At 27 months after completing treatment, she remained in complete clinical, biological and radiological remission, although the long-term effects of chemotherapy and unilateral adnexal surgery on her reproductive health could not yet be determined. Sertoli–Leydig cell tumors are rare ovarian sex cord–stromal tumors, representing less than 0.5% of all ovarian neoplasms and occurring predominantly in adolescents and young adults. They account for approximately 4% of ovarian tumors diagnosed during childhood, and ovarian malignancies themselves constitute about 1% of childhood cancers.

This patient had an unusual, predominantly estrogenic presentation. Her estradiol concentration was 378 pg/mL, against a reported reference level below 35 pg/mL, while follicle-stimulating hormone and luteinizing hormone were suppressed. The investigators interpreted this pattern as peripheral, gonadotropin-independent precocious puberty caused by ovarian hormone production rather than activation of the central pubertal axis.

The child was first evaluated after her family noticed progressive abdominal distension over two months and reported intermittent vaginal bleeding. Ultrasonography and contrast-enhanced computed tomography showed a large, well-defined, multiloculated solid-cystic abdominopelvic mass measuring 135 by 85 by 165 mm. It displaced the bladder anteriorly and the uterus laterally, with loss of the intervening fat planes around the bladder, abdominal wall, rectum and adjacent bowel loops.

A small amount of free fluid was present, but the exact organ of origin could not be established from the initial scans. Because the appearance raised concern for a sarcomatous lesion, a transabdominal biopsy was performed. Histology showed an undifferentiated neoplastic proliferation, and immunohistochemical positivity for calretinin and inhibin supported classification as a sex cord–stromal tumor, prompting referral to the treating institution for further evaluation.

Contrast-enhanced magnetic resonance imaging at the specialist center demonstrated a lobulated mass measuring 135 by 90 by 195 mm, with heterogeneous signal and both solid and cystic components. Marked enlargement of the left ovarian vascular pedicle, extending superiorly toward the ipsilateral renal vein, suggested a left ovarian origin. The right ovary appeared normal, and no lymphadenopathy or other upper-abdominal abnormality was detected.

Chest CT identified five pulmonary micronodules measuring 2–5 mm, which investigators considered nonspecific rather than definite metastases. Bone age assessed from a hand-and-wrist radiograph was consistent with the girl’s chronological age. On examination, she was 230 by 140 mm below the abdominal wall, with Tanner stage II breast development, Tanner stage III pubic hair and Tanner stage I axillary hair.

No virilization or disorder of sexual differentiation was observed. In addition to the markedly elevated estradiol, inhibin B exceeded 5,000 pg/mL and anti-Müllerian hormone measured 30.2 ng/mL. Testosterone was moderately elevated at 0.479 ng/mL and delta-4-androstenedione at 0.862 ng/mL, while dehydroepiastrosterone sulfate remained within its reported normal range of 2.8–85.2 μg/dL.

Alpha-fetoprotein and beta-human chorionic gonadotropin were also within normal limits. The investigators considered a malignant, hormone-secreting ovarian sex cord–stromal tumor, but the estrogenic presentation clinically overlapped with juvenile granulosa cell tumor. Histopathological and immunohistochemical findings therefore remained essential for distinguishing the tumor and resolving the initial diagnostic uncertainty.

Because the mass was exceptionally large and closely related to adjacent pelvic structures, the multidisciplinary team considered immediate complete resection difficult. The selected strategy was neoadjuvant chemotherapy intended to shrink the tumor and make subsequent surgery less challenging. The girl received three cycles of VIP, comprising etoposide, ifosfamide and cisplatin, every 21 days.

Etoposide was administered at 75 mg/m² on days 1–5, ifosfamide at 3,000 mg/m² on days 1–2 and cisplatin at 20 mg/m² on days 1–5. Follow-up contrast-enhanced CT showed an approximately 65% reduction in tumor size. Estradiol fell to 12.79 pg/mL, inhibin B to 580 pg/mL and testosterone to below 0.025 ng/mL, paralleling the measured reduction in tumor volume.

No specific fertility-preservation procedure was performed before chemotherapy began. Laparotomy subsequently revealed a large encapsulated mass arising from the left ovary and adherent to the omentum. The uterus, contralateral ovary and peritoneum appeared macroscopically normal.

