Acta haemat. 55: 123-128 (1976)
Plasmocytoma with IgM Paraproteinemia. A Case Report E nzo F agiolo Istituto di Clinica Medica, Universita Cattolica del Sacro Cuore, Roma
Key Words. Macroglobulinemia • Paraproteins • Plasmocytoma Abstract. A case of typical diffuse plasmocytoma with IgM paraproteinemia is described. The patient presented with systemic and monomorphic proliferation of atypical and immature plasma cells, osteolytic lesions, retinal venous thrombosis and hemorrhagic diathesis. The therapy with steroids and alkeran produced clinical and hematological remission for 1'/2 year with a decrease of macroglobulins in the serum. Cell and paraprotein type remained unchanged during the course of the dis ease. This case, and similar ones already reported in the literature, suggest that neo plastic plasma cell proliferation is accompanied by synthesis of paraproteins including the IgM type. However, this is not characteristic for Waldenstrom’s macroglobulinemia. The author concludes that differential diagnosis in these cases can only be made by cytologic examination.
Proliferating neoplastic plasma cells synthesize ‘monoclonal’ immu noglobulins of different types (G, A, M, D, E), and/or exclusively light chains. IgM plasmocytoma is very rare, thus differential diagnostic prob lems with Waldenstrom’s macroglobulinemia might arise. Monoclonal macroglobulinemia has been found in patients showing atypical cytological findings resembling those of Waldenstrom’s cases, and in some pa tients with typical plasmocytoma. These cases have been differently inter preted and classified. In this paper, a typical case of diffuse plasmocyto ma with IgM paraproteinemia, hemorrhagic diathesis and osteolytic le sions is described.
Patient M. B., a 53-year-old man, admitted to the Policlinico Gemelli in October 1969 wtih a 4-month history of recurrent bronchitis, pallor, progressive reduction of
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Case Report
124
Fig. 1. Sternal Giemsa. X 800.
F agiolo
marrow:
proplasmocytes and
plasmoblasts.
May-Griinwald-
vision and repeated epistaxis. On physical examination, he presented great pallor and apical systolic murmur. Examination of the fundus revealed bilateral thrombo sis of central retinal veins. Erythrocytes, 1,860,000///1; Hb, 4.2 g%; white blood cells, 5.800///1 with 40% neutrophils, 53°/o lymphocytes, 5% monocytes, 2%> myelocytes. Erythrocytes present ed anisocytosis and rouleaux formation. Platelets, 80,000///1. Sternal puncture showed marked cellularity, 70% of which composed mostly by proplasmocytes and by some plasmablasts with light basophilia, generally eccentric nuclei and prominent rate, 90 mm/h. Total serum proteins, 11.6°/o. Serum electrophoresis on cellulose acetate showed: albumin, 27%; «,-globulin, 3%; a2-globulin, 6%; //-globulin, 7%; y-globulin, 57%. The y-peak is of the ‘monoclonal’ type. The serum immunoelectrophoresis with polyvalent and specific immunoglobulin antisera IgG, IgA, lgM, IgD, IgE showed a very thin but normal IgG and IgA precipitation line, while the lgM line was deformed and very thick (fig. 2). The macroglobulins separated on Sephadex G-200 were formed by light chains of the A"-type. Immunoglobulin levels with radial immunodiffusion: IgG, 160 mg%; IgA, 20 mg%; IgM, 4,200 mg%. Serum ultracentrifugation showed a large fraction (40.5%) of 16.7 S. The serum kept at 4 °C showed a modest amount of cryoglobulin precipitate. The SIA test was positive. There was no proteinuria. Tourniquet test was negative, bleeding time,
