CIC-rearranged sarcoma:a clinicopathological analysis of 10 cases

Abstract

Objective: To investigate the clinicopathologic features, immunophenotype and prognosis of CIC-rearranged sarcoma (CRS). Methods: The clinical and pathological data of 10 cases of CRS diagnosed between January 2017 and December 2018 at the Department of Pathology,Fudan University Shanghai Cancer Center were analyzed. Immunohistochemical study and fluorescence in situ hybridization (FISH) were performed. The literature was reviewed. Results: There were five males and five females with a mean age of 28 years (range, 5 to 63 years). Eight tumors developed in the somatic soft tissues, including trunk (n=3),head and neck (n=3),and extremities (n=2). One case each arose in the small intestine and the occipital lobe. The average size was 4.9 cm (range,1.5-8.0 cm). Microscopically,all cases were composed of small to medium-sized round, oval to short spindled cells, showing nodular or lobular architecture, or were arranged in sheets. Compared with Ewing sarcoma, tumor cells of CRS usually showed irregular nuclear outline, coarse chromatin with prominent nucleoli and brisk mitotic activity. Necrosis was present in four cases with one showing geographic necrosis. Immunohistochemically, tumor cells usually showed focal or patch staining of CD99 (9/10),diffuse and strong nuclear expression of WT1 in half cases (2/4),and a high Ki-67 index (median 70%). By FISH, nine cases demonstrated convincing break-apart signal of CIC gene. Follow-up data available in seven cases (mean 12.1 months); of these two patients died of disease (2/7), whereas one patient was alive with unresectable recurrent tumor,the remaining four patients were alive with no evidence of disease. Five patients (5/7) experienced local recurrence and two patients (2/7) developed metastasis. The mean and median intervals to recurrence/metastasis were eight months and four months, respectively. Conclusions: CRS is the most common type of EWSR1-negative small round cell sarcoma (SRCS). Although it has clinical and pathological overlapping features with Ewing sarcoma,the prognosis is comparatively poor. Focal or patch staining of CD99 but diffuse staining of WT1 in a case of small RCS should raise the possibility of CRS. FISH assay is required for the final diagnosis.