KSHV-associated and EBV-associated Germinotropic Lymphoproliferative Disorder

Abstract

We report two cases of Kaposi sarcoma associated herpesvirus (KSHV) - and Epstein Barr Virus (EBV)-associated germinotropic lymphoproliferative disorder (GLPD). Both cases arose in patients from regions endemic for KSHV, Cape Verde and the Democratic Republic of the Congo, presenting as localized lymphadenopathy. The affected lymph nodes showed colonization of the follicles by clusters of large atypical plasmablasts, but also showed regressive changes with vascular proliferation and interfollicular plasmacytosis, both reminiscent of HHV8-positive multicentric Castleman disease (MCD). The atypical plasmablasts showed dual positivity for HHV-8 and EBV, being positive for LANA and viral IL-6, as well as EBER by in-situ hybridization. They showed a Latency I phenotype, being negative for LMP1, EBNA2 and BZLF-1. The plasmablasts were negative for immunoglobulin light chains, and in one case with successful DNA amplification had a polyclonal immunoglobulin rearrangement pattern. GLPD is a rare disorder, with only 6 cases reported in the literature. We demonstrate for the first time the expression of HHV-8 viral IL-6 and provide evidence for Latency I phenotype for EBV. Additionally, one case progressed to an EBV-positive diffuse large B-cell lymphoma, but interestingly was negative for KSHV/HHV-8, likely indicative of tumor derived from an independent clone.

Kaposi sarcoma–associated herpesvirus/human herpesvirus 8–associated lymphoproliferative disorders

“…GLPD is a very rare condition, usually presenting as a localized lymphadenopathy in an asymptomatic, immunocompetent, or HIV-infected patient. 7,29 Lymph node biopsy shows GC expansion by an atypical plasmablastic cell population showing dual positivity for KSHV/HHV-8 and EBV. Interestingly, most cases show Castleman-like changes with marked plasmacytosis.…”

“…However, only GLPD is coinfected by both KSHV/HHV-8 and EBV, a finding that overlaps with PEL. 29 Posttransplant KSHV/HHV-8associated LPD Posttransplant primary KSHV/HHV-8 infection can be either asymptomatic or associated with disseminated KS, sometimes with an acute syndrome of fever, splenomegaly, cytopenia, and marrow failure with plasmacytosis or hemophagocytic syndrome. 6 These features are very similar to that observed in MCD or KSHV inflammatory cytokine syndrome and highlight the overlap between what can be considered as an acute infectious disease and the spectrum of posttransplant LPD.…”

Lymphoproliferative disorders with concurrent HHV8 and EBV infection: beyond primary effusion lymphoma and germinotropic lymphoproliferative disorder

“…Primary effusion lymphoma and germinotropic LPD are two entities that show concurrent HHV8 and EBV infection. Both are rare, especially germinotropic LPD, as only a few cases were described in the literature . In this study, we report two cases of HHV8 + , EBV + lymphoma that show unique clinicopathological features, expanding the spectrum of HHV8 + /EBV + LPD.…”

“…Both are rare, especially germinotropic LPD, as only a few cases were described in the literature. 3,[19][20][21][22][23][24][25][26] In this study, we report two cases of HHV8 + , EBV + lymphoma that show unique clinicopathological features, expanding the spectrum of HHV8 + /EBV + LPD. Of note, although both patients had no history of HIV or other immunosuppression, given the patients' age immunosenescence may have played a role in disease development.…”

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

“…This lymphoproliferative disorder is seen in HIV‐negative individuals, usually presents as a lower stage disease and has an indolent clinical course. The large atypical infiltrating germinal centers have plasmablastic features, are negative for CD20, CD10, BCL6, CD138, show light chain restriction, but are polyclonal …”