The value of MRI for differentiating benign from malignant sex cord-stromal tumors of the ovary: emphasis on diffusion-weighted MR imaging

Ovarian sex cord-stromal tumors (SCSTs) are a group of neoplasm arising from stromal cells and primitive sex cord, accounting for 8% of all ovarian tumors [1‐3]. They can affect women of any age [4, 5]. Patients with SCSTs often present virilization syndromes or hyperestrogenic manifestations associated with steroid hormone overproduction [6, 7]. According to World Health Organization (WHO) classification of the ovarian tumors (2014), SCSTs are divided into three clinicopathologic subcategories as pure stromal tumors, pure sex cord tumors and mixed sex cord-stromal tumors [3].

Morphologically, SCSTs often present as a solid mass [8‐13]. On conventional MRI, some features have been found to distinguish SCSTs: Fibromas, known as the most common type of SCSTs, are characterized by very low signal intensity on T2WI and delayed mild enhancement. Sclerosing stromal tumor shows low signal intensity in peripheral area and moderate to high signal intensity in central area on T2WI with intense enhancement. Granulosa cell tumor is multiloculated cystic mass with thickened wall or mixed cystic and solid mass [9, 10]. Sertoli-Leydig cell tumor shows as a well-defined solid mass with numerous intratumoral cysts [1]. However, it is still a challenge for radiologists to differentiate benign from malignant SCSTs based on conventional MRI preoperatively [1‐3]. Diffusion-weighted MR imaging has been proved to be helpful in characterizing epithelial tumors of the ovary. To our knowledge, a comprehensive study on diffusion-weighted MR imaging features specific to SCSTs have not been reported [8]. In this study, we investigate diffusion-weighted imaging of 42 ovarian sex cord-stromal tumors in 41 patients (29 benign SCSTs in 28 patients and 13 malignant SCSTs in 13 patients) to differentiate benign from malignant sex cord-stromal tumors of the ovary. T2 signal intensity and contrast enhancement pattern were also assessed and compared between benign and malignant SCSTs.

Forty-two primary SCSTs were comprised of 29 benign lesions and 13 malignant lesions. The majority of malignant lesions were on stage I (FIGO) except for two lesions (granulosa cell tumors) on stage II (FIGO).

T2 signal intensity of the 42 ovarian sex cord-stromal tumors are summarized in Table 2. Malignant SCSTs showed higher T2 SI than benign SCSTs (Wilcoxon rank sum test, p = 0.04). T2 hypointensity was only seen in benign SCSTs with a sensitivity of 58.6% and specificity of 92.3% in diagnosing benign SCSTs which yield an accuracy of 69.0% for differential diagnosis of the two groups. All of the 10 fibromas were T2 hypointensity (Figs. 1 and 2).

Contrast enhancement pattern of the 42 ovarian sex cord-stromal tumors are summarized in Table 3. Malignant SCSTs did not show more enhancement than benign SCSTs (Wilcoxon rank sum test, p >  0.05). However, mild enhancement was only seen in benign SCSTs with a sensitivity of 58.6% and specificity of 100% in diagnosing benign SCSTs which yield an accuracy of 71.4% for differential diagnosis of the two groups (Figs. 1 and 2).

Fibromas were the tumors with the lowest observed ADC value (0.470 × 10^− 3 mm²/s) (Table 1, Figs. 1 and 2). Sclerosing stromal tumors were the tumors with the highest observed ADC value (2.291 × 10^− 3 mm²/s) (Table 1, Fig. 3).

DW imaging findings of the 42 ovarian sex cord-stromal tumors are summarized in Table 4. The solid component showed high SI in 12 of 13 (92.3%) malignant SCSTs versus in 3 of 29 (10.3%) benign SCSTs (p = 0.000) (Fig. 4).

There was no significant difference in ADC values of solid component between the two groups when fibromas were included (p = 0.639). However, ADC value of solid component was significantly lower in malignant SCSTs (0.825 ± 0.129 × 10^− 3 mm²/s) than in benign SCSTs (1.343 ± 0.528 × 10^− 3 mm²/s) when fibromas were excluded (p = 0.024) (Figs. 4 and 5). ROC curve analysis yielded an optimal ADC value threshold of 0.838 × 10^− 3 mm²/s for differentiating malignant from benign tumors with a sensitivity of 61.5%, a specificity of 89.5% and an accuracy of 78.1%.

