• To review the MR imaging spectrum of granulosa cell tumors • To discuss the pearls and pitfalls in the differential diagnosis
Background Granulosa cell tumor (GCT) is the most common malignant sex-cord stromal tumor of the ovary and well-known for its estrogen-producing feature (1). GCTs differ from epithelial and sex-cord stromal ovarian tumors in histologic appearance, biological profile, clinical course and imaging findings. There are two histopathological subtypes of GCT, adult and juvenile types, presenting with different clinical implications (2). Adult granulosa cell tumors are far more common than the juvenile type and accounts for 95% of all granulosa cell tumors. Due to hyperestrogenism, endometrial hyperplasia, polyps or endometrial carcinomas may accompany to GCT. GCTs are known for their and propensity for late recurrence, which may present with recurrence even decades after diagnosis (3). In this educational poster, we aim to review the clinical features and MR imaging spectrum of ovarian granulosa cell tumors with emphasis on pearls and pitfalls in the diagnosis. Clinical symptoms Patients may be asymptomatic or have abnormal uterine bleeding, abdominal pain, or distention due to torsion, hemorrhage, or rupture (2). About two thirds of patients present with endocrine manifestations due to hormone secretion by the tumor, leading to early diagnosis (4). GCTs originate from granulosa cells which are hormonally active components of ovarian stroma and responsible for estradiol production. Because of estrogen production, patients frequently present with menometrorrhagia or postmenopausal bleeding due to disordered proliferative endometrial patterns and irregular breakdown. Patients have increased risk of concurrent endometrial hyperplasia (up to 50%) and endometrial adenocarcinoma (up to 10%) (1). In prepubertal period, patient may present with isosexual pseudo precocity. Rarely, GCTs may be androgenic and may cause virilization. If tumor is not associated with hormone secretion, patients typically present with abdominal pain, which may create acute conditions associated with rupture and hemoperitoneum. Imaging features There is a wide spectrum of imaging features in adult ovarian granulosa cell tumors, varying from homogeneous solid masses to tumors with different degrees of hemorrhagic or fibrotic changes, multilocular cystic lesions, to completely cystic tumors. GCTs have predominantly solid or solid-cystic gross pathological morphology. Occasionally, they may present as uni or multilocular cysts. On T2-weighted images, different signs have been reported such as honeycomb or Swiss-cheese sign for multiloculated form. Intratumoral hemorrhage, infarcts, fibrous degeneration, and irregular arrangement of tumor cells may explain the heterogeneity in solid GCTs. When compared to the epithelial neoplasm of the ovary, GCTs do not have intracystic papillary projections. On diffusion-weighted-imaging, ADC values may overlap with ovarian fibromas. Enhancement may vary from mild to avid. Recurrent tumors may present as discrete peritoneal or retroperitoneal masses with variable imaging appearances similar to the primary GCTs. According to the imaging appearances on MRI, GCTs could be classified as follows: • Solid, homogeneous GCT GCT may grow in an entirely solid pattern (Fig 1). These tumors are almost always well-demarcated and non-invasive (5). The solid component of the tumor tends to how show low to intermediate signal intensity on T2WI, reflecting the rich fibrous stroma characterizing the sex-cord stromal tumor group (Fig 2). They show diffuse homogeneous diffusion restriction. • Solid heterogeneous GCT Diffuse adult GCTs may sometimes have striking fibromatous background, which may mimic cellular ovarian fibromas. In addition, the prominent thecomatous stromal component in GCTs may cause challenges in distinguishing GCTs from thecomas or fibrothecomas. T2 signal intensity becomes heterogeneous in those solid heterogeneous GCTs with intermediate signal referring to GCT and low signal referring to fibromotous or thecomatous stromal component (Fig 3). • Solid GCT with cystic / necrotic component Occasionally, a cystic or necrotic component may occur in the solid GCTs (Fig 4). It may be challenging to differentiate between malignant ovarian epithelial tumor and GCT in those cases. Necrotic areas appear as irregular T2 hyperintense areas in the solid parenchyma (Fig 5). • Unilocular/oligolocular cystic GCT Rarely GCTs may present as a unilocular or oligolocular cystic morphology without obvious solid tissue or septa. In those cases, it may be difficult to differentiate from benign cystic lesions of the ovary such as cystadenoma (Fig 6). • Multilocular GCT o Multilocular with “honeycomb sign” “Honeycomb sign” is used to describe multiple rounds cystic loculi in the solid component of ovarian tumors (3). Those cysts range in size and resemble honeycomb (6). The proportion of cystic components is usually higher than that of solid components on T2WI with high signal or mixed signal intensity resembling sponge like changes (Fig 7). o Multilocular with “Swiss-cheese sign” “Swiss-cheese sign" also describes multiple locules of fluid in the GCT as honeycomb sign. However, this sign refers to more solid components than “honeycomb sign”, fewer and scattered larger cysts with thicker separation between multiple cystic foci (Fig 8) (3). Fluid-hemorrhage level or diffuse hemorrhagic signal in the cystic loculi can be seen which is the characteristic feature of cystic GCTs.