Downloaded by: East Carolina University - Laupus Library 150.216.68.200 - 1/16/2019 7:21:55 AM
nucleoli (fig. 1). The norm al myeloid cells were altogether scarce. Sedimentation
Plasmocytoma with IgM Paraproteinemia
125
/ /
1X
6 min, coagulation time, 3 min 30 sec; Quick time, 19 sec; prothrombin activity, 35°/o; fibrinogen, 70 mg°/o. Thromboelastogram showed R, 24 min and MA, 20 mm. Blood urea nitrogen, 18 mg°/o; creatinin clearance, 126 ml/min; blood calcium, 9.6 mg°/o; total cholesterol, 75 mg0/«. Complete and incomplete erythrocyte antibod ies were absent. Rheuma and Waler Rose tests were negative. X-ray examination of chest bones, vertebral column and skull showed no alterations. The patient was treated with blood transfusions, prednisone (lOOmg/day) and alkcran (8 mg/day). Clinical conditions progressively ameliorated and after several therapy cycles, the situation was as follows (October 1970): erythrocytes, 4,700,000/ »1; Hb, 14.3 g°/o; white blood cells, 5,900/ul; platelets, 340,000/nl. Total serum pro teins, 6.8 g%> with 26°/o of /-globulins. Immunoglobulin levels: IgG, 400 mg°/o; IgA. 13mg°/o; IgM, 440°/o. The sternal marrow showed repopulation of normal myeloid cells, with 17%> plasma cells. The coagulation tests were normal. In June 1971, the patient commenced to suffer from progressive chest pains, fe ver, pallor and epistaxis. X-ray examination showed marked osteoporosis of the ver tebral column and ribs, conical crush of thoracic vertebrae VI, VII and XI and microalveolar skull structure. The patient was again admitted and treated as previous ly but his clinical conditions worsened (anemia, bone lesions, hemorrhagic diathesis with epistaxis, hematemesis and melena). In December 1971, the following data were available: erythrocytes, 2,600,000/«!; Hb, 7.2 g°/o; white blood cells, 4,500/ mI; platelets, 80,000/,« 1. Total serum proteins, 12.3 g%>. Serum electrophoresis showed 61°/o /-globulins with monoclonal peaks. Immunoglobulin levels: IgG, 140 mg°/o, IgA, 30 mg°/o; IgM, 3,800 mg°/o. Immunoelectrophoresis showed a deformed and very thick IgM line. Quick time. 15 sec; prothrombin activity, 62%>; fibrinogen, 86 m°/o; coagulation time, 12 min; bleeding time, 5 min. Blood calcium, 13mg°/o. There was no proteinuria. The sternal marrow was composed almost exclusively by plasma cells. The patient died in February 1972. Autopsy revealed pulmonary edema with bi lateral pneumonic foci, turbid myocardosis, gastric and intestinal hemorrhages, splenomegaly with hyperplasia of the red pulp and indistinct Malpighian bodies, plasma cell nodules in the vertebrae and ribs. Histology showed plasma cell infiltra tions in vertebrae, ribs, liver, spleen and kidneys (fig. 3).
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Fig. 2. Immunoelectrophoretic patterns of serum proteins with specific IgM rab bit antiserum.
126
F agiolo
b
a
Fig. 3. Histologic patterns: monomorphic infiltration of plasma cells in the spleen (a) and the dorsal vertebrae (b). HE. X 400.
