title: 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: Primary effusion lymphoma (PEL) is a rare non-Hodgkin lymphoma subtype primarily seen in human immunodeficiency virus (HIV)-infected individuals with low CD4(+) cell counts and elevated HIV viral loads. It has always been associated with human herpesvirus type 8 (HHV-8) and in 80% of cases has also been associated with Epstein-Barr virus (EBV). Less commonly, PEL has presented in patients with advanced age and other conditions associated with an 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 will 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, with an average median survival of < 1 year. HHV-8-associated large B-cell lymphoma (HHV-8-LBL) is a second variant of PEL that is both solid and extracavitary. It has immunoblastic and/or anaplastic morphologic features and a distinct immunohistochemical staining pattern. It could also have a different clinical presentation than that of classic PEL.
  
  
  
  We describe the case of a 57-year-old HIV-infected man who presented with a slow-growing and asymptomatic abdominal mass. Examination of an excisional biopsy specimen 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. The Ki-67 labeling index was 90%. The diagnosis was stage IIIA HHV-8-LBL, and he was treated with 6 cycles of R-EPOCH (rituximab, etoposide, vincristine, doxorubicin, cyclophosphamide, and prednisone) infusion chemotherapy. At 12 months after treatment, he was in complete remission. We also performed a Medline and Embase search to better understand the clinical findings of our patient and the unique attributes of HHV-8-LBL. Focusing our search on English language studies, we identified 83 cases of HHV-8-LBL without an effusion component. We compared these 83 cases with 118 reported cases of classic PEL.
  
  
  
  The median age of the patients with HHV-8-LBL was 41 years (range, 24-77), and 96% of the cases were associated with HIV. The median age of the patients with classic PEL was 41 years (range, 26-86), and 96% of the cases were associated with HIV. Of those with HHV-8-LBL, 31 of 61 (51%) had a pre-existing diagnosis of acquired immunodeficiency syndrome (AIDS) and 47 of 63 (75%) were coinfected with EBV. In contrast, 69 of 96 patients (72%) with classic PEL had a pre-existing AIDS diagnosis and 40 of 49 (82%) were coinfected with EBV. The mean CD4(+) count of the HHV-8-LBL patients was 256 cells/μL (range, 18-1126 cells/μL) compared with 139 cells/μL (range, 2-557 cells/μL) in the classic PEL patients. The median survival time for both groups was similar at 5.5 months (range, 25 days to ≥ 25 months) for patients with HHV-8-LBL and 4 months (range, 2 days to ≥ 113 months) for those with classic PEL. More patients with HHV-8-LBL were alive at the last follow-up point (59% vs. 18%). The percentage of patients achieving complete remission was 54% (30 of 56) and 36% (32 of 89) for HHV-8-LBL and classic PEL, respectively.
  
  
  
  Our patient's high CD4(+) cell count, the lack of a pre-existing AIDS diagnosis, and the excellent response to chemotherapy highlights that HHV-8-LBL might have distinct clinical features and possibly a better response to chemotherapy than classic PEL. HHV-8-LBL should be included in the differential diagnosis of HIV patients with solid lesions. It is essential that patients' Centers for Disease Control and Prevention HIV clinical status and HIV viral load at the diagnosis of PEL and HHV-8-LBL be reported and that the reported clinical results include longer term follow-up data. Only then will a more complete clinical picture of this little-appreciated and little-understood PEL variant be defined.
authors.affiliation: School of Medicine, New York Medical College, Valhalla, NY.
authors.forename: William R
authors.initials: WR
authors.lastname: Foster
authors.affiliation: Section of Hematology and Oncology, Virginia Mason Medical Center, Seattle, WA.
authors.forename: Alina
authors.initials: A
authors.lastname: Bischin
authors.affiliation: Section of Hematology and Oncology, Virginia Mason Medical Center, Seattle, WA.
authors.forename: Russell
authors.initials: R
authors.lastname: Dorer
authors.affiliation: Section of Hematology and Oncology, Virginia Mason Medical Center, Seattle, WA; Division of Hematology, University of Washington, Seattle, WA. Electronic address: david.aboulafia@virginiamason.org.
authors.forename: David M
authors.initials: DM
authors.lastname: Aboulafia
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology; D001706:Biopsy; D060085:Coinfection; D015658:HIV Infections / Q000150:complications / Q000175:diagnosis / Q000276:immunology / Q000821:virology; D006566:Herpesviridae Infections / Q000150:complications*; D019288:Herpesvirus 8, Human; D018451:Homosexuality, Male; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D054685:Lymphoma, Primary Effusion / Q000175:diagnosis* / Q000188:drug therapy / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D000072078:Positron Emission Tomography Computed Tomography; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D055815:Young Adult
keywords: AIDS; HHV-8-LBL; HIV-associated non-Hodgkin lymphoma; Human immunodeficiency virus; Nonserous PEL