July 2020 — Bone and Soft Tissue & Pulmonary

The correct answer is BCOR-CCNB3.

This is a case of a BCOR-IHCBCOR positive high-grade sarcoma which most commonly have BCOR-CCNB3 translocations. These sarcomas have a variable mixture of round cells that have uniform nuclei, fine chromatin pattern, and monomorphic spindle cells arranged in a fascicular pattern with variable myxoid stroma. These tumors were first described in 2012 and typically have a paracentric inversion on the short arm of chromosome X, resulting in the fusion of BCOR and CCNB3 that leads to the overexpression of CCNB3 (Cyclin B3).

The tumors arise almost exclusively in the soft tissue of young adult males and account for between 4% to 13% of undifferentiated small round cell sarcomas without an EWSR1 rearrangement. There are case reports of primary tumors in the paranasal sinus and lung. However, tumors in the soft tissue will also frequently metastasize to the lungs.

The IHC for BCOR is relatively sensitive/specific but molecular testing is required to confirm the diagnosis. BCOR tumors have a better outcome than CIC-DUX4 fusion tumors.

CIC-DUX4 typically show a higher degree of nuclear variability, with prominent nucleoli.

SS18-SSX is seen in synovial sarcoma which would be expected to be positive for TLE1 and rarely for BCOR by immunohistochemistry.

EWSR1-FLI1 is seen in ewing sarcoma which typically has a more uniform round cell appearance. However, a subset of cases of Ewing sarcoma can be positive for BCOR by IHC.

References
1. Am J Surg Pathol. 2017 Dec;41(12):1713-1721
2. Am J Surg Pathol. 2018 May ; 42(5): 604–615.