Comparison of Clinical Characteristics and Ultrasound Features of Ovarian Clear Cell Carcinoma and Ovarian High-Grade Serous Carcinoma

Purpose To investigate clinical and ultrasound features for differentiating ovarian clear cell carcinoma (OCCC) from ovarian high-grade serous carcinoma (HGSC). Methods Forty-five patients with OCCC and 72 patients with HGSC were retrospectively studied. Patient clinical characteristics and ultrasound features of tumors were evaluated. The differences, including laterality, menopausal status, Federation of Gynecology and Obstetrics (FIGO) stage between OCCC and HGSC patients were compared by Fisher’s exact test. The ultrasound features of tumors, including laterality, shape, configuration, color score, peritoneal implantation, and ascites, were evaluated and compared between the two groups. boundary; the papillary projections of OCCC are larger and round. In contrast, HGSC was typically a large, irregular tumor with solid masses or mixed cystic-solid masses with small papillary projections.

boundary; the papillary projections of OCCC are larger and round. In contrast, HGSC was typically a large, irregular tumor with solid masses or mixed cystic-solid masses with small papillary projections.
Keywords Ovary, Clear cell carcinoma, High-grade serous carcinoma, Ultrasound Ovarian clear cell carcinoma (OCCC) is a rare subtype of epithelial ovarian cancer (EOC) and comprises approximately 5-10% of ovarian carcinomas. OCCC is different from ovarian high-grade serous carcinoma (HGSC), which is the most common subtype of EOC [1][2][3]. There are many differences in clinical behavior between OCCC and HGSC. Patients with OCCC are younger than patients with HGSC [4,5]. The incidence of venous thromboembolic events was significantly higher in patients with OCCC than in patients with HGSC [6,7]. OCCC has a high frequency of hypercalcemia [8,9]. In general, the therapeutic strategy for OCCC is different from that for HGSC. Therefore, discriminations between these tumors are critical.
Ultrasound is a useful tool for describing characteristics in the preoperative diagnosis of an ovarian lesion.

Study subjects
This retrospective study was approved by the institutional review board of the Beijing

Data collection
Data were collected from all enrolled patients and were compared between the two groups. Assessments included basic characteristics, such as menopausal status, whether with endometriosis, and FIGO stage (postsurgical stage).

Ultrasound examination
All 117 patients underwent presurgical ultrasound examinations of the pelvis with transvaginal ultrasound (supplemented with a transabdominal scan, if necessary).
Standard ultrasonographic examinations were performed using a Logiq E9 or Voluson

Statistical analyses
Statistical analyses were performed with SPSS 19.0 for Windows (SPSS, Inc.,Chicago, IL,USA). The differences between OCCC and HGSC in regard to laterality, shape, mass configuration, color score, ascites, peritoneal metastasis, menopausal status and clinical stage were compared using Fisher's exact test. A P-value less than 0.05 was considered statistically significant.

Results
The maximum diameter of OCCC ranged from 4.8 to 17.6 cm, and those of HGSC ranged from 4.2 to 16.8 cm. Forty-six tumors were found in 45 patients with OCCC; bilateral tumors were found in one patient, and unilateral tumors were found in forty-five patients. Ninety-eight tumors were found in 72 patients with HGSC; bilateral tumors were found in twenty-six patients, and unilateral tumors were found in forty-six patients. The clinical features of OCCC and HGSC are compared in Table 1.
There was a statistically significant difference in the laterality, clinical stage, and FIGO stage(postsurgical stage) between OCCC and HGSC (P <0.05). No statistically significant differences were found in menopause status between the two groups (P=0.805).
The ultrasound features of OCCC and HGSC are compared in There was a statistically significant difference between the two groups in the color score (P=0.025). There were no significant differences between the OCCC and HGSC groups in the mass configuration (P=0.072) and ovarian size(P=0.077). The size of the papillary projections in the OCCC group was 5.40±0.7 cm, while the size of the HGSC group was 2.06±0.4 cm(P<0.001)(Figs1、2、3).

