Human Herpesvirus Type 8-associated Large B-cell Lymphoma: A Nonserous Extracavitary Variant of Primary Effusion Lymphoma in an HIV-infected Man: A Case Report and Review of the Literature

Abstract

BACKGROUND Primary effusion lymphoma (PEL) is a rare non-Hodgkin lymphoma subtype primarily seen in human immunodeficiency virus (HlV)-infected individuals with low CD4+ cell counts and elevated HIV viral loads. It is always associated with human herpesvirus type-8 (HHV-8) and in 80% of cases is also associated with Epstein Barr Virus (EBV). Less commonly, PEL presents in patients with advanced age and other conditions associated with altered immunity, including malignancy, liver cirrhosis, and immunosuppressive medications. It is a tumor of B-cell lineage; however, it shows a “null” phenotype, rarely expressing pan-B cell surface antigens. It does usually express CD45, CD30, CD38, CD138 and MUM1 and is characterized by lymphomatous effusions in body cavities but not lymphadenopathy. It is an aggressive lymphoma; average median survival time is less than a year. HHV-8-associated large B-cell Lymphoma (HHV-8-LBL) is a second variant of PEL that is both solid and extra-cavitary. It has immunoblastic and/or anaplastic morphological features, a distinct immuno-histochemical staining pattern, and may have a different clinical presentation than classic PEL. METHODS We describe the case of a 57-year-old HIV-infected man who presented with a slow growing and asymptomatic abdominal mass. An excisional biopsy showed malignant large cells with prominent cytoplasm that were positive for pan-B cell antigen CD20, HHV-8 and EBV, and negative for CD138, CD10, BCL-6, CD3 and CD30. Ki-67 labeling index was 90%. He was diagnosed with stage IIIA HHV-8-LBL, and he was treated with six cycles of R-EPOCH (rituximab, etoposide, vincristine, doxorubicin, cyclophosphamide, and prednisone) infusion chemotherapy. He remains in complete remission (CR) 12 months post-treatment. We also performed a Medline and Embase search to better understand the clinical findings of this patient and the unique attributes of HHV-8-LBL. Focusing our search on English language articles, we identified 83 cases of HHV-8-LBL without an effusion component. We compared this to 118 reported cases of classic PEL. RESULTS The median age of HHV-8-LBL patients was 41 years (range, 24–77) and 96% were HIV-associated vs. 41 years (range, 2686) and 96% HIV–association for patients with classic PEL. Fifty-one percent (31/61) of HHV-8-LBL patients had a pre-existing AIDS diagnosis, and 75% (47/63) were co-infected with EBV. In contrast, 72% (69/96) of classic PEL patients had a pre-existing AIDS diagnosis and 82% (40/49) were co-infected with EBV. The mean CD4+ count of HHV-8-LBL patients was 256 cell/uL (range, 18–1126) compared to 139 cell/uL (range, 2–557) for classic PEL patients. Median survival time for both groups was similar; 5.5 months for patients with HHV-8-LBL (range, 25 days – 25+ months) and 4 months (range, 2 days –113+ months) for those with classic PEL. More patients with HHV-8-LBL were alive at time of the followup (59% vs 18%). The percent of patients achieving a complete remission (CR) was 54% (30/56) and 36% (32/89) for HHV-8-LBL and classic PEL, r...

Epidemiology of Non-Hodgkin’s Lymphoma

“…Of PEL cases, 80% also show concomitant EBV infection. HHV-8-associated large B-cell Lymphoma (HHV-8-LBL) is a variant of PEL that demonstrates both lymphadenopathy and lymphomatous effusions in bodily cavities [ 35 ].…”

Extracavitary primary effusion lymphoma recurring with syphilis in an HIV-infected patient

“…Therefore, as most cases of PEL and EC-PEL occur in the context of HIV, it is not surprising that over 80% of these lymphomas are associated with EBV coinfection. 9 Nevertheless, cases of PEL without EBV coinfection in the neoplastic cells are occasionally reported, as in our patient, although this is most common in elderly non-immunocompromised individuals living in Eastern Mediterranean regions. Despite decades of successful ART and non-detectable HIV plasma viral load, the patient had a low stable CD4 T cell count (100×10 6 /L) and a low CD4:CD8 ratio (0.4), indicating a reduced capacity of immune reconstitution.…”

“…[6][7][8] Human herpes virus-8 (HHV8)/Kaposi sarcoma-associated herpesvirus (KSHV) is an oncogenic virus involved in all cases of PEL, with 80% concomitant association with Epstein-Barr virus (EBV). 9 Conversely, while HIV-negative patients with PEL from HHV8 endemic areas such as the Mediterranean are older, EBV infection occurs in only 50% of cases and is associated with more extracavitary involvement. 10 11 PEL typically presents as a malignant effusion in the pleural, pericardial or peritoneal cavities.…”

Sars-CoV-2: Lessons from Both the History of Medicine and from the Biological Behavior of Other Well-Known Viruses

“…Primary varicella-zoster virus establishes a lifelong latent infection in ganglionic neurons. Its reactivation in infected individuals induces a disease known as Herpes Zoster, associated with neurological complications [134][135][136]. According to these observations, it is possible that even SARS-CoV-2 may become persistent in infected cells.…”