar34. MARSHALLROBERTS WHKB: Tuberculin-induced mitosis in peripheral leukocytes (letter to the editor). Ibid., p. 773. Google Scholar35. HASHEMSEDLISHIRSCHHORNHOLT NEKLE: Infantile eczema. Evidence of autoimmunity to human skin. Lancet 2: 269, 1963. CrossrefMedlineGoogle Scholar36. NOSSALMÄKELÄ GJO: Autoradiographic studies on the immune response. I. The kinetics of plasma cell proliferation. J. Exp. Med. 115: 209, 1962. CrossrefMedlineGoogle Scholar37. HOLUBJAROŠKOVÁ ML (ed.) Mechanisms of Antibody Formation, Proceedings of the Symposium in Prague, 1959. Academic Press, New York, 1960. Google Scholar38. ROBERTSDIXON JCFJ: The transfer of lymph node cells in the study of the immune response to foreign proteins, J. Exp. Med. 102: 379, 1955. CrossrefMedlineGoogle Scholar39. ROBERTSDIXONWEIGLE JCFJWO: Antibody-producing lymph node cells and peritoneal exudate cells. Arch. Path. (Chicago) 64: 324, 1957. MedlineGoogle Scholar40. VAZQUEZ JJ: Antibody- or gamma globulin-forming cells as observed by the fluorescent antibody technique. Lab. Invest. 10: 1110, 1961. MedlineGoogle Scholar41. NEILDIXON ALFJ: Immunohistochemical detection of antibody in cell-transfer studies. Arch. Path. (Chicago) 67: 643, 1959. MedlineGoogle Scholar42. ORTEGAMELLORS LGRC: Cellular sites of formation of gamma globulin. J. Exp. Med. 106: 627, 1957. CrossrefMedlineGoogle Scholar43. MELLORSHEIMERCORCOSKORNGOLD RCRJL: Cellular origin of rheumatoid factor. J. Exp. Med. 110: 875, 1959. CrossrefMedlineGoogle Scholar44. FINKMILLERDORWARDLOSPALLUTO CWWEBJ: The formation of macroglobuoin antibodies. II. Studies on neonatal infants and older children. J. Clin. Invest. 41: 1422, 1962. CrossrefMedlineGoogle Scholar45. SMITH RT: Response to active immunization of human infants during the neonatal period, in CIBA Foundation Symposium On Cellular Aspects of Immunity. Edited by Wolstenholme, G. E. W., and O'Connor, M. Little, Brown and Co., Boston, 1960, p. 348. CrossrefGoogle Scholar46. BRIDGESCONDIEZAKGOOD RARMSJRA: The morphologic basis of antibody formation development during the neonatal period. J. Lab. Clin. Med. 53: 331, 1959. MedlineGoogle Scholar47. KUNKEL HG: Macroglobulins and high molecular weight antibodies, in Plasma Proteins, Vol. I, edited by Putnam, F. W., Academic Press, Inc., New York, 1960, p. 279. CrossrefGoogle Scholar48. MÜLLER-EBERHARDKUNKELFRANKLIN HJHGEC: Two types of gamma-globulin differing in carbohydrate content. Proc. Soc. Exp. Biol. Med. 93: 146, 1956. CrossrefMedlineGoogle Scholar49. MÜLLER-EBERHARDKUNKEL HJHG: The carbohydrate of gamma-globulin and myeloma proteins. J. Exp. Med. 104: 253, 1956. CrossrefMedlineGoogle Scholar50. OSSERMANTAKATSUKI EFK: Plasma cell myeloma: Gamma globulin synthesis and structure. Medicine (Baltimore) 42: 357, 1963. CrossrefMedlineGoogle Scholar51. DEUTSCHMORTON HFJI: Human serum macroglobulins and dissociation units. I. Physicochemical properties. J. Biol. Chem. 231: 1107, 1958. CrossrefMedlineGoogle Scholar52. FRANKLINKUNKEL ECHG: Immunologic differences between the 19 S and 7S components of normal human gamma-globulin. J. Immun. 78: 11, 1957. MedlineGoogle Scholar53. KORNGOLDVAN LEEUWEN LG: Macroglobulinemia I. The antigenic relationship of pathological macroglobulins to normal gamma globulins and II. Antisera specific for pathological macroglobulins. J. Exp. Med. 106: 467, 477, 1957. CrossrefMedlineGoogle Scholar54. MORTONDEUTSCH JIHF: Human serum macroglobulins and dissociation units. II. Immunochemical properties. J. Biol. Chem. 231: 1119, 1958. CrossrefMedlineGoogle Scholar55. MACKAY IR: Macroglobulinaemia. Aust. Ann. Med. 5: 244, 1956. CrossrefMedlineGoogle Scholar56. EDELMANBENACERRAF GMB: On structural and functional relations between antibodies and proteins of the gamma-system. Proc. Nat. Acad. Sci. USA 48: 1035, 1962. CrossrefMedlineGoogle Scholar57. PORTER RR: The structure of gamma-globulin and antibodies, in Basic Problems in Neoplastic Disease. Columbia University Press, N. Y., 1962, p. 177. Google Scholar58. FAHEY JL: Structural basis for the differences between Type I and Type II human gamma-globulin molecules. J. Immun. 