Malignant transformation of endometriosis into endometrioid ovarian carcinoma with a contralateral borderline seromucinous tumour: A rare case report

A 43-year-old parous woman presented with chronic abdominal pain for 5 years, which had worsened 2 weeks before presentation. The pain was insidious, intermittent and radiated to the lower back, and was not relieved with medication. She also had complaints of severe dysmenorrhea since menarche, aggravated recently, and heavy menstrual bleeding for 10 years. She had undergone multiple evaluations and had been diagnosed with bilateral ovarian endometriotic cysts, for which she received alternative treatments in addition to allopathic treatment without relief. A formal diagnosis of endometriosis had been made approximately 5 years before the current presentation; although her severe dysmenorrhea dated from menarche, the exact duration of endometriosis prior to this was not diagnosed. There was no significant past or family history of malignancy. Cervical cytology was negative for intraepithelial lesion or malignancy. Mammography was categorized as BI-RADS 3, and the findings remained unchanged on subsequent follow-up. On examination, the patient was moderately built and nourished with tenderness in the hypogastric and left iliac regions. On bimanual pelvic examination, the uterus was bulky with restricted mobility. Ultrasonography in April 2024 showed bilateral ovarian cysts suggestive of endometriomas, measuring 1.8 × 1.9 cm in the right ovary and 6.1 × 6.8 × 5.2 cm in the left ovary. In April 2025, following sudden-onset pain, repeat ultrasonography showed bilateral hemorrhagic cysts measuring 2.5 × 2.5 cm in the right ovary and 8.8 × 9 × 9.5 cm in the left ovary. MRI pelvis demonstrated a large, well-encapsulated, complex cystic lesion with solid components in the left ovary, measuring approximately 10.5 × 8 × 9.5 cm and categorized as O-RADS MRI 5 ( Fig. 1 ). Fig. 1 MRI pelvis showing a large complex cystic lesion in the left ovary with solid components suggestive of malignancy (O-RADS MRI 5). MRI pelvis showing a large complex cystic lesion in the left ovary with solid components suggestive of malignancy (O-RADS MRI 5). Laboratory investigations revealed elevated tumour markers: CA-125 408.6 U/mL and CA 19-9 643.58 U/mL, while CEA was within normal limits. The Risk of Malignancy Index I (RMI-I) was 1225.8, calculated as U × M × CA-125 = 3 × 1 × 408.6 = 1225.8. The patient was premenopausal (M=1), and the ultrasound score was U = 3. After surgical oncologist review, the patient underwent staging laparotomy in May 2025 with extrafascial hysterectomy, bilateral salpingo-oophorectomy, infracolic omentectomy, and pelvic and para-aortic lymphadenectomy. Intraoperatively, uterus was normal in size. Bladder was adherent to anterior surface of the uterus. Bilateral tubes were normal. Right ovary intra-operatively appeared normal. The left ovary was enlarged (~ 10 × 8 cm) and densely adherent to posterior surface of the uterus, sigmoid colon, and lateral pelvic wall. Solid areas were noted within the lesion. There was no ascites or peritoneal/omental deposits. No significant lymphadenopathy was noted. Peritoneal fluid was sent for cytology. Intraoperative spill occurred during adhesiolysis. Histopathology confirmed grade 2 endometrioid adenocarcinoma arising in an endometriotic cyst of the left ovary. The tumour showed cystic and solid areas with glands, papillary structures and solid nests, with moderate nuclear pleomorphism and hyperchromasia. Tumour necrosis was focal; vascular, lymphatic and neural invasion were not identified. The tumour was classified as FIGO stage IC1 because of intraoperative spill. The right ovary, which appeared grossly normal intraoperatively, showed a borderline seromucinous tumour with endometrioid differentiation. Histology showed cystic spaces, glands, papillary structures and solid nests lined by multilayered cells with loss of polarity and nuclear pleomorphism, with mucinous, clear-cell and endometrioid-type differentiation. No stromal invasion was identified. The uterus showed proliferative endometrium without glandular dysplasia or atypia, two leiomyomas, and no malignancy. The cervix showed chronic cervicitis without dysplasia or malignancy. The vaginal cuff margins were free of tumour. Both fallopian tubes showed normal histology. The infracolic omentum contained mature adipose tissue and fibrous stroma without metastatic tumour. All 9 right pelvic, 11 left pelvic, and 11 retroperitoneal lymph nodes showed reactive changes without metastatic carcinoma (0/31). The tissue adherent to the rectum showed fibrofatty stroma with scattered lymphocytes and no tumour invasion. Peritoneal fluid cytology was negative for malignancy. Immunohistochemistry showed WT1 negativity, patchy ER positivity, wild-type p53, and negative Napsin A, supporting the diagnosis of endometrioid carcinoma and arguing against a high-grade serous component. ARID1A and PTEN were not assessed. Postoperatively, the patient received six cycles of adjuvant paclitaxel and carboplatin. BRCA mutation testing was negative.

