High-grade undifferentiated small round cell sarcoma with t(4;19)(q35;q13.1) CIC-DUX4 fusion: emerging entities of soft tissue tumors with unique histopathologic features--a case report and literature review

Abstract

Background: A subset of undifferentiated small round cell sarcomas (USRCSs) is currently being recognized as emerging entities with unique gene fusions: CIC-DUX4 (the area of focus in this article), BCOR-CCNB3, or CIC-FOXO4 gene fusions. CIC-DUX4 and CIC-FOXO4 fusions have been reported in soft tissue tumors, while BCOR-CCNB3 fusion with an X chromosomal inversion was described in both bone and soft tissue tumors. CIC-DUX4 fusion can either harbor t(4;19)(q35;q13.1) or t(10;19)(q26.3;q13), while t(4;19)(q35;q13.1) is reported more commonly.

Case report: The aim of this study is to share a new case report of a 36-year-old woman who had a rapidly growing mass in her right upper thigh, which was found to be an undifferentiated small round cell sarcoma with t(4;19)(q35;q13.1) CIC-DUX4 fusion was confirmed by cytogenetic testing. Combined modality treatment with surgery, radiation, and chemotherapy was used and achieved a good response. A review of the literature of the reported cases with CIC-DUX4 fusions including both t(4;19) and t(10;19) translocations revealed a total of 44 cases reported. Out of these 44 cases, 33 showed t(4;19)(q35;q13.1) translocation compared to 11 cases with t(10;19)(q26.3;q13).

Conclusions: Undifferentiated small round cell sarcomas are aggressive tumors. Their treatment includes surgery, chemotherapy, and radiation. Resistance to chemotherapy is common. Lung and brain are common sites of metastasis, with associated poor prognosis. Generally, median survival is less than 2 years. Newer techniques have been developed recently which helped identify a subset of previously unclassifiable sarcomas, with promising prognostic value.

Figure 1.

(A) CT scan of the femur at diagnosis which shows a 4.3×5.6×6.2 cm of an extra muscular mass in the proximal, medial right thigh, see arrow. (B) MRI of the right femur 11 months later showing no residual lesions or masses.

Figure 2.

(A) 100× magnification Round cell sarcoma at center of photo, left: geographic tumoral necrosis, right: fibrous septa. (B) 400× magnification Round cell sarcoma with moderate nuclear pleomorphism, coarse nuclear chromatin and prominent nucleoli, variably scant cytoplasm, and numerous abnormal mitotic figures.

Figure 3.

Immunohistochemical stain (400×): (A) Ki-67: Strong nuclear staining in >90% of tumor cells. (B) Bcl-2: 100% strong cytoplasmic staining of tumor cells. (C) Pankeratin: Focal, strong cytoplasmic staining of tumor cells. (D) CD31: Patchy, strong cytoplasmic staining of tumor cells. (E) CD99: Focal, weak membranous staining pattern of tumor cells.

Figure 4.

CIC-DUX4 fusion detected by FISH using a dual-color, single-fusion probe: BAC clone RP11-521G19 (green) centromeric to DUX4 on chromosome 4 and RP11-778C1 (red) telomeric to CIC on chromosome 19. CICDUX4 translocation results in 1 fused (yellow), 1 red, and 1 green signal (normal 2R: 2G; fused 1R: 1G: 1Y). RP11-108K14 (centromeric to DUX4L, light blue on chromosome 10) is also shown. There is no evidence of a t10;19 fusion.