A Case Report of Endometrioid Carcinoma of the Ovary: A Comprehensive Clinical, Pathological, and Molecular Perspective

A 64-year-old female, postmenopausal since 12 years belonging to upper middle socioeconomic class, came to the OBGY outpatient department with complaints of postmenopausal bleeding per vaginum for 10 days with similar episode 1 month back. It was not associated with clots, pain, urinary symptoms, or white discharge per vaginal examination. She had no history of mass per abdomen, weight loss, or loss of appetite. She had no significant medical history, and there was no history of usage of any type of contraception. On per abdominal examination, an abdominopelvic mass of approximately 20 weeks size was found which was firm in consistency and its lower margin could not be reached. On per vaginal examination, a mass of size 20–22 weeks of gravid uterus was felt. On investigation, CA 125 was found to be elevated to 198 U/ml and magnetic resonance imaging (MRI) findings showed a well-defined lobulated lesion arising from the left adnexa extending into the midline of the pelvis to lie superior and anterior to uterus. The left ovary was not seen separately. Left parametrial vessels appeared dilated. The uterus was AV, AF, and measured 7.8 cm × 3.1 cm × 4.7 cm in size. The right ovary was seen separately from the lesion and measured 24 mm × 33 mm. Endometrial thickness was 4 mm and showed focal thickening in the lower uterine segment. Free fluid was noted in pelvis suggestive of moderate ascites. A right renal cortical cyst measuring 2.2 cm × 1.9 cm was also found and there was no history of metabolic syndrome or endometriosis. Patient underwent surgery of bilateral salpingoophorectomy with hysterectomy along with omental biopsy; peritoneal biopsy was sent for histopathological examination. The left ovary appeared bosselated, measured 10 cm × 10 cm × 6 cm while tumor was 9.5 cm × 9 cm × 6.5 cm. It was a single, irregular, solid, and capsulated tumor. Cut surface was solid, homogenous, and nodular. Grossly, there was no necrosis and few pinpoint hemorrhages were present. Representative sections were taken from the specimen and histopathological examination was done. Microscopy of the left ovary showed infiltrative tumor arranged in back to back glands with individuals cells show scant to moderate eosinophilic cytoplasm, round to oval nucleus, and many cells showing prominent nucleoli, marked areas of necrosis [ Figures 1 - 4 ]. Cervix showed chronic cervicitis with no evidence of cervical intraepithelial neoplasm or malignancy, endometrium showed endometrial gland atrophy as well as cystically dilated glands. Myometrium showed thick-walled blood vessels and unremarkable muscular wall. The right ovary shows a cyst lined by low cuboidal lining epithelium; rest of the ovarian parenchyma shows corpus albicans and blood vessels. Sections from the fallopian tubes, omentum, and peritoneum were free of tumor deposit. Final impression was given as EC, left ovary, and stage-pT1aNxMo. Single, irregular, solid capsulated tumor measuring 9.5 cm × 9 cm × 6.5 cm, bosselated and glistening external surface Solid, homogenous, nodular, gray white cut surface with few pinpoint hemorrhages Complex glandular proliferation with vascularized papillae of varying size (H and E, ×4) Pseudostratified epithelium with elongated nuclei and mild atypia (H and E, ×40)

Ovarian cancer is a leading cause of gynecological cancer-related deaths worldwide, with epithelial ovarian tumors being the most prevalent subtype. Among these, endometrioid carcinoma (EC) stands out due to its unique histological resemblance to endometrial carcinoma and its frequent association with endometriosis and hormonal factors.[ 1 2 3 ] EC typically presents in peri- or postmenopausal women, with a mean age at diagnosis around 55 years. However, younger women with a history of infertility or endometriosis are also at risk. The pathogenesis of EC is complex and multifactorial, involving hormonal imbalance (particularly unopposed estrogen), chronic inflammation, and genetic mutations. Key molecular alterations include mutations in PTEN, ARID1A, PIK3CA, CTNNB1, and (mismatch repair) MMR genes, many of which overlap with those seen in endometrial carcinoma. Moreover, the recognition of Lynch syndrome in a subset of patients with EC necessitates a detailed molecular workup, particularly in cases lacking traditional risk factors.[ 4 5 6 ] In this report, we present the case of a postmenopausal woman diagnosed with ovarian EC. Alongside her clinical and pathological findings, we discuss the current literature to provide a broader perspective on the diagnostic challenges and evolving molecular landscape of this tumor subtype.

