Pathology (1991), 23, pp. 339-343
FOUR CASES OF IgD MULTIPLE MYELOMA DAVIDR. DEAM*, INNY A. SUJIVARATNAIKE*
BUSMANIS?,
SONAYHUSSEINS, AND
*Biochemistry Department, ?Department of Anatomical Pathology and $Department of Diagnostic Haematology, Royal Melbourne Hospital, Melbourne, Victoria
Summary The pathological and clinical findings in 4 cases of IgD multiple myeloma are presented. Two patients presented with renal failure and 2 with bone pain and weight loss. Three had IgD lambda paraproteins and 1 an IgD kappa paraprotein. One patient also developed hypercalcemia and extraosseous spread of tumor to pleura, skin, and palate. There were no distinctive bone marrow or histological findings which suggested this unusual type of myeloma. Key words: Multiple myeloma, IgD.
Accepted June 13, 1990
INTRODUCTION Immunoglobulin D (IgD) multiple myeloma is a relatively rare disease and forms only 1.5-2070 of all myeloma cases.’.’ It was first described by Rowe and Fahey3 in 1965 and as it is relatively uncommon we report the pathological findings in 4 patients with this condition. The patients’ clinical and laboratory features are also discussed and compared with previous reports.
CASE HISTORIES Case I Patient 1 was a 69 yr old man who presented with renal failure and increasing shortness of breath over a 3 wk period. On examination he had a clear chest and no hepatomegaly, splenomegaly nor lymphadenopat hy. The routine biochemical investigations showed the features of renal failure (see Table I). The liver function tests were normal. Serum protein electrophoresis showed the presence of 2 distinct abnormal bands and diminished gamma globulins. On immunofixation 1 band was an IgD lambda paraprotein (4 g/L) and the other was a free lambda light chain (12 g/L). Urine protein electrophoresis showed 1.6 g/L of free lambda light chain which had a pl of between 6.5 and 6.6. An x-ray skeletal survey and computerized tomography showed a destructive lesion in the wing of the right iliac bone. A bone marrow biopsy from the iliac crest showed mildly increased cellularity with normal erythropoiesis, granulopoiesis and megakaryocytes. Plasma cells were increased in number comprising 15% of nucleated cells and displayed considerable variation in size with many large and occasional multinucleated forms with basophilic cytoplasm and eccentric nuclei with coarse chromatin; some contained 1 or 2 nucleoli. Other relevant pathology findings are shown in Table 1. A renal biopsy was performed which demonstrated moderate chronic interstitial nephritis with a diffuse pattern of interstitial fibrosis and
tubular atrophy. Occasional protein casts were surrounded by attenuated tubular epithelium (Fig. 1). No diagnostic myeloma casts were seen. Five of 32 glomeruli were globally sclerosed, and most of these were situated in areas of cortical scarring. Mild, hyaline arteriolosclerosis was present. No plasma cell infiltrate or amyloid material was identified. The changes of interstitial nephritis in this case may be attributable to urine outflow obstruction, possibly related to urate deposition within collecting tubules, ischemic damage or drug therapy. Previous infection would seem less likely due to the diffuse pattern of scarring. At the time of biopsy the patients urate level was 0.43 mmol/L (reference range 0.30-0.47 mmol/L). The patient’s renal failure was managed without dialysis and he was commenced on 6 wkly courses of melphalan (18 mg for 5 days) and prednisolone (60 mg for 5 days). A repeat electrophoresis after 1 course showed that the serum paraprotein level had diminished and could no longer be quantitated. It became undetectable 5 mths after diagnosis and his chemotherapy was subsequently ceased. However his paraprotein returned after 7 mths and chemotherapy has been recommenced.
