Clear cell carcinoma arising in a seromucinous borderline tumor with co-existing endometriosis- Case report of a rare association

Dear Editor, Seromucinous tumors are a raelatively recent addition to the various types of epithelial ovarian neoplasms, including their benign, borderline and malignant counterparts.[] Uncommonly, these tumors have been found to be associated with various carcinomas, including their rare co-existence with clear cell carcinomas (CCCs).[] A 50-year-old, postmenopausal lady presented with complaints of heaviness and bloating in her lower abdomen accompanied with pain over a duration of 15 days. Her abdominal and vaginal examination was unremarkable. Her blood counts and routine biochemical test results were within normal limits. Her abdominopelvic ultrasonogram revealed a 6.4 cm × 3 cm multicystic left adnexal mass with an unremarkable right-sided ovary and uterus. A computed tomogram (CT) scan showed a multiloculated cystic adnexal mass with a mural nodule. Her serum tumor marker level for CA-125 was 2552 U/mL (normal range = 0–35 units/mL) and for CA19.9 was 1545 U/mL (normal range = 0–37 units/mL). She underwent an exploratory laparotomy, including excision of the left adnexal mass, which was reported as a serous borderline tumor of the ovary, during the intraoperative frozen section examination. Thereafter, she underwent a total hysterectomy, along with right salpingo-oophorectomy and omentectomy. The cytology smears prepared from minimal intraperitoneal fluid were negative for malignant cells. On gross examination, the left adnexal mass measured 8.8 cm × 5.3 cm × 3.4 cm. The external surface was bosselated and the capsule was intact. Tumor mass was predominantly cystic, containing brown viscous fluid and few solid areas with papillary excrescences. The right-sided ovary, uterus with cervix and omentum were unremarkable. Microscopic examination of the multiple sections of the left adnexal mass revealed features of a borderline epithelial neoplasm, composed of ciliated epithelium (serous-type) along with interspersed cells containing intracytoplasmic mucin. One of the sections, in addition, showed features of invasive carcinoma with cells displaying prominent nucleolization, vacuolated cytoplasm, indicative of a CCC. By immunohistochemistry tumor cells in the areas of CCC showed diffuse granular cytoplasmic positivity for Napsin and negativity for estrogen receptor (ER) and WT1. On the other hand, cells in the areas of the seromucinous borderline tumor showed diffuse immunostaining for ER and negativity for WT1. P53 immunostain was focally positive (wild-type). [Figure 1] Another section showed foci of endometriosis, which was reinforced by CD10 immunostaining [Figure 2]. The final diagnosis offered was CCC ovary, co-existing with seromucinous borderline tumor and endometriosis. The patient was rendered with Stage I CCC ovary. She received 6 cycles of adjuvant Paclitaxel and Carboplatin and is currently asymptomatic. Prior to its recognition as a distinct entity, a seromucinous borderline tumor was included in the category of mucinous tumors. However, these tumors failed to exhibit distinct histopathological and immunohistochemical profile of mucinous tumors.[] Architecturally, these tumors resemble serous borderline tumors and show immunoexpression of ER and PR, similar to serous tumors. However, they lack WT1 immunostaining, unlike serous tumors. This has led to their categorization as a distinct entity.[] The present case showed similar histopathological features, including papillary architecture, ciliated lining epithelial cells, focally containing intracytoplasmic mucin, exhibiting diffuse ER immunostaining, but lacking WT1 immunostaining. In addition, we observed distinct tumor areas of CCC, reinforced with Napsin A immunostaining. Nakamura et al.[] described the first case of bilateral ovarian seromucinous borderline tumors associated with CCC, in association with polypoid endometriosis, in the ovaries and in the colon. Similar to the present case, borderline seromucinous tumor component, in that case, was immunopositive for ER and PR and negative for Napsin A and hepatocyte nuclear factor (HNF) 1β, whereas the CCC component showed the reverse immunostaining pattern. Earlier, seromucinous borderline tumors have been found to be associated with an endometrioid adenofibroma and a squamous cell carcinoma, in a single case, each, respectively.[] The ovarian carcinomas, known to be associated with endometriosis are CCCs and endometrioid adenocarcinomas.[] A subset of seromucinous borderline ovarian tumors has also been reported with co-existing endometriosis.[] The loss of tumor suppressor ARID1A has been associated with malignant transformation.[] However, presently in view of the lack of this test in our molecular laboratory, we could not test our case for ARID1A mutation. Nonetheless, the present case reinforces the association of endometriosis with both, seromucinous tumor and CCC, constituting the second such case report. However, it is difficult to ascertain whether these tumors arose from endometriosis. The value of extensive tissue sampling in cases of ovarian tumors, including seromucinous type, cannot be overemphasized, considering these are heterogeneous. An exact diagnosis has treatment implications. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest. REFERENCES - 1. Kurman RJ CM, Herrington CS, Young RHKurman RJ CM, Herrington CS, Young RH. Seromucinous tumors WHO Classification of Tumors of Female Reproductive Organs. 2014 Lyon IARC:307 - 2. Kurman RJ, Shih IeM. Seromucinous tumors of the ovary. what's in a name? Int J Gynecol Pathol. 2016;35:78–81 - 3. Vang R, Gown AM, Barry TS, Wheeler DT, Ronnett BM. Ovarian atypical proliferative (borderline) mucinous tumors: Gastrointestinal and seromucinous (endocervical-like) types are immunophenotypically distinctive Int J Gynecol Pathol. 2006;25:83–9 - 4. Nakamura E, Sato Y, Moriguchi S, Yamashita A, Higo T, Asada Y. Ovarian seromucinous borderline tumor and clear cell carcinoma: An unusual combination Case Rep Obstet Gynecol. 2015;2015:690891. - 5. Samartzis EP, Samartzis N, Noske A, Fedier A, Caduff R, Dedes KJ, et al Loss of ARID1A/BAF250a-expression in endometriosis: A biomarker for risk of carcinogenic transformation? Mod Pathol. 2012;25:885–92