Malignant Brenner tumor of ovary: A case report and review of literature

doi:10.21203/rs.3.rs-3097598/v1

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Case Report

Malignant Brenner tumor of ovary: A case report and review of literature

https://doi.org/10.21203/rs.3.rs-3097598/v1

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Background: Brenner tumours of ovary are rare representing 1-5% of epithelial ovarian tumours. They are further categorized as benign, proliferative (borderline), or malignant. Diagnosis of Malignant Brenner requires surgical excision and histopathological examination as tumor does not possess pathognomonic imaging features. Further, histological diagnosis of malignant Brenner tumor is challenging due to overlapping morphologic and histopathological features with benign and proliferative Brenner tumours, and transitional cell carcinoma.

Case details: A 49 years old female presented with history of vague abdominal pain for 2 months. A computerized tomography scan revealed a mixed cystic and solid anterior mass with thickened septations and peripheral nodularity. She underwent Total abdominal hysterectomy and bilateral salphingo-oophorectomy. Histopathological examination and immunohistochemistry was suggestive of malignant Brenner tumor of ovary. 2 years later she presented with nodal recurrence of disease for which she was started on Gemcitabine and Cisplatin combination chemotherapy.

Conclusion: Malignant Brenner tumor has poor prognosis. The treatment approach is not well established in view of its rarity, while surgical excision of the tumour remains the constant. The real benefit of the adjuvant chemotherapy remains unclear. Treatment options for disease recurrence included gemcitabine, tamoxifen, doxorubicin, and eribulin, though disease recurred after all of these regimens

Malignant Brenner tumor

epithelial ovarian tumor

Brenner tumours (BTs) of ovary are a subtype of epithelial stromal cell neoplasms. These are rare representing 1–5% of epithelial ovarian tumours ⁽¹⁾ and less than 2% of all ovarian tumours ⁽²⁾. BTs are further categorized as benign, proliferative (borderline), or malignant. Histological features of a Brenner tumor includes varying numbers of rounded nests of transitional or squamous cells like epithelium and glandular structures of cylindrical cells within abundant fibrous non-epithelial tissue ⁽³⁾. Most BTs are benign or proliferative, only less than 5% being malignant ⁽⁴⁾. Histologically malignant tumours shows heterogeneous epithelial growth and atypia with intervening stroma consist of transitional cells, squamous or undifferentiated carcinoma or an admixture of these types ⁽³⁾. These tumors are usually identified incidentally during imaging studies or surgery in the peri-menopausal and post-menopausal women with median age of 50 years for benign tumors and 60 years for proliferative and malignant tumors ⁽⁵⁾. Patient may also present with abdominal distension, pelvic discomfort, or postmenopausal bleeding ⁽⁶⁾. Diagnosis of Malignant Brenner requires surgical excision and histopathological examination as tumor does not possess pathognomonic imaging features. Further, histological diagnosis of malignant Brenner tumor is challenging due to overlapping morphologic and histopathological features with benign and proliferative BTs, and transitional cell carcinoma. We report a case of ovarian Malignant BT with nodal recurrence of disease, and a detailed review of clinical features, diagnosis, pathology, imaging findings, and management of BTs.

This 49 years old female with a history of diabetes mellitus type 2 and asthma initially presented to a local hospital in June 2019 with complaints of vague abdominal pain for 2 months which was dull aching in nature, intermittent, radiating to back. Transvaginal ultrasound (TVUS) revealed a normal uterus and a right adnexal mass measuring 12 × 8.6 × 10.6 cm, suspicious for ovarian neoplasm. A computerized tomography (CT) scan revealed a mixed cystic and solid anterior mass with thickened septations and peripheral nodularity. She underwent Total abdominal hysterectomy and bilateral salphingo-oophorectomy. Histopathological examination and immunohistochemistry was suggestive of Malignant Brenner tumor of ovary.

CT whole abdomen was done post operatively in July 2019 which showed evidence of thickening of vaginal stump, pelvic mesentery - possibly postoperative inflammation, though possibility of residual/secondary infiltration could not be ruled out. She underwent staging re-laparotomy followed by Infracolic omentectomy with bilateral pelvic lymphadenectomy. Histopathological examination of omental fatty tissue and gall bladder were free of tumour, and right and left pelvic lymph node showed no metastasis (0/4). Follow-up PET CT whole body done in September 2019 did not show any metabolically active lesion in the operated utero-ovarian site and no abdomino-pelvic lymph node enlargement to suggest local residual disease/recurrence and there was thickened vaginal vault without any hypermetabolic activity due to operative fibrosis.

She presented with complaints of progressively increasing left inguinal region swelling in May 2022. Fine needle aspiration cytology from left inguinal lymph node was suggestive of metastatic adenocarcinoma. Tumor markers showed elevated CA-125 levels (CA 125–395 U/ml, CA 19 − 9–20.50 U/ml and CEA- 3.92 ng/ml). Biopsy of left inguinal node was suggestive of metastatic deposits of poorly differentiated carcinoma and areas of necrosis.

