title: CD3-CD4+ lymphoid variant of hypereosinophilic syndrome: nodal and extranodal histopathological and immunophenotypic features of a peripheral indolent clonal T-cell lymphoproliferative disorder.
abstract: The CD3(-)CD4(+) lymphoid variant of hypereosinophilic syndrome is characterized by hypereosinophilia and clonal circulating CD3(-)CD4(+) T cells. Peripheral T-cell lymphoma has been described during this disease course, and we observed in our cohort of 23 patients 2 cases of angio-immunoblastic T-cell lymphoma. We focus here on histopathological (n=12 patients) and immunophenotypic (n=15) characteristics of CD3(-)CD4(+) lymphoid variant of hypereosinophilic syndrome. Atypical CD4(+) T cells lymphoid infiltrates were found in 10 of 12 CD3(-)CD4(+) L-HES patients, in lymph nodes (n=4 of 4 patients), in skin (n=9 of 9) and other extra-nodal tissues (gut, lacrymal gland, synovium). Lymph nodes displayed infiltrates limited to the interfollicular areas or even an effacement of nodal architecture, associated with proliferation of arborizing high endothelial venules and increased follicular dendritic cell meshwork. Analysis of 2 fresh skin samples confirmed the presence of CD3(-)CD4(+) T cells. Clonal T cells were detected in at least one tissue in 8 patients, including lymph nodes (n=4 of 4): the same clonal T cells were detected in blood and in at least one biopsy, with a maximum delay of 23 years between samples. In the majority of cases, circulating CD3(-)CD4(+) T cells were CD2(hi) (n=9 of 14), CD5(hi) (n=12 of 14), and CD7(-)(n=4 of 14) or CD7(low) (n=10 of 14). Angio-immunoblastic T-cell lymphoma can also present with CD3(-)CD4(+) T cells; despite other common histopathological and immunophenotypic features, CD10 expression and follicular helper T-cell markers were not detected in lymphoid variant of hypereosinophilic syndrome patients, except in both patients who developed angio-immunoblastic T-cell lymphoma, and only at T-cell lymphoma diagnosis. Taken together, persistence of tissular clonal T cells and histopathological features define CD3(-)CD4(+) lymphoid variant of hypereosinophilic syndrome as a peripheral indolent clonal T-cell lymphoproliferative disorder, which should not be confused with angio-immunoblastic T-cell lymphoma.
authors: Institute of Immunology, French Eosinophil Network and Research Unit EA2686, Lille University Hospital, Université Lille Nord de France, Lille Department of Internal Medicine - Clinical Immunology Unit and Research Unit EA2686, Lille University Hospital, Université Lille Nord de France, Lille guillaume.lefevre@chru-lille.fr.
authors: Guillaume
authors: G
authors: Lefèvre
authors: Institute of Pathology and CNRS Unit Research UMR 8161, Lille University Hospital, Université Lille Nord de France, Lille.
authors: Marie-Christine
authors: MC
authors: Copin
authors: Institute of Hematology and Inserm Unit U837, Lille University Hospital, Université Lille Nord de France, Lille.
authors: Christophe
authors: C
authors: Roumier
authors: Department of Dermatology, Nantes University Hospital, Nantes.
authors: Hélène
authors: H
authors: Aubert
authors: Department of Dermatology, Angers University Hospital and UNAM University, Angers.
authors: Martine
authors: M
authors: Avenel-Audran
authors: Institute of Hematology and Inserm Unit U837, Lille University Hospital, Université Lille Nord de France, Lille.
authors: Nathalie
authors: N
authors: Grardel
authors: Institute of Hematology and Inserm Unit U837, Lille University Hospital, Université Lille Nord de France, Lille.
authors: Stéphanie
authors: S
authors: Poulain
authors: Department of Dermatology, Lille University Hospital, Université Lille Nord de France, Lille.
authors: Delphine
authors: D
authors: Staumont-Sallé
authors: Department of Dermatology and Pediatric Dermatology, National Reference Center for Rare Skin Diseases and Inserm Unit Research U1035, Bordeaux University Hospital, Bordeaux.
authors: Julien
authors: J
authors: Seneschal
authors: Department of Hematology, Lyon Sud University Hospital, Hospices Civils de Lyon, Lyon 1 University, Bron.
authors: Gilles
authors: G
authors: Salles
authors: Department of Onco-Hematology, Beauvais Hospital.
authors: Kamel
authors: K
authors: Ghomari
authors: Department of Internal Medicine - Clinical Immunology Unit and Research Unit EA2686, Lille University Hospital, Université Lille Nord de France, Lille.
