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Background: To explore the clinical characteristics of ovarian Brenner tumors and provide some basis for the treatment regimen of ovarian Brenner tumors., Methods: A retrospective analysis of the pathology database of surgical specimens at the Huzhou Maternal and Child Health Hospital from September 2008 to February 2023 was conducted. Patients who were pathologically diagnosed with ovarian Brenner tumors were included. Clinical data of patients was collected, and their diagnostic and treatment characteristics were summarized and analyzed., Results: A total of 20 cases were included in this study, all of which were histologically confirmed by surgical pathology. Among them, 8 cases (40%) were combined with serous, mucinous cystadenoma, or simple cyst. One case presented with a benign ovarian Brenner tumor combined with mucinous cystadenoma, underwent right adnexectomy, and relapsed 5 years later as a malignant Brenner tumor (MBT) coexisting with ovarian squamous cell carcinoma. Multiple tumor markers were elevated malignantly, with CA199 being the most significant. Treatments included unilateral adnexectomy in 7 cases, bilateral adnexectomy in 3 cases, total hysterectomy with bilateral adnexectomy in 7 cases, radical hysterectomy in 1 case, and 2 cases underwent ovarian staging surgery. MBT patients received three cycles of postoperative chemotherapy with the carboplatin-paclitaxel (TC) regimen., Follow-Up: One case with concomitant cervical cancer was lost to follow-up after surgery in an external hospital; one case with concomitant ovarian cancer received no further treatment after surgery and was lost to follow-up after 2 years; one case with concomitant endometrial cancer received no further treatment after surgery, and had no recurrence after 4 years of follow-up. Regular follow-up for MBT patients continued for 5 years without recurrence. The remaining 16 cases were followed up for a period ranging from 6 months to 7 years, with no reported recurrences., Conclusion: Clinical manifestations and auxiliary examinations of ovarian Brenner tumors lack obvious specificity. When necessary, a combination of tumor markers and imaging examinations can aid in diagnosis. Surgical strategies should be selected according to the patient's menopausal status., Trial Registration: Not applicable., (© 2024. The Author(s).)

BACKGROUND Ovarian cancer is the leading cause of death in women with gynecological cancers. Ovarian Brenner tumor (BT) is an extremely rare type of epithelial ovarian cancer that accounts for about 1-3% of all ovarian cancers. Herein, we report a rare case of ruptured malignant ovarian Brenner tumor. CASE REPORT A 39-year-old P0A0 woman came to the Emergency Department (ED) with abdominal pain and tenderness. Perforated appendicitis was initially suspected and an emergency laparotomy was performed by the General Surgery Department. Then, a 25×20×15 cm grayish cystic mass originating from the right adnexa was found. We consulted intraoperatively with the Gynecology Oncology Department and decided to perform complete surgical staging. Histopathological examination confirmed the diagnosis of malignant Brenner tumor (MBT). The patient was then given adjuvant chemotherapy with a paclitaxel carboplatin regimen. In this case report, we present our case along with a review of the current literature regarding the diagnosis and therapy of malignant Brenner tumor. CONCLUSIONS Ovarian MBT is an extremely rare ovarian cancer. Diagnosing MBT can be challenging as there are no clinical, laboratory, or imaging features typical for it. Surgery is the mainstay treatment in MBT cases. The role of adjuvant chemotherapy in MBT is still being debated.

Brenner tumors (BTs) are surface-epithelial stromal cell tumors that are categorized by the World Health Organization as benign, borderline, and malignant. Due to the rarity of BTs, the published literature on these tumors is comprised primarily of case reports and small retrospective studies. We performed a pathology database review spanning the last ten years at our institution revealing nine reported benign BTs. We collected the clinical and pathological data of patients associated with those BTs, describing the clinical presentation and imaging results, and assessing the possible risk factors associated with them. The average age at diagnosis was 58 years. BTs were discovered incidentally in 7/9 cases. The tumor was multifocal and bilateral in 1/9 cases and ranged in size from 0.2 cm to 7.5 cm. Associated Walthard rests were found in 6/9 cases and transitional metaplasia of surface ovarian and/or tubal epithelium was found in 4/9 cases. One patient had an associated mucinous cystadenoma in the ipsilateral ovary. Another patient had an associated mucinous cystadenoma in the contralateral ovary. In conclusion, we found that Walthard rests and transitional metaplasia are common findings in association with BTs. Additionally, pathologists and surgeons need to be aware of the association between mucinous cystadenomas and BTs.

