A rare IgM multiple myeloma with aberrant PAX5 expression mimicking lymphoplasmacytic lymphoma

Abstract

Dear Editor, A 64-year-old Caucasian male who had weakness and confusion with a markedly elevated IgM protein was referred for p o s s i b l e Wa l d e n s t r om ’s ma c r o g l o b u l i n em i a / lymphoplasmacytic lymphoma. The patient had a short history of fatigue and weakness starting 6 months ago. He then developed progressive bone pain. On physical examination, he had no lymphadenopathy and organomegaly. Laboratory investigations showed a bicytopenia with Hgb 83 g/l, MCV 94 fl, and PLT 58×10/L and a normal WBC count. Ionized calcium was elevated to 3.56 mmol/L (normal 2.51 to 2.52) and creatinine was 233 μmol/L. LD was normal and immunoglobulin IgM was elevated with 55.1 g/L. CT of thorax/ abdomen/pelvis demonstrated extensive lytic bone lesions and mild wedge compression fractures of T5, T11, and T12. Microscopic evaluation of peripheral blood film revealed normocytic anemia with background staining and rouleaux formation, increased lymphoplasmacytoid cells, and thrombocytopenia. Bone marrow aspirate showed increased lymphoplasmacytoid cells (Fig. 1a); the nuclei feature was consistent with lymphoma cells but not plasma cells. By morphology, it was suggestive of LPL/WM. Bone marrow biopsy demonst ra ted increased ce l lu lar i ty wi th lymphoplasmacytoid-looking cells, which were forming a sheet or diffuse infiltration pattern. The malignant cells had the morphology in between the lymphoma cells and plasma cells (Fig. 1b). Immunostaining with PAX5 was positive (Fig. 1c), showing strong diffuse nuclear stain, CD79a was positive in a similar pattern as PAX5, CD20 was weakly positive in 30 % of the malignant cells, CD19, and CD10 were negative. CD138, IgM, and Kappa light chain demonstrated strong positivity with a diffuse pattern (Fig. 1d–f), whereas Lambda light chain was negative. Because the malignant cells were expressing both B cell (PAX5, CD20, CD79a) and plasma cells markers (CD138), additional marker cyclin D1 was ordered to make the differentiation between MM and LPL. Cyclin D1 illustrated diffuse positivity (Fig. 1g) as CD138 and Kappa light chain, which confirmed that the malignant cells were multiple myeloma plasma cells as 40 % of MMwas positive for cyclin D1 but it was negative for LPL [1, 2]. Fluorescence in situ hybridization (FISH) study using a dual fusion probe for loci CCND1 (11q13) and IGH (14q32) (Abbott Molecular, Inc.) showed a fusion pattern consistent with t(11;14) (Fig. 1h), which confirmed the immunohistochemistry (IHC) findings. Based on clinical features of normocytic anemia, hypercalcemia, renal dysfunction, and diffuse lytic bone lesions (CRAB), the bone marrow IHC pattern, the diagnosis was consistent with a rare IgMMM with aberrant PAX5 expression. The patient was treated with bortezomib, cyclophosphamide, and dexamethasone and auto-BMTwas planned. Multiple myeloma comprises about 10–15 % of hematopoietic neoplasms [1], a subset of MM has the typical t(11;14) and cyclin D1 expression and is associated with a lymphoplasmacytic morphologic appearance with good prognosis [1, 3, 4]. IgMMM is an extremely rare subset of plasma cell neoplasms, accounting for only about 0.5% of plasma cell neoplasms cases in one study [5]. B cell lineage markers such Z. Xu (*) Department of Pathology and Laboratory Medicine, Division of Hematopathology, The Ottawa Hospital, 451 Smyth Road, Ottawa, ON, Canada K1H 8M5 e-mail: zxu@toh.on.ca