Epstein-Barr virus-positive follicular lymphoma

Abstract

Epstein-Barr virus (EBV) -associated follicular lymphoma is only rarely reported. Herein, we report the largest series analyzing prevalence and clinicopathologic characteristics of EBV-associated follicular lymphoma occurring in unselected cases. Out of 382 analyzed cases, 10 EBV-positive follicular lymphomas were identified (prevalence=2.6%, 95% confidence interval 1.3-4.0%). All EBV-positive follicular lymphomas showed EBV-encoded small RNA-positive lymphoma cells present in a follicular distribution. Of these, eight also had tissue available for testing of expression of latent membrane protein 1 (LMP1), out of which six (75%) were positive. There was a significant association with grades 3A-3B follicular lymphoma (P<0.0001) and CD30 expression (P=0.0002). EBV-positive follicular lymphomas were otherwise morphologically and immunophenotypically indistinguishable from EBV-negative cases of similar grade. Nine of the EBV-positive follicular lymphomas occurred in patients with no known history of immunosuppression, while one patient had a history of hydroxychloroquine administration for Sjögren's syndrome. The mean age in the EBV-positive and -negative follicular lymphomas was 56 (range 31-83 years) and 49 years (range 25-92 years), respectively, with no statistically significant difference. Seven of the patients with EBV-positive follicular lymphoma had additional biopsies from different time points available for review, all of which showed progression of disease in the form of progression of tumor grade. Five of these progressed to diffuse large B-cell lymphoma, one of which had tissue available for testing and was EBV-positive. Our findings suggest that EBV infection may have a role in lymphomagenesis and/or disease progression in a subset of follicular lymphomas, thereby expanding the spectrum of recognized EBV-associated B-cell lymphomas.

Prevalence, clinical characteristics and prognosis of EBV‐positive follicular lymphoma

“…We previously reported the largest series of EBV-positive FL, occurring with a prevalence of 2.6% in an unselected cohort of 382 FL patients. 3 Other than that study, the association between EBV and FL is not well recognized, with only few sporadic cases documented in the literature. In our prior study, the majority of patients with EBV-positive FL progressed to either a higher grade FL or to diffuse large B-cell lymphoma (DLBCL).…”

“…Tissue microarrays were stained for EBER by in situ hybridization, and for LMP1 and EBNA2 by immunohistochemistry, as previously described. 3 EBV-positive FL were those with tumor cells positive for one or more of these markers. Cases with staining of only "bystander" lymphocytes (small lymphocytes outside of neoplastic follicles) were considered negative for EBV.…”

EBV‐positive, HHV8‐negative large B‐cell lymphoma with an unusual germinotropic growth pattern in an immunocompetent patient

“…We conducted a comprehensive literature search to look for similar cases. Mackrides et al tested EBV expression in 382 cases of follicular lymphoma and identified 10 EBV‐positive follicular lymphomas (prevalence 2.6%). About 80% of these patients were immunocompetent and presented with lymphadenopathy and initial clinical stage between IIA and IVA.…”

Primary Cutaneous Follicle Centre Lymphoma with Hodgkin and Reed-Sternberg Like Cells: A Case Report and Review of the Literature

“…In addition, their presence may be significantly underreported, with the H/RS-like cells being counted as centroblasts in FLs. While their immunophenotype has generally variations from the classic (CD45−, CD30+, PAX5 weak+, and CD15 variably+) Hodgkin lymphoma immunophenotype [ 22 – 24 ], a common germinal centre origin has been suggested for both [ 22 , 25 ]. In the majority of the reported FL cases their H/RS cells were CD30 positive and coexpressed B-cell markers (CD20, BOB1, PAX5, and OCT.2) and bcl6, were variably CD45 and bcl2 positive, and were less often CD15 or CD10 positive.…”