Acta haemat. 5S: 307-311 (1977)

Macroglobulinemia of Waldenstrom Associated with Severe Osteolytic Lesions1 Y odphat K rausz and A vinoam Z lotnick Department of Medicine A, Hadassah University Hospital and Medical School, Jerusalem

Key Words. Macroglobulinemia • Osteolytic lesions Abstract. Osteolytic lesions are not known to be associated with chronic lympho­ cytic leukemia and are rare in macroglobulinemia of Waldenstrom. In the present paper we report a patient suffering from macroglobulinemia associated with chronic lymphocytic leukemia in whom osteolytic lesions, resembling those of multiple mye­ loma were found. Treatment with chlorambucil resulted in normalization of the peripheral blood smear, but the malignant infiltration of the bone marrow contin­ ued and manifested itself by appearance of new osteolytic lesions, though some of the old lesions underwent recalcification after treatment.

Macroglobulinemia of Waldenstrom, first described in 1944 [11] was considered to be free of osteolytic lesions and this criterion was used to differentiate it from multiple myeloma [2, 3, 10, 12]. Recently, several re­ ports [4, 6, 7, 9, 10] have indicated that osteolytic lesions are part of this disease spectrum. In the present paper we report an unusual case of ma­ croglobulinemia associated with chronic lymphocytic leukemia in whom severe osteolytic lesions resembling those of multiple myeloma were found. These lesions underwent partial recalcification after treatment.

Case Report M. R., a 68-year-old woman was hospitalized elsewhere in 1969 for generalized lymphadenopathy, splenomegaly and 20,000 WBC/mI with 80°/o lymphocytes (table

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< This paper was supported in part by a grant from the Joint Research Fund of the Hebrew University and Hadassah.

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K rausz/Z lotnick

Table I. Laboratory findings Date

HB WBC g/dl per/d

Mono. Lymph. Band Neutr. Eosin. IgG IgA IgM % % % % % mg/dl mg/dl mg/dl

1969 20,000 1 Oct. 1973 13 13,000 2 Dec. 1973 9.5 3,500 9 13.4 9,200 4 June 1974 March 1975 11.6 4,200 17

80 63 45 22 5

1 2 9

2 -

16 29 9

67 76

2 4 9

5 2

_ -

470 -

620

-

76 -

109

_ -

380 -

190

Fig. I. Immunoelectrophoresis of the patient serum in the central well and of a normal control serum in the outer well. The lower trough contains an anti-whole human serum and the upper trough - an anti-IgM serum. Note the pathological configuration of the IgM of the patient, marked by an arrow. Fig. 2. X-ray of the skull before treatment. Note the extensive osteolytic lesions. Fig. 3. X-ray of the skull after treatment. Note the recalcification of many of the lesions.

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I). A diagnosis of chronic lymphatic leukemia was made and no treatment was giv­ en. In 1972 she was admitted for severe oral moniliasis. Her bone marrow was infil­ trated with small lymphocytes and a monoclonal IgM was detected in the serum. She was given chlorambucil and remained asymptomatic until 1973 when she was admitted to Hadassah University Hospital because of bone pain and extreme fa­ tigue. The main physical findings were pallor, palpable masses on the skull, en larged lymph nodes in the neck, axillae and groins and palpable liver (3 cm) and spleen (5 cm) below the costal margin. Her sedimentation rate was 85/120, hemoglobin 9.5 g/dl, WBC 3,500/nl with 45°/o lymphocytes (table 1). Total protein 6.1 g/dl with albumin 3.2 g/dl and globulin 2.9 g/dl. Calcium 7.5-8 mg/dl and alkaline phosphatase 550IU/ml, mainly of bone origin (normal 80). On serum electrophoresis there was a monoclonal protein fraction between the fi- and the y-region, which was identified as IgM type K (fig. 1). The serum level of IgG was 470 mg/dl, IgA 76 mg/dl and IgM 380 mg/dl (table I). A skeletal survey revealed osteolytic lesions in the skull (fig. 2), distal part of right humerus and radius and compressed fracture of the 12th thoracic vertebra. The bone marrow was infiltrated by small lymphocytes and plasma cells. The patient was diagnosed as suffering from Waldenstrom's macroglobulinemia and was treated with chlorambucil, vitamin D and calcium supplement. During the following 6 months, the Hb level rose to 13.4 g/dl, WBC 9,200 with a normal dif­ ferential count (table I). The tumor masses in the skull disappeared and the osteoly­ tic lesions declined in size (fig. 3). The patient discontinued treatment on her own and 2 months later a tumor mass appeared in the right mandible which on biopsy

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Macroglobulinemia of Waldenstrom with Severe Osteolytic Lesions 309

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proved to be a non-Hodgkin lymphoma. It regressed following local X-ray irradia­ tion. The patient remained well on chlorambucil therapy until November 1974, when she complained of severe low back pain and difficulty in walking. X-ray examina­ tion disclosed osteolytic lesions in the right ilium. Local irradiation resulted in a mild symptomatic relief. In January 1975, she was readmitted because of recurrence of tumors in the skull. Hepatosplenomegaly was evident, without lymphadenopathy. The paraprotein persisted. The immunoglobulin levels were IgG 620 mg/dl, IgA 109 mg/dl and IgM 190 mg/dl. Calcium 12.2 mg/dl and alkaline phosphatase 170 IU/ml. The patient was given combined chemotherapy with BCNU, endoxan, leukeran and prednisone. In addition she was treated parenterally with fluids, corticosteroids and furosemide. However, she died in hypercalcemic coma within several days.

