HHV8-related lymphoid proliferations: a broad spectrum of lesions from reactive lymphoid hyperplasia to overt lymphoma

Abstract

Human herpesvirus 8 (HHV8)-associated lymphoid proliferations are uncommon and poorly characterized disorders mainly affecting immunosuppressed patients, especially with HIV infection. They encompass different diseases with overlapping features that complicate their classification. In addition, the role of HHV8 in reactive lymphoid hyperplasia is not well known. To analyze the clinicopathological spectrum of these lesions, we have reviewed 66 biopsies of 61 patients with HHV8 infection. All cases were also investigated for Epstein-Barr virus (EBV) and HIV infection. We identified 13 (20%) cases of HHV8-related reactive lymphoid hyperplasia, 2 (3%) HHV8 plasmablastic proliferations of the splenic red pulp, 28 (42%) multicentric Castleman disease, 6 (9%) germinotropic lymphoproliferative disorders, and 17 (26%) HHV8-related lymphomas. As expected, the pathologic subtype was predictive of overall survival (P<0.05). Forty-seven of our cases were HIV positive (77%). In addition to the classical presentation of the different entities, we identified novel and overlapping features. Reactive HHV8 proliferations were frequently associated with systemic symptoms but never progressed to overt HHV8-positive lymphoma. Two cases had a plasmablastic proliferation limited to spleen. Eight cases of multicentric Castleman disease had a previously unrecognized presentation shortly after the diagnosis of HIV infection, six cases had cavity effusions, and three showed plasmablast enriched proliferations. One germinotropic lymphoproliferative disorder was EBV negative and three occurred in HIV-positive patients, who had distinctive clinical and morphological features. Two of the HHV8-related lymphomas did not fulfill the criteria for previously recognized entities. All these findings expand the clinical and pathological spectrum of HHV8-related lymphoid proliferations, which is broader than current recognized.

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 HHV8 and EBV are associated with the pathogenesis of various lymphoproliferative disorders. Similar to EBV infection, HHV8‐related lymphoid proliferations can range from reactive lymphoid hyperplasia to overt lymphoma . HHV8 is seen characteristically in PEL, germinotropic LPD, HHV8‐associated MCD and HHV8‐associated DLBCL.…”

“…Similar to EBV infection, HHV8-related lymphoid proliferations can range from reactive lymphoid hyperplasia to overt lymphoma. 19 HHV8 is seen characteristically in PEL, germinotropic LPD, HHV8associated MCD and HHV8-associated DLBCL. The first two entities are associated with concurrent infection by EBV, whereas the HHV8-associated MCD and DLBCL are usually EBV-negative.…”

“…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.…”

Pathology and classification of aggressive mature B‐cell lymphomas

“…HHV8 induces a spectrum of lymphoproliferative diseases with 2 subtypes of lymphomas, Primary effusion lymphoma (PEL) and HHV8+ DLBCL, NOS . PEL occurs mainly in cavities without a tumor mass.…”