The Spectrum of B-cell and Plasma Cell Proliferations in Nodal T Follicular Helper Cell Lymphomas

Abstract

B-cell and plasma cell proliferations are frequently observed in nodal T follicular helper (nTfh) cell lymphomas and can present a diagnostic challenge. These proliferations can be monotypic or monoclonal and morphologically resemble lymphoma or plasmacytoma, but their clinical behavior is poorly defined. In this study, we reviewed 414 cases of nTfh lymphoma seen over the past decade at our institution. We identified 78 (19%) cases that exhibited B-cell or plasma cell proliferation detected by morphology, flow cytometry, immunohistochemistry, and/or molecular techniques. The B-cell/plasma cell proliferations occurred before (22%), concurrently with (50%), or after (28%) the diagnosis of nTfh lymphoma. We divided them into 3 categories: (1) focal or scattered B-immunoblastic proliferations recognized morphologically without a monotypic/monoclonal B-cell population (17%), (2) monotypic/monoclonal B-cell/plasma cells identified solely by flow cytometry or molecular clonality studies without morphologic confirmation (11%), and (3) unequivocal B-cell/plasma cell expansions recognized by morphologic assessment (72%). We further subdivided group 3 into proliferations associated with and possibly dependent on neoplastic Tfh cells versus those proliferations occurring in the absence of neoplastic Tfh cells and likely bona fide lymphomas. Follow-up biopsy specimens showed persistence of B-cell/plasma cell proliferations in various patient subcategories, with transformation to higher-grade B-cell proliferation or persistence without Tfh cells in some cases. In conclusion, our data support the notion that most B-cell and plasma cell proliferations associated with neoplastic Tfh clones have little impact on the clinical course of patients with nTfh lymphoma and likely do not constitute an independent B-cell lymphoma, especially those of small B cells of plasma cells. However, B-cell expansions exhibiting aggressive morphologic features may represent an independent B-cell lymphoma.