Granulosa cell tumours are oestrogen-secreting ovarian sex cord-stromal large cystic tumours with Call-Exner bodies which can present as post-menopausal bleeding in adults or precious puberty in adolescents.
Description
Granulosa cell tumours (GCTs) are a rare form of ovarian neoplasms, constituting approximately 2-5% of all ovarian cancers. These tumours originate from the granulosa cells, which are part of the sex cord-stromal tissue of the ovary and involved in oestrogen production. GCTs are notorious for secreting hormones, specifically oestrogen, which can present with corresponding clinical symptoms.
Pathogenesis
The pathogenesis of GCTs is not fully understood. They are believed to be due to genetic alterations in the FOXL2 gene, a transcription factor necessary for ovarian development. The FOXL2 mutation is thought to induce uncontrolled cell growth and proliferation, resulting in tumour formation.
Subtypes
GCTs are classified into two main types, Adult type and Juvenile type.
- Adult type: More common, accounting for about 95% of all GCTs and typically affecting perimenopausal women.
- Juvenile type: Rare and usually affects girls and adolescents.
Epidemiology, Risk Factors & Associations
- Most common type of ovarian sex cord-stromal tumours (~70%).
- Typically affects perimenopausal or postmenopausal women, but can occur at any age.
- Juvenile type occurs in infants and young girls. May be associated with Maffucci syndrome.
- No well-defined risk factors.
Clinical Features
- Hormonal manifestations due to oestrogen secretion, such as
- Abnormal uterine bleeding: amenorrhea, menometrorrhagia, or postmenopausal bleeding
- Early puberty (in Juvenile GCT)
- Endometrial hyperplasia.
- Pelvic pain or a palpable mass.
Complications
- Risk of malignant transformation and metastasis, particularly to the peritoneum, lymph nodes and lungs.
- High recurrence rate, even several years post initial diagnosis and treatment.
Pathological Features
Histopathology
- Macroscopic: Tumours are typically unilateral, large, cystic, and may contain haemorrhage and necrosis.
- Microscopic: Characterised by the presence of Call-Exner bodies (small cystic spaces filled with eosinophilic fluid, surrounded by granulosa cells).
Serology
- Elevated inhibin B and anti-Müllerian hormone levels.
Biochemistry
- May cause elevated oestrogen levels.
Radiological Features
General Features
- Characteristically demonstrates a large cystic ovarian mass.
- May show solid components, haemorrhage or necrosis.
- Calcification can occur but is relatively rare.
CT
- Non-contrast: Shows a well-defined cystic mass with thin or thick walls.
- Contrast-enhanced: Solid components may show enhancement.
MRI
- T1WI: Cystic components are hypointense, haemorrhage may appear hyperintense.
- T2WI: Cystic components are hyperintense, solid parts are hypointense.
- T1 C+: Solid parts may show enhancement.
US
- B-mode: Shows a multilocular cystic mass with internal echoes.
- Colour Doppler: May show blood flow in the solid parts of the tumour.
NM
- PET FDG: Not typically used in the evaluation of GCTs.
Grading and Staging
The FIGO staging system is used for granulosa cell tumours, similar to other ovarian cancers.
Diagnosis
Diagnosis typically requires a combination of clinical features, imaging findings, and confirmatory surgical biopsy or removal followed by histological analysis.
Differential Diagnosis
- Epithelial ovarian cancer: Typically middle-aged to older women. Often presents with solid and cystic components with enhancing solid areas. Elevated CA-125.
- Ovarian fibroma: Typically seen in postmenopausal women. Characteristically demonstrates a homogeneous, hypoechoic, solid ovarian mass on ultrasound. On MRI, the mass is often hypointense on both T1WI and T2WI.
- Thecoma: Occurs in postmenopausal women and can cause endometrial hyperplasia due to oestrogen secretion, similar to GCT. Radiologically, it is a solid ovarian mass that is hypoechoic on ultrasound and shows delayed enhancement on CT or MRI.
- Metastases to the ovary: Patients typically have a known primary cancer. Ovarian metastases are often bilateral and may present as solid, cystic, or mixed solid-cystic masses. Known as Krukenberg tumours when the metastases originate from the gastrointestinal tract, particularly the stomach.
Management
Surgical removal of the tumour is the mainstay of treatment, with fertility-preserving surgery often possible in younger women. Adjuvant chemotherapy may be required in advanced or recurrent cases.