Clear Cell Borderline Tumor of the Ovary: A Case Report.

A 22-year-old female visited the gynecology department with a history of menstrual irregularity for 2 months. The patient exhibited no additional symptoms and had no recorded medical history. Physical examination revealed a soft abdomen with no palpable masses. Initial tumor markers, such as cancer antigen (CA) 125 and CA 19-9 were within the normal range. Transabdominal pelvic ultrasonography revealed a 10-cm mass in the pelvic cavity. The mass was mainly echogenic with multiple small peripheral cystic portions ( Fig. 1A ). Pelvic MRI revealed a solid mass with small peripheral cystic areas in the right pelvic cavity. The mass abutted the right ovary anteriorly; the uterus and left ovary appeared to be normal. On T2-weighted image (T2WI), the tumor showed mostly low signal intensity, similar to that of muscles, with multiple variably sized cysts at the periphery ( Fig. 1B ). The tumor showed iso-signal intensity on the T1-weighted image (T1WI) compared to that of the muscle. The mass displayed mild enhancement on contrast-enhanced T1WI ( Fig. 1C ). It showed a mildly high signal intensity on diffusion-weighted imaging and low signal intensity on the apparent diffusion coefficient map ( Fig. 1D ). Based on the MRI findings and considering the hypointense nature of the mass on T2WI, the preoperative differential diagnoses included fibrotic ovarian tumors, such as fibroma, fibrothecoma, and Brenner tumor with cystic changes. During surgery, the mass appeared to be abutting the right ovary. Subsequently, the patient underwent resection of the right pelvic mass, without requiring oophorectomy or pelvic lymphadenectomy. The cut section showed a whitish and fibrotic tumor, with peripheral multilocular cysts ( Fig. 1E ). Microscopically, the tumor contained glands lined by cuboidal cells with atypia and clear cytoplasm, without evidence of stromal invasion ( Fig. 1F ). The final pathological diagnosis was confirmed as CCBOT with an adenofibromatous background associated with endometriosis in the right ovary. Regular follow-up was performed after surgery, without chemotherapy or radiation therapy. No recurrence was observed in the post-operative one year. This study was approved by the Institutional Review Board of our institution (IRB No. 2022GR0330). Informed consent was waived due to the retrospective nature of the study.

Clear cell tumors are a subtype of epithelial ovarian tumors. Most clear cell ovarian tumors are malignant, while benign and borderline clear cell tumors are rare. Clear cell borderline ovarian tumors (CCBOTs) account for less than 1% of all borderline ovarian tumors ( 1 ). CCBOT is defined as “a tumor composed of glands or cysts lined by bland cuboidal to flattened cells with clear or eosinophilic cytoplasm and atypia, but without stromal invasion” ( 2 ). Due to the rarity of CCBOTs, few cases have been reported in the literature ( 1 3 4 ). Herein, we present a case of surgically confirmed CCBOT, and discuss the MRI findings and clinicopathological features.

Borderline ovarian tumors are noninvasive epithelial tumors, which present with higher levels of cytologic atypia and epithelial proliferation compared to benign tumors. Most borderline tumors of the ovary are serous and mucinous tumors ( 3 ). CCBOT is a rare subtype of borderline ovarian tumors. CCBOT is pathologically defined as ‘‘an adenofibromatous clear cell tumor with glandular crowding and low-grade nuclear atypia without stromal invasion” in the 2020 World Health Organization classification ( 1 ). Majority of patients with CCBOT are postmenopausal. In the literature, the mean age of patients was reported as 61 years (range, 30–86 years). Only four cases of CCBOT in premenopausal female have been reported so far ( 1 ). In our case, the patient was a premenopausal 22-year-old female, making her the youngest patient with CCBOT reported, to our knowledge. Patients with CCBOT have a nonspecific clinical presentation; most are asymptomatic, although potential symptoms include abdominal pain, distention, and abnormal uterine bleeding ( 4 ). In our case, the patient’s only complaint was an irregular menstrual cycle. Due to its rarity, the etiology of CCBOT is not yet fully understood. A previous report hypothesized that two possible pathways exist for all types of clear cell ovarian tumors derived from endometriosis. In the first possible pathway, cystic clear cell carcinoma evolves from an endometriotic cyst with epithelial atypia. Second, clear cell adenofibroma develops from a fibromatous reaction in endometriotic cysts, which then progresses to CCBOT and ultimately to adenofibromatous clear cell carcinoma ( 2 ). This hypothesis was consistent with our case, as histopathologic examination revealed an endometriotic background associated with the tumor. Typical MRI findings for most borderline ovarian tumors are purely or predominantly cystic, with papillary projections. This is because over 95% of all borderline ovarian tumors are serous or mucinous ( 5 ). In two published reports by Kleebkaow et al. ( 3 ) and Lee et al. ( 6 ), these tumors appeared as solid or mixed solid and cystic masses. This is consistent with the pathological finding of CCBOT, which is almost always adenofibromatous. In the present case, the tumor appeared as a solid mass with peripheral cysts. The solid portion of the tumor showed low signal intensity on T2WI, which may correlate to fibrotic nature of the tumor. The differential diagnosis for CCBOT includes fibroma, fibrothecoma, and Brenner tumor. These neoplasms have solid components with low T2 signal intensity due to the fibrous stromal tissue ( 7 ). According to Kato et al. ( 8 ), ovarian fibromas are observed in cysts in approximately 53% of the cases. These intratumoral cysts are located at the periphery of the masses, and exophytic cyst formation may be observed in ovarian fibromas. In our case, the cystic portions of the mass were smaller in size, more numerous, and distributed circumferentially along the border of the tumor compared to that of fibromas. Brenner tumors are primarily solid tumors, but several small cysts are often observed in the solid components. The cystic portions are often multilocular, as Brenner tumors are frequently associated with mucinous cystic tumors. Amorphous calcification also occurs more frequently in Brenner tumors than in other fibrous tumors ( 9 ). In the present case, it was difficult to distinguish the origin of the mass in the right pelvic cavity due to the detection of a normal-looking crescent-shaped ovary along the anterior border of the tumor. Oh et al. ( 10 ) previously reported that normal-appearing ipsilateral ovaries were noted in 50% of the ovarian fibromas. The shape of the ovary may be preserved in a fibrotic mass growing outward from the ovary. Thus, we believed that the tumor was not an extraovarian mass, but an exophytic ovarian mass. All reported cases of CCBOT, including ours, represent stage I disease and have a relatively good prognosis ( 1 ). Most CCBOTs are confined to the ovaries at the time of identification ( 1 ). Thus, adjuvant therapy and complete surgical staging can be omitted in most CCBOT cases, and fertility-sparing surgery can be a reasonable option in young patients ( 6 ). In our case, the patient did not undergo ipsilateral oophorectomy or additional treatment after surgery, and was cancer-free in the post-operative one year. Here, we present a rare case of CCBOT in a 22-year-old female. The tumor was a fibrotic ovarian mass, exhibiting T2 low signal intensity with multiple peripherally located small cystic areas on MRI. Although CCBOT is very rare, it can be considered as a differential diagnosis upon discovery of an ovarian fibrotic mass accompanying a cystic portion.