title: CIC-rearranged Sarcomas: A Study of 20 Cases and Comparisons With Ewing Sarcomas.
abstract: The CIC gene rearrangement exists in a subset of small round cell sarcomas. As the nosologic relationship of these sarcomas to Ewing sarcomas remains undetermined, we examined 20 CIC-rearranged sarcomas to compare their clinicopathologic features with those of Ewing sarcomas. The CIC-rearranged sarcomas were from a group of 14 men and 6 women with a median age of 24.5 years. The primary tumor sites included the limbs, trunk wall, internal trunk, lung, cerebrum, and pharynx. A comparison of the demographic and clinical characteristics of the 20 patients with CIC-rearranged sarcomas with those of the 53 near-consecutive patients with EWSR1-rarranged Ewing sarcomas showed that there were no differences with respect to their ages and sexes. Although none of the CIC-rearranged sarcomas arose in the bone, 40% of the Ewing sarcomas primarily affected the skeleton. The overall survival of patients with Ewing sarcomas was significantly better than that for patients with CIC-rearranged sarcomas. A histologic comparison of the CIC-rearranged sarcomas with 20 EWSR1-rearranged Ewing sarcomas showed significantly higher degrees of lobulation, nuclear pleomorphism, the prominence of the nucleoli, spindle cell elements, and myxoid changes in the CIC-rearranged sarcomas. Distinguishing immunohistochemical features included heterogenous CD99 reactivity, nuclear WT1 expression, and calretinin expression in the CIC-rearranged sarcomas and NKX2.2 expression in the Ewing sarcomas. CIC-rearranged sarcomas are distinct from Ewing sarcomas clinically, morphologically, and immunohistochemically, and they should be considered a separate entity rather than being grouped within the same family of tumors.
authors.affiliation: Departments of *Pathology and Clinical Laboratories §Medical Oncology ∥Musculoskeletal Oncology ¶Pediatric Oncology #Head and Neck Oncology †Rare Cancer Center, National Cancer Center Hospital §§Department of Pathology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo Departments of ‡Diagnostic Pathology **Neurosurgery, Kainan Hospital, Aichi Departments of ††Orthopedic Surgery ‡‡Clinical Laboratory Medicine and Diagnostic Pathology, Shiga University of Medical Science, Shiga, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Yoshida
authors.forename: Keisuke
authors.initials: K
authors.lastname: Goto
authors.forename: Makoto
authors.initials: M
authors.lastname: Kodaira
authors.forename: Eisuke
authors.initials: E
authors.lastname: Kobayashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawamoto
authors.forename: Taisuke
authors.initials: T
authors.lastname: Mori
authors.forename: Seiichi
authors.initials: S
authors.lastname: Yoshimoto
authors.forename: Otone
authors.initials: O
authors.lastname: Endo
authors.forename: Narihito
authors.initials: N
authors.lastname: Kodama
authors.forename: Ryoji
authors.initials: R
authors.lastname: Kushima
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Hiraoka
authors.forename: Toru
authors.initials: T
authors.lastname: Motoi
authors.forename: Akira
authors.initials: A
authors.lastname: Kawai
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D001859:Bone Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D002148:Calmodulin-Binding Proteins / Q000235:genetics*; D003937:Diagnosis, Differential; D005260:Female; D015321:Gene Rearrangement; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins; D011237:Predictive Value of Tests; D011379:Prognosis; D034802:RNA-Binding Protein EWS; D016601:RNA-Binding Proteins / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D012509:Sarcoma / Q000737:chemistry / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D012512:Sarcoma, Ewing / Q000737:chemistry / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D014157:Transcription Factors; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C498610:CIC protein, human; D002148:Calmodulin-Binding Proteins; C500986:EWSR1 protein, human; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins; C000715631:NKX2-2 protein, human; D009687:Nuclear Proteins; D034802:RNA-Binding Protein EWS; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; D014157:Transcription Factors