Ancillary tools for the diagnosis of CIC-rearranged sarcoma: A comprehensive review Review


Authors: Cloutier, J. M.; Al-Rohil, R. N.; Patel, R. M.; Ko, J. S.; Linos, K.
Review Title: Ancillary tools for the diagnosis of CIC-rearranged sarcoma: A comprehensive review
Abstract: CIC-rearranged sarcoma is a rare and aggressive undifferentiated round cell sarcoma that presents significant diagnostic challenges due to its histologic overlap with other round cell sarcomas. This review, conducted on behalf of the American Society of Dermatopathology Appropriate Use Criteria Committee (soft tissue subgroup), provides an overview of current immunohistochemical, cytogenetic, and molecular tests used to support the diagnosis of CIC-rearranged sarcoma. This comprehensive analysis included 36 studies, encompassing 436 CIC-rearranged sarcomas. The immunohistochemical markers, CD99 (typically non-diffuse), nuclear WT1, ETV4, and DUX4, were found to be relatively highly sensitive for CIC-rearranged sarcoma (CD99: 87%, WT1: 83%, ETV4: 85%, DUX4: 97%). However, the specificity of these markers is variable, with CD99 being highly non-specific, while WT1 (81%–90%), ETV4 (95%), and DUX4 (100%) offering greater specificity. CIC break-apart FISH can be a helpful and cost-effective assay for detection of CIC-rearrangements, but has a false-negative rate that ranges from 26% to 43%. Next-generation sequence RNA fusion analysis also carries a risk of false negatives, which may be partly mitigated through manual data review. Ultimately, an accurate diagnosis of CIC-rearranged sarcoma requires careful morphologic assessment in combination with immunohistochemical studies and cytogenetics/molecular assays. © 2025 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Keywords: immunohistochemistry; genetics; metabolism; in situ hybridization, fluorescence; homeodomain proteins; pathology; tumor marker; sarcoma; fluorescence in situ hybridization; gene rearrangement; diagnosis; homeodomain protein; repressor protein; repressor proteins; soft tissue neoplasms; soft tissue tumor; wt1; procedures; humans; human; cd99; biomarkers, tumor; cic; dux4; etv4; cic protein, human; dux4l1 protein, human
Journal Title: Journal of Cutaneous Pathology
Volume: 52
Issue: 4
ISSN: 0303-6987
Publisher: John Wiley & Sons  
Date Published: 2025-04-01
Start Page: 324
End Page: 331
Language: English
DOI: 10.1111/cup.14792
PUBMED: 39921488
PROVIDER: scopus
DOI/URL:
Notes: Source: Scopus
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  1. Konstantinos Linos
    55 Linos