A 35-year-old woman with a history of dysmenorrhea and infertility undergoes transvaginal ultrasound, which reveals a 6 cm right adnexal mass with mixed echogenicity. Serum CA-125 is 85 U/mL (normal <35 U/mL) and serum inhibin A is elevated at 150 pg/mL (normal <45 pg/mL). Which investigation is most appropriate to confirm the diagnosis of granulosa cell tumor of the ovary?

Explanation

## Granulosa Cell Tumor (GCT): Diagnosis by Histology **Key Point:** Granulosa cell tumors are sex cord-stromal tumors of the ovary that are diagnosed **definitively by histopathology**, not by imaging or serum markers alone. ### Clinical Presentation of GCT Granulosa cell tumors typically present with: - Abnormal uterine bleeding or postmenopausal bleeding (due to estrogen production) - Infertility or amenorrhea - Pelvic mass on imaging - Elevated inhibin A and inhibin B (most sensitive tumor markers) - Elevated estradiol and/or anti-müllerian hormone (AMH) ### Tumor Markers in GCT | Marker | Sensitivity | Specificity | Role | |--------|-------------|-------------|------| | Inhibin A/B | 90–95% | High | Best for monitoring; not diagnostic | | AMH | 85–90% | Moderate | Reflects granulosa cell function; not diagnostic | | Estradiol | Variable | Low | Reflects hormone production; non-specific | | CA-125 | 50–70% | Low | Non-specific; seen in many ovarian pathologies | **High-Yield:** Inhibin elevation is characteristic of GCT but is **not pathognomonic**. Diagnosis requires histology. ### Why Histopathology is Essential **Clinical Pearl:** GCT has a distinctive histological pattern: - **Call-Exner bodies** (follicle-like structures with central eosinophilic material) - Grooved or "coffee-bean" nuclei - Immunohistochemistry positive for inhibin, calretinin, and WT1 These features differentiate GCT from other ovarian tumors (dysgerminoma, yolk sac tumor, mature cystic teratoma) that may present with similar imaging and clinical features. **Warning:** Elevated inhibin A and AMH suggest a granulosa cell tumor but do NOT confirm it. Other sex cord-stromal tumors (Sertoli-Leydig cell tumor, thecoma) can also produce inhibin. Only histology is diagnostic. ### Role of Imaging (MRI) MRI is useful for: - Characterizing the mass (solid vs. cystic, vascularity) - Assessing local extension and staging - **But imaging cannot differentiate GCT from other ovarian tumors** **Mnemonic: GCT-HI** — **G**ranulosa **C**ell **T**umor diagnosis = **H**istology + **I**mmunohistochemistry (inhibin, calretinin, WT1). [cite:Robbins 10e Ch 22]