Discussion

This case illustrates the diagnostic and therapeutic complexity of advanced poorly differentiated ovarian Sertoli-Leydig cell tumors in elderly patients. Although most Sertoli-Leydig cell tumors are diagnosed at an early stage and have favorable outcomes, poorly differentiated tumors are associated with a higher risk of recurrence, extraovarian spread, and reduced survival [1-5]. Presentation in older women is uncommon and may be associated with non-specific symptoms, larger tumor burden, and delayed diagnosis [1,2]. Presentation in older women and outcomes in advanced disease have also been described in institutional series and retrospective cohorts [14].

The diagnostic pathway in this case was particularly challenging. Initial biopsies showed overlapping epithelial and mesenchymal features, raising the possibility of alternative diagnoses, including mesenchymal tumors of uterine or adnexal origin. This reflects a recognized pitfall of poorly differentiated sex cord-stromal tumors, which may display heterogeneous morphology and a broad immunohistochemical profile [3,5]. In such cases, expert pathology review is essential to avoid misclassification and to guide appropriate management [3,5].

Hormonal evaluation was a useful diagnostic clue. Markedly elevated estradiol levels, together with mildly increased testosterone, supported the diagnosis of a hormonally active sex cord-stromal tumor. Estrogen-producing Sertoli-Leydig cell tumors are uncommon but have been reported, and endocrine evaluation may provide additional diagnostic information in atypical cases [6,7]. Persistent postoperative estradiol elevation was observed throughout follow-up. This finding was most consistent with active residual disease, although hormonal markers should be interpreted in conjunction with clinical and radiological findings, as their relationship with tumor burden may be variable.

Surgery remains the cornerstone of treatment for Sertoli-Leydig cell tumors, particularly in advanced or poorly differentiated disease [8,9]. Advanced stage, poor differentiation, and residual macroscopic disease were all adverse prognostic factors [4,9]. Complete macroscopic cytoreduction (R0/CC-0) remains one of the most important prognostic factors in ovarian malignancies and should be pursued whenever safely feasible. In the present case, complete resection was precluded by extensive unresectable disease and the anticipated risk of severe surgical morbidity, highlighting the adverse prognostic implications of residual disease.

Molecular characterization may also be relevant. DICER1 mutations have been frequently described in moderately and poorly differentiated Sertoli-Leydig cell tumors, whereas FOXL2 testing may assist in the differential diagnosis with other ovarian sex cord-stromal tumors [3,10,11]. In the present case, molecular testing was attempted, but suboptimal sample quality prevented completion of the analysis.

The optimal systemic treatment for advanced ovarian sex cord-stromal tumors remains uncertain. Bleomycin, etoposide, and cisplatin have historically been used, particularly in younger patients, but bleomycin- and cisplatin-related toxicities may limit its use in elderly or comorbid patients [12]. Carboplatin-paclitaxel may therefore represent a reasonable alternative when the goal is to achieve disease control with a more favorable tolerability profile [12,13]. In this patient, carboplatin-paclitaxel allowed the completion of nine cycles, but the disease ultimately progressed.

This case also underscores the need for early integration of palliative care in aggressive rare ovarian tumors. When evidence-based options are limited and prognosis is poor, treatment decisions should incorporate patient preference, symptom burden, frailty, expected toxicity, and quality of life [8,9,12,15].