Figure 1. A 37-year-old woman with a left ovarian mass. Sagittal (A) and axial (B) T2W images show a solid tumor (arrows) with lobulated well-defined borders and homogeneous intermediate signal intensity. Histopathology confirmed granulosa cell tumor of the ovary.
Figure 2. A 57-year-old woman with a right ovarian mass. Sagittal (A) and axial (B) T2W images show a solid tumor (arrows) with well-defined borders and homogeneous low signal intensity. Diffusion-weighted imaging with b value 800 (C) and ADC map (D) show marked diffusion restriction. Histopathology confirmed granulosa cell tumor of the ovary on the background of a fibroma.
Figure 3. A 87-year-old woman with a left adnexal mass. Sagittal (A) and axial (B) T2W images show a solid tumor (arrows) with lobulated well-defined borders and heterogeneous low-to-intermediate signal intensity. Histopathology confirmed granulosa cell tumor of the ovary with fibrothecomatous stroma.
Figure 4. A 52-year-old woman with a 24 cm pelvic mass. Sagittal (A) and axial (B) T2W images show a solid tumor (arrows) with lobulated well-defined borders and heterogeneous signal intensity. There is a large necrotic area in the center of the tumor (asterisk). Histopathology confirmed diffuse type granulosa cell tumor of the ovary.
Figure 5. A 54-year-old woman with a 13 cm pelvic mass. Coronal (A) and axial (B) T2W images show a solid tumor (arrows) with irregular borders and heterogeneous signal intensity. There is an intermediate signal to hyperintense large necrotic area in the center of the tumor (asterisk). Histopathology confirmed adult type granulosa cell tumor of the ovary with necrosis.
Figure 6. A 83-year-old woman with a gross cystic mass filling the intraperitoneal cavity. Coronal localizer image (A) and axial (B) T2W images show a cystic tumor with thin wall and few septa. There are three T2 hyperintense homogeneous cystic locules (asterisk) without solid component regarding an oligocystic tumor. Note that there is accompanying ascites. Histopathology confirmed adult type granulosa cell tumor of the ovary.
Figure 7. A 48-year-old woman with a cystic mass in the right adnexa. Sagittal (A) and axial (B) T2W images show a multiloculated cystic tumor with numerous T2 hyperintense small cystic locules in consistent with “honeycomb sign”. There are also small scattered solid areas with intermediate signal intensity. Histopathology confirmed granulosa cell tumor of the ovary.
Figure 8. A 48-year-old woman with a large cystic mass in the right adnexa. Sagittal (A) and axial (B) T2W images show a multiloculated cystic tumor with multiple T2 hyperintense cystic locules in different size in consistent with “Swiss-cheese sign”. Note that there are solid areas in between locules with intermediate signal intensity. A fluid-fluid level is seen in one of the locules (arrows). Histopathology confirmed granulosa cell tumor of the right ovary.
The radiologic appearance of ovarian granulosa cell tumors varies from a small solid mass to a large cystic mass. Knowledge of key imaging features and imaging spectrum of GCTs may allow the specific diagnosis, hence appropriate surgical planning.