A peculiar case of cyclin D1–positive lymphoplasmacytic lymphoma

A 76-year-old man previously diagnosed with lymphoplasmacytic lymphoma (LPL) upon lymph node biopsy alongside immunoglobulin M (IgM) paraproteinemia and hyperviscosity was initially treated with rituximab, cyclophosphamide, vincristine, and prednisone followed by rituximab-bendamustine at relapse. The LPL was negative for cyclin D1 during the initial diagnosis. He presented again with new omental and mesenteric masses, pancytopenia, lymphocytosis (panel A, 63× objective), serum IgM-κ M-protein, and a faint IgA-κ band. Bone marrow aspirate and biopsy were hypercellular, showing 90% interstitial and paratrabecular involvement by κ-restricted medium-sized B cells with plasmacytoid differentiation (panels B-C, 63× objective; panel G), and 1% polytypic background plasma cells. The lymphoma strongly expressed cyclin D1 and p53 (panel D-E, 63× objective) and was negative for CD5/CD10/SOX11/LEF1/CD23 (panel F, 63× objective; panel G) with partial/dim CD25/CD103/CD11c (panel H). Fluorescence in situ hybridization study was negative for CCND1::IGH rearrangement. Therefore, small lymphocytic lymphoma, hairy cell leukemia, and mantle cell lymphoma were excluded. The strong expression of CD19/CD20/CD79a/CD45 and lack of CD138/CD38 excluded lymphoplasmacytic variant of plasma cell myeloma. Next generation sequencing confirmed a pathogenic variant of TP53 (p.Val173Met) but no MYD88 hotspot mutation.

The findings were compatible with recurrent MYD88^WT LPL with acquired cyclin D1 expression and TP53 mutation. The patient responded well to zanubrutinib with significant shrinkage of masses and reduction of serum IgM. To our knowledge, this represents the first reported instance of cyclin D1-expressing LPL in the literature.

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