CA 125 level re-checked in our institute in January 2023 was 601.8 U/mL. PET CT whole body done (Figure:1) for disease reassessment showed post total abdominal hysterectomy and bilateral salphingo-oophorectomy status with no definite local recurrence at the vaginal vault, a hypermetabolic left inguinal and low-grade FDG avid left external iliac, internal iliac and common iliac lymph nodes. No other demonstrable metabolically active disease elsewhere in the whole body survey.

Tissue from left inguinal lymph node (outside slide and block) reviewed here suggestive of metastatic poorly differentiated adenocarcinoma. Patient was started on Gemcitabine and Cisplatin combination chemotherapy.

The first malignant Brenner tumor was described in 1945 by von Numers ⁽⁷⁾. MBTs like most other ovarian malignancies present with vague symptoms as seen in our patient who presented with vague abdominal discomfort. Our patient was in fifth decade of age which is the typical age of presentation for MBTs. MBT is bilateral unlike the benign or borderline forms which are mostly unilateral. There are no specific diagnostic features on ultrasound imaging for MBTs, but usually presents with a large size and an admixture of solid and cystic components ⁽⁸⁾.. Further, utility of CT or magnetic resonance imaging in diagnosing the various types of transitional cell tumors pre-operatively is limited. Thus, surgical resection of the ovarian tumor and histopathological evaluation is necessary for definitive diagnosis.

Transitional cell carcinoma (TCC) with more aggressive clinical behavior is one of the close differentials of MBT; both share histological features making it challenging for definitive diagnosis. Immunohistochemical markers like over expression of cytokeratin 7 (CK7) and lack p16 expression is seen in MBT, while TCC cells overexpress p16. BTs are also positive for S100 p in 88% of cases, GATA3 in 96% of cases and P63 in 100% of cases ⁽⁹⁾

Currently there are no reliable tumor markers for diagnosis of malignant Brenner tumour, although CA-125 has been found to be increased in 30–70% of cases ^{(8) (10)}. Our patient when she presented with relapsed disease, had elevated CA-125 levels. A high level of CA 125 should raise the high index of suspicion of malignant nature of the tumor, but CA 125 can even be normal in MBTs ⁽¹¹⁾. Surgical debulking is the initial treatment of choice in MBTs like in other epithelial ovarian tumours.

There is no clear data on role of lymph node dissection (LND) in MBTs. Nasioudis et al. demonstrated that only 49% (99/202) of all MBT patients undergoing surgery received LND. Of these patients, only 5% were diagnosed with positive nodal disease ⁽⁷⁾. It was concluded that Disease-Specific Survival did not differ among patients who underwent lymphadenectomy and those who did not, where as overall survival was higher in those who underwent lymph node staging. LND during initial operative management should consider imaging studies and physical exam findings, as well as the morbidity risk of added surgical time and procedures in the context of each patient ⁽¹²⁾.

The role of adjuvant chemotherapy is not clearly demonstrated. Authors like Gezging et al. (nine out of ten patients) and Han et al. demonstrated a complete response when using Carboplatin-Taxol chemotherapy ⁽⁶⁾⁽⁹⁾. Extrapolating the general treatment recommendations for high-grade early stage epithelial ovarian cancer, it is reasonable to consider 3–6 cycles of adjuvant chemotherapy. In view of rarity, adjuvant chemotherapy for MBTs has not been well-studied or standardized. Patients should be counseled that the absolute benefit of adjuvant chemotherapy therapy is unknown.

The mean time to recurrence of disease is 11 months ⁽⁴⁾, whereas our patient presented with nodal recurrence 2 years after initial treatment. Many authors reported loco-regional recurrence as seen in our patient and distant metastasis during follow-up. Outcome was favorable with chemotherapy in the treatment of recurrent cases ^(6),(8),(9). Treatment options for disease recurrence included gemcitabine, tamoxifen, doxorubicin, and eribulin, though disease recurred after all of these regimens ⁽¹²⁾. The role of radiation therapy in patients with recurrence is limited to palliation and local control following recurrence of tumor.

Most ovarian BTs are incidentally detected and benign in nature. MBT is a rare disease with a poor prognosis. The treatment approach of MBT of the ovary is not well established in view of its rarity, while surgical excision of the tumour remains the constant. The real benefit of the adjuvant chemotherapy remains unclear. Thus, more case series should be conducted; the best treatment strategy will likely be developed through the reporting of clinical experience.

Acknowledgements: The authors thank the family of the patient for their assistance in preparing the manuscript.

Authors’ contributions: All the authors prepared the manuscript and collected all data and suitable references. All authors read and approved the final manuscript.

Funding: Nil

Ethics approval and consent to participate: As per our institutional ethics committee guidelines we do not require ethics approval for case reports.

Consent for publication: Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent form is available for review by the Editor-in-Chief of this journal.

Competing interests: The authors declare that they have no competing interests.

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No competing interests reported.

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Malignant Brenner tumor of ovary: A case report and review of literature

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