Adnexal Endometrioid Carcinomas With Sex Cord-Like Morphology are Frequently PAX8-Negative, SOX17-Positive, and Enriched for CTNNB1 Alterations

Sex cord-like morphology is now a well-known feature of occasional examples of endometrioid carcinoma of the ovary or fallopian tube. Recently, we have observed that these tumors are frequently negative for PAX8, prompting us to review their morphologic, immunohistochemical, and genomic spectrum. Twenty tumors (17 ovarian, 3 fallopian tube) with available tissue were identified in patients ranging from 32 to 78 (median 60) years. Sex cord-like patterns included cords/trabeculae (n=17), small tubular glands (n=16), and "granulosa-like" nests (n=12). In addition, 1 had ependymoma-like features with perivascular pseudorosettes and 3 had focal spindled cells. Conventional endometrioid glands were often sparse. All had conspicuous fibromatous stroma and 11 tumors had background endometrioid adenofibromas. Six tumors had associated endometriosis. PAX8 was positive in only 2/20 (diffuse in both), while SOX17 was positive in all (focal in 1, diffuse in 19). Beta-catenin showed aberrant nuclear staining in 17/20. Of the 10 sequenced tumors, 9 showed activating pathogenic variants in CTNNB1; each of these also showed nuclear beta-catenin staining. All lacked alterations in mismatch repair genes, TP53, and POLE. In summary, adnexal endometrioid carcinomas with sex cord-like features are frequently PAX8-negative, which may result in diagnostic difficulty. However, SOX17 is typically positive and thus useful to establish the diagnosis. Most of these tumors are classified in the "no specific molecular profile" subgroup and have high rates of nuclear beta-catenin/CTNNB1 alterations. Awareness of these morphologic and immunohistochemical associations may help avoid misclassification as sex cord-stromal or other neoplasms.