Clinicopathological features of CIC-rearranged sarcomas: a retrospective study including novel visceral locations and methylation profile analysis

CIC-rearranged sarcomas represent a distinct rare pathological entity within the spectrum of undifferentiated small round cell sarcomas. This single institution retrospective study investigates the histopathological, molecular, and clinical characteristics of a cohort of 14 CIC-rearranged sarcomas. These tumors were diagnosed in eight male and six female patients, with the age at initial diagnosis ranging from 8 to 67 years and a mean age of 23.7 years. Among the patients, three novel locations of CIC::DUX4 sarcomas were detected in the mesentery, pancreas, and pterygopalatine fossa. Genetically, we identified 12 cases as CIC::DUX4 sarcomas and two as sarcomas with CIC gene rearrangement detected by break-apart fluorescence in situ hybridization only. The most common gene translocation had a breakpoint located in exon 20 of the CIC gene and exon 1 of the DUX4 gene; this alteration was found in 83% of all CIC::DUX4 cases we identified. We also performed DNA methylation analysis on seven cases, which was proven to be a reliable method with high sensitivity for clustering CIC-rearranged sarcomas.