| Summary: | Marginal zone lymphomas (MZLs) are a heterogeneous group of neoplasms that resemble the normal B-cell populations of the marginal zone of a lymph node. It includes three different subtypes, nodal, splenic, and extra -nodal, each, with overlapping features and yet unique characteristics. Nodal Marginal Zone lymphoma (NMZL) accounts for only 1% of all Non-Hodgkin Lymphoma (NHL). Marginal Zone lymphoma with plasmacytic differentiation is not very common. We report a unique case of Nodal marginal zone lymphoma initially presenting with lymphocytosis and lymphadenopathy, work up indicating low grade lymphoma, subsequently developing hyper viscosity syndrome due to symptomatic IgM monoclonal gammopathy. A 68 year old female was noted to have persistent leukocytosis with lymphocytic predominance after completing treatment for a urinary tract infection. Clinical exam revealed bilateral axillary adenopathy. CT scan of neck, chest, abdomen and pelvis revealed axillary, mediastinal and retroperitoneal adenopathy with splenomegaly. Chronic lymphocytic leukemia (CLL) was suspected and work up initiated. Peripheral blood Flow-cytometry revealed 24% small B-cells with surface kappa light chain restriction consistent with mature B-cell lymphoma or leukemia without typical immune phenotype of CLL. Lab reported significant elevation of total protein at 10 g/dl. Workup for para-proteinemia consistent with IgM level over 5000 mg/dl, with serum viscosity of 8. Axillary lymph node excisional biopsy reported marginal zone lymphoma with plasmacytic differentiation. Bone marrow biopsy demonstrated 42% monoclonal B-cells without co-expression of CD5 and CD23. FISH studies positive for duplication 1q and Molecular testing negative for MYDD88 mutation. Decision was made to initiate chemo therapy with R-CVP for a total of six cycles. Her treatment course was complicated by symptomatic hyper viscosity syndrome necessitating therapeutic plasmapheresis. Patient successfully completed chemo immunotherapy with normalization of blood counts, resolution of palpable adenopathy and splenomegaly. Nodal marginal lymphoma (NMZL) originates from nodal mono-cytoid or marginal zone B cells and the pathogenesis usually involves acquired mutations in oncogenes and tumor suppressor genes involving MLL2, PTTPRD, NOTCH2, and KLF2 genes. The median age is round 70 years with slight male predominance. The clinical picture varies and usually includes generalized lymphadenopathy along with B symptoms and infrequently with mild monoclonal gammopathy (any immunoglobulin subtype-IgM uncommon). Marginal Zone lymphoma with plasmacytic differentiation is not as common and shares immuno-histochemical features with lympho-plasmacytic lymphoma (LPL). They both express B cell markers CD19, CD20, and CD22) and not CD5, CD10 or CD23. Clinically, NMZL is more likely to present with prominent lymphadenopathy, while LPL can exclusively affect the marrow without extramedullary involvement. IgM levels in NMZL tend to be lower than in LPL, typically lower than 1000 mg/d. MYD88 mutation is very common in LPL, and can be seen in 10-15% NMZL. The presence of IgM monoclonal gammopathy increases the serum viscosity which can lead to serious neurologic and ophthalmologic complications. Treatment involves emergent plasmapheresis. Our case highlights a less common NHL, presenting with significant paraproteinemia and developing hyper viscosity syndrome with impressive response to plasmapheresis and chemo immunotherapy.
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