title: Epithelioid rhabdomyosarcoma: a clinicopathologic and molecular study.
abstract: Rhabdomyosarcoma (RMS) is the most common pediatric soft tissue sarcoma and is mostly represented by the embryonal (ERMS) and alveolar (ARMS) histotypes. Whereas ERMS shows variable genetic alterations including TP53, RB1, and RAS mutations, ARMS carries a gene fusion between PAX3 or PAX7 and FOXO1. Epithelioid RMS is a morphologic variant of RMS recently described in adults. Five cases of epithelioid RMS were identified after histologic review of 85 cases of ARMS enrolled in Italian therapeutic protocols. Immunostaining analyses (muscle-specific actin, desmin, myogenin, AP-2β, EMA, cytokeratins, INI-1) and reverse transcription polymerase chain reaction assays to detect MyoD1, myogenin, and PAX3/7-FOXO1 transcripts were performed. In 4 cases DNA sequencing of TP53 was performed; and RB1 allelic imbalance and homozygous deletion were analyzed by quantitative real-time polymerase chain reaction. Histologically, epithelioid RMS displayed sheets of large cells without rhabdomyoblastic differentiation or anaplasia in 3 and prominent rhabdoid cells in 2; necrosis was evident in 4, often with a geographic pattern. Immunostainings for INI, desmin, myogenin (scattered cells in 4, diffuse in 1) were positive in all; EMA and MNF116 were positive in 2; AP-2β was negative. PAX3/7-FOXO1 transcripts were absent. In all cases RB1 was wild type, and a TP53 mutation at R273H codon was found in 1. All patients are in complete remission, with a median follow-up of 6 years. Epithelioid RMS may occur in children and is probably related to ERMS, as suggested by lack of fusion transcripts, weak staining for myogenin, negative AP-2β, evidence of TP53 mutation (although only in 1 case), and a favorable clinical course.
authors.affiliation: *Pediatric Hematology-Oncology Clinic Departments of ‡Molecular Immunology and Oncology §Department of Pediatric Surgery, University Hospital of Padova #Section of Pathology, Department of Medicine, DIMED †Istituto di Ricerca Pediatrica Città della Speranza, Padova ∥Department of Pediatric Hematology/Oncology, Giannina Gaslini Children's Hospital ¶Department of Research and Diagnostic, IRCCS Istituto G. Gaslini, Genova, Italy.
authors.forename: Angelica
authors.initials: A
authors.lastname: Zin
authors.forename: Roberta
authors.initials: R
authors.lastname: Bertorelle
authors.forename: Patrizia
authors.initials: P
authors.lastname: Dall'Igna
authors.forename: Carla
authors.initials: C
authors.lastname: Manzitti
authors.forename: Claudio
authors.initials: C
authors.lastname: Gambini
authors.forename: Gianni
authors.initials: G
authors.lastname: Bisogno
authors.forename: Angelo
authors.initials: A
authors.lastname: Rosolen
authors.forename: Rita
authors.initials: R
authors.lastname: Alaggio
mesh_terms: D000293:Adolescent; D000367:Age Factors; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics*; D002648:Child; D015622:Epithelioid Cells / Q000737:chemistry* / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D007558:Italy; D008297:Male; D010641:Phenotype; D012074:Remission Induction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012208:Rhabdomyosarcoma / Q000737:chemistry* / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor