Synchronous endometrial and ovarian carcinoma is a rare instance and it accounts for 50 to 70% of all synchronous female genital tract tumors. However, it is very rare to find synchronous endometrial carcinoma and ovarian sex cord–stromal tumor (thecoma). The present case is a 75-year-old woman with a complaint of post-menopausal vaginal bleeding. Radiologically, the magnetic resonance imaging (MRI) pelvis revealed altered signal intensity mass in the uterus. Frozen section and routine histopathological examination were done on radical hysterectomy. Microscopically, serous carcinoma involving uterine corpus and left Fallopian tube was identified along with the unusual finding of contralateral ovarian sex cord–stromal tumor (thecoma), which was confirmed on immunohistochemical examination. It is a very rare association and is first reported in the present study after a thorough search of the published literature. Their relationship based on a high level of estrogen produced by the hyperactive ovary is controversial as serous carcinomas are less hormone-dependent.
Keywords: Serous carcinoma, sex cord–stromal tumor, synchronous tumors, thecoma
|How to cite this article:
Sethi N, Sharma R, Khunteta N, Vijay MK, Mehrol C, Yadav M L. Synchronous uterine serous carcinoma and ovarian sex cord stromal tumor (thecoma)–A rare first case report. Indian J Pathol Microbiol 2022;65:437-9
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Sethi N, Sharma R, Khunteta N, Vijay MK, Mehrol C, Yadav M L. Synchronous uterine serous carcinoma and ovarian sex cord stromal tumor (thecoma)–A rare first case report. Indian J Pathol Microbiol [serial online] 2022 [cited 2022 May 3];65:437-9. Available from: https://www.ijpmonline.org/text.asp?2022/65/2/437/343193
Synchronous malignancies of the female genital tract are very difficult to diagnose. As per the literature, their incidence varies from 0.5 to 1.7%. Synchronous endometrial and ovarian carcinoma is a rare instance but it accounts for 50 to 70% of all synchronous female genital tract tumors. Amongst them, the most common is synchronous endometrial and ovarian cancer (SEOC). The present case shows a rare association of the uterus and Fallopian tube cancer with benign ovarian tumor. Synchronous tumors are defined as two or more neoplasms identified simultaneously in separate organs or within 6 months after the first diagnosis. It poses a diagnostic challenge to the pathologist as well as the treating physician about their histogenesis and origin as either primary or metastasis (in case of similar tumors). Hence comes the importance of histopathological examination along with immunohistochemistry (IHC) to reach the final diagnosis.
A 75-year-old woman presented with post-menopausal bleeding for 1 year. The PAP smear examination showed moderate to severe dysplastic cells. On radiological examination, magnetic resonance imaging (MRI) pelvis revealed an altered signal intensity mass involving the endometrium, junction, and infiltrating the inner half of the myometrium. An 18FDG whole-body PET/CT scan was done that showed a primary mitotic disease in the uterus and suspicious for synchronous second primary mitotic pathology in the ovary. Then, the patient underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy. A frozen section and routine histopathological examinations were done.
Frozen section examination was done for diagnosing and observing the extent of endometrial growth in the myometrium, which was less than half of the myometrium. Also, the left Fallopian tube showed the presence of a tumor of similar morphology. On gross examination, proliferative growth was identified involving the whole of the uterus. The left Fallopian tube also showed a gray–white nodule in the lumen. The right ovary on the cut section showed a gray–yellow homogenous tumor mass [Figure 1]. The right Fallopian tube and the left ovary were unremarkable. On microscopic examination of endometrial growth, malignant cells were arranged in a back-to-back glandular and focal papillary pattern, having a vesicular hobnail nucleus and prominent nucleoli. No foci of complex endometrial hyperplasia were seen. High mitotic activity was identified. Tumor involving the left Fallopian tube showed similar morphology [Figure 2]a. On IHC, tumor cells were immunopositive for p53 [Figure 2]b and ER, which favored the diagnosis of serous carcinoma. The contralateral right ovarian mass showed sheets of polygonal cells having eosinophilic cytoplasm, centric nucleus, and prominent nucleoli favoring sex cord–stromal tumor of benign nature [Figure 2]c. On IHC, these cells showed cytoplasmic strong positivity for inhibin and calretinin [Figure 2]d and negativity for EMA and CK7.
|Figure 1: Gross image showing proliferative uterine growth and homogenous ovarian tumor.|
|Figure 2: (a)- H and E 40× uterus with inset showing 400× serous carcinoma of the uterus. (b)- 400× IHC showing diffuse positivity of p53 in serous carcinoma. (c)- H and E 40× of the ovary with inset 400× showing luteinized thecoma. (d)- 400× IHC showing cytoplasmic strong positivity of calretinin in ovarian thecoma.|
Hence, the final diagnosis of synchronous uterine serous carcinoma and ovarian sex cord–stromal tumor (thecoma) was made. Because of a larger tumor mass in the uterus than in the Fallopian tube and the involvement of less than half of the myometrium, the uterine origin of serous carcinoma was suggested with pathological stage pT3N0. Also, no tumor deposits were seen on the uterine surface and parametrium and over the serosa of the Fallopian tube that suggested a uterine origin.
