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

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, one 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 7-119 months), 3 of them along 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 comprised 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 comprised of nests of "neuroendocrine-appearing" round cells surrounded by spindled cells (6 cases). Individual cases in the 2 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 FISH 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.