title: Primary cutaneous CD4+ small/medium-sized pleomorphic T-cell lymphoma expresses follicular T-cell markers.
abstract: Cutaneous CD4 small/medium-sized pleomorphic T-cell lymphoma (CSTCL) is a cutaneous T-cell lymphoma defined by a predominance of small-to-medium-sized CD4 pleomorphic T cells, with a favorable clinical course. Cases are also characterized by the presence of a rich infiltrate of reactive B cells. Recently, it has been reported that follicular helper T cells (TFH cells) display a distinct gene expression profile, positive for PD-1, CXCL13, and BCL-6. We report for the first time the expression of PD-1 and other TFH cell markers in CSTCLs and discuss its biologic significance. Sixteen CSTCLs were included in this study, and also 20 reactive inflammatory conditions, 10 primary cutaneous marginal zone, 10 follicular center lymphomas, and 5 primary CD30 cutaneous lymphomas. They were immunohistochemically analyzed for a large panel of markers. Double immunoperoxidase labeling of paraffin sections was performed for PD-1, OCT-2, and BCL-6. Clonal Ig and T-cell receptor rearrangements and Epstein-Barr virus-encoded RNA expression were also evaluated. Morphologic and clinical data were reviewed. Histologic examination showed a dense polymorphic lymphoid infiltrate throughout the dermis. Atypical large CD4 cells were positive for PD-1, CXCL13, and BCL-6 in all cases, and were attached in small clusters, or formed rosettes around CD30/OCT-2+ B blast cells. Epstein-Barr virus was not apparent in any of the cases. A dominant T-cell clone was identified in 14 cases, whereas polymerase chain reaction IgH gene rearrangement studies showed that all cases were polyclonal. None of the patients had lymphadenopathy or showed any evidence of systemic disease, nor did they have any previous history of mycosis fungoides or drug reactions. FTH cell markers are not exclusive to angioimmunoblastic lymphadenopathy but may also be seen in neoplastic cells of CSTCLs. Moreover, these findings suggest that B-cell stimulation by FTH could also take place in some cutaneous T-cell lymphomas.
authors.affiliation: Lymphoma Group, Molecular Pathology Programme, Monoclonal Antibody Unit, Biotechnology Programme, Spanish National Cancer Research Centre, Hospital Universitario 12 de Octubre, Madrid, Spain. smrodriguez@cnio.es
authors.forename: Socorro Maria
authors.initials: SM
authors.lastname: Rodríguez Pinilla
authors.forename: Giovanna
authors.initials: G
authors.lastname: Roncador
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Rodríguez-Peralto
authors.forename: Manuela
authors.initials: M
authors.lastname: Mollejo
authors.forename: Juan Fernando
authors.initials: JF
authors.lastname: García
authors.forename: Santiago
authors.initials: S
authors.lastname: Montes-Moreno
authors.forename: Francisca Inmaculada
authors.initials: FI
authors.lastname: Camacho
authors.forename: Pablo
authors.initials: P
authors.lastname: Ortiz
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Limeres-González
authors.forename: Angeles
authors.initials: A
authors.lastname: Torres
authors.forename: Elías
authors.initials: E
authors.lastname: Campo
authors.forename: Pedro
authors.initials: P
authors.lastname: Navarro-Conde
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Piris
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000096:biosynthesis; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis; D014408:Biomarkers, Tumor / Q000032:analysis*; D054382:Chemokine CXCL13 / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D005260:Female; D005455:Fluorescent Antibody Technique; D015322:Gene Rearrangement, B-Lymphocyte; D015329:Gene Rearrangement, T-Lymphocyte; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D016399:Lymphoma, T-Cell / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D061026:Programmed Cell Death 1 Receptor; D051560:Proto-Oncogene Proteins c-bcl-6; D012878:Skin Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; C084103:BCL6 protein, human; D014408:Biomarkers, Tumor; C110663:CXCL13 protein, human; D054382:Chemokine CXCL13; D004268:DNA-Binding Proteins; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D051560:Proto-Oncogene Proteins c-bcl-6