Case 2 Patient 2 was a 61 yr old man who presented with renal failure. He complained of a 1 mth history of increasing lethargy, dizziness, several episodes of nausea and vomiting and of losing 2.5 kg in weight. On examination the liver was palpable 3 cm below the costal margin. There was no lymphadenopathy or other relevant findings. The routine initial biochemical investigations showed the presence of renal failure and are summarized in Table 1 . Liver function tests were normal. Serum protein electrophoresis showed the presence of 2 abnormal bands in the gamma region and diminished immunoglobulins. Immunofixation proved these bands to be an IgD lambda paraprotein (5 g/L) and free lambda light chains (3 g/L). No Bence Jones protein was detected in the urine. A bone marrow biopsy of the iliac crest showed mildly increased cellularity with normal erythropoiesis, granulopoiesis and megakaryocytes. Plasma cells were increased in number. They comprised 35% of nucleated cells and were abnormal with many very large and occasional multinucleated forms. The cytoplasm was abundant and appeared mostly basophilic with a few cells showing an eosinophilic periphery of cytoplasm (flame cells). The nuclei appeared eccentric and showed a coarse chromatin patrern with some cells containing 1-2 nucleoli. Other relevant pathology investigations are shown in Table I . A renal biopsy showed moderate to diffuse interstitial fibrosis and a mild chronic inflammatory cell infiltrate. No linear scarring was identified. Many tubules contained necrotic cellular casts as well as dense, occasionally fractured eosinophilic myeloma casts surrounded by necrotic tubular epithelial cells and associated with a mononuclear cell response (Fig. 2). Small numbers of glomeruli showed ischemic damage, and interlobular arteries were moderately arteriosclerotic. Congo red staining identified amyloid within scattered blood vessels, and also focally within the interstitium. The interstitial nephritis in this case may
340
Pathology (1991), 23, October
DEAM er a/.
TABLE 1 Results of Pathology Tests in 4 patients with IgD multiple myeloma ~~
Age/sex
Case 1
Case 2
Case 3
Case 4
69 male
61 male
63 female
49 female
0.05-0. I 1 2.5-8.3 2.13-2.62 61-83 35-50 6-16 0.8-4.1 0.6-2.6 16
IgD A 5 g/L Free A 3 g/L ND 1.88 76.2 2.26 73 43 6.0 0.5 0.4 44
IgD A 3.4 g/L Free A* Free A 0.09 g/L 0.10 4.1 2.48 64 39 5.9 1.1 0.5 3.0
IgDK 12.3 g/L Free K * Free K 2.4 g/L 0.15 11.7 2.42 80 41 2.6 0.1 0. I 14.3
Male 130-180 Female 1 15- 160 < 15
FOUR CASES OF IgD MULTIPLE MYELOMA DAVIDR. DEAM*, INNY A. SUJIVARATNAIKE*
BUSMANIS?,
SONAYHUSSEINS, AND
*Biochemistry Department, ?Department of Anatomical Pathology and $Department of Diagnostic Haematology, Royal Melbourne Hospital, Melbourne, Victoria
Summary The pathological and clinical findings in 4 cases of IgD multiple myeloma are presented. Two patients presented with renal failure and 2 with bone pain and weight loss. Three had IgD lambda paraproteins and 1 an IgD kappa paraprotein. One patient also developed hypercalcemia and extraosseous spread of tumor to pleura, skin, and palate. There were no distinctive bone marrow or histological findings which suggested this unusual type of myeloma. Key words: Multiple myeloma, IgD.
Accepted June 13, 1990
INTRODUCTION Immunoglobulin D (IgD) multiple myeloma is a relatively rare disease and forms only 1.5-2070 of all myeloma cases.’.’ It was first described by Rowe and Fahey3 in 1965 and as it is relatively uncommon we report the pathological findings in 4 patients with this condition. The patients’ clinical and laboratory features are also discussed and compared with previous reports.