Surgeons performed a left salpingo-oophorectomy and resected the adherent segment of omentum for histopathological assessment; peritoneal washings contained no malignant cells, and the omental tissue was free of tumor. The surgical specimen measured 100 by 90 mm and had a solid-cystic cut surface. Microscopy showed solid sheets and nests of round-to-polygonal cells with clear or eosinophilic cytoplasm, moderately enlarged nuclei and increased mitotic activity.

Necrosis, calcification and fibro-inflammatory changes were interpreted as an approximately 70% treatment response. The initial surgical impression was a sex cord–stromal tumor suggestive of juvenile granulosa cell tumor, but positive androgen-receptor staining supported the final diagnosis of residual Sertoli–Leydig cell tumor. The tumor was classified as FIGO stage IC2 because the transabdominal biopsy performed before treatment had breached the capsule.

This stage assignment was clinically consequential because capsular rupture is regarded as a recurrence risk factor and prompted the decision to administer a fourth cycle of VIP after surgery. Surgical resection remains the main treatment for Sertoli–Leydig cell tumors, while the use of postoperative chemotherapy depends on factors such as stage, differentiation, rupture and histological aggressiveness. Platinum-based combinations are commonly used, with bleomycin, etoposide and cisplatin the most widely reported protocol and VIP an alternative that avoids bleomycin.

The source emphasizes that no universally established standard regimen exists and that evidence is limited by the rarity of these tumors; this single case therefore cannot establish the comparative effectiveness of either regimen. End-of-treatment contrast-enhanced CT of the chest, abdomen and pelvis showed no residual pelvic mass, lymphadenopathy, distant metastatic lesions or ascites. Estradiol, inhibin B, testosterone and delta-4-androstenedione normalized, the gonadotropins were no longer suppressed and anti-Müllerian hormone had fallen below 0.01 ng/mL.

The girl entered follow-up every three months, with clinical assessment, abdominal ultrasound, chest radiography and hormonal testing. Fifteen months after treatment, inhibin B and estradiol rose again, but thoracoabdominal-pelvic CT found no abnormalities other than two pulmonary micronodules measuring 3 and 6 mm, and positron emission tomography showed no significant abnormalities. A repeat assessment found that the hormones had normalized again.

The transient elevations were not accompanied by evidence of recurrence on imaging and should be interpreted cautiously rather than as proof of residual disease. The case illustrates several distinctive features of pediatric ovarian sex cord–stromal tumors: very young age at diagnosis, a giant mass, an estrogen-secreting phenotype that differed from the more common androgenic presentation, and substantial diagnostic overlap with juvenile granulosa cell tumor. It also demonstrates how clinical, radiological, pathological and hormonal evidence can converge in a complex case while remaining distinct forms of evidence.

Inhibin B and estradiol tracked treatment response in this patient, and the later isolated hormone rise showed why hormonal surveillance may be considered alongside imaging, although this single observation does not establish a definitive biomarker strategy. Recent studies have associated Sertoli–Leydig cell tumors, particularly in children, with DICER1 mutations and a broader tumor-predisposition syndrome, but genetic testing was unavailable at the treating institution. The girl had no personal or family history suggesting predisposition.

Her premature breast development progressively regressed, she remained free of detectable disease at 27 months, and continued monitoring of ovarian function and reproductive health remains necessary because the long-term consequences of treatment remain unknown.

Subject of Research: Multidisciplinary management and hormonal monitoring of a pediatric estrogen-secreting ovarian Sertoli–Leydig cell tumor.

Article Title: Multidisciplinary Management of a Giant Ovarian Sertoli–Leydig Cell Tumor Presenting With Isosexual Precocious Puberty: A Pediatric Case Report

Article References: Bouramdane, S., Elmkaddem, K., Hammas, N., Boubbou, M., Alaoui, O., Khattala, K., Bouabdellah, Y., & Benmiloud, S. (2026). Multidisciplinary Management of a Giant Ovarian Sertoli–Leydig Cell Tumor Presenting With Isosexual Precocious Puberty: A Pediatric Case Report. Clinical Case Reports, 14(10), Article e73700. https://doi.org/10.1002/ccr3.73700

Image Credits: AI Generated

DOI: 10.1002/ccr3.73700

Keywords: pediatric oncology, Sertoli–Leydig cell tumor, precocious puberty, ovarian tumor, neoadjuvant chemotherapy, VIP regimen, fertility-sparing surgery, inhibin B, estradiol, DICER1, Multidisciplinary, Management