[1455] IgM Multiple Myeloma Has Unique Attributes Distinguishing It from Other Plasma Cell Neoplasms and Lymphoplasmacytic Lymphoma

Rebecca L King, Matthew T Howard, Janice M Hodnefield, William G Morice. Mayo Clinic, Rochester, MN

Background: It is recognized that in a minority of multiple myeloma (MM) cases the abnormal plasma cells (PC) produce an IgM paraprotein; however, the bone marrow (BM) pathology of IgM MM is not well characterized. This knowledge deficit is significant, as bone marrow biopsy is often obtained to help discriminate IgM MM from lymphoplasmacytic lymphoma (LPL), particularly if some clinical attributes of MM (CRAB-hypercalcemia, renal insufficiency, anemia, and bone lesions) are absent. This distinction is critical, as therapies are vastly different for the two diseases. To address this issue, the morphologic, immunophenotypic, and genetic features of BM involvement in well-established IgM MM was studied, and the findings compared to LPL and other types of MM.
Design: BM biopsies from 16 cases satisfying all clinical MM criteria with isolated IgM serum paraproteins were studied. In each, the BM pathology and immunohistochemistry (IHC) were reviewed individually and by multiple authors together.
Results: All 16 patients (mean age 65 years) had an IgM paraprotein (Median: 2.5, range: 0.3 – 5.1 g/dL) and CRAB symptoms (7 with lytic bone lesions) as well as at least 10% clonal BM PC. The BM PC showed a spectrum of cytologies ranging from large, atypical forms to those with a smaller, lymphoplasmacytoid appearance. The latter had features overlapping with LPL, however no cases had monotypic B cells by flow cytometry or IHC. All cases were positive for the PC–associated antigens CD138 and MUM1 by IHC; however our study showed an unusually high frequency of B cell antigen expression as compared to other MM.

Positive1(69%)7 (44%)8(50%)11(69%)

Some CD19 positive cases also had PC with lymphoplasmacytoid cytology, complicating their distinction from LPL. Many of these cases were cyclinD1 positive by IHC including one case which lacked t(11;14) CyclinD1-IgH translocation. The IHC and FISH results were concordant in 7 other cases in which t(11;14) FISH was performed(5 FISH positive, 2 FISH negative).
Conclusions: IgM MM is a rare MM subtype that is distinguished by its frequent lymphoplasmacytoid histology and expression of B cell antigens including CD19, which is nearly always negative in other types of MM. These attributes could lead to an erroneous diagnosis of LPL. If positive, Cyclin D1 may be helpful in confirming a diagnosis of IgM MM, and in some cases may be aberrantly expressed in the absence of t(11;14). However, Cyclin D1 negative cases of IgM MM do exist, and require further study to understand their biology.
Category: Hematopathology

Wednesday, March 21, 2012 1:00 PM

Poster Session VI # 218, Wednesday Afternoon


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