CASE HISTORIES Case I Patient 1 was a 69 yr old man who presented with renal failure and increasing shortness of breath over a 3 wk period. On examination he had a clear chest and no hepatomegaly, splenomegaly nor lymphadenopat hy. The routine biochemical investigations showed the features of renal failure (see Table I). The liver function tests were normal. Serum protein electrophoresis showed the presence of 2 distinct abnormal bands and diminished gamma globulins. On immunofixation 1 band was an IgD lambda paraprotein (4 g/L) and the other was a free lambda light chain (12 g/L). Urine protein electrophoresis showed 1.6 g/L of free lambda light chain which had a pl of between 6.5 and 6.6. An x-ray skeletal survey and computerized tomography showed a destructive lesion in the wing of the right iliac bone. A bone marrow biopsy from the iliac crest showed mildly increased cellularity with normal erythropoiesis, granulopoiesis and megakaryocytes. Plasma cells were increased in number comprising 15% of nucleated cells and displayed considerable variation in size with many large and occasional multinucleated forms with basophilic cytoplasm and eccentric nuclei with coarse chromatin; some contained 1 or 2 nucleoli. Other relevant pathology findings are shown in Table 1. A renal biopsy was performed which demonstrated moderate chronic interstitial nephritis with a diffuse pattern of interstitial fibrosis and
tubular atrophy. Occasional protein casts were surrounded by attenuated tubular epithelium (Fig. 1). No diagnostic myeloma casts were seen. Five of 32 glomeruli were globally sclerosed, and most of these were situated in areas of cortical scarring. Mild, hyaline arteriolosclerosis was present. No plasma cell infiltrate or amyloid material was identified. The changes of interstitial nephritis in this case may be attributable to urine outflow obstruction, possibly related to urate deposition within collecting tubules, ischemic damage or drug therapy. Previous infection would seem less likely due to the diffuse pattern of scarring. At the time of biopsy the patients urate level was 0.43 mmol/L (reference range 0.30-0.47 mmol/L). The patient’s renal failure was managed without dialysis and he was commenced on 6 wkly courses of melphalan (18 mg for 5 days) and prednisolone (60 mg for 5 days). A repeat electrophoresis after 1 course showed that the serum paraprotein level had diminished and could no longer be quantitated. It became undetectable 5 mths after diagnosis and his chemotherapy was subsequently ceased. However his paraprotein returned after 7 mths and chemotherapy has been recommenced.
Case 2 Patient 2 was a 61 yr old man who presented with renal failure. He complained of a 1 mth history of increasing lethargy, dizziness, several episodes of nausea and vomiting and of losing 2.5 kg in weight. On examination the liver was palpable 3 cm below the costal margin. There was no lymphadenopathy or other relevant findings. The routine initial biochemical investigations showed the presence of renal failure and are summarized in Table 1 . Liver function tests were normal. Serum protein electrophoresis showed the presence of 2 abnormal bands in the gamma region and diminished immunoglobulins. Immunofixation proved these bands to be an IgD lambda paraprotein (5 g/L) and free lambda light chains (3 g/L). No Bence Jones protein was detected in the urine. A bone marrow biopsy of the iliac crest showed mildly increased cellularity with normal erythropoiesis, granulopoiesis and megakaryocytes. Plasma cells were increased in number. They comprised 35% of nucleated cells and were abnormal with many very large and occasional multinucleated forms. The cytoplasm was abundant and appeared mostly basophilic with a few cells showing an eosinophilic periphery of cytoplasm (flame cells). The nuclei appeared eccentric and showed a coarse chromatin patrern with some cells containing 1-2 nucleoli. Other relevant pathology investigations are shown in Table I . A renal biopsy showed moderate to diffuse interstitial fibrosis and a mild chronic inflammatory cell infiltrate. No linear scarring was identified. Many tubules contained necrotic cellular casts as well as dense, occasionally fractured eosinophilic myeloma casts surrounded by necrotic tubular epithelial cells and associated with a mononuclear cell response (Fig. 2). Small numbers of glomeruli showed ischemic damage, and interlobular arteries were moderately arteriosclerotic. Congo red staining identified amyloid within scattered blood vessels, and also focally within the interstitium. The interstitial nephritis in this case may
340
Pathology (1991), 23, October
DEAM er a/.
TABLE 1 Results of Pathology Tests in 4 patients with IgD multiple myeloma ~~
Age/sex
Case 1
Case 2
Case 3
Case 4
69 male
61 male
63 female
49 female
0.05-0. I 1 2.5-8.3 2.13-2.62 61-83 35-50 6-16 0.8-4.1 0.6-2.6 16
IgD A 5 g/L Free A 3 g/L ND 1.88 76.2 2.26 73 43 6.0 0.5 0.4 44
IgD A 3.4 g/L Free A* Free A 0.09 g/L 0.10 4.1 2.48 64 39 5.9 1.1 0.5 3.0
IgDK 12.3 g/L Free K * Free K 2.4 g/L 0.15 11.7 2.42 80 41 2.6 0.1 0. I 14.3
Male 130-180 Female 1 15- 160 < 15
