Transformation of Follicular Lymphoma into CD30-Large Cell Lymphoma with Anaplastic Cytologic Features

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Abstract
The natural history of follicular lymphoma is to accrue large cells and become diffuse, resulting in progression/transformation to a higher-grade lymphoma. Histologic transformation occurs in approximately 60% of patients. Most often, follicular lymphomas transform into diffuse large cell lymphoma, but transformation to lymphomas classified using the Working Formulation as diffuse mixed, large cell immunoblastic, or small noncleaved cell also have been reported. Evidence of transformation may be found over time in sequential biopsy specimens, or may coexist in the same biopsy specimen. Here, we describe six cases of follicular lymphoma, large cell in five cases and mixed in one case, that transformed into a diffuse or sinusoidal CD30 antigen-positive large cell lymphoma with anaplastic cytologic features. Both the follicular and diffuse/sinusoidal components were of B-cell lineage, positive for the CD20 antigen and negative for the CD3 and CD43 antigens. The neoplastic cells expressed monotypic immunoglobulin light chain in five cases, three kappa and two lambda. BCL-2 protein was positive in four tumors, in both the follicular and diffuse/sinusoidal components in three cases, and only in the latter component in one case. Using the polymerase chain reaction (PCR), three of six cases had monoclonal immunoglobulin heavy chain gene rearrangements. The t(14;18) was not amplified in any case. Using reverse transcriptase (RT)-PCR, the t(2;5) was amplified in one of four tumors. This report highlights the heterogeneity of B-lineage anaplastic large cell lymphomas and indicates the need to consider antecedent follicular lymphoma in any B-cell lymphoma with anaplastic cytologic features.