Brenner tumor associated with mucinous cyst and endometriosis: a case report

A 54-year-old postmenopausal woman, gravida 3 para 3, with a history of abnormal uterine bleeding (AUB) persisting for 9 years, presented to the gynecology outpatient clinic for further evaluation. She had entered menopause at the age of 45 and had no prior history of hormone replacement therapy. Her medical history was otherwise unremarkable, and she was not on anticoagulation therapy. Pelvic ultrasound demonstrated a thickened endometrial stripe measuring 12 mm with heterogeneous echotexture, increased vascularity, and an ill-defined endometrial-myometrial interface. The patient has a private office endometrial biopsy reporting that revealed suspicious for endometrioid adenocarcinoma, grade 1. Laboratory investigations showed a hemoglobin level of 11.23 g/dL and a serum cancer antigen 125 (CA125) of 105.63 U/mL. Transabdominal ultrasonography revealed a complex mass originating from the left adnexa. The patient underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymphadenectomy. Intraoperatively, the uterus and adnexa appeared grossly normal except for a slightly enlarged left ovary. A firm and mobile abdomino-pelvic mass with a smooth surface and a regular border was identified. Gross pathology of the left ovary showed a 3 × 2 × 0.7 cm organ with a brown-creamy external surface. Cut sections revealed a homogeneous brown-creamy texture and a well-demarcated golden-yellow nodule (0.6 cm diameter) embedded within the ovarian stroma. A 5 × 5 × 5 mm orange-colored mass was found adherent to the ovarian surface, arising from the ovarian parenchyma without gross connection to the fallopian tube. Microscopically, the ovarian nodule consisted of smooth contoured nests of bland transitional epithelium within fibromatous stroma. Histopathological findings: Histopathological evaluation of the hysterectomy specimen revealed a well-differentiated (grade 1) endometrioid adenocarcinoma confined to the endometrium, with no myometrial invasion identified. The tumor consisted of back-to-back endometrioid-type glands with mild cytologic atypia. No lymphovascular invasion was observed. The cervix, bilateral fallopian tubes, and the contralateral ovary were unremarkable. Pelvic lymph nodes were free of tumor. Transitional cells have uniform oval nuclei and may have a longitudinal nuclear groove. And a mucinous lined cyst and a foci composed of endometrial type glands and stroma with hemosiderin laden macrophages is noted. Histopathological analysis confirmed a benign Brenner tumor, with adjacent mucinous cystic changes and endometriotic foci [ 1 ] . The histopathologic criteria used to identify the Brenner tumor component were based on the WHO classification system, including well-circumscribed nests of transitional epithelium with longitudinal nuclear grooves and dense fibrous stroma, as described by Tavassoli and Devilee (Reference 1). To further characterize the ovarian lesions, an immunohistochemical panel was performed. The Brenner tumor component demonstrated strong nuclear positivity for GATA3 and cytoplasmic expression of CK7, consistent with urothelial-type differentiation. The mucinous cystic component showed CK7 positivity and was negative for GATA3, supporting a separate mucinous epithelial lineage. The endometriotic foci showed typical ER and PR positivity within the glandular epithelium and stromal cells. The proliferative index (Ki-67) was low (<5%) across all components, confirming the benign nature of the lesions. These IHC findings supported the diagnosis of a benign Brenner tumor with adjacent mucinous cystadenoma and endometriosis, without evidence of atypia or malignancy (Figs. 4 - 6 ). Figure 4. GATA3 immunostaining demonstrating strong nuclear positivity within the Brenner tumor nests, supporting urothelial-type differentiation.. Figure 5. P63 immunostaining demonstrating strong nuclear positivity within the Brenner tumor nests. Figure 6. CK20 immunostaining is negative. GATA3 immunostaining demonstrating strong nuclear positivity within the Brenner tumor nests, supporting urothelial-type differentiation.. P63 immunostaining demonstrating strong nuclear positivity within the Brenner tumor nests. CK20 immunostaining is negative. After surgery, the patient showed marked clinical improvement and resumed her regular daily activities in 3 months, and no recurrence has occurred during her long follow up. As the coexistence of these mixed tumors is not uncommon, a thorough pathologic evaluation is necessary, and health professionals should be aware of the mixed occurrence of epithelial as not on anticoagulation therapy. The work has been reported in line with the SCARE criteria [ 2 ] .

