PTCH1::GLI1 Fusion Tumors of the Ovary: A Clinicopathologic Study of 3 Cases.

GLI1-altered tumors of the gynecologic tract are extremely rare. We report 3 cases of ovarian PTCH1::GLI1 fusion tumor in patients ranging from 54 to 58 yrs of age, who presented with unilateral FIGO stage I tumors. The tumors ranged from 12 to 20 cm and consisted of uniform epithelioid cells with eosinophilic/clear cytoplasm, arranged in nests and trabeculae surrounded by delicate vessels. Variable features included short spindle cells within a myxoid stroma, follicles, small glands/Call-Exner body-like structures, dilated vessels/blood lakes, focal pleomorphism, nuclear grooves, and necrosis. Mitoses ranged from 1 to 10/10 HPFs. Immunohistochemical marker results/number of tumors tested (including primary tumors and recurrences) were as follows: positive for SF-1 (6/6), CD56 (4/4), EMA (3/5), keratins (3/5), SMA (2/5), CD10 (3/4), S100 (3/4), caldesmon (2/3), D2-40 (2/2), Ber-EP4 (2/2), and MOC-31 (1/1), and negative for WT-1 (5/5), calretinin (5/5), inhibin (4/5), ER (4/5), and PR (5/5). Diagnoses initially rendered included adult granulosa cell tumor, unclassified sex cord-stromal tumor, low-grade Müllerian adenocarcinoma, and low-grade endometrioid stromal sarcoma. Surgery was the primary treatment for all. One patient had multiple recurrences at 7, 9, and 13 yrs, had additional surgery, received chemotherapy and radiotherapy, and was alive with no evidence of disease at 13.6 yrs. Another patient had omental recurrence at 5 yrs, received chemotherapy, immunotherapy, and tyrosine kinase inhibitor-targeted therapy, and was alive with disease at 7.9 yrs. The third patient was alive with no evidence of disease at 2 mos. Ovarian PTCH1::GLI1 fusion tumors represent a diagnostic challenge and may recur after several years. Their proper recognition may prompt the use of targeted therapy.