title: Autoimmune lymphoproliferative syndrome (ALPS) caused by Fas (CD95) mutation mimicking sarcoidosis.
abstract: Autoimmune lymphoproliferative syndrome (ALPS) is an inherited disorder associated with defects in apoptosis, characterized by childhood onset of lymphadenopathy, splenomegaly, hyperimmunoglobulinemia, and autoimmune disease. ALPS is most frequently associated with a mutation in the cell death receptor Fas (CD95). Very rarely a mutation in caspase 10 is present. An increase of CD4/CD8 double negative T cells in the peripheral blood and lymph nodes is a feature characteristic of ALPS. Additionally, histiocytic proliferations resembling sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease) were reported recently in patients with ALPS. In the rare cases with a caspase 10 mutation an accumulation of dendritic cells in lymphoid organs was noted. We describe a different, sarcoidosislike, histiocytic infiltration of lymph nodes that persisted for years in a girl, that was initially supposed to suffer from sarcoidosis, but was eventually diagnosed as ALPS, associated with a missense mutation in the intracellular death domain of Fas. This sarcoidosislike histologic picture extends the spectrum of histiocytic lymph node alterations observed in ALPS and alerts of a potential diagnostic pitfall.
authors.affiliation: Institute of Pathology, Medical University Vienna, Vienna, Austria. leonhard.muellauer@meduniwien.ac.at
authors.forename: Leonhard
authors.initials: L
authors.lastname: Müllauer
authors.forename: Josef
authors.initials: J
authors.lastname: Emhofer
authors.forename: Sabine
authors.initials: S
authors.lastname: Wohlfart
authors.forename: Bettina
authors.initials: B
authors.lastname: Pichlhöfer
authors.forename: Susanne
authors.initials: S
authors.lastname: Stary
authors.forename: Georg
authors.initials: G
authors.lastname: Ebetsberger
authors.forename: Christine
authors.initials: C
authors.lastname: Mannhalter
authors.forename: Andreas
authors.initials: A
authors.lastname: Chott
mesh_terms: D000293:Adolescent; D001327:Autoimmune Diseases / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D003937:Diagnosis, Differential; D005260:Female; D015618:Histiocytosis, Sinus / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D008232:Lymphoproliferative Disorders / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D020125:Mutation, Missense; D012507:Sarcoidosis / Q000175:diagnosis*; D017422:Sequence Analysis, DNA; D019014:fas Receptor / Q000235:genetics*
chemical_list: D015415:Biomarkers; C491901:FAS protein, human; D019014:fas Receptor