title: Association of the t(12;22)(q13;q12) EWS/ATF1 rearrangement with polyphenotypic round cell sarcoma of bone: a case report.
abstract: The t(12;22)(q13;q12) chromosomal rearrangement results in an EWS/ATF1 fusion transcript and is associated with clear cell sarcoma (CCS). CCS is an uncommon tumor arising in tendons and aponeuroses of the extremities and shows evidence of melanocytic differentiation at the light microscopic, immunohistochemical, and/or ultrastructural level. Only 5 cases have been reported to arise in bone, none of which had molecular confirmation of the diagnosis. The current report describes a 7-year-old girl with a primary round cell sarcoma of the left humerus showing polyphenotypic differentiation on immunohistochemical analysis. Antibodies directed at melanocytic antigens were negative, and there was no evidence of melanocytic differentiation by light microscopy or ultrastructural analysis. Cytogenetic analysis revealed rearrangement of the EWS locus within 22q12. RT-PCR and sequence analysis revealed the presence of a fusion transcript bringing together exon 7 of EWS with exon 5 of ATF1, consistent with a type 2 transcript reported in association with CCS. However, given the lack of morphologic features usually present in CCS, a diagnosis of polyphenotypic round cell sarcoma was made. This tumor thus expands the spectrum of neoplasms associated with the t(12;22)(q13;q12) rearrangement.
authors.affiliation: Department of Paediatric Laboratory Medicine, Hospital for Sick Children, Toronto, Ontario, Canada. gino.somers@sickkids.ca
authors.forename: Gino R
authors.initials: GR
authors.lastname: Somers
authors.forename: Sandra
authors.initials: S
authors.lastname: Viero
authors.forename: Paul C
authors.initials: PC
authors.lastname: Nathan
authors.forename: Ikuko
authors.initials: I
authors.lastname: Teshima
authors.forename: Carlos
authors.initials: C
authors.lastname: Pereira
authors.forename: Maria
authors.initials: M
authors.lastname: Zielenska
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001483:Base Sequence; D001706:Biopsy; D002648:Child; D002881:Chromosomes, Human, Pair 12; D002892:Chromosomes, Human, Pair 22; D020732:Cytogenetic Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D018572:Disease-Free Survival; D005091:Exons; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006811:Humerus / Q000000981:diagnostic imaging / Q000473:pathology / Q000601:surgery; D007150:Immunohistochemistry; D008197:Lymph Node Excision; D008279:Magnetic Resonance Imaging; D008969:Molecular Sequence Data; D009367:Neoplasm Staging; D015514:Oncogene Proteins, Fusion / Q000737:chemistry / Q000235:genetics*; D011859:Radiography; D011877:Radionuclide Imaging; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018227:Sarcoma, Clear Cell / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology* / Q000601:surgery / Q000648:ultrastructure; D017422:Sequence Analysis, DNA; D013997:Time Factors; D014178:Translocation, Genetic; D016896:Treatment Outcome
chemical_list: D004273:DNA, Neoplasm; D015514:Oncogene Proteins, Fusion