Human Herpesvirus Type 8-positive Multicentric Castleman Disease

Abstract Castleman disease (CD) is rare lymphoproliferative disorder with local lesionsor with multiple lessions (multicentric CD [MCD]–usually with plasma cell or mix cell morphology). Patients with human herpesvirus (HHV) type 8-positive MCD were included in a separate group owing to its extremely aggressive course and the high risk of transformation into HHV8 + plasmablastic lymphoma. At our hematologic center, from 1996 to the present, the clinical and morphologic features of 87 patients with CD were analyzed. Immunohistochemical examination revealed DNA HHV8 + lymph node tissue in patients with plasma cell and mixed cell morphology. In 45 patients, plasma cell or mixed cell variant CD was diagnosed. In 21 patients (8%), the manifestation of CD was local and in 29 (9%), it was multicentric. HHV8 was identified in only 6 cases (23.1%) of MCD (5 men and 1 woman, with a median age of 48.2 years; range, 36-77 years). The median follow-up point was 39.2 months. In 4 patients, the mixed cell variant was diagnosed and in 2, the plasma cell variant was diagnosed. In all the patients, constitutional symptoms, generalized lymphadenopathy, and hepatosplenomegaly were detected. Various laboratory changes were observed, but the most significant were anemia, thrombocytopenia, hypergammaglobulinemia, M-component, increased erythrocyte sedimentation rate, and circulating immune complexes. In 2 cases of HHV8 + CD, MCD was combined with autoimmune hemolytic anemia and in 2 cases with non-Hodgkin lymphoma. At the last follow-up point, 2 patients were still alive after CHOP (cyclophosphamide, prednisone, Adriamycin, vincristine) and R-CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate [Oncovin], prednisone) therapy with rituximab maintenance. HHV8 + MCD results in aggressive multiorgan lesions and pronounced changes in laboratory test results. It is characterized by an unfavorable prognosis with a high risk of transformation to plasmablastic lymphoma and a lethal outcome. Timely chemotherapy for patients with HHV8 + MCD can result in remission and prolong life.