Considering each of the three sequences of T2, DCE and DW imaging has a limited value on the differential diagnosis of the benign and malignant SCSTs with an accuracy of 69.0%,71.4% and 78.1% respectively, we developed a multiparametric assessment which combined T2 with DCE and DW imaging. The assessment uses a 3-point scale based on the likelihood that the MRI findings correlates with the malignance of an ovarian sex cord-stromal tumor (Table 5). The assessment of the ovarian sex cord-stromal tumors was categorized as: 1- benign; 2- high likelihood to be benign; 3- high likelihood to be malignant. Category 1 (benign) was defined as a lesion which has typical MRI findings of T2 hypointensity or mild enhancement (Figs. 1 and 2). In case DCE showed non-mild enhancement, the lesion is further assessed on DW imaging. Category 2 (high likelihood to be benign) was define as a lesion which has non-mild enhancement with a high ADC value(Fig. 3). When a lesion showed moderate enhancement, a lower ADC value than 0.838 × 10^− 3 mm²/s uprate the lesion to category 3(high likelihood to be malignant) (Fig. 4). When a lesion showed intense enhancement, a lower ADC value than 1.000 × 10^− 3 mm²/s uprate the lesion to category 3(high likelihood to be malignant).

Combination of T2, DCE and DW imaging is helpful for differential diagnosis of benign and malignant SCSTs with an accuracy of 88.0%.

Degeneration in SCSTs demonstrated as edema, hemorrhage and demarcated cysts (Table 6).

Edema and hemorrhage was only found in benign SCSTs. Edema area in lesion showed moderate signal intensity on DW imaging with a high ADC value. Hemorrhage showed high signal intensity on DW imaging with a low ADC value. Demarcated cysts were found in 14% of benign lesions versus 90% of malignant lesions. Numerous mini cysts within the solid mass were only seen in malignant lesions.

Fibromas can be distinguished from other types of SCSTs based on the specific features on conventional MR imaging. Shinagare [14] reported that fibromas are abundant in bland spindle cells and intercellular collagen which contribute to the remarkable low signal intensity on T2WI and slight enhancement by contrast agent [15‐18]. In this study, we found that T2 hypointensity is more specific than mild enhancement to fibromas. So T2WI is the dominant sequence to distinguish fibromas from the the rest of SCSTs. Also, fibromas were the tumors with the lowest ADC value. Bland spindle cells and intercellular collagen lined so densely that water molecule movement is more restricted in less intercellular space.

Although both T2 hypointensity and mild enhancement play a role in distinguishing benign SCSTs with a specificity of 100%, mild enhancement is more sensitive to benign SCSTs (Category 1). In case a lesion has a non-mild enhancement, the lesion should be further assessed on DW imaging (Category 2). The ADC value threshold to uprate a lesion of Category 2 to Category 3 was 0.838 × 10^− 3 mm²/s.

Sclerosing stromal tumors were the only subtype of benign SCSTs which were enhanced intensely [2, 3]. We found that sclerosing stromal tumors were the tumors with the highest observed ADC value (2.291 × 10^− 3 mm²/s). The explanation may be that the tumor has a characteristic microscopic pattern with pseudolobulation of the cellular areas separated by hypocellular areas of loose edematous connective tissue. Atram [19] reported that the edematous stromal change is a constant feature of sclerosing stromal tumors of the ovary. Sertoli-leydig tumors were the subtype of malignant SCSTs which were enhanced intensely [2, 3, 20]. The mean ADC value of sertoli-leydig tumors was 1.009 × 10^− 3 mm²/s. So when a lesion showed intensely enhancement, we recommended a much higher ADC value threshold of 1.000 × 10^− 3 mm²/s to uprate the lesion to Category 3.

Degeneration in SCSTs is common which demonstrated as edema, hemorrhage and cyst change [14, 21]. Edema and hemorrhage were only observed in benign lesions. However, demarcated cysts were observed in benign and malignant lesions. Kato [21] reported that up to 53% of fibromas demonstrated intratumoral cysts in their study.

There are some limitations in our study. First, it is a retrospective study. We just try to discuss about differentiation between benign and malignant sex cord-stromal tumors. We did not discuss about how to differentiate SCSTs from other pathological types of ovarian solid tumors. Prospective large sample investigation merits further study. Secondly, completely objective measurements of ADC value are usually difficult because sex cord-stromal tumors tumors tend to be heterogeneous masses. Thirdly, the variation in ADC between the subtypes of sex cord-stromal tumors is large.

T2, DCE and DW imaging has a limited value on the differential diagnosis of the benign and malignant SCSTs with an accuracy of 69.0%,71.4% and 78.1% respectively. Combination of T2, DCE and DW imaging is more helpful which permit the distinction with an accuracy of 88.0%.