Discussion
The clinical characteristics of CCC and HGSC have been widely explored. OCCC presents more often in younger and premenopausal women than ovarian HGSC [4,12]. The average age at diagnosis in the OCCC group was 57.6±11.1 years, and 35.56% of the patients were premenopausal. However, the average age at diagnosis was 63.4±12.2 years and 33.33% of the patients were premenopausal in the HGSC group. Many researchers have found that OCCC presents more often in the early stages of disease. However, HGSC are more likely to present as advanced-stage disease [13,14]. Our results indicate that 77.78% of OCCC was in the early stage compared with 29.17% of HGSC. There are some reasons why OCCC is diagnosed at an early stage. One of the reasons is that growing tumors are more likely to be confined to the ovary for a longer period of time before spreading, allowing them to be diagnosed at an earlier stage. Another reason may be the higher frequency of symptoms and signs in patients with early-stage OCCC, which leads to early detection.
However, advanced stage OCCC has a worse prognosis than HGSC, because OCCC is less sensitive to platinum-based chemotherapy than HGSC [15,16]. Endometriosis was most frequently associated with OCCC. Several studies confirmed that endometriosis is significantly associated with an increased risk of OCCC. It has been reported that approximately one-third of OCCC arises from endometriosis. In contrast, only 7% of ovarian HGSC patients have a history of ovarian endometriosis [4,5,[17][18][19]. However, Fei-Chun Ku et al. found that a history of endometriosis was not associated with invasive ovarian HGSC [12].
In our clinical practice, we found that ultrasound features differ between OCCC and HGSC. Therefore, we investigated the characteristic features of OCCC and evaluated the use of ultrasound for distinguishing CCC from HGSC. Although ultrasound examinations cannot clearly diagnose the specific histological type of ovarian tumor, some imaging features were more common and more suggestive of particular histologic types.
The sonographic features of OCCC included a well-demarcated hypoechoic mass with smooth and clear margins in 86.96% of patients (40/46); however, HGSC were mostly masses with unclear boundaries (73.47%, 72/98). There was a statistically significant difference between the two groups. It is rare to encounter bilateral involvement among patients with OCCC. Several studies have indicated that patients with OCCC are more likely to present with a unilateral pelvic mass; in contrast, patients with HGSC are more likely to present with a bilateral mass [20,21]. Our results indicate that significant differences were found in unilaterality (97.78% vs 63.89%) between ovarian OCCC and HGSC. In general, OCCC tumors do not have rich al [4]. confirmed that papillary projections are particularly common in OCCC (41.7%) arising from endometriosis. Mural nodules and papillary processes are effective methods for distinguishing the two groups of lesions.
Our study had several limitations. The main limitation was the number of OCCC; therefore, larger samples are necessary to confirm the value of these imaging features for diagnosing OCCC. Second, this was a retrospective study that may lack a desirable study design, and there may have been some selection bias in the patients included in the analyses. Third, the interreader variability was not evaluated.
In our study, we found that there are many differences between OCCC and HGSC. The combination of clinical examinations and different imaging features is conducive to the differential diagnosis of these two tumors, which is helpful for providing valuable imaging information in clinical practice.

Abbreviations
OCCC：ovarian clear cell carcinoma；HGSC：ovarian high-grade serous carcinoma   A 52-year-old woman with pelvic mass was found by physical examination. A A heterogeneous solid mass with an irregular shape was detected in the right ovary by ultrasound examination; B minimal blood flow signals were detected in the mass. C pathological findings showed ovarian clear cell carcinoma.

Fig.2
A 66-year-old woman with pelvic mass was found by physical examination. On ultrasound examination, A In the right ovary, a well-circumscribed cystic mass with papillary projections was seen, the size of which was 3.97×2.39cm. B minimal Doppler flow signals were detected in the papillary projections. C pathological findings showed ovarian clear cell carcinoma.

Fig.3
A 62-year-old woman with pelvic mass was found by ultrasound examination. A A well-circumscribed mass was detected in the left ovary by ultrasound examination; B minimal blood flow signals were detected in the mass. C pathological findings showed ovarian high-grade serous carcinoma.