91: 448, 1963. MedlineGoogle Scholar59. CURTAINO'DEA CCJF: Possible sites of macroglobulin synthesis: a study made with fluorescent antibody. Aust. Ann. Med. 8: 143, 1959. MedlineGoogle Scholar60. CLARKSONBurchenal BDJH: Review—progress in leukemias, in Progress in Clinical Cancer, edited by Ariel, I. Grune and Stratton Inc., New York, 1965, pp. 625-663. Google Scholar61. BENIRSCHKEBROWNHILLEBAUGH KLFG: Chromosomal abnormalities in Waldenström's macroglobulinemia (letter to the editor). Lancet 1: 594, 1962. CrossrefGoogle Scholar62. GERMANBIROBEARN JLCEAG: Chromosomal abnormalities in Waldenström's macroglobulinaemia (letter to the editor). Lancet 2: 48, 1961. CrossrefGoogle Scholar63. ELVESISRAËLS MWMC: Chromosomes and serum proteins. A linked abnormality. Brit. Med. J. 2: 1024, (Oct. 26) 1963. CrossrefMedlineGoogle Scholar64. REISMANZUELZERTHOMPSON LEWWRI: Further observation on the role of aneuploidy in acute leukemia. Cancer Res. 24: 1448, 1964. MedlineGoogle Scholar65. KIOSSOGLOUMITUS KAWJ: Chromosomal aberrations in acute leukemia (abstract). Blood 22: 839, 1963. Google Scholar66. BLOCHPRASADANASTASIBRIGGS HSAADR: Serum protein changes in Waldenström's macroglobulinemia during administration of low molecular weight thiol (penicillamine). J. Lab. Clin. Med. 56: 212, 1960. Google Scholar67. GLENCHURZINNEMANBRIGGS HHHDR: Macroglobulinemia: report of two cases. Ann. Intern. Med. 48: 1055, 1958. LinkGoogle Scholar68. HINES DR: Macroglobulinemia: report of 10 cases. Henry Ford Hosp. Med. Bull. 10: 297, 1962. MedlineGoogle Scholar69. LONGRIOPELLEFRANCCEURPAREPOIRIERGEORGESCOCOLPRON LAJLMAPMG: Macroglobulinaemia. Effect of macroglobulins on prothrombin conversion accelerators. Canad. Med. Ass. J. 73: 726, 1955. MedlineGoogle Scholar70. FERRIMANANDERSON DGAB: Macroglobulinaemia of Waldenström. Brit. Med. J. 2: 402, 1956. CrossrefMedlineGoogle Scholar71. BAYRD ED: Continuous chlorambucil therapy in primary macroglobulinemia of Waldenström: report of 4 cases. Proc. Mayo Clin. 36: 135, 1961. MedlineGoogle Scholar72. CLATANOFFMEYER DVOO: Response to chlorambucil in macroglobulinemia. JAMA 183: 40, 1963. CrossrefMedlineGoogle Scholar73. SNAPPERTURNERMOSCOVITZ ILBHL: Multiple Myeloma. Grune and Stratton, New York, 1953. Google Scholar74. RIVERSWHITTINGTONPATNO SLRMME: Comparison of effect of cyclophosphamide and a placebo in treatment for multiple myeloma. Cancer Chemother. Rep. 29: 115, 1963. MedlineGoogle Scholar75. KORSTWILSONFOWLERWILLCLIFFORDLOUIS DRHEWMJGOJ: Treatment of multiple myeloma. An analysis of cyclophosphamide (cytoxan) therapy in 170 patients (abstract). J. Lab. Clin. Med. 62: 990, 1963. Google Scholar76. LIEBLINGGRIZZLEHAMMACKRUNDLES MEJWRW: Comparison of chlorambucil and prednisone with urethan and prednisone regimens in the treatment of multiple myeloma. Cancer Chemother. Rep. 16: 253, 1962. Google Scholar77. OSSERMAN EF: Therapy of plasma cell myeloma with melphalan (1-phenylalanine mustard) (abstract no. 197). Proc. Amer. Ass. Cancer Res. 4: 50, 1963. Google Scholar78. COSTA G: An assessment of L-phenylalanine mustard in human multiple myeloma (abstract no. 46). Ibid., p. 12. Google Scholar79. BERGSAGELSPRAGUEAUSTINGRIFFITH DECCCKM: Evaluation of new chemotherapeutic agents in the treatment of multiple myeloma. IV. L-Phenylalanine mustard (NSC-8806). Cancer Chemother. Rep. 21: 87, (August) 1962. MedlineGoogle Scholar80. WALDENSTRÖM J: Melphalan treatment of myeloma. Trans. Ass. Amer. Physicians 126: 57, 1963. Google Scholar81. HITCHINGSELION GHGB: Chemical suppression of the immune response. Pharmacol. Rev. 15: 365, June 1963. MedlineGoogle Scholar82. SCHWARTZEISNERDAMESHEK RAW: The effect of 6-mercaptopurine on primary and secondary immune responses. J. Clin. Invest. 