title: HHV-8+, EBV+ multicentric plasmablastic microlymphoma in an HIV+ Man: the spectrum of HHV-8+ lymphoproliferative disorders expands.
abstract: Human herpesvirus-8 (HHV-8) is associated with several distinct lymphoproliferative disorders: primary effusion lymphoma, multicentric Castleman disease (MCD), MCD-associated plasmablastic lymphoma and HHV-8+, Epstein-Barr virus (EBV)+ germinotropic lymphoproliferative disorder. We report the case of a human immunodeficiency virus (HIV)+ male with fever, generalized lymphadenopathy, and splenomegaly. Two peripheral lymph nodes were excised and showed features of MCD and a prominent proliferation of HHV-8+, EBV+, CD20, CD138, MUM1+, lambda dim+, Ig heavy chain plasmablasts and immunoblasts replacing some follicles. Subsequently, a splenectomy and biopsy of retroperitoneal lymph nodes were performed; the retroperitoneal and splenic hilar lymph nodes showed changes similar to those in the peripheral lymph nodes while the markedly enlarged spleen showed replacement of occasional white pulp by the HHV-8+, EBV+ large cells. The histologic features and coinfection by EBV and HHV-8 suggested a diagnosis of HHV-8+ germinotropic lymphoproliferative disorder. However, the occurrence in an HIV+ individual, the background of MCD, the widespread anatomic distribution and the aggressive clinical course tended to exclude germinotropic lymphoproliferative disorder, and to favor multifocal plasmablastic microlymphoma. The patient died shortly after surgery; postmortem examination showed progression to overt lymphoma. The marrow showed extensive hemophagocytosis, consistent with development of a hemophagocytic syndrome. This unique case has clinical features compatible with a MCD-associated plasmablastic lymphoproliferative disorder, with pathologic features intermediate between HHV-8+ plasmablastic microlymphoma, and HHV-8+ germinotropic lymphoproliferative disorder, although in contrast to both of these, in our case, light chain expression was dim and heavy chain was not detected.
authors.affiliation: *The James Homer Wright Pathology Laboratories of the Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Rania M
authors.initials: RM
authors.lastname: Seliem
authors.forename: Rogers C
authors.initials: RC
authors.lastname: Griffith
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Harris
authors.forename: Javad
authors.initials: J
authors.lastname: Beheshti
authors.forename: Fred J
authors.initials: FJ
authors.lastname: Schiffman
authors.forename: Janina
authors.initials: J
authors.lastname: Longtine
authors.forename: Jeffery
authors.initials: J
authors.lastname: Kutok
authors.forename: Judith A
authors.initials: JA
authors.lastname: Ferry
mesh_terms: D018951:Antigens, CD20 / Q000032:analysis; D001854:Bone Marrow Cells / Q000473:pathology / Q000821:virology; D005871:Castleman Disease / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology / Q000821:virology; D049109:Cell Proliferation; D003937:Diagnosis, Differential; D018450:Disease Progression; D017809:Fatal Outcome; D006679:HIV Seropositivity / Q000150:complications*; D004854:Herpesvirus 4, Human / Q000302:isolation & purification*; D019288:Herpesvirus 8, Human / Q000302:isolation & purification*; D006801:Humans; D050835:Interferon Regulatory Factors / Q000032:analysis; D019394:Ki-67 Antigen / Q000032:analysis; D008198:Lymph Nodes / Q000473:pathology / Q000821:virology; D051359:Lymphohistiocytosis, Hemophagocytic / Q000473:pathology / Q000821:virology; D008223:Lymphoma / Q000276:immunology / Q000473:pathology / Q000821:virology*; D008232:Lymphoproliferative Disorders / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D017464:Receptors, Complement 3d / Q000032:analysis; D013163:Splenomegaly / Q000473:pathology / Q000821:virology; D053668:Syndecan-1 / Q000032:analysis; D000099218:Interferon Regulatory Factor-4
chemical_list: D018951:Antigens, CD20; D050835:Interferon Regulatory Factors; D019394:Ki-67 Antigen; D017464:Receptors, Complement 3d; D053668:Syndecan-1; D000099218:Interferon Regulatory Factor-4; C508241:SDC1 protein, human