title: Fatal HHV-8-associated hemophagocytic syndrome in an HIV-negative immunocompetent patient with plasmablastic variant of multicentric Castleman disease (plasmablastic microlymphoma).
abstract: Virus-associated hemophagocytic syndrome (VAHS) triggered by HHV-8 is extremely rare and has been reported only in 9 immunocompromised patients. We report the first case of HHV-8-associated VAHS in an HIV-negative, immunocompetent patient with plasmablastic variant (plasmablastic microlymphoma) of multicentric Castleman disease (MCD). This 61-year-old man presented with fever, cough, and bilateral inguinal lymphadenopathy. Biopsy of the right inguinal lymph node revealed plasmablastic MCD with nodular aggregates of plasmablasts expressing IgM, MUM1, HHV-8 latency-associated nuclear antigen, and viral interleukin-6. These plasmablasts were monotypic for Iglambda light chain expression but not Igkappa. All the B-cell clonality assays, including IgH-FR2, IgH-FR3, DH-JH, Igkappa, and Iglambda PCR, showed a polyclonal pattern. His serum human interleukin-6 level was markedly elevated and was negative for EBV acute infection/reactivation. The marrow aspirate showed florid hemophagocytosis. His disease progressed rapidly to multisystemic illness, and he died of acute respiratory failure in 1 month. Our case showed that HHV-8 might trigger VAHS in an immunocompetent patient with plasmablastic MCD. We speculated that our patient developed VAHS under the cytokine storm associated with the proliferating HHV-8-infected plasmablasts, similar to the EBV-triggered VAHS in patients with EBV-associated T-cell lymphoma.
authors.affiliation: Department of Pathology, Chi-Mei Foundation Medical Center, 901 Chung-hwa Road, Yung-kang City, Tainan 710, Taiwan.
authors.forename: Chien-Feng
authors.initials: CF
authors.lastname: Li
authors.forename: Hongtao
authors.initials: H
authors.lastname: Ye
authors.forename: Hongxiang
authors.initials: H
authors.lastname: Liu
authors.forename: Ming-Qing
authors.initials: MQ
authors.lastname: Du
authors.forename: Shih-Sung
authors.initials: SS
authors.lastname: Chuang
mesh_terms: D000956:Antigens, Viral / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D001854:Bone Marrow Cells / Q000473:pathology; D005871:Castleman Disease / Q000150:complications*; D017809:Fatal Outcome; D018023:HIV Seronegativity; D006566:Herpesviridae Infections / Q000150:complications* / Q000276:immunology; D019288:Herpesvirus 8, Human / Q000276:immunology; D006801:Humans; D007075:Immunoglobulin M / Q000096:biosynthesis; D007146:Immunoglobulin lambda-Chains / Q000096:biosynthesis; D007150:Immunohistochemistry; D050835:Interferon Regulatory Factors / Q000096:biosynthesis; D015850:Interleukin-6 / Q000097:blood; D051359:Lymphohistiocytosis, Hemophagocytic / Q000150:complications* / Q000821:virology*; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000096:biosynthesis; D010950:Plasma Cells / Q000276:immunology / Q000378:metabolism; D000099218:Interferon Regulatory Factor-4
chemical_list: D000956:Antigens, Viral; D007075:Immunoglobulin M; D007146:Immunoglobulin lambda-Chains; D050835:Interferon Regulatory Factors; D015850:Interleukin-6; D009687:Nuclear Proteins; D000099218:Interferon Regulatory Factor-4; C109540:latency-associated nuclear antigen