Human herpesvirus 8- and Epstein–Barr virus-associated solitary B cell lymphoma with a T cell immunophenotype

Abstract

Two subtypes of human herpesvirus 8 (HHV8)-associated lymphomas are described in the 2008 World Health Organization (WHO) classifi cation of hematopoietic malignancies [1]. Primary eff usion lymphoma (PEL) is a B cell malignancy primarily presenting with malignant serous eff usions in body cavities, without a solid mass. It is characteristically associated with both HHV8 and Epstein – Barr virus (EBV). Th e lymphoma cells exhibit variable plasmacytoid features and express plasma cell antigens MUM1 and CD138, but lack pan B- and T-cell antigens in general. Apart from extracavitary involvement occurring in a typical PEL, PEL-like lymphomas presenting with a tumor mass without eff usion have been termed extracavitary PEL, which is nearly always a disseminated disease. HHV8-associated large B cell lymphoma arising from multicentric Castleman disease (MCD) typically presents as a nodal lymphoma exclusively associated with HHV8, without EBV co-infection. Th e tumor cells express weak CD20 and/or CD79a, lack CD138 expression despite being consistently MUM1 positive, and always express strong cytoplasmic immunoglobulin M (IgM) and are nearly always lambda-restricted. Rare variants of HHV8and EBV-associated B cell lymphoma beyond these two subtypes were reported to only partially or focally involve lymph nodes, such as germinotropic lymphoproliferative disorder [2], Hodgkin-like large B cell lymphoma and intravascular large cell lymphoma [3]. We report an unusual lymphoma originally presenting as a left axillary mass with no eff usions typical of PEL or evidence of disease dissemination. It was characterized by tumor cells uniformly expressing EBV-encoded RNA (EBER) and multiple pan-T cell antigens, including CD3, resembling a rare primary lymph node-based, EBV-associated T/natural killer (NK) cell lymphoma. However, they were also homogeneously HHV8 positive, and its B cell origin was established by detection of a clonal immunoglobulin heavy chain ( IGH ) gene rearrangement in the absence of detectable T cell monoclonality. Th e patient was a 54-year-old man who was diagnosed with human immunodefi ciency virus (HIV) infection 14 years prior to lymphoma work-up and had been on highly active antiretroviral therapy (HAART; lamivudine, zidovudine, efavirenz) for 5 years. He presented with fevers and a new left axillary mass that developed over a 1-month period. His lactate dehydrogenase (LDH) was 485 U/L and the HIV viral load was undetectable. Th e CD4 count was documented to be 114/ μ L two and a half months earlier. A small incisional biopsy of the mass revealed a focal involvement by an EBV T/NK-cell lymphoma based on the immunophenotypic profi le. Th e patient was fi rst treated with antibiotics for a potential infectious process while undergoing additional studies. Th ere was no evidence of MCD, monoclonal gammopathy or bone marrow involvement by lymphoma. A positron emission tomography (PET) scan did not reveal clear evidence of additional lesions. Two months after the initial biopsy, he was admitted for recurrent fevers and enlargement of the left axillary mass. Given the clinical question to the original diagnosis, an excisional biopsy was performed to better diagnose lymphoma and exclude infection. Th e results of all cultures for microorganisms from the biopsy were negative. Th e morphology and immunophenotype of the second biopsy were similar to those of the fi rst, except for total displacement of the normal tissue by tumor cells. Th erefore, the same diagnosis was again considered. During the hospital stay, the patient had fevers, hypotension, hypoalbuminemia and pancytopenia requiring supportive care. He received two cycles of cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) with initial improvement, followed by deterioration. Meanwhile, additional studies for HHV8 and gene rearrangements on the second biopsy led to a diff erent fi nal diagnosis, the patient was transferred to the National Cancer Institute. At the time of his re-evaluation, he was found to have residual lymphoma in the axillary mass, a newly developed large lymphomatous eff usion in the left pleural cavity and advanced Kaposi sarcoma (KS) with tumor-associated edema. KS was diagnosed 5 years earlier, and had never been treated with chemotherapy, although this information was not