Brenner's tumour of the ovary is a rare diagnosis that is usually incidental in either clinical finding or laparotomy. Pathologically, it can be classified as being an uncommon surface epithelial tumour. Originally known as a transitional cell tumour due to its histological similarity to the urothelium, Brenner is usually an unilateral and benign tumour. The site of incidence is predominantly the ovary and can very rarely occur in other locations including the testis. The following is a case of Brenner's tumour of the ovary in a postmenopausal woman after surgical treatment, the features of which will be discussed briefly., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Malignant Brenner tumor is a rare primary ovarian carcinoma subtype that may present diagnostic and therapeutic conundrums. Here, we characterize the genomics of 11 malignant Brenner tumors, which represented 0.1% of 14,153 clinically advanced ovarian carcinomas submitted for genomic profiling during the course of clinical care. At the time of molecular profiling, there was no evidence of a primary urothelial carcinoma of the urinary tract in any case. Cases with transitional-like morphologic features in the setting of variant ovarian serous or endometrioid carcinoma morphology were excluded from the final cohort. Malignant Brenner tumors exhibited CDKN2A/2B loss and oncogenic FGFR1/3 genomic alterations in 55% of cases, respectively; including recurrent FGFR3 S249C or FGFR3-TACC3 fusion in 45% of cases. FGFR3-mutated cases had an associated benign or borderline Brenner tumor pre-cursor components, further confirming the diagnosis and the ovarian site of origin. Malignant Brenner tumors were microsatellite stable, had low tumor mutational burden and exhibited no evidence of homologous recombination deficiency. PIK3CA mutations were enriched with FGFR3 alterations, while FGFR3 wild-type cases featured MDM2 amplification or TP53 mutations. The FGFR3 S249C short variant mutation was absent in 14,142 non-Brenner, ovarian carcinomas subtypes. In contrast to malignant Brenner tumors, FGFR1/2/3 alterations were present in ~5% of non-Brenner, ovarian serous, clear cell and endometrioid carcinoma subtypes, most often as FGFR1 amplification in serous carcinoma or FGFR2 short variant alterations in clear cell or endometrioid carcinomas, respectively. Finally, malignant Brenner tumors had overall distinct genomic signatures compared to FGFR-mutated ovarian serous, endometrioid, and clear cell carcinoma subtypes. This study provides insights into the molecular pathogenesis of malignant Brenner tumors, contrasts the extent of FGFR1/2/3 alterations in ovarian serous, clear cell and endometrioid carcinomas and emphasizes the potential value of novel and FDA-approved, anti-FGFR inhibitors, such as erdafitinib and pemigatinib, in refractory, FGFR3-mutated malignant Brenner tumors.

A rare case of malignant Brenner tumour of ovary manifesting with intestinal perforation due to colonic infiltration is elaborated in the present report. Brenner's tumour accounts for 1%-2% of all ovarian neoplasms and malignant Brenner tumour is even rarer and only about 5% of Brenner tumours are malignant. A 62-year-old woman came to surgical emergency with 1-month history of abdominal pain, vomiting and constipation with a palpable mass in right iliac fossa. Abdominal radiograph was suggestive of colonic obstruction. Contrast-enhanced CT of the abdomen revealed cystic right ovarian mass of 10.2×8.8 cm 2 with pneumoperitoneum. Exploratory laparotomy was done, which revealed mass arising from right ovary involving terminal ileum, cecum and ascending colon. Possibility of ovarian malignancy was kept. Patient underwent debulking surgery along with ileostomy and descending colon mucous fistula was created. Histology was compatible with malignant Brenner tumour of the ovary., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

