EWSR1::POU2AF3(COLCA2) Sarcoma: An Aggressive, Polyphenotypic Sarcoma With a Head and Neck Predilection

• Published in: Modern pathology Vol. 36; no. 12; p. 100337
• Main Authors: Koshyk, Olena, Dehner, Carina A., van den Hout, Mari F.C.M., Bempt, Isabelle Vanden, Sciot, Raf, Huang, Hsuan-Ying, Agaimy, Abbas, Din, Nasir Ud, Klubíčková, Natálie, Mosaieby, Elaheh, Skálová, Alena, Michalová, Květoslava, Schöffski, Patrick, Oliveira, Andre M., Halling, Kevin C., Gupta, Sounak, Gross, John M., Nin, Johanna W.M., Michal, Michal, Folpe, Andrew L., Kosemehmetoglu, Kemal, Torres-Mora, Jorge, Michal, Michael
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2023
• Subjects: COLCA2; EWSR1::POU2AF3; gene fusion; neuroendocrine-like; sarcoma; sinonasal tract; soft tissues; spindle cell sarcoma; sinonasal tract; EWSR1::POU2AF3; sarcoma; soft tissues; COLCA2; gene fusion; spindle cell sarcoma; neuroendocrine-like
• ISSN: 0893-3952; 1530-0285
• DOI: 10.1016/j.modpat.2023.100337

EWSR1::POU2AF3 (COLCA2) sarcomas are a recently identified group of undifferentiated round/spindle cell neoplasms with a predilection for the head and neck region. Herein, we report our experience with 8 cases, occurring in 5 men and 3 women (age range, 37-74 years; median, 60 years). Tumors involved the head/neck (4 cases), and one each the thigh, thoracic wall, fibula, and lung. Seven patients received multimodal therapy; 1 patient was treated only with surgery. Clinical follow-up (8 patients; range, 4-122 months; median, 32 months) showed 5 patients with metastases (often multifocal, with a latency ranging from 7 to 119 months), and 3 of them also with local recurrence. The median local recurrence–free and metastasis-free survival rates were 24 months and 29 months, respectively. Of the 8 patients, 1 died of an unknown cause, 4 were alive with metastatic disease, 1 was alive with unresectable local disease, and 2 were without disease. The tumors were composed of 2 morphologic subgroups: (1) relatively bland tumors consisting of spindled to stellate cells with varying cellularity and fibromyxoid stroma (2 cases) and (2) overtly malignant tumors composed of nests of “neuroendocrine-appearing” round cells surrounded by spindled cells (6 cases). Individual cases in the second group showed glandular, osteogenic, or rhabdomyoblastic differentiation. Immunohistochemical results included CD56 (4/4 cases), GFAP (5/8), SATB2 (4/6), keratin (AE1/AE3) (5/8), and S100 protein (4/7). RNA sequencing identified EWSR1::POU2AF3 gene fusion in all cases. EWSR1 gene rearrangement was confirmed by fluorescence in situ hybridization in 5 cases. Our findings confirm the head/neck predilection and aggressive clinical behavior of EWSR1::POU2AF3 sarcomas and widen the morphologic spectrum of these rare lesions to include relatively bland spindle cell tumors and tumors with divergent differentiation.