IgM Myeloma: Report of Two Cases of a Rare Entity with Unusual Immunophenotype.

Plasma cell myeloma is characterized by clonal proliferation of plasma cells and serum and/or urine paraprotein, most commonly IgG, IgA or light chain only. IgM, IgD, IgE and non-secretory variants are infrequent. IgM myeloma comprises less than 0.5% of myelomas. These should not be confused with B-cell non-Hodgkin lymphoma showing plasmacytoid differentiation and an IgM paraprotein, particularly lymphoplasmacytic lymphoma. Two cases are reported herein.

A 57 year old female with known MGUS, type II diabetes, rheumatoid arthritis, underwent total thyroidectomy for papillary thyroid carcinoma. Two months later she required excision of a cervical lymph node, identified by radioactive iodine scanning, revealing metastatic papillary thyroid carcinoma. However, during pre-operative evaluation, cytopenias were noted (hemoglobin 7.8 g/dL, platelets 86 × 10⁹L), and renal insufficiency (creatinine 2.1 mg/dL). Subsequent laboratory findings included a serum IgM kappa paraprotein of 6158 mg/dL, normal IgA, decreased IgG of 423 mg/dL, elevated beta-2 microglobulin (7.7 mg/L), elevated serum viscosity (3 cp), mildly decreased serum calcium (8.2 mg/dL). A skeletal survey was negative. Pathologic findings: Peripheral blood showed pancytopenia, marked RBC rouleaux, and occasional atypical plasmacytoid cells (5%). Bone marrow biopsy sections revealed marked hypercellularity with a predominance of plasmacytoid cells. By immunohistochemistry (IHC), these were CD138+, CD117+. MUM1+, weak cytoplasmic kappa+, weak CD79a+, CD45-, CD19-, CD20-, PAX 5-, CD5-, CD10-, CD23-, CD56-, cyclin D1-. Flow cytometry (FC) of peripheral blood also revealed abnormal cells, of comparable phenotype (CD45-, CD19-, CD20-, CD38+, CD138+, CD56-), though CD117 and cytoplasmic light chain expression were not evident. Clinical course: Management included plasma exchange for serum hyperviscosity, pulse steroids and thalidomide. Despite these interventions, her condition worsened, including a progressive decline in renal function, requiring hemodialysis. Eventually she declined further treatment, and expired two months after diagnosis.

An 83 year old male patient presented with fatigue, dyspnea, diffuse pain, paresthesias involving hands and feet of two weeks duration. Past history was remarkable for COPD, lower extremity DVT, and hyperlipidemia. Physical examination revealed no lymphadenopathy or organomegaly. Laboratory studies revealed pancytopenia, IgM kappa paraprotein of 4664 mg/dL, normal serum IgG, diminished IgA, elevated serum creatinin (1.7 mg/dL), normal serum calcium, elevated beta-2 microglobulin (4.9 mg/L) and elevated serum viscosity (3.4 cp). A skeletal survey was negative. Pathologic findings: Peripheral blood revealed pancytopenia with marked RBC rouleaux. Marrow aspirate smears showed abundant abnormal plasma cells, many showing numerous, azurophilic, crystalline cytoplasmic inclusions, Auer rod-like. Bone marrow biopsy was hypercellular and heavily infiltrated by abnormal plasma cells. By IHC, these were CD138+, MUM1+, cyclin D1+, CD56+, cytoplasmic kappa+, CD20+ (sub-set), weak CD117+. FC of marrow aspirate yielded comparable results (CD56 co-expression, bright CD38+ and CD138+, CD19-, CD20-, CD45-). Conventional cytogenetics revealed a normal male karyotype. Interphase FISH revealed t(11; 14), trisomies 11, 13, 14 and 17, with 13q14 and 17p13 deletions. Clinical course: The patient rapidly deteriorated, and expired shortly after hospital admission.

We describe two cases of IgM myeloma. The diagnosis in each case was supported by morphology and immunophenotype and, in one case, by interphase FISH. These add to our limited knowledge regarding the biology of this disorder. Recently, it has been suggested that such cases are of relatively uniform immunophenotype, in particular lacking either CD56 or CD117 expression (Feyler S et al, BJH 140, 547-551, 10/2007). Our cases show that the spectrum of immunophenotypic findings in IgM myeloma is broader than has been suggested. In addition, one of the two cases showed Auer-rod like crystalline cytoplasmic inclusions in malignant plasma cells, also a rare finding in this setting.

No relevant conflicts of interest to declare.