The origin of primary mucinous ovarian tumors is unknown. We explore the hypothesis that they originate from either Brenner tumors or teratomas and examine differences between the tumors that arise in these settings. A total of 104 Brenner tumor-associated mucinous tumors and 58 teratoma-associated mucinous tumors were analyzed. Immunohistochemistry for 21 antigens and fluorescence in situ hybridization for ERBB2 and MYC were performed. Genome-wide copy number analysis and mutation analysis for 56 cancer-related genes was carried out on a subset of mucinous ovarian tumors and their complementary Brenner tumor or teratoma. Patients with teratoma-associated mucinous tumors were significantly younger than patients with Brenner tumor-associated mucinous tumors (43 vs. 61 years). During progression from cystadenoma to atypical proliferative mucinous (borderline) tumor to carcinoma expression of typical gastrointestinal markers was increased in both Brenner tumor-associated and teratoma-associated mucinous tumors. Brenner tumor-associated mucinous tumors showed more frequently calcifications and Walthard cell nests, rarely expressed SATB2 and showed more often co-deletion of CDKN2A and MTAP. Teratoma-associated mucinous tumors were characterized by mucinous stromal dissection, SATB2 expression and RNF43 mutations. Other frequent mutations in both Brenner tumor-associated and teratoma-associated mucinous tumors were TP53 and KRAS mutations. Based on identical mutations or copy number profiles clonal relationships were indicated in two mucinous tumors and their associated Brenner tumor. Teratomas and Brenner tumors give rise to different subtypes of mucinous ovarian tumors. Subsequent progression pathways are comparable since both Brenner tumor-associated and teratoma-associated mucinous tumors develop a gastrointestinal immunophenotype during progression and show early mutations in KRAS and TP53. Teratoma-associated mucinous tumors may more closely resemble true gastrointestinal tumors, indicated by their expression of SATB2 and the presence of RNF43 mutations.

Background: Extraovarian Brenner tumors (EOBTs) are extremely rare and can be observed incidentally in both female and male patients, raising concerns regarding the origin of Brenner tumors., Case Presentation: A 53-year-old postmenopausal woman presented with a nodular lesion in the left side of the corpus uteri, which was found at a routine health check. Macroscopically, the lesion appeared as a solid nodule with a yellowish-gray cut surface, approximately 6 cm in greatest diameter. Microscopically, the lesion consisted of well-defined epithelial nests and spindled stromal cells. Parenchymal cells expressed CK7, GATA3, CK5/6, 34βE12, and p63. A single layer of cavity-lined cells with umbrella-like shape showed apical Uroplakin III positivity. Stromal cells were positive for SMA, ER, and PR. The final diagnosis was EOBT and the patient was followed for 2 months with no recurrence., Conclusions: We report here the third case of EOBTs in the uterus. The combination of morphologic and immunohistochemical results supported the involvement of urothelial metaplasia in the development of EOBTs. The similarities between EOBTs and Walthard nests made Müllerian epithelium an attractive candidate as the cellular origin. Changes of tissue structure or sex hormones imbalance may lead to the translocation of Müllerian remnants to distant organs, explaining the pathogenesis of EOBTs.

Brenner tumors arise from ovarian epithelium, accounting for approximately 5% of benign ovarian epithelial tumors. The World Health Organization classification groups them into benign, borderline, and malignant on the basis of proliferation and invasiveness, and borderline Brenner tumor is defined as "displaying epithelial proliferation beyond that seen in benign Brenner's tumor, but lacking stromal invasion." Borderline Brenner tumors are rare. Fewer than 60 cases have been reported. The more recent articles mostly focus on pathogenesis. We reviewed the literature on borderline Brenner tumor and have summarized the clinical and pathologic findings, as well as the treatment, differential diagnoses, and recent advances in histogenesis and molecular pathogenesis.

