CIC-rearranged sarcoma in the breast: A series of 3 rare cases with literature review.

Abstract

Capticua transcriptional repressor (CIC)-rearranged sarcoma represents a distinct highly aggressive, undifferentiated round cell sarcomas, which most commonly affects young adults. The tumor typically arises in the deep soft tissues of the limbs and trunk, followed by the head and neck region, and is rarely found in visceral organs. CIC-rearranged sarcoma originating in the breast is extremely rare with only one case having been reported in the literature. We report three cases of CIC-rearranged sarcoma in the breast, all occurring in young females and exhibiting aggressive clinical behavior. Microscopically, all three cases showed diffuse or lobular growth of small round blue tumor cells with vesicular nuclei, prominent nucleoli, and clear cytoplasm. Focal reticular growth pattern and myxoid stroma were also observed. The diagnosis of CIC-rearranged sarcoma was confirmed through either fluorescence in situ hybridization (FISH) or RNA sequencing; two of the three cases were confirmed to harbor CIC::DUX4 fusion. This case series, to the best of our knowledge, represents the largest report of CIC-rearranged sarcoma in the breast. It highlights the importance of recognizing this rare entity in the breast due to its aggressive clinical course, poor response to chemotherapy, and high tendency for metastasis. It also emphasizes the utility of molecular studies in distinguishing CIC-rearranged sarcoma from poorly differentiated carcinoma, as CIC-rearranged sarcoma has significantly worse prognosis than poorly differentiated carcinoma of breast.