KSHV/HHV8+ Large B-Cell Lymphoma

Kaposi sarcoma-associated herpesvirus (KSHV), also known as human herpervirus-8 (HHV-8), is associated with the pathogenesis of several distinct HIV-associated lymphoproliferative diseases, particularly primary effusion lymphoma (PEL), multicentric Castleman’s disease (MCD), and multicentric Castleman’s disease associated plasmablastic lymphoma (MCD-PBL). PEL has been recognized by the World Health Organization (WHO) as a distinct entity; it primarily occurs in HIV+ patients, and typically presents as lymphomatous effusions in the body cavities without associated solid tumor at the time of presentation. Rare cases of KSHV+ extracavitary solid lymphoma have been observed before, during or after development of PEL; these cases, so-called “solid PEL”, represent part of the spectrum of the classic PEL with different clinical manifestations.

In extraordinarily rare circumstances, KSHV+ large B-cell lymphomas (KSHV-LBL) may occur in HIV+ patients without lymphomatous effusions in the body cavities during the course of disease, which may be very challenging for the pathologists to give an accurate diagnosis. Generally, these KSHV-LBLs are very similar to classic PEL, with immunoblastic, plasmablastic or anaplastic morphology and lack of B- and T-cell markers. However, the clinicopathologic features of this entity are not fully understood, and it is uncertain whether it is a distinct entity or belongs to the spectrum of PEL. So far, there is no consensus diagnostic term for KSHV-LBL, and it has been diagnosed as “KSHV-associated solid lymphoma”, “KSHV-associated lymphoma”, “extracavitary PEL”, “KSHV+ solid lymphoma”, “KSHV associated extracavitary lymphoma without effusions”, “Solid variant of PEL”, “HHV8+, EBV+ Hodgkin lymphoma-like large B-cell lymphoma”, “KSHV+ intravascular large B-cell lymphoma”, and “KSHV -associated extracavitary lymphoma”. Therefore, we here summarized 47 cases, including four cases in the current study, with a detailed discussion of the clinicopathologic features of this entity, differential diagnoses, and comparison with the classic PEL.

• Almost exclusively affects HIV+ male patients.
• Common locations: lymph node, gastrointestinal tract, spleen, skin, and liver.
• Morphology: immunoblastic, plasmablastic, or anaplastic.
• Immunophenotype: CD45+, CD20-, CD79a-, Ig light chains-, EMA+, CD30+, CD138+, CD3 -/+, KSHV+.
• EBV+ and clonal Ig rearrangement in most cases.
• Clinically aggressive.