Synchronous tumours of two different histological type are not uncommon in the female genital tract. But triple synchronous tumours of three or more different histological types is extremely rare. We describe a case of a 48-year-old female patient who presented with cervical growth and bilateral ovarian masses. Pathological evaluation of the surgical specimen revealed synchronous cervical squamous cell carcinoma, right ovarian dermoid cyst and left ovarian benign Brenner tumour. The patient was treated as per the carcinoma cervix protocol and is disease free at 1-year follow-up. To our knowledge this is the first report of such an occurrence. This occurrence cannot be related to any known hereditary syndromes, hence may be considered a chance association. Although rare, awareness of such an occurrence is important for the surgeon, radiologist and the surgical pathologist for proper diagnosis and management., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: To investigate clinicopathological parameters and histotype-specific survival of epithelial ovarian cancer by stage using the 2014 WHO classification. Patients & methods: Patients were obtained from the SEER database. Multivariate and univariate Cox regression analyses were applied to assess survival outcomes. Results: Irrespective of stages, low-grade serous and endometrioid had the best survival rates. In localized and regional stages, the poorest survival rates were detected for carcinosarcoma and malignant Brenner tumors, but in distant stage, the worst prognoses were observed in mucinous, clear cell and carcinosarcoma (p < 0.05 for all). Conclusion: Our study displayed significant differences in clinicopathological parameters and histotype-specific survival by stages that reflected current consensus on histotype classification and pathogenesis of epithelial ovarian cancer.

Rationale: Ovarian mucinous tumor with malignant mural nodule is exceedingly rare. We report a case of ovarian mucinous cystic tumor associated with sarcomatous mural nodule and benign Brenner tumor and accompanied by nodular histiocytic aggregates in the greater omentum., Patient Concerns: A 60-year-old postmenopausal woman was presented with a history of one month of lower abdominal discomfort, abdominal distension, nausea, and vomiting. A physical examination revealed a hard, palpable mass with mild tenderness in her right lower abdomen., Diagnoses: The mucinous tumor was solid and cystic and contained benign, borderline, and malignant elements. Within the solid areas, two nodules representing pleomorphic undifferentiated sarcoma and benign Brenner tumor were identified. The diagnosis of malignant mural nodule was based on vascular invasion and marked nuclear atypia, including atypical mitoses and mitotic activity., Interventions: Bilateral salpingo-oophorectomy and partial omentectomy were performed. Malignant cells were not found on cytologic examination of the peritoneal washing fluid. The patient underwent three cycles of chemotherapy with 210 mg paclitaxel liposome via an intravenous drip, 20 mg nedaplatin via an intravenous drip, and 80 mg nedaplatin via intraperitoneal perfusion., Outcomes: The patient has been followed up for 3 years without evidence of tumor recurrence and metastasis., Lessons: Careful classification of a mural nodule is important to triage patients in need of aggressive adjuvant treatment.

Objectives: To describe the ultrasound features of benign Brenner tumor in the background of complex clinical and histopathological pictures., Material and Methods: We retrospectively identified patients with histologically confirmed benign Brenner tumor of the ovary who were treated in our institution in 2003-2016, and for whom complete imaging, clinical, perioperative and histopathological data were available in the database. Ultrasound findings were drawn from images and reports using terms and definitions of the International Ovarian Tumor Analysis group and pattern recognition description was applied., Results: Twenty-three patients were identified, most postmenopausal and asymptomatic. On ultrasound, 19/23 tumors were found unilaterally, 4/23 bilaterally, and 82% of tumors were detected in the left ovary. Most Brenner tumors (16/23) contained solid components and revealed no or minimal blood flow by subjective color score upon Doppler examination (19/23, 83%). Calcifications with shadowing were observed in 57% of all Brenner tumors and in 81% of tumors containing solid components. The complex appearance of the tumor misled the sonographers to describe the mass as malignant in 9 cases (39%), and frozen section was performed perioperatively. Surgery was performed via laparoscopy in 11 (48%) and via laparotomy in 12 (52%) cases., Conclusions: The complexity of the ultrasound picture, consisting of features like calcifications with acoustic shadowing, a poorly vascularized solid mass, and a left-sided localization could be signs of a benign Brenner tumor and could preop-eratively help to differentiate between benign and malignant tumor.

