Comparative Molecular Profiling of "Mixed Endometrioid Adenocarcinoma and Adenosarcoma" of the Uterus and Ovary: A Multi-institutional Series of 14 Cases.

Abstract

"Mixed endometrioid adenocarcinoma and adenosarcoma" is a recently described malignancy of the uterus and ovary characterized by discrete components of Mullerian adenosarcoma and typically low-grade endometrioid adenocarcinoma. Its molecular biology, natural history, and proper classification remain uncertain. We analyzed clinicopathologic data and performed comparative molecular analysis on the adenocarcinomatous and adenosarcomatous components of 14 tumors using a 168-gene next-generation sequencing panel (n=11) and the MSK-IMPACT assay (n=3). Thirteen tumors were stage I, and 1 stage II. The epithelial component was endometrioid carcinoma in 12 (86%), endometrioid intraepithelial neoplasia in 1 (7%), and mesonephric-like adenocarcinoma in 1. The adenosarcomatous component showed sarcomatous overgrowth in 8 (57%), high-grade atypia in 4 (29%), heterologous differentiation in 10 (71%), and lymphovascular invasion in 3 (21%). The adenocarcinomatous and adenosarcomatous components shared molecular alterations in all cases, including mutations in ARID1A (10, 71%), KRAS (8, 57%), DICER1 (7, 50%), PIK3CA (7, 50%), PTEN (6, 43%), and PIK3R1 (4, 29%). Twelve tumors were of no specific molecular profile and 2 were microsatellite instability-high. Four (31%) patients recurred, and 3 (23%) died of disease 7, 8, and 18 months after hysterectomy. Prognosis correlated with high-risk morphologic features in the adenosarcomatous component, including sarcomatous overgrowth, extensive rhabdomyosarcomatous differentiation, vascular invasion, and high-grade nuclear atypia. "Mixed endometrioid adenocarcinoma and adenosarcoma" is a clonal biphasic malignant neoplasm of uncertain histogenesis, with a high frequency of DICER1 mutations.