The patient was then given anastrozole (hormonal therapy) 1 mg daily for 2 months to prevent the recurrence.
Synchronous uterine serous carcinoma and sex cord–stromal tumor of the ovary is a very rare association as per the published literature. Combinations of endometrial carcinoma with tumors, such as granulosa cell tumor and benign cystic teratoma, have been reported. As per the extensive literature search and as per our knowledge, this is the first case showing a rare association of serous carcinoma of the uterus and Fallopian tube with ovarian thecoma.
Bacalbasa et al. has reported a rare case of endometrial carcinoma associated with ovarian granulosa cell tumor. Among synchronous tumors, the most common histological pattern of endometrial cancer is endometrioid type in both cancer sites (45.6%), followed by endometrioid endometrial cancer with non-endometrioid cancer (33%) and non-endometrioid types at both sites account for 16.1%. Serous carcinoma accounts for less than 10% of all endometrial cancers. Thecoma accounts for 1% of all ovarian tumors.
As sex cord–stromal tumors such as thecoma have estrogenic manifestations, which are not evident in the case of uterine serous carcinoma, the relationship of these synchronous tumors from sites having different embryological origin and histological appearance is unexplainable. Hence, confirmation by IHC is required.
Synchronous tumors are more common in hereditary mutation syndromes such as Li-Fraumeni syndrome and Lynch syndrome. However, the present case had no clinical evidence of any syndromic association.
As per the literature, if the endometrium showed a co-existing precursor lesion (serous intraepithelial carcinoma), then it will support a primary endometrial origin of the tumor. WT-1 staining is typically strong and diffuse in tubo-ovarian, high-grade serous carcinoma and weak/focal or negative in endometrial serous carcinoma. However, WT-1 is not completely sensitive or specific in determining the primary site. Serous carcinoma of the endometrium can also give rise to Fallopian tube mucosal involvement.
Serous carcinoma should be differentiated from endometrioid carcinoma as both the tumors have different clinical behavior and prognosis. Serous carcinoma shows highly malignant cells arranged in a glandular and papillary pattern with cells showing a hyperchromatic hobnail nucleus, vesicular chromatin, and prominent nucleoli. Endometrioid carcinoma shows glands lined by malignant columnar to ovoid cells. The IHC panel to differentiate between the two include p53, beta-catenin, vimentin, and ER. Endometrioid carcinoma cells are p53 negative but are positive for beta-catenin, ER, and vimentin, whereas serous carcinoma cells show diffuse p53 positivity.
Ovarian thecomas should be differentiated from ovarian granulosa cell tumors and epithelial malignancies. Thecomas are homogenous solid tumors showing round polygonal cells having a clear to pale cytoplasm with centric round nuclei and finely dispersed chromatin. They are CK7 and EMA negative, which is helpful in differentiating them from carcinoma. A granulosa cell tumor consists of sheets of small ovoid cells having a uniform grooved nucleus. On IHC, granulosa cells show positivity for inhibin and calretinin.,
Surgery is the first treatment for almost all women with endometrial cancer including total hysterectomy with bilateral salpingo-oopherectomy (TAH/BSO) along with lymph node dissection. Depending on the stage of cancer, other treatments, such as radiation and/or chemotherapy may be recommended. Irradiation has been used both as adjuvant treatment following surgery and for recurrent disease, and adjuvant chemotherapy may be used including the drug paclitaxel or cisplatin.
Thecomas, in general, have not exhibited metastatic potential, but rare tumors have proved fatal as a result of complications such as sclerosing peritonitis caused by currently unknown mechanisms. In contrast, serous endometrial carcinomas carry a poor prognosis, high recurrence rate, and much lower 5-year survival rate. However, the prognostic relation of synchronous uterine serous carcinoma and thecoma of the ovary is still unknown.
Synchronous association of uterine and Fallopian tube serous carcinoma and sex cord–stromal tumor (thecoma) of the ovary is a very rare occurrence. As per our knowledge, this is the first case to be reported after an extensive literature search. The diagnosis of such synchronous tumors poses a diagnostic challenge for pathologists and clinicians. The relationship between the serous uterine carcinoma and ovarian sex cord–stromal tumor based on a high level of the estrogen-producing hyperactive ovary is controversial as serous carcinomas are less hormone-dependent. Hence, another pathological pathway might be incriminated in the development of serous carcinoma. As per the literature, serous carcinomas are more likely to be related to p53 mutation than to hormones. The importance of IHC lies in the confirmation of a diagnosis of such rare cases.
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