38: 1394, 1959. CrossrefMedlineGoogle Scholar83. LAPLANTECONDIEGOOD ESRMRA: Prevention of secondary immune response with 6-mercaptopurine. J. Lab. Clin. Med. 59: 542, 1962. MedlineGoogle Scholar84. WOLFFGOODMAN SMHC: Effect of purine antimetabolites on serum globulins in the rabbit (28062). Proc. Soc. Exp. Biol. Med. 112: 416, 1963. CrossrefMedlineGoogle Scholar85. WOLFFGOODMAN SMHC: "Hypogamma globulinemia" produced by the administration of 6-thioguanine to patients with nephrosis (abstract). J. Clin. Invest. 41: 1413, 1962. Google Scholar86. LEEMEISELASZINGALERICHMAN SLLESBSM: Effect of 6-mercaptopurine administration on antibody production and clinical course in systemic lupus erythematosus. Report of a case. Arthritis Rheum. 4: 56, 1961. CrossrefMedlineGoogle Scholar87. EISENDEMISCROSBY BDJWH: Thioguanine therapy: systemic lupus erythematosus, atopic dermatitis and other nonmalignant diseases. JAMA 179: 789, 1962. MedlineGoogle Scholar88. SCHWARTZDAMESHEK RW: The treatment of autoimmune hemolytic anemia with 6-mercaptopurine and thioguanine. Blood 19: 483, 1962. CrossrefMedlineGoogle Scholar89. WEISSDEMISELGARTBROWNCROSBY HJDJMLCSWH: Treatment of two cases of hyperglobulinemic purpura with thioguanine. New Eng. J. Med. 268: 753, 1963. CrossrefMedlineGoogle Scholar90. ANDRÉSCHWARTZMITUSDAMESHEK JARSWJW: The morphologic responses of the lymphoid system to homografts I. First and second set responses in normal rabbits. II. The effects of antimetabolites. Blood 19: 313, 334, 1962. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: New York, New YorkFrom the Division of Clinical Chemotherapy, Sloan-Kettering Institute for Cancer Research, the Departments of Medicine, Memorial Hospital for Cancer and Allied Diseases and James Ewing Hospital, and the Sloan-Kettering Division of the Graduate School of Medical Sciences, Cornell University Medical College, New York, N. Y.This investigation was supported in part by research grant CA-03215 from the National Institutes of Health, U. S. Public Health Service, Bethesda, Md.Requests for reprints should be addressed to Dr. Bayard Clarkson, Sloan-Kettering Institute for Cancer Research, 425 E. 68th Street, New York, N. Y. 10021. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByImmunoblastic lymphoma and associated non-lymphoid malignancies following two cases of Waldenström's macroglobulinemia. A review of the literatureChanges in the appearance of hematopoietic and lymphoid neoplasms: Clinical, pathologic, and biologic implicationsB-Lymphoproliferative disorders: A Proposed unified pathogenetic pathway“Waldenström's macroglobulinemia” terminating in immunoblastic sarcoma: A case reportKlinik der malignen LymphomeCase 6-1978Biology, Clinical Patterns, and Treatment of Multiple Myeloma and Related Plasma–Cell DyscrasiasConstipated plasma cells associated with monomeric macroglobulinemiaLymphosarcoma of the lung with monoclonal (IgM) gammopathy.A clinicopathologic, histochemical, immunologic, and ultrastructural studyRETICULUM CELL SARCOMA IN WALDENSTRÖM'S MACROGLOBULINEMIA AFTER CHLORAMBUCIL TREATMENTTHERAPY OF MACROGLOBULINAEMIAPrimary macroglobulinemiaDysimmunoglobulinemia in the absence of clinical features of multiple myeloma and macroglobulinemiaWaldenström's macroglobulinemia 1 May 1965Volume 62, Issue 5Page: 1025-1045KeywordsBloodCancer chemotherapyCellsHospital medicineLymphocytesPrevention, policy, and public healthProteinsResearch grantsSarcomaSpleen Issue Published: 1 May 1965 PDF DownloadLoading ...