The tumor showed an undifferentiated phenotype, including negativity for cytokeratin, although it was immunoreactive to BCOR and MUC4, and was initially suspected as BCOR-associated sarcoma.
Accumulating evidence suggests that internal tandem duplications (ITD) of BCOR are oncogenic drivers in a subset of pediatric sarcomas and rare adult tumors.
The BCOR-CCNB3 positive sarcoma is a recently identified sarcoma morphologically and clinically similar to Ewing sarcoma in adolescents and young adults.
These include gene fusions in vascular neoplasms (FOSB, CAMTA1 and TFE3), round cell sarcomas (BCOR, DUX4 and WT1), and fibroblastic/myofibroblastic tumors (STAT6, ALK and Pan-TRK); amplifications in well-differentiated and dedifferentiated liposarcomas (MDM2 and CDK4); and deletions in several aggressive neoplasms (SMARCB1 and SMARCA4).
More than 50% of cases stained positive for SATB2 and Pax8, raising the hypothesis of a potential use of these markers in the identification of BCOR-CCNB3 positive undifferentiated/unclassified sarcomas.
BCOR-CCNB3 fusion sarcoma is cyclin B3-positive, usually occurs in bone or soft tissue of children, and may mimic a poorly differentiated synovial sarcoma.
BCOR ITD were present in 1 uterine sarcoma diagnosed as HG-ESS and 2 undifferentiated sarcomas with uniform nuclear features, all of which lacked any of the recurrent chromosome translocations known to occur in ESS.
Unsupervised clustering by RNAseq data revealed that tumors with BCOR genetic alterations, including BCOR-CCNB3, BCOR-MAML3, and BCOR ITD, formed a tight genomic group distinct from ES and CIC-rearranged sarcomas.
We herein focus on novel immunohistochemical markers, based on molecular genetic alterations, which are particularly useful in the diagnostic workup of selected groups of soft tissue and bone tumors, including recently described entities, specifically round cell sarcomas (Ewing sarcoma, CIC-rearranged sarcoma, and BCOR-rearranged sarcoma), vascular tumors (epithelioid hemangioma, epithelioid hemangioendothelioma, and pseudomyogenic hemangioendothelioma), SMARCB1-deficient neoplasms, adipocytic tumors (spindle cell/pleomorphic lipoma, atypical spindle cell lipomatous tumor, and conventional atypical lipomatous tumor), giant cell-rich bone tumors (giant cell tumor of bone and chondroblastoma), and biphenotypic sinonasal sarcoma.
We discuss the spectrum of these tumors, from the benign endometrial stromal nodule to low-grade endometrial stromal sarcoma to uterine undifferentiated sarcomas with a special emphasis on the expanding group of high-grade stromal sarcomas, recently added to the 2014 WHO classification, not only discussing the well-established YWHAE-FAM22 tumors but also two new groups, presenting with BCOR alterations including those with BCOR tandem internal duplications or NTRK fusions.
These results are in keeping with a "BCOR-alteration family" of renal and extrarenal neoplasms which includes CCSK and undifferentiated round cell sarcomas of soft tissue/primitive myxoid mesenchymal tumor of infancy (which typically harbor BCOR internal tandem duplication), and BCOR-CCNB3 sarcomas, all of which are primarily driven by BCOR overexpression and have overlapping (but not identical) clinicopathologic features.
Heterogeneous elements included a myxoid spindle cell component in three BCOR-CCNB3 sarcomas and an epithelioid cell component in two CIC-associated sarcomas (one CIC-DUX4-positive and one CIC-DUX4-negative sarcomas).
The spectrum of ELS is now expanding, and additional gene fusion partners besides DUX4 or CCNB3 have been detected, and the terms CIC or BCOR-rearranged sarcomas have recently been proposed.