EC of the ovary, although uncommon, represents a clinically and molecularly distinct entity within epithelial ovarian cancers. Early recognition and accurate histopathological and molecular characterization are pivotal for optimal management and prognosis. This case exemplifies the classical features of EC and underscores the evolving landscape of personalized oncology in gynecological cancers. The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. There are no conflicts of interest.

EC of the ovary typically arises de novo or from preexisting endometriotic cysts. The association with endometriosis is particularly significant, as 15%–20% of ECs are found in patients with a documented history of endometriosis.[ 6 7 ] These tumors often show a favorable prognosis when detected early, particularly when confined to the ovary and lacking lymphovascular invasion. Histologically, EC must be distinguished from other primary ovarian neoplasms, including clear cell carcinoma, serous carcinoma, and sex cord-stromal tumors.[ 8 9 ] Immunohistochemical (IHC) stains such as CK7, ER, PR, WT-1, and β-catenin assist in differentiating EC from mimickers.[ 1 10 ] ECs are typically WT-1 negative and show nuclear localization of β-catenin in cases with CTNNB1 mutations.[ 3 5 ] Molecularly, ECs demonstrate a high frequency of mutations in PTEN, ARID1A, and CTNNB1. These genes are involved in key signaling pathways such as PI3K/AKT/mammalian target of rapamycin (mTOR) and Wnt/β-catenin, which drive tumorigenesis through enhanced cellular proliferation and survival.[ 3 5 9 ] The identification of microsatellite instability (MSI) through loss of MMR proteins (MLH1, MSH2, MSH6, and PMS2) is crucial for detecting Lynch syndrome and guiding immunotherapy decisions.[ 2 11 ] Recent studies emphasize the prognostic relevance of molecular classification over traditional histologic grading. According to the cancer genome atlas, ECs can be stratified into four molecular subtypes with distinct prognostic implications: DNA polymerase epsilon (POLE) gene ultramutated, MSI-high, copy-number low (endometrioid-like), and copy-number high (serous-like).[ 5 ] Our patient’s tumor, being well-differentiated and organ-confined, would likely fall into the copy-number low category, suggesting a favorable outcome. Management of EC typically involves surgical staging followed by adjuvant therapy based on stage, grade, and molecular features. In early-stage disease, surgery alone may suffice. However, high-grade or advanced-stage tumors may benefit from chemotherapy or targeted therapies such as mTOR inhibitors or immune checkpoint inhibitors in cases with MMR deficiency.[ 9 12 ] This case underscores the importance of a multidisciplinary approach involving radiologists, pathologists, surgeons, and oncologists. It also highlights the role of molecular diagnostics in tailoring treatment and follow-up strategies. Furthermore, radiological modalities including MRI and CT imaging play a critical role in preoperative evaluation. In cases with atypical imaging features, such as complex cystic-solid lesions or hemorrhagic components, EC should be considered in the differential diagnosis, especially in patients with endometriosis.[ 7 ] Radiologists must be vigilant, as early-stage tumors may mimic benign processes. Comparative case reports also highlight the occurrence of dedifferentiated or high-grade variants of EC, which are associated with poorer prognosis and may present diagnostic challenges. Such variants often necessitate ancillary IHC staining and possibly genomic profiling to arrive at a definitive diagnosis.[ 4 ] Moreover, a multicenter retrospective study noted that endometrioid ovarian carcinomas commonly present with concurrent endometriosis and show a more indolent clinical behavior compared to high-grade serous carcinomas, supporting tailored therapeutic approaches.[ 8 ] Hormone receptor positivity in EC also offers a therapeutic avenue for hormone-based therapy in select cases. Histologically, the presence of squamous differentiation or morules is a unique feature of EC, not commonly seen in other ovarian carcinomas. These histological hallmarks aid in distinguishing EC from serous or mucinous carcinomas and even from metastatic endometrial carcinoma involving the ovary.[ 1 11 ] Finally, clinical practice guidelines such as those published by European Society for Medical Oncology provide frameworks for diagnosis, treatment, and follow-up of endometrial and ovarian cancers. These guidelines recommend molecular testing for MMR and POLE mutations as standard of care in newly diagnosed cases.[ 12 ] As more cases incorporate molecular and immunological profiling into routine practice, we anticipate improved stratification and outcomes for patients with endometrioid ovarian carcinoma.