title: Neuroendocrine carcinoma associated with X-linked hyper-immunoglobulin M syndrome: report of four cases and review of the literature.
abstract: X-linked hyper-immunoglobulin M syndrome (XHIGM) is a primary immunodeficiency disorder characterized by severe defects of both cellular and humoral immunity due to impaired expression of CD40 ligand on activated T lymphocytes. Patients with XHIGM usually present with a wide variety of infections caused by common and opportunistic pathogens including Pneumocystis jirovecii. In addition, subjects with XHIGM have an increased risk for hepatocellular and bile duct carcinomas, which are rarely observed in other primary immunodeficiencies. We present here clinical, immunological, and molecular findings of four patients with CD40 ligand deficiency associated with neuroendocrine carcinoma (NEC). NEC developed as a rapidly disseminated solid cancer leading to death in three patients. Data presented here and published previously suggest that CD40 ligand deficiency may predispose patients for the development of NEC. Histochemical findings suggested that CD56, in addition to cytokeratin and chromogranin A, may be a useful marker for early detection of NEC. We conclude that patients with XHIGM should be carefully followed to diagnose and treat NEC, a formidable neuroendocrine cancer.
authors.affiliation: Department of Infectious and Pediatric Immunology, Medical and Health Science Center, University of Debrecen, Nagyerdei krt. 98, H-4032 Debrecen, Hungary.
authors.forename: Melinda
authors.initials: M
authors.lastname: Erdos
authors.forename: Miklós
authors.initials: M
authors.lastname: Garami
authors.forename: Eva
authors.initials: E
authors.lastname: Rákóczi
authors.forename: Attila
authors.initials: A
authors.lastname: Zalatnai
authors.forename: Daniel
authors.initials: D
authors.lastname: Steinbach
authors.forename: Ulrich
authors.initials: U
authors.lastname: Baumann
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Kropshofer
authors.forename: Beáta
authors.initials: B
authors.lastname: Tóth
authors.forename: László
authors.initials: L
authors.lastname: Maródi
mesh_terms: D000293:Adolescent; D023201:CD40 Ligand / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D018278:Carcinoma, Neuroendocrine / Q000150:complications* / Q000235:genetics / Q000276:immunology; D002648:Child; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004067:Digestive System Neoplasms / Q000150:complications* / Q000235:genetics / Q000276:immunology; D017809:Fatal Outcome; D006801:Humans; D053307:Hyper-IgM Immunodeficiency Syndrome, Type 1 / Q000150:complications* / Q000235:genetics / Q000276:immunology; D007132:Immunoglobulin Isotypes / Q000097:blood; D008297:Male
chemical_list: D007132:Immunoglobulin Isotypes; D023201:CD40 Ligand; D004247:DNA