All authors have contributed significantly to this work. The manuscript is original and has not been published elsewhere. It is not under consideration in any other journal. There are no conflicts of interest. No funding was received. Patient consent has been obtained.

Rao Asha: Writing – review & editing, Validation, Supervision. Rao Damodar R: Writing – review & editing, Validation, Supervision, Investigation, Data curation. T Kiruthika: Writing – review & editing, Writing – original draft, Visualization, Methodology, Data curation, Conceptualization. G Padmashri: Writing – review & editing, Validation, Supervision.

Written informed consent was obtained from the patient for publication of this case report and the accompanying MRI image.

This case highlights the need for increased degree of suspicion when an ovarian endometrioma shows rapid interval growth, new solid components, or other suspicious imaging features. It also demonstrates that a grossly normal-appearing contralateral ovary may harbour clinically relevant borderline pathology and that complete histopathological assessment can reveal synchronous bilateral ovarian tumours. The novelty of this report lies in the coexistence of a left endometriosis-associated grade 2 endometrioid adenocarcinoma and a contralateral borderline seromucinous tumour with endometrioid differentiation, despite the right ovary appearing normal intraoperatively. This clinicopathological discordance emphasizes the value of integrating imaging, tumour markers, surgical findings and comprehensive pathological examination.

The principal clinical and pathological interest of this case is the synchronous bilateral ovarian pathology: a grade 2 endometrioid adenocarcinoma arising in an endometriotic cyst in the left ovary and a contralateral borderline seromucinous tumour with endometrioid differentiation in right ovary. The two lesions were discordant in both biological behaviour and intraoperative appearance. Recent clinicopathological work has emphasized that endometriosis-associated ovarian cancers may represent biologically distinct groups, depending on whether there is a demonstrable transition from endometriosis to carcinoma [5] . The presence of a borderline lesion contralateral to the carcinoma in this case further illustrates the heterogeneous epithelial pathology that may coexist in women with endometriosis. The right ovary was considered normal on intraoperative inspection but was found on final histopathology to harbour a borderline seromucinous tumour. This discrepancy demonstrates an important limitation of gross intraoperative assessment: absence of a visible or palpable abnormality does not exclude clinically relevant microscopic disease. In a patient with suspected ovarian malignancy, the decision regarding bilateral salpingo-oophorectomy should therefore not be based on gross appearance alone. It should incorporate the preoperative imaging of both adnexa, tumour markers, age, fertility and endocrine goals, and the anticipated need for oncological staging. At the same time, this finding should not be interpreted as a justification for routine bilateral oophorectomy in every premenopausal woman with endometriosis; fertility-sparing options may be appropriate in selected patients when oncologically safe. The interval growth of the left ovarian lesion was another warning feature. Based on the reported dimensions, an ellipsoid-volume approximation increased from approximately 113 cm³ (6.1 × 6.8 × 5.2 cm × π/6) to 394 cm³ (8.8 × 9 × 9.5 cm × π/6) over approximately one year, representing about a 3.5-fold increase in estimated volume (approximately 249% increase). There is no universally validated volume-growth threshold that independently diagnoses malignant transformation of an endometrioma. Nevertheless, rapid interval enlargement is a recognized warning sign. In a series of ovarian cancers arising in endometriomas, the tumour diameter doubled during the preceding 6 months in 30 of 33 patients [6] . In the present case, the growth was accompanied by a change from a presumed endometrioma/hemorrhagic cyst to a complex lesion with solid components and O-RADS MRI 5 features, strengthening the indication for definitive evaluation. The markedly elevated CA 19-9 level (643.58 U/mL) also deserves contextual interpretation. CA 19-9 can be elevated in endometriosis, particularly with advanced disease or acute haemorrhage, and higher CA 19-9 levels have been reported in endometriosis-related ovarian neoplasms than in benign endometriomas [7] . In addition, seromucinous ovarian tumours have a recognized association with endometriosis [8] . Thus, the high CA 19-9 in this case may reflect the endometriotic background and/or the coexisting mucinous/seromucinous component, rather than indicating a pure endometrioid phenotype. It should not be interpreted as a specific marker of histological subtype. The pathogenesis linking endometriosis and ovarian carcinoma is multifactorial and includes chronic inflammation, oxidative stress, hormonal influences and alterations in pathways such as PI3K/AKT/mTOR. The latter pathway is aberrantly activated in endometriosis-associated ovarian carcinoma, while alterations involving ARID1A and PTEN are also reported in endometriosis-associated endometrioid and clear cell carcinomas [9] . In this case, ARID1A and PTEN immunohistochemistry were not performed, so no case-specific inference regarding these molecular alterations can be made. The existing immunophenotype was supportive of endometrioid carcinoma and helped exclude a high-grade serous component. Distinguishing benign endometriomas from malignant transformation remains a clinical challenge. Imaging plays a crucial role, particularly when complex cystic lesions with solid components are identified. Ultrasound remains the first-line modality, MRI provides additional value in characterising indeterminate adnexal masses and improving diagnostic accuracy [1] . In this case, the combination of interval growth, solid components and O-RADS MRI 5 classification prompted definitive surgical evaluation. Endometriosis-associated ovarian cancers are often reported to present at an earlier stage and may demonstrate a relatively favourable prognosis compared with high-grade serous carcinoma, although data remain inconsistent across studies [4] . The association between endometriosis and seromucinous tumours is also relevant to the contralateral lesion. Published series have reported endometriosis in a proportion of seromucinous tumours, and seromucinous borderline tumours may show Müllerian-type epithelial components including endometrioid differentiation [8] . Recent studies have further highlighted the heterogeneity of endometriosis-associated ovarian neoplasia and the importance of expert pathological classification, including recognition of uncommon histotypes [5] , [10] . The present case therefore adds clinical value not simply by illustrating malignant transformation, which is a recognized phenomenon, but by documenting synchronous bilateral lesions of different pathological categories with a contralateral tumour that was not apparent on gross intraoperative examination. Histopathological examination remains essential when an ovarian lesion is removed or when a suspicious adnexal mass is encountered. In this case, the uterus, both ovaries and tubes, omentum, lymph nodes and tissue adherent to the rectum were examined, allowing confirmation of the primary tumour, identification of the contralateral borderline tumour, and documentation of the absence of extraovarian metastatic disease. Given the low but definite risk of malignant transformation, careful evaluation and a high index of suspicion are necessary in patients with endometriosis. Combining clinical findings, interval imaging, MRI-based O-RADS stratification, tumour markers and comprehensive histopathological assessment is essential for early diagnosis and appropriate management.

Endometriosis is an oestrogen-dependent inflammatory condition characterized by the presence of ectopic endometrial glands and stroma outside the uterine cavity, affecting nearly 10% of women of reproductive age [1] . Although benign, it exhibits features such as recurrence, local invasion and resistance to apoptosis, which are also seen in malignancy [2] . Malignant transformation of endometriosis is uncommon but well recognized, particularly in ovarian endometriomas. Endometriosis-associated ovarian cancers (EAOC) most commonly include histological subtypes like endometrioid and clear cell carcinoma [3] . Epidemiological studies suggest that women with endometriosis have an increased risk of developing ovarian malignancy, with reported relative risks ranging from 1.2 to 3-fold [4] . Recent studies suggest that malignant transformation represents a change from benign endometriosis through atypical endometriosis to carcinoma, by chronic inflammation, oxidative stress, and molecular alterations in the local microenvironment [1] , [3] .

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.