Follicular lymphoma with EBV-associated transformation, a single institution experience

Follicular lymphoma (FL) is one of the most common subtypes of B-cell lymphoma. While often following an indolent course, a subset of patients develop histologic transformation to an aggressive B-cell or classic Hodgkin lymphoma (CHL). Transformation of other subtypes of low-grade B-cell lymphoma, such as chronic lymphocytic leukemia, are often associated with Epstein-Barr virus (EBV). However, EBV is only rarely associated with histologic transformation of FL. We encountered two rare occurrences of EBV-associated lymphoproliferative disease (EBV-LPD) arising in patients with FL and sought to further characterize the circumstances under which they arise. Pathology archives were searched for relevant cases following institutional review board approval. Seventeen patients with diagnoses of EBV-LPD and synchronous (11, same site in 8/11), metachronous (4) or suspected (2) diagnoses of FL were identified. The patients were predominantly elderly (median age 72, range 50-80 years) including 9 men and 8 women. At least four patients had known immune deficiency/dysfunction. The FL were predominantly low grade by 4th Revised Edition World Health Organization morphologic criteria (79%; 11/14 grade 1-2; 3/14 grade 3A) with detectable BCL2-rearrangements (90%, 9/10). All FL were negative for EBV where evaluable. The FL and associated EBV-LPD were often clonally related, including all evaluable cases with large B-cell morphology. Overall, EBV-associated histologic transformation is a rare complication of FL and is often synchronous and clonally related to the FL. Most patients were elderly, including a subset with additional known causes of immune dysfunction and other immunodeficiency-associated complications.