The CIC-DUX4 sarcoma is a small round blue cell sarcoma which presents like extraskeletal Ewing sarcoma, but is negative for the EWSR1 gene translocation.
In light of morphologic features that overlap with those of NC from typical anatomical sites we have seen previously, the tumor was best classified as falling within the NC spectrum rather than CIC-associated sarcoma.
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.
In conclusion, NKX2.2, ETV4 and BCOR IHC may be helpful in daily practice for distinguishing ESFT from CIC or BCOR-associated sarcomas, especially in hospitals without access to molecular assays.
Primitive round- or spindle-cell EWSR1-negative undifferentiated sarcomas harboring CIC-DUX4 gene fusion are the most common form of Ewing-like sarcomas.
The diagnosis of sarcoma with CIC-DUX4 gene fusion is difficult in lack of specific pathological characteristics emphasizing the need for molecular analysis.
As such the WHO classification temporarily grouped the CIC-rearranged tumors under undifferentiated sarcomas with round cell phenotype, until further clinical evidence was available.
ETV transcriptional upregulation is more reliable than RNA sequencing algorithms and FISH in diagnosing round cell sarcomas with CIC gene rearrangements.
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).
This case report describes an additional case of <i>CIC-DUX4</i> sarcoma with a novel fusion breakpoint, and demonstrates the value of this next-generation sequencing-based anchored multiplex PCR technique (Archer FusionPlex Sarcoma Panel) in both diagnosis for patient care and in identification of a novel fusion breakpoint in this tumour type.
We performed a detailed immunohistochemical analysis to investigate ETV4 expression in CIC-rearranged undifferentiated round-cell sarcomas and their potential mimics (especially Ewing 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.