Subtle bone marrow involvement by large B-cell lymphoma with pronormoblast-like morphology and prominent but not exclusive sinusoidal distribution

Primary bone marrow presentation of diffuse large B-cell lymphoma (DLBCL) is unusual, and appreciation of the diffuse growth pattern may be difficult in cases with low-level involvement. In particular, subtle sinusoidal and interstitial bone marrow involvement and morphologic overlap of the tumor cells with pronormoblasts may result initially in a missed diagnosis. We describe the clinicopathologic features of 13 cases of morphologically subtle DLBCL involving the bone marrow, which were only identified with the aid of immunohistochemistry. The overwhelming majority of cases (12/13, 92%) presented with cytopenias, and 5 of 7 cases, with available information, had splenomegaly. The morphology of the tumor cells in the aspirate smears overlapped with pronormoblasts (immature erythroid precursors) in 12 of 13 cases. Similarly, in histologic sections, the tumor cells in virtually all cases (12/13) demonstrated round nuclear contours and oblong nucleoli, mimicking pronormoblasts. A CD20 immunohistochemical stain was essential in identifying the neoplastic infiltrate in all cases. The majority of cases (73%, 10/13) showed low-level bone marrow involvement by lymphoma, 10% or less. CD20 immunohistochemistry highlighted individually dispersed and small clusters of large lymphoid cells in a sinusoidal and/or interstitial growth pattern. Most of the cases that were assessed showed a non-germinal center phenotype (CD10-, BCL6-/+, IRF4/MUM1+). There was an aggressive disease course with a median overall survival of 6 months. We would recommend performing a CD20 immunostain in patients who present with unexplained cytopenias and/or splenomegaly. Further investigation is warranted to better describe the features of this unique and aggressive variant of DLBCL.