Abstract
Kaposi sarcoma-associated herpesvirus (KSHV) is known to be associated with 3 distinct lymphoproliferative disorders: primary effusion lymphoma (PEL), multicentric Castleman disease (MCD), and MCD-associated plasmablastic lymphoma. We report 3 cases of a previously undescribed KSHV-associated lymphoproliferative disorder. The disease presented as localized lymphadenopathy and showed a favorable response to chemotherapy or radiotherapy. Histologically, the lymphoproliferation is characterized by plasmablasts that preferentially involved germinal centers of the lymphoid follicles, forming confluent aggregates. They were negative for CD20, CD27, CD79a, CD138, BCL6, and CD10 but showed monotypic kappa or lambda light chain. Clusters of CD10(+)CD20(+) residual follicle center cells were identified in some of the follicles. The plasmablasts were positive for both KSHV and EBV, and most of them also expressed viral interleukin-6 (vIL-6). Unexpectedly, molecular analysis of whole tissue sections or microdissected KSHV-positive aggregates demonstrated a polyclonal or oligoclonal pattern of immunoglobulin (Ig) gene rearrangement. The plasmablasts showed somatic mutation and intraclonal variation in the rearranged Ig genes, and one case expressed switched Ig heavy chain (IgA), suggesting that they originated from germinal center B cells. We propose calling this distinctive entity "KSHV-associated germinotropic lymphoproliferative disorder."
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Combined Chemotherapy Protocols / administration & dosage
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use
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Biopsy
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Clone Cells / chemistry
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Clone Cells / pathology
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Cyclophosphamide / administration & dosage
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Doxorubicin / administration & dosage
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Epstein-Barr Virus Infections / drug therapy
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Epstein-Barr Virus Infections / pathology
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Epstein-Barr Virus Infections / radiotherapy
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Epstein-Barr Virus Infections / virology
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Female
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Gene Rearrangement, B-Lymphocyte
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Germinal Center / pathology
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Herpesviridae Infections / drug therapy
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Herpesviridae Infections / pathology*
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Herpesviridae Infections / radiotherapy
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Herpesviridae Infections / virology
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Herpesvirus 4, Human / isolation & purification
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Herpesvirus 4, Human / pathogenicity*
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Herpesvirus 8, Human / isolation & purification
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Herpesvirus 8, Human / pathogenicity*
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Humans
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Immunoglobulin kappa-Chains / analysis
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Immunoglobulin lambda-Chains / analysis
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Immunophenotyping
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Lymphoproliferative Disorders / drug therapy
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Lymphoproliferative Disorders / etiology*
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Lymphoproliferative Disorders / pathology
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Lymphoproliferative Disorders / radiotherapy
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Lymphoproliferative Disorders / virology
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Male
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Middle Aged
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Plasma Cells / chemistry
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Plasma Cells / pathology*
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Plasma Cells / virology
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Prednisone / administration & dosage
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Remission Induction
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Vincristine / administration & dosage
Substances
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Immunoglobulin kappa-Chains
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Immunoglobulin lambda-Chains
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Vincristine
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Doxorubicin
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Cyclophosphamide
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Prednisone