The described case is a diffuse plasmocytoma characterized by (1) monomorphic proliferation of atypical immature plasma cells in the bone marrow, liver, spleen and kidneys; (2) osteolytic lesions in the skull, ver tebrae and ribs, and (3) hemorrhagic diathesis with prolonged bleeding and coagulation times, reduced prothrombin activity and hypofibrinogenemia. An early symptom was reduction of vision due to bilateral thrombosis of central retinal veins. Paraproteinemia was of IgM type, A'-light-chains, 16.7 S. The cellular aspects and paraprotein pattern re mained constant during the course of the disease, although they were quantitatively reduced by steroid and alkeran therapy which induced a 1Vo-ycar period of clinical and hematological remission. The case presented the typical cellular aspect of plasmocytoma and the paraprotein type of Waldenstrom’s macroglobulinemia. Difficulty arised for differential diagnosis and nosologic classification since some cases considered as plasmocytoma or plasma cell leukemia with macroglobulin-
Downloaded by: East Carolina University - Laupus Library 150.216.68.200 - 1/16/2019 7:21:55 AM
Discussion
Plasmocytoma with IgM Paraproteinemia
127
emia, presented histologic aspects of the lympho-plasmocytic or lymphoreticulo-plasmocytic type, intermediate between plasmocytoma and Wal denstrom’s macroglobulinemia [4, 8, 9, 14]. These cases, however, because of the cellular polymorphism they present are closer to Waldenstrom’s disease than to plasmocytoma. It should also be considered that in these cases, it is difficult to establish if the synthesis of ‘monoclonal’ immuno globulins is due to neoplastic immunocompetent cells or to immunologically reactive phenomena. Moreover, recent studies have shown the frequency of osteolytic lesions in Waldenstrom’s macroglobulinemia, similar to those found in plasmocytoma [15]. On the other hand, the existence of typical diffuse plasmocytoma with IgM paraproteinemia has been demonstrated [1, 2, 11, 13, 16], IgG and IgM double paraproteinemia has been recognized in 1 case of diffuse plas mocytoma [10], in liver solitary plasmocytoma [12] and in plasma cell leukemia [6]. IgM paraproteinemia and IgG heavy chains have been found in 1 case of plasma cell leukemia [5], All these cases, plus the ex perimental evidence in BALB mice [3, 7], show that neoplastic plasma cells can synthesize IgM as well as the other types of immunoglobulins. Therefore, the presence of a certain immunoglobulin type alone cannot differentiate the various paraproteinemic diseases. The terms ‘Waldenstrom’s macroglobulinemia type’ or ‘myeloma type’ paraprotein are thus unsuitable to designate the ‘monoclonal’ synthesis of IgM or of the other classes of immunoglobulins. Since the presence of IgM parapro teinemia is by no means pathognomonic of Waldenstrom’s disease and since osteolytic lesions are not exclusive of plasmocytoma, differential di agnosis and classification of the different forms of paraproteinemic hemoblastoses can be best made by cytologic examination.
Acknowledgements. The author thanks Dr. L ucia Q uintiliani (National Red Cross Blood Transfusion Center) for kindly providing ultracentrifugation data.
References
sis. Acta med. scand. 168: 431^437 (1960). 2 Bureau, Y.; Senelar, R.; Barriere, H.; Bureau, B.; L itoux , P. et Bray, B.: Ma croglobulinémie au cours d’une maladie de Kahler. Presse méd. 76: 961-964 (1968).
Downloaded by: East Carolina University - Laupus Library 150.216.68.200 - 1/16/2019 7:21:55 AM
1 A dner , L.; W allenius , G., and W erner , I.: Macroglobulinemia and myelomato
128
F agiolo
Prof. E nzo F agiolo, Istituto di Clínica Medica, Universitá Cattolica del Sacro Cuore, 526, Via della Pineta Sacchetti, 1-00168 Roma (Italy)
Downloaded by: East Carolina University - Laupus Library 150.216.68.200 - 1/16/2019 7:21:55 AM
