EBV+ HHV8- Germinotropic Large B Cell Lymphoma: A Lymphoproliferative Disorder with Intermediate Features between EBV+ Large B Cell Lymphomas and Classical Hodgkin Lymphoma
Luisa Lorenzi, Simona Fisogni, Wilma Pellegrini, Anna Gazzola, William Vermi, Claudio Agostinelli, Giovannino Massarelli, Stefano A Pileri, Fabio Facchetti. University of Brescia, Brescia, Italy; University of Bologna, Bologna, Italy; University of Sassari, Sassari, Italy
Background: EBV-related lymphoproliferative diseases include benign and malignant lesions with a wide array of morphologic and phenotypic features, ranging from lymphoid hyperplasia to frank lymphoma.
Design: Three patients, two women and a man, aged 63, 77 and 65 years, presented with a high stage lymphoproliferative disease. One died of disease after 18 months from diagnosis, one is alive with disease after 12 months, the third is free of disease after 28 months. FFPE sections of the lymph nodes were used to perform immunohistochemistry (IHC) for several anti-leucocyte antigens, HHV8 and EBV (LMP1), in situ hybridization (ISH) for the EBV-encoded RNA (EBER), κ and λ light chains mRNA and FISH to detect MYC, BCL6, BCL2 and PAX5 translocations. In two cases, DNA extracted from paraffin sections was used for clonality analysis of IG heavy and light chains and for EBV clonality using the 33bp repeats of LMP1.
Results: Lymph nodes showed an effaced architecture with follicles colonized by large atypical cells, resembling centroblasts, immunoblasts or Reed-Sternberg-like cells. Follicles showed a disrupted network of follicular dendritic cells, with Castleman-like features in two cases. Large atypical cells were strongly positive for CD20, CD30, PAX5, OCT2, BOB1 and IRF4, for CD15 in one case, for BCL6 and CD10 focally in another while BCL2 was negative in all. All atypical cells were positive for EBV on both IHC and ISH; HHV8 was negative. The germinotropic large cells were negative for IG light and heavy chains and light chains mRNA. No translocations were detected by FISH. Molecular studies showed a polyclonal profile in 2 tested lymphomas. EBV was monoclonal in one.
Conclusions: Large B-cell lymphoma with a distinctive tropism for germinal centers have been originally described by Suster et al. (1992) and by Du et al. (2002). In both series tumor cells showed monoclonal restriction for IG light chains on IHC and, in the series of Du et al. coinfection by EBV and HHV8. In the present three cases germinotropic EBV+ large B cells showed no IG expression and displayed features intermediate between large B cells and Reed-Sternberg cells, expanding the spectrum of the borderline neoplasms provisionally included in the WHO classification.
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 225, Monday Morning