Co-expression of ERG and CD31 in a subset of CIC-rearranged sarcoma: a potential diagnostic pitfall

Naoki Kojima, Yasuhito Arai, Kaishi Satomi, Takashi Kubo, Yuko Matsushita, Taisuke Mori, Hiromichi Matsushita, Toshikazu Ushijima, Yasushi Yatabe, Tatsuhiro Shibata, Kan Yonemori, Koichi Ichimura, Hitoshi Ichikawa, Akira Kawai, Akihiko Yoshida

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)


CIC-rearranged sarcoma is characterized by round cell undifferentiated histology, frequent expression of ETV4 and WT1, and aggressive behavior. A clinical encounter of a case with CIC-DUX4 fusion and ERG/CD31 co-expression prompted us to systematically investigate ERG and CD31 expression status in 30 archival cases of CIC-rearranged sarcoma. Half (15) of them showed moderate or strong ERG expression in <5–100% of tumor cells, among which nine showed heterogeneous membranous CD31 reactivity, including four cases each showing diffuse or strong expression. None of them showed uniformly strong and diffuse ERG/CD31 co-expression; however, three cases were initially interpreted and treated as angiosarcoma without response. Except for smaller superficial tumor enrichment, the clinicopathological characteristics of these nine cases of ERG+/CD31+ CIC-rearranged sarcoma did not differ from those of remaining 21 cases. Five showed focal hemorrhagic clefts/cysts, mimicking vascular spaces. All tumors expressed ETV4 and/or nuclear WT1, and fusion to DUX4 was confirmed in seven cases. Four tumors examined by next-generation sequencing harbored no CIC missense mutations. Using DNA methylation profiling, one CD31+ CIC-rearranged sarcoma was clustered with CD31− CIC-rearranged sarcomas, but distant from angiosarcomas. When compared with epithelioid angiosarcomas lacking CIC rearrangements, ERG+/CD31+ CIC-rearranged sarcomas were distinguished by focal myxoid change and the entire lack of vasoformative architecture. The angiosarcomas were characterized by uniform strong expression of ERG and CD31, but none of them were found positive for ETV4 or nuclear WT1. Heterogeneous ERG/CD31 co-expression in a subset of CIC-rearranged sarcoma is a clinically relevant pitfall for angiosarcoma, as these two diseases are treated differently.

Original languageEnglish
Pages (from-to)1439-1448
Number of pages10
JournalModern Pathology
Issue number10
Publication statusPublished - 2022 Oct
Externally publishedYes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine


Dive into the research topics of 'Co-expression of ERG and CD31 in a subset of CIC-rearranged sarcoma: a potential diagnostic pitfall'. Together they form a unique fingerprint.

Cite this