Brenner tumors are rare epithelial ovarian neoplasms accounting for approximately 1%–2% of all ovarian tumors and are most often detected incidentally in postmenopausal women. Although typically benign, they present a unique diagnostic challenge because they frequently coexist with other ovarian epithelial tumors – most notably mucinous cystadenomas. This association has been reported in up to 16% of cases and is thought to reflect a possible shared histogenetic origin, potentially arising from Walthard cell nests capable of urothelial-type and mucinous differentiation (Figs 1 and 2 ). Figure 1. Microscopic examination showing sharply circumscribed nests of transitional-type epithelial cells with longitudinal nuclear grooves (“coffee-bean” appearance) embedded in dense fibromatous stroma, consistent with a benign Brenner tumor. Figure 2. Mucinous cystic lesion lined by tall columnar mucin-producing epithelium without atypia, adjacent to the Brenner tumor component. Microscopic examination showing sharply circumscribed nests of transitional-type epithelial cells with longitudinal nuclear grooves (“coffee-bean” appearance) embedded in dense fibromatous stroma, consistent with a benign Brenner tumor. Mucinous cystic lesion lined by tall columnar mucin-producing epithelium without atypia, adjacent to the Brenner tumor component. Coexistence of Brenner tumors with endometriosis, however, is exceedingly rare and remains poorly documented. Endometriosis is known to alter the local ovarian microenvironment through chronic inflammation, estrogen-driven proliferation, and stromal remodeling, all of which may facilitate metaplastic or neoplastic transformation. When Brenner tumor, mucinous cystadenoma, and endometriosis occur simultaneously within the same ovary – as in the present case – the diagnostic complexity increases substantially and underscores the need for thorough histopathological assessment supported by immunohistochemistry (IHC) HIGHLIGHTS Brenner tumors are rare ovarian neoplasms. It can coexist with other ovarian pathologies like mucinous cyst and endometriosis. This case underscores the importance of thorough histopathological evaluation in patients with synchronous gynecological neoplasms. (Fig. 3 ). Figure 3. Endometriotic focus composed of endometrial glands and stroma with hemosiderin-laden macrophages in the ovarian cortex. HIGHLIGHTS Brenner tumors are rare ovarian neoplasms. It can coexist with other ovarian pathologies like mucinous cyst and endometriosis. This case underscores the importance of thorough histopathological evaluation in patients with synchronous gynecological neoplasms. Endometriotic focus composed of endometrial glands and stroma with hemosiderin-laden macrophages in the ovarian cortex. From a diagnostic standpoint, benign Brenner tumors demonstrate sharply defined nests of transitional-type epithelium with characteristic nuclear grooves within a dense fibromatous stroma. Immunophenotypically, they commonly express CK7 and GATA3, aiding in distinction from other ovarian neoplasms, particularly transitional cell carcinoma. Incorporating IHC markers is therefore essential when multiple histologic components exist in the same ovary to ensure accurate classification and to avoid misinterpretation of borderline or malignant epithelial elements. Given the rarity of this triad – Brenner tumor, mucinous cyst, and endometriosis – reporting such cases contributes to the limited literature on their coexistence and provides valuable insight into possible shared pathogenic mechanisms. This case emphasizes the importance of comprehensive gross, microscopic, and immunohistochemical evaluation in complex ovarian lesions to guide appropriate clinical management and prevent diagnostic.

Brenner tumors are rare epithelial ovarian neoplasms composed of nests of transitional (urothelial-like) epithelium embedded within a dense fibrous stroma. They account for approximately 1.4%–3% of all ovarian tumors and are typically benign, unilateral, and found incidentally in postmenopausal women [ 1 ] . While most Brenner tumors are asymptomatic, larger lesions may present with nonspecific pelvic symptoms or AUB [ 3 ] . The coexistence of Brenner tumors with other ovarian epithelial neoplasms, particularly mucinous tumors, has been reported in up to 16% of cases, suggesting a potential shared histogenetic origin [ 4 ] . One hypothesis is that both tumor components may arise from Walthard cell nests, which have the capacity to differentiate into both transitional and mucinous-type epithelium [ 4 ] . In our case, the mucinous cystadenoma and Brenner tumor were adjacent, supporting this hypothesis. The association of Brenner tumors with endometriosis is exceedingly rare and not well characterized in the literature. Endometriosis is typically considered a separate entity arising from ectopic endometrial tissue, often under hormonal influence. The simultaneous presence of these three distinct lesions in the same ovary, as in our case, is exceptional. While the coexistence with mucinous tumors has plausible histogenetic linkage, the presence of endometriosis may be coincidental, or alternatively may reflect a local environment conducive to metaplastic change or shared hormonal responsiveness [ 5 , 6 ] . Histologically, benign Brenner tumors are characterized by sharply demarcated nests of transitional epithelium with longitudinal nuclear grooves (“coffee-bean” appearance) surrounded by dense fibrous stroma. Immunohistochemical staining aids in confirming the diagnosis; typical markers include CK7 and GATA3, both of which were positive in our case, supporting a diagnosis of benign Brenner tumor [ 7 ] . The major differential diagnosis is transitional cell carcinoma of the ovary, which shows cytologic atypia, mitotic activity, and lack of the characteristic fibromatous stroma. In our case, the absence of mitoses or nuclear atypia, along with bland cytology and low proliferative index, favored a benign lesion. From a clinical standpoint, identifying and classifying these tumors accurately is essential to avoid overtreatment. While benign Brenner tumors have an excellent prognosis and usually require no further therapy following surgical excision, their association with mucinous neoplasms – some of which may harbor borderline or malignant features – necessitates comprehensive histopathologic evaluation. Furthermore, the incidental finding of endometriosis warrants awareness due to its known association with clear cell and endometrioid carcinomas [ 8 , 9 ] . In summary, this case represents a rare combination of benign Brenner tumor, mucinous cystadenoma, and ovarian endometriosis. The synchronous presence of these lesions highlights the complexity of ovarian tumor pathology and underscores the importance of thorough histologic and immunophenotypic assessment.

This case underscores the importance of meticulous histopathological evaluation in complex ovarian lesions. The coexistence of a benign Brenner tumor, mucinous cystadenoma, and endometriosis within the same ovary is an exceptionally rare finding that may reflect either a shared histogenetic pathway or a coincidental convergence of distinct pathologies. Recognition of such associations is critical not only for accurate diagnosis but also for guiding appropriate surgical management and vigilant histopathological assessment to rule out malignancy.