Macroglobulinemia was first described by W aldenstrom in 1944 [11]. Since then, several reviews dealing with this disease have been pub­ lished [2-4, 6-10, 12]. The association of macroglobulinemia with chron­ ic lymphocytic leukemia has been reported [13] and it has been suggested that macroglobulinemia and chronic lymphatic leukemia are the expres­ sions of the same disease entity. The finding of IgM markers on the sur­ face of the lymphocytes of chronic lymphatic leukemia lend further sup­ port to this contention. Our case started as chronic lymphatic leukemia with an IgM parapro­ tein. Treatment with chlorambucil arrested or rather ‘cured’ the leukemic process but did not arrest the proliferation of the cells in the bone marrow which led to osteolytic lesions in different bones. Osteolytic lesions in ma­ croglobulinemia are considered to be very rare [2, 3, 8, 10, 12]. Howev­ er, recently, several reports have been published stressing the presence of small osteolytic lesions in this disease [4, 6, 7, 9]. Our case is conspicuous in that the osteolytic lesions were very large and are compatible with those found in multiple myeloma. This diagnosis was ruled out by repeated bone marrow biopsies, which showed the presence of lymphoid cells char­ acteristic of a lymphomatous process. Therapy with chlorambucil or X-rays, together with vitamin D and calcium led, in the beginning, to the disappearance of the tumors of the skull and the mandible and recalcification of the osteolytic lesions. This is most remarkable and to the best of our knowledge it has not been report­ ed previously.

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Discussion

Macroglobulincmia of Waldenstrom with Severe Osteolytic Lesions

311

L ee el al. [5] have treated 2 patients with macroglobulinemia of Waldenstrom with a combination therapy of BCNU, cytoxan, alkeran, prednisone and vincristine with good results. Similar results were ob­ tained by him and A zam and D elamore [1] in treating patients with mye­ lomatosis. Our experience with this kind of therapy in this case and in an­ other case of macroglobulinemia of Waldenstrom was disappointing.

References

Dr. Y. K rausz, Department of Medicine A, Hadassah University Hospital, Jerusa­ lem (Israel)

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1 A zam, L. and D elamore, 1. W.: Combination therapy for myelomatosis. Br. med. J. tv: 560 564 (1974). 2 C ohen , C. R. J.; Bohannon , R. A., and W allerstein, R. O.: Waldenstrom’s ma­ croglobulinemia. Am. J. Med. 41: 274-284 (1966). 3 D utcher, T. F. and F ahey, J. L.: The histopathology of the macroglobulinemia of Waldenstrom. J. natn. Cancer Inst. 22: 887-917 (1959). 4 H auswaldt, V. C.; E mmrich , J. und H unstein , W.: Osteoporose, Osteolyse und Osteosklerose im Röntgenbild bei Plasmozytom und Morbus Waldenstrom. Med. Klin. 63: 1756-1757 (1968). 5 L ee , B. L; Sahakian, G.; C larkson, B. D., and K rakoff, I. H.: Combination chemotherapy of multiple myeloma with alkeran, cytoxan, vincristine, predni­ sone and BCNU. Cancer 33: 533-538 (1974). 6 L iaudet, J. et C hapireau , P.: Un cas de macroglobulinémie de Waldenstrom avec tumeur osseuse. Presse méd. 78: 2381 (1970). 7 M ackenzie , M. R. and F udenberg , H. H.: Macroglobulinemia. Analysis for forty patients. Blood 39: 874-889 (1972). 8 P ruzanski, W.; U nderdown , B.; S ilver, E. H., and K atz, A.: Macroglobuli­ nemia - myeloma double gammopathy. Am. J. Med. 57: 259-266 (1974). 9 Schwarz, L A.; H ufnagel , H. D.; J ost , H. und Scheurlen , P. G.: Subleu­ kämischer Verlauf einer Macroglobulinämie Waldenstrom mit Osteolysen IgMKappa-Kryoglobulin mit antinukleärer Aktivität und /i-Kettenfragment. Klin. Wschr. 51: 900-906 (1973). 10 V ermess. M.; P earson, K. D.; E instein , A. B., and F ahey, J. L.: Osseous mani­ festations of Waldenstrom’s macroglobulinemia. Radiology 102: 497-504 (1972). 11 W aldenstrom , J.: Incipient myelomatosis or essential hyperglobulinemia with fibrinogenopenia - a new syndrome? Acta med. scand. 117: 216-247 (1944). 12 W elton , J.; W alker, S. R.; Sharp, G . C.; H erzenberg , L. A.; W istar, R., and C regar, W. P.: Macroglobulinemia with bone destruction. Am. J. Med. 44: 280-288 (1968). 13 Z lotnick , A. and R obinson , E.: Chronic lymphatic leukemia associated with macroglobulinemia. Israel J. med. Scis 6: 365-372 (1970).

Macroglobulinemia of Waldenström associated with severe osteolytic lesions.

Acta haemat. 5S: 307-311 (1977) Macroglobulinemia of Waldenstrom Associated with Severe Osteolytic Lesions1 Y odphat K rausz and A vinoam Z lotnick D...
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