authors: Louis
authors: L
authors: Terriou
authors: Department of Dermatology, Angers University Hospital and UNAM University, Angers.
authors: Christian
authors: C
authors: Leclech
authors: Department of Internal Medicine, Annecy Hospital, Annecy.
authors: Chafika
authors: C
authors: Morati-Hafsaoui
authors: Department of Internal Medicine, Bicêtre University Hospital - APHP, Paris Sud XI University, Le Kremlin-Bicêtre.
authors: Franck
authors: F
authors: Morschhauser
authors: Department of Hematology, Lille University Hospital, Université Lille Nord de France, Lille.
authors: Olivier
authors: O
authors: Lambotte
authors: Department of Hematology, Lille University Hospital, Université Lille Nord de France, Lille.
authors: Félix
authors: F
authors: Ackerman
authors: Institute of Immunology, French Eosinophil Network and Research Unit EA2686, Lille University Hospital, Université Lille Nord de France, Lille.
authors: Jacques
authors: J
authors: Trauet
authors: Institute of Hematology and Inserm Unit U837, Lille University Hospital, Université Lille Nord de France, Lille.
authors: Sandrine
authors: S
authors: Geffroy
authors: Institute of Hematology and Inserm Unit U837, Lille University Hospital, Université Lille Nord de France, Lille.
authors: Florent
authors: F
authors: Dumezy
authors: Inserm Unit Research U995, Lille University Hospital, Université Lille Nord de France, Lille.
authors: Monique
authors: M
authors: Capron
authors: Institut de Génétique Médicale, Inserm Unit U837, Lille University Hospital, Université Lille Nord de France, Lille.
authors: Catherine
authors: C
authors: Roche-Lestienne
authors: Department of Dermatology and Pediatric Dermatology, National Reference Center for Rare Skin Diseases and Inserm Unit Research U1035, Bordeaux University Hospital, Bordeaux.
authors: Alain
authors: A
authors: Taieb
authors: Department of Internal Medicine - Clinical Immunology Unit and Research Unit EA2686, Lille University Hospital, Université Lille Nord de France, Lille.
authors: Pierre-Yves
authors: PY
authors: Hatron
authors: Institute of Immunology, French Eosinophil Network and Research Unit EA2686, Lille University Hospital, Université Lille Nord de France, Lille.
authors: Sylvain
authors: S
authors: Dubucquoi
authors: Institute of Immunology, French Eosinophil Network and Research Unit EA2686, Lille University Hospital, Université Lille Nord de France, Lille Department of Internal Medicine - Clinical Immunology Unit and Research Unit EA2686, Lille University Hospital, Université Lille Nord de France, Lille.
authors: Eric
authors: E
authors: Hachulla
authors: Institute of Immunology, French Eosinophil Network and Research Unit EA2686, Lille University Hospital, Université Lille Nord de France, Lille.
authors: Lionel
authors: L
authors: Prin
authors: Institute of Immunology, French Eosinophil Network and Research Unit EA2686, Lille University Hospital, Université Lille Nord de France, Lille.
authors: Myriam
authors: M
authors: Labalette
authors: Institute of Immunology, French Eosinophil Network and Research Unit EA2686, Lille University Hospital, Université Lille Nord de France, Lille Department of Internal Medicine - Clinical Immunology Unit and Research Unit EA2686, Lille University Hospital, Université Lille Nord de France, Lille.
authors: David
authors: D
authors: Launay
authors: Institute of Hematology and Inserm Unit U837, Lille University Hospital, Université Lille Nord de France, Lille.
authors: Claude
authors: C
authors: Preudhomme
authors: Institute of Immunology, French Eosinophil Network and Research Unit EA2686, Lille University Hospital, Université Lille Nord de France, Lille Department of Internal Medicine, Foch Hospital and Versailles-Saint-Quentin-en-Yvelines University, Suresnes, France.
authors: Jean-Emmanuel
authors: JE
authors: Kahn
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D017252:CD3 Complex / Q000378:metabolism*; D015704:CD4 Antigens / Q000378:metabolism*; D060965:Clonal Evolution; D003937:Diagnosis, Differential; D005260:Female; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor; D006801:Humans; D017681:Hypereosinophilic Syndrome / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D007150:Immunohistochemistry; D016130:Immunophenotyping; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D016411:Lymphoma, T-Cell, Peripheral / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012867:Skin / Q000378:metabolism / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000378:metabolism* / Q000473:pathology*; D055815:Young Adult
chemical_list: D017252:CD3 Complex; D015704:CD4 Antigens