3 Buxbaum, J. and Schraff , M. D.: The synthesis, assembly and secretion of gam ma globulin by mouse myeloma cells. VI. Assembly of IgM proteins. J. exp. Med. 138: 278-288 (1973). 4 C reyssf.l, R.; C harvillat, L.; M orel, P.; M atray, F.; M ende , S. de et C roizat, P.: Myélome multiple et dysprotéinémies malignes. Revue lyonn. Méd. 5: 119-171 (1956). 5 K eller , K.; Splenglf.r , G. A.; Skvaril, F.; F llry , W.; N oseda, G. und R iva, G.: Zur Frage der Heavy chain disease. Ein Fall von IgG-heavy-chain-Fragment und IgM-Typ K-Paraproteinämie mit Plasmazellenleukämie. Schweiz, med. Wschr. WO: 1012-1022 (1970). 6 M archal, G.; F ine, J. M. et Bilski-P asquier, G.: Macroglobulinémie dans un cas de leucose plasmocytaire. Presse méd. 70: 425-428 (1962). 7 M c I ntire , K. R.; A sofski, R. M.; Potter , M., and K liff, E. L.: Macroglobulinproducing plasma-cell tumor in mice: identification of a new light chain. Science, N.Y. 150: 361-363 (1965). 8 Mc N utt , D. R. and F udenberg , H. H.: IgG myeloma with Waldenstrom macroglobulinemia. Archs intern. Med. 131: 731-734 (1973). 9 M oeschlin , S.: Macroglobulinemia Waldenstrom with miliary lung infiltrations and terminal plasma cell-leukemia. Acta med. scand. 445: suppl., pp. 154—162 (1966). 10 P enn , G. M.; K unkel , H. G., and G rey, H. M.: Sharing of individual antigenic determinants between an yG and a yM protein in the same myeloma serum. Proc. Soc. exp. Biol. Med. 135: 660-665 (1970). 11 P ignataro, L.; Bolognesi, G.; M arinoni, G. F. e R izza, O.: Presenza di macroglobulina patologica e fisiologica in un caso di plasmocitoma. Boll. Soc. ital. Biol. sper. 28: 228-230 (1962). 12 P ruzanski, W.; U nderdown , B.; S ilver, E. H., and K atz, A.: Macroglobulinemia-myeloma double gammapathy. Am. J. Med. 57: 259-266 (1974). 13 R aynaud, R.; Brochier , M.; G riguer , P. et T adei, A.: Sur un cas associant la maladie de Kahler et la macroglobulinémie. Sang 30: 822-830 (1959). 14 V anner, J. und S iedenmann , R.: Uber eine subacut verlaufende osteolytische Form der Makroglobulinämie Waldenstrom mit Plasmazellenleukämie. Schweiz, med. Wschr. 87: 1243-1246 (1957). 15 V ermess, M.; P earson, K. D.; E instein , A. B., and F ahey, J. L.: Osseous mani festation in Waldenstrom’s macroglobulinemia. Radiology 102: 497-504 (1972). 16 W elton , J.; W alker, S. R.; Scharf, C.; H erenberg, L. A.; W istar, R„ and G reger , W. P.: Macroglobulinemia with bone destruction. Am. J. Med. 44: 280-288 (1968).
Plasmocytoma with IgM Paraproteinemia. A Case Report E nzo F agiolo Istituto di Clinica Medica, Universita Cattolica del Sacro Cuore, Roma
Key Words. Macroglobulinemia • Paraproteins • Plasmocytoma Abstract. A case of typical diffuse plasmocytoma with IgM paraproteinemia is described. The patient presented with systemic and monomorphic proliferation of atypical and immature plasma cells, osteolytic lesions, retinal venous thrombosis and hemorrhagic diathesis. The therapy with steroids and alkeran produced clinical and hematological remission for 1'/2 year with a decrease of macroglobulins in the serum. Cell and paraprotein type remained unchanged during the course of the dis ease. This case, and similar ones already reported in the literature, suggest that neo plastic plasma cell proliferation is accompanied by synthesis of paraproteins including the IgM type. However, this is not characteristic for Waldenstrom’s macroglobulinemia. The author concludes that differential diagnosis in these cases can only be made by cytologic examination.
Proliferating neoplastic plasma cells synthesize ‘monoclonal’ immu noglobulins of different types (G, A, M, D, E), and/or exclusively light chains. IgM plasmocytoma is very rare, thus differential diagnostic prob lems with Waldenstrom’s macroglobulinemia might arise. Monoclonal macroglobulinemia has been found in patients showing atypical cytological findings resembling those of Waldenstrom’s cases, and in some pa tients with typical plasmocytoma. These cases have been differently inter preted and classified. In this paper, a typical case of diffuse plasmocyto ma with IgM paraproteinemia, hemorrhagic diathesis and osteolytic le sions is described.
Patient M. B., a 53-year-old man, admitted to the Policlinico Gemelli in October 1969 wtih a 4-month history of recurrent bronchitis, pallor, progressive reduction of
Downloaded by: East Carolina University - Laupus Library 150.216.68.200 - 1/16/2019 7:21:55 AM
Case Report
124
Fig. 1. Sternal Giemsa. X 800.
F agiolo
marrow:
proplasmocytes and
plasmoblasts.
May-Griinwald-
vision and repeated epistaxis. On physical examination, he presented great pallor and apical systolic murmur. Examination of the fundus revealed bilateral thrombo sis of central retinal veins. Erythrocytes, 1,860,000///1; Hb, 4.2 g%; white blood cells, 5.800///1 with 40% neutrophils, 53°/o lymphocytes, 5% monocytes, 2%> myelocytes. Erythrocytes present ed anisocytosis and rouleaux formation. Platelets, 80,000///1. Sternal puncture showed marked cellularity, 70% of which composed mostly by proplasmocytes and by some plasmablasts with light basophilia, generally eccentric nuclei and prominent rate, 90 mm/h. Total serum proteins, 11.6°/o. Serum electrophoresis on cellulose acetate showed: albumin, 27%; «,-globulin, 3%; a2-globulin, 6%; //-globulin, 7%; y-globulin, 57%. The y-peak is of the ‘monoclonal’ type. The serum immunoelectrophoresis with polyvalent and specific immunoglobulin antisera IgG, IgA, lgM, IgD, IgE showed a very thin but normal IgG and IgA precipitation line, while the lgM line was deformed and very thick (fig. 2). The macroglobulins separated on Sephadex G-200 were formed by light chains of the A"-type. Immunoglobulin levels with radial immunodiffusion: IgG, 160 mg%; IgA, 20 mg%; IgM, 4,200 mg%. Serum ultracentrifugation showed a large fraction (40.5%) of 16.7 S. The serum kept at 4 °C showed a modest amount of cryoglobulin precipitate. The SIA test was positive. There was no proteinuria. Tourniquet test was negative, bleeding time,
Downloaded by: East Carolina University - Laupus Library 150.216.68.200 - 1/16/2019 7:21:55 AM
nucleoli (fig. 1). The norm al myeloid cells were altogether scarce. Sedimentation
Plasmocytoma with IgM Paraproteinemia
125
/ /
1X
6 min, coagulation time, 3 min 30 sec; Quick time, 19 sec; prothrombin activity, 35°/o; fibrinogen, 70 mg°/o. Thromboelastogram showed R, 24 min and MA, 20 mm. Blood urea nitrogen, 18 mg°/o; creatinin clearance, 126 ml/min; blood calcium, 9.6 mg°/o; total cholesterol, 75 mg0/«. Complete and incomplete erythrocyte antibod ies were absent. Rheuma and Waler Rose tests were negative. X-ray examination of chest bones, vertebral column and skull showed no alterations. The patient was treated with blood transfusions, prednisone (lOOmg/day) and alkcran (8 mg/day). Clinical conditions progressively ameliorated and after several therapy cycles, the situation was as follows (October 1970): erythrocytes, 4,700,000/ »1; Hb, 14.3 g°/o; white blood cells, 5,900/ul; platelets, 340,000/nl. Total serum pro teins, 6.8 g%> with 26°/o of /-globulins. Immunoglobulin levels: IgG, 400 mg°/o; IgA. 13mg°/o; IgM, 440°/o. The sternal marrow showed repopulation of normal myeloid cells, with 17%> plasma cells. The coagulation tests were normal. In June 1971, the patient commenced to suffer from progressive chest pains, fe ver, pallor and epistaxis. X-ray examination showed marked osteoporosis of the ver tebral column and ribs, conical crush of thoracic vertebrae VI, VII and XI and microalveolar skull structure. The patient was again admitted and treated as previous ly but his clinical conditions worsened (anemia, bone lesions, hemorrhagic diathesis with epistaxis, hematemesis and melena). In December 1971, the following data were available: erythrocytes, 2,600,000/«!; Hb, 7.2 g°/o; white blood cells, 4,500/ mI; platelets, 80,000/,« 1. Total serum proteins, 12.3 g%>. Serum electrophoresis showed 61°/o /-globulins with monoclonal peaks. Immunoglobulin levels: IgG, 140 mg°/o, IgA, 30 mg°/o; IgM, 3,800 mg°/o. Immunoelectrophoresis showed a deformed and very thick IgM line. Quick time. 15 sec; prothrombin activity, 62%>; fibrinogen, 86 m°/o; coagulation time, 12 min; bleeding time, 5 min. Blood calcium, 13mg°/o. There was no proteinuria. The sternal marrow was composed almost exclusively by plasma cells. The patient died in February 1972. Autopsy revealed pulmonary edema with bi lateral pneumonic foci, turbid myocardosis, gastric and intestinal hemorrhages, splenomegaly with hyperplasia of the red pulp and indistinct Malpighian bodies, plasma cell nodules in the vertebrae and ribs. Histology showed plasma cell infiltra tions in vertebrae, ribs, liver, spleen and kidneys (fig. 3).
Downloaded by: East Carolina University - Laupus Library 150.216.68.200 - 1/16/2019 7:21:55 AM
Fig. 2. Immunoelectrophoretic patterns of serum proteins with specific IgM rab bit antiserum.
126
F agiolo
b
a
Fig. 3. Histologic patterns: monomorphic infiltration of plasma cells in the spleen (a) and the dorsal vertebrae (b). HE. X 400.
The described case is a diffuse plasmocytoma characterized by (1) monomorphic proliferation of atypical immature plasma cells in the bone marrow, liver, spleen and kidneys; (2) osteolytic lesions in the skull, ver tebrae and ribs, and (3) hemorrhagic diathesis with prolonged bleeding and coagulation times, reduced prothrombin activity and hypofibrinogenemia. An early symptom was reduction of vision due to bilateral thrombosis of central retinal veins. Paraproteinemia was of IgM type, A'-light-chains, 16.7 S. The cellular aspects and paraprotein pattern re mained constant during the course of the disease, although they were quantitatively reduced by steroid and alkeran therapy which induced a 1Vo-ycar period of clinical and hematological remission. The case presented the typical cellular aspect of plasmocytoma and the paraprotein type of Waldenstrom’s macroglobulinemia. Difficulty arised for differential diagnosis and nosologic classification since some cases considered as plasmocytoma or plasma cell leukemia with macroglobulin-
Downloaded by: East Carolina University - Laupus Library 150.216.68.200 - 1/16/2019 7:21:55 AM
Discussion
Plasmocytoma with IgM Paraproteinemia
127
emia, presented histologic aspects of the lympho-plasmocytic or lymphoreticulo-plasmocytic type, intermediate between plasmocytoma and Wal denstrom’s macroglobulinemia [4, 8, 9, 14]. These cases, however, because of the cellular polymorphism they present are closer to Waldenstrom’s disease than to plasmocytoma. It should also be considered that in these cases, it is difficult to establish if the synthesis of ‘monoclonal’ immuno globulins is due to neoplastic immunocompetent cells or to immunologically reactive phenomena. Moreover, recent studies have shown the frequency of osteolytic lesions in Waldenstrom’s macroglobulinemia, similar to those found in plasmocytoma [15]. On the other hand, the existence of typical diffuse plasmocytoma with IgM paraproteinemia has been demonstrated [1, 2, 11, 13, 16], IgG and IgM double paraproteinemia has been recognized in 1 case of diffuse plas mocytoma [10], in liver solitary plasmocytoma [12] and in plasma cell leukemia [6]. IgM paraproteinemia and IgG heavy chains have been found in 1 case of plasma cell leukemia [5], All these cases, plus the ex perimental evidence in BALB mice [3, 7], show that neoplastic plasma cells can synthesize IgM as well as the other types of immunoglobulins. Therefore, the presence of a certain immunoglobulin type alone cannot differentiate the various paraproteinemic diseases. The terms ‘Waldenstrom’s macroglobulinemia type’ or ‘myeloma type’ paraprotein are thus unsuitable to designate the ‘monoclonal’ synthesis of IgM or of the other classes of immunoglobulins. Since the presence of IgM parapro teinemia is by no means pathognomonic of Waldenstrom’s disease and since osteolytic lesions are not exclusive of plasmocytoma, differential di agnosis and classification of the different forms of paraproteinemic hemoblastoses can be best made by cytologic examination.
Acknowledgements. The author thanks Dr. L ucia Q uintiliani (National Red Cross Blood Transfusion Center) for kindly providing ultracentrifugation data.
References
sis. Acta med. scand. 168: 431^437 (1960). 2 Bureau, Y.; Senelar, R.; Barriere, H.; Bureau, B.; L itoux , P. et Bray, B.: Ma croglobulinémie au cours d’une maladie de Kahler. Presse méd. 76: 961-964 (1968).
Downloaded by: East Carolina University - Laupus Library 150.216.68.200 - 1/16/2019 7:21:55 AM
1 A dner , L.; W allenius , G., and W erner , I.: Macroglobulinemia and myelomato
128
F agiolo
Prof. E nzo F agiolo, Istituto di Clínica Medica, Universitá Cattolica del Sacro Cuore, 526, Via della Pineta Sacchetti, 1-00168 Roma (Italy)
Downloaded by: East Carolina University - Laupus Library 150.216.68.200 - 1/16/2019 7:21:55 AM
3 Buxbaum, J. and Schraff , M. D.: The synthesis, assembly and secretion of gam ma globulin by mouse myeloma cells. VI. Assembly of IgM proteins. J. exp. Med. 138: 278-288 (1973). 4 C reyssf.l, R.; C harvillat, L.; M orel, P.; M atray, F.; M ende , S. de et C roizat, P.: Myélome multiple et dysprotéinémies malignes. Revue lyonn. Méd. 5: 119-171 (1956). 5 K eller , K.; Splenglf.r , G. A.; Skvaril, F.; F llry , W.; N oseda, G. und R iva, G.: Zur Frage der Heavy chain disease. Ein Fall von IgG-heavy-chain-Fragment und IgM-Typ K-Paraproteinämie mit Plasmazellenleukämie. Schweiz, med. Wschr. WO: 1012-1022 (1970). 6 M archal, G.; F ine, J. M. et Bilski-P asquier, G.: Macroglobulinémie dans un cas de leucose plasmocytaire. Presse méd. 70: 425-428 (1962). 7 M c I ntire , K. R.; A sofski, R. M.; Potter , M., and K liff, E. L.: Macroglobulinproducing plasma-cell tumor in mice: identification of a new light chain. Science, N.Y. 150: 361-363 (1965). 8 Mc N utt , D. R. and F udenberg , H. H.: IgG myeloma with Waldenstrom macroglobulinemia. Archs intern. Med. 131: 731-734 (1973). 9 M oeschlin , S.: Macroglobulinemia Waldenstrom with miliary lung infiltrations and terminal plasma cell-leukemia. Acta med. scand. 445: suppl., pp. 154—162 (1966). 10 P enn , G. M.; K unkel , H. G., and G rey, H. M.: Sharing of individual antigenic determinants between an yG and a yM protein in the same myeloma serum. Proc. Soc. exp. Biol. Med. 135: 660-665 (1970). 11 P ignataro, L.; Bolognesi, G.; M arinoni, G. F. e R izza, O.: Presenza di macroglobulina patologica e fisiologica in un caso di plasmocitoma. Boll. Soc. ital. Biol. sper. 28: 228-230 (1962). 12 P ruzanski, W.; U nderdown , B.; S ilver, E. H., and K atz, A.: Macroglobulinemia-myeloma double gammapathy. Am. J. Med. 57: 259-266 (1974). 13 R aynaud, R.; Brochier , M.; G riguer , P. et T adei, A.: Sur un cas associant la maladie de Kahler et la macroglobulinémie. Sang 30: 822-830 (1959). 14 V anner, J. und S iedenmann , R.: Uber eine subacut verlaufende osteolytische Form der Makroglobulinämie Waldenstrom mit Plasmazellenleukämie. Schweiz, med. Wschr. 87: 1243-1246 (1957). 15 V ermess, M.; P earson, K. D.; E instein , A. B., and F ahey, J. L.: Osseous mani festation in Waldenstrom’s macroglobulinemia. Radiology 102: 497-504 (1972). 16 W elton , J.; W alker, S. R.; Scharf, C.; H erenberg, L. A.; W istar, R„ and G reger , W. P.: Macroglobulinemia with bone destruction. Am. J. Med. 44: 280-288 (1968).