Rationale: Adnexal torsion is 1 of the most common emergency gynecological disease. It is more often diagnosed in reproductive age, but rarely in postmenopausal women. The clinical symptoms of adnexal torsion are nonspecific in postmenopausal women. Epithelial ovarian tumors are common in adults, and the risk of malignancy increases with age, especially after menopause. So, it is difficult to diagnose adnexal torsion precisely compared with reproductive women, and most cases of adnexal torsion with postmenopausal women are diagnosed as a malignancy preoperatively. We report a case of ovarian torsion with mixed epithelial tumor misdiagnosed as a malignancy in postmenopausal woman., Patient Concerns: A 65-year-old woman presented lower left abdominal pain, and there was slight abdominal distension, but no tenderness or rebound tenderness on abdominal palpation., Diagnoses: Radiologic assessments showed a huge multiseptated cystic mass with solid portion in the left ovary, and malignancy was suspected. The test for serum tumor markers revealed normal levels of cancer antigen 125 (CA-125)., Interventions: The patient underwent a laparotomy and there was torsion of the left ovary. We conducted frozen biopsy of left ovary for confirming malignancy before performing staging surgery., Outcomes: The result of a frozen section biopsy confirmed a borderline Brenner tumor associated with a benign mucinous tumor. Subsequently, total hysterectomy and right salpingo-oophorectomy were performed. The operation was completed without addition procedures LESSONS:: Ovarian torsion is benign in most cases and malignancy is rare. Although very rare, ovarian torsion can occur in postmenopausal women, and it should be taken into consideration that the possibility of malignancy is low in postmenopausal women with normal CA-125 levels. Instead of performing staging surgery, it appears to be appropriate to carry out surgery based on the result of intraoperative frozen section biopsy so that we were able to avoid unnecessary surgical procedures.

Introduction: Epidemiological evidence strongly suggests that steroid hormones are implicated in the pathogenesis of ovarian cancer. Estrogen receptor (ER) and Progesterone receptor (PR) are prognostic indicators for a number of epithelial tumors and may play the same role in ovarian cancers. This study aims to evaluate the expression of ER and PR in epithelial ovarian cancer (EOC) in an African population and compare it with other prognostic factors such as age, International Federation of Gynaecology and Obstetrics (FIGO) stage, grade and histological subtype., Methods: Ninety cases of histologically confirmed EOC were reviewed. Immunohistochemistry was used to assess their ER and PR expression status and was then compared with other demographic variables using statistical methods, with level of significance set at p < 0.05., Results: 30.2% and 8.3% of serous and mucinous carcinomas respectively were ER positive while 41.2% and 22.5% of both tumour types were PR positive. One of the two endometrioid carcinomas showed PR expression but neither were positive for ER. The only case of Brenner tumour in the series was ER positive but negative for PR. There was a significant association between ER and the histological subtypes (p = 0.042) while no significant association was found between PR expression and histological subtypes (p = 0.650). No significant association was found between hormone receptor status, age and stage of the EOC., Conclusion: The study showed a lower ER expression in serous carcinoma compared to large cohorts from developed countries. Future translational studies could be used to determine response of EOC to endocrine therapy.

Background: Brenner tumors almost always develop in the ovary. Exceptionally, extraovarian Brenner tumors have been reported in the lower abdomen or pelvic organs. Here, we introduce a peculiar case of an extraovarian Brenner tumor arising in the omentum., Case Presentation: A 43-year-old woman presented with a palpable abdominal mass. Computed tomography (CT) scan revealed a 9.0-cm solid mass in the omentum. The tumor was not associated with pelvic structures, including the ovaries. It was excised under the clinical impression of an extragastrointestinal stromal tumor or neurogenic tumor. Grossly, the mass was a well-circumscribed solid tumor, with yellow-tan cut surface and minute cystic spaces. Microscopically, the tumor showed well-defined epithelial nests with variable cystic changes embedded in an abundant fibrous stroma. The cells within the nests were reminiscent of benign urothelial cells in that they had oval, frequently grooved nuclei. The epithelial cells focally showed a gradual transition into the surrounding stromal cells with short spindled features. The urothelium-like cells were positive for pancytokeratin, WT-1, p63, CK7, uroplakin-III, and GATