Malignant transformation of a testosterone-secreting ovarian steroid cell tumor: a case report

• Benign-appearing SCT-NOS transformed into metastatic disease three years after initial surgical resection. • Sequencing showed tumor evolution with mutations in ATM , LZTR1 , and later STK11 during disease progression. • Benign-appearing SCT-NOS carries malignant potential; patients should be counseled on the rare but real risk of recurrence. Ovarian Steroid Cell Tumors (SCT) are rare sex cord–stromal tumors accounting for less than 0.1% of ovarian neoplasms. Most are hormonally active and present with symptoms of androgen excess. Steroid cell tumor, not otherwise specified (SCT-NOS), represents the majority of cases and carries the greatest malignant potential, although most tumors are benign and cured with surgical excision. Malignant transformation of an initially benign SCT-NOS is rarely reported, and the molecular mechanisms underlying progression remain poorly characterized. A 41-year-old woman presented with amenorrhea, acne, and hirsutism with markedly elevated testosterone. Imaging demonstrated an 8-cm predominantly solid right adnexal mass. She underwent laparoscopic right salpingo-oophorectomy, and pathology revealed SCT-NOS without histologic features of malignancy. Testosterone normalized postoperatively, and she was managed with surveillance. Three years later, she presented with dyspnea and abdominal pain; imaging demonstrated pleural effusion, ascites, pelvic masses, and peritoneal carcinomatosis. Cytoreductive surgery confirmed malignant SCT-NOS with nuclear atypia, necrosis, and increased mitotic activity. Despite adjuvant carboplatin, paclitaxel, and bevacizumab followed by maintenance therapy, she developed platinum-resistant progression with peritoneal and nodal disease and is currently receiving additional systemic therapy with poor response. Longitudinal next-generation sequencing demonstrated molecular evolution during disease progression. The recurrent, malignant tumor harbored variants in ATM and LZTR1 , and the platinum-resistant recurrence showed an additional deletion of STK11 . These alterations involve pathways regulating DNA damage response, RAS/MAPK signaling, and cellular growth. This case presents a rare ovarian steroid cell tumor, not otherwise specified, initially managed with unilateral salpingo-oophorectomy and surveillance given its benign pathologic features. Three years later, the patient developed malignant recurrence. Despite complete surgical cytoreduction and administration of platinum-based adjuvant chemotherapy, the patient experienced disease progression. This case highlights the potential for malignant transformation in benign-appearing SCT-NOS and underscores the importance of counseling patients on the rare risk of recurrence and the need for novel therapeutic strategies in recurrent disease. Integration of clinical, pathologic, and molecular data may improve risk stratification and management of this rare tumor. Ovarian Steroid Cell Tumors (SCT) are a rare subgroup of sex cord-stromal tumors that account for less than 0.1% of primary ovarian neoplasms ( Hayes and Scully, 1987 , Qian et al., 2016 ). They are most commonly diagnosed in women between the ages of 20 and 60, with a peak incidence in the fourth decade of life. Approximately 56–77% of ovarian steroid cell tumors secrete testosterone or other androgens with one-third of patients presenting with signs of androgen excess − such as hirsutism, acne, or virilization − due to tumor-related steroid hormone secretion ( Chung et al., 2014 , Wang et al., 1998 ). Despite their rarity, their hormonal activity often leads to early clinical detection compared to other ovarian neoplasms.