Demylinating Peripheral Neuropathy and Lymphoplasmacytic Lymphoma

Abstract 5090

Lymphoplasmacytic lymphoma (LPL) is a neoplasm of small B lymphocytes, plasmacytoid lymphocytes, and plasma cells, which does not fulfill criteria for any of the other small B-cell lymphoid neoplasms (WHO 2008). Neuropathy has been described in association with Waldenstrom's macroglobulinemia, but less so with LPL. We present 7 cases of neuropathy and LPL to highlight the variable presentations. 1) A 56 year old man developed sensory ataxia with an IgM kappa non-MAG paraprotein. CSF protein was 97. Stabilized on MMF, he slowly worsened. Plasma exchange (PE) was given with improvement. Bone marrow (BM) 4 years into his course revealed LPL. Rituximab was given, and his PE reduced. 2) A 49 year old woman developed progressive weakness with rapid decline in January 2010. NCS showed demyelinating polyneuropathy, and CSF protein was 179. An IgM kappa non-MAG paraprotein was found. BM was normal. PE was given with improvement but later prednisone, IVIg and rituximab twice did not help. Repeat BM revealed 2% clonal CD20⁺ CD5^negCD10^neg B cells by flow cytometry. PE was given with modest improvement. Cyclophosphamide 1 gm/m² monthly was given with improvement. 3) A 53 year old man noted imbalance and distal weakness. NCS showed absent SAPs and prolonged distal and F wave latencies. An anti-MAG positive, IgM kappa paraprotein was found. In 2002 BM was normal. He received rituximab weekly × 4 doses. 7 years later, he developed anemia and worsening neuropathy. Repeat BM showed 0.5% CD20⁺CD5^negCD10^neg kappa-restricted B cells by flow cytometry and weekly rituximab was reinitiated. 4) A 62 year old man developed weakness and areflexia. NCS showed asymmetric demyelinating polyneuropathy. Biclonal gammopathy of IgM kappa and IgG kappa was found. BM showed LPL by histopathology. Prednisone was given with improvement. Later two courses of weekly rituximab were given. 5) A 55 year old woman developed asymmetric weakness. NCS showed asymmetric demyelinating polyneuropathy. MRI showed enlargement, abnormal signal intensity, and abnormal enhancement of bilateral radial, median, and ulnar nerves. She was found to have an IgG kappa paraprotein and LPL on BM biopsy. She was treated with rituximab, cyclophosphamide, fludarabine, and PE. In each case, the primary feature driving the need for therapy was the neuropathy and not the underlying hematologic process. Further, worsening neuropathy in 3 cases led to repeat bone marrow biopsies revealing a clonal B cell process and a diagnosis of lymphoplasmacytic lymphoma. Thus, in the presence of an IgM monoclonal gammopathy and peripheral neuropathy, we suggest bone marrow examination for LPL and then consideration of therapy directed toward the abnormal B cell clone.