Follicular large cleaved cell (centrocytic) lymphoma: A distinctive but unrecognized variant of follicular lymphoma

Abstract

Introduction: The WHO classification recommends the subdivision of follicular lymphoma (FL) into three grades based on the average number of centroblasts per high-power field in the neoplastic follicles. However, we have encountered cases of FL in which the follicles are comprised predominately of large cells with cleaved nuclei (large centrocytes), but without enough centroblasts to meet the WHO criteria for grade 3 FL (FL3), and have classified such cases as follicular large cleaved cell lymphoma (FLC). The objective of this study was to describe the pathologic and clinical features of a large series of patients with FLC. Methods: The pathologic features of 72 cases of FLC were evaluated, including morphometry, immunostaining, and cytogenetic studies. Clinical features were tabulated and compared to a series of patients with the other subtypes of FL (332 FL1/2, 181 FL3), and survivals were compared for those treated with anthracycline-based chemotherapy plus rituximab. Results: FLC has a follicular growth pattern with pale follicles at low magnification and frequent follicular and/or interfollicular fibrosis. Cytologically, the cells are predominantly large cleaved cells (centrocytes) with moderately coarse to fine chromatin, absent or inconspicuous nucleoli, and small to moderate amounts of pale cytoplasm. The mean nuclear diameter of the large cleaved cells was 10.1 μ, similar to centroblasts and approximately twice that of small lymphocytes. The t(14;18) was present in 83% of the cases, and a high proportion expressed BCL2 (84%), BCL6 (100%), and CD10 (88%) and had high (≥30%) Ki67 proliferation (81%). However, almost one-half of the cases of FLC were misdiagnosed as low-grade FL. The clinical features of patients with FLC were similar to those with the other types of FL, and survival was excellent with anthracycline-based chemotherapy plus rituximab. The 5-year overall survival (OS) of these patients was 95% and the 5-year event-for survival (EFS) was 90%. No significant differences in OS were found between FLC, FL1/2, FL3A, or FL3B. However, FLC and FL3A had significantly better EFS than either FL1/2 (P = .05) or FL3B (P = .028). Conclusions: FLC is a distinctive variant of follicular lymphoma, which should be recognized in future lymphoma classifications. The correct diagnosis of FLC is critical for the selection of appropriate therapy. Keywords: B-cell lymphoma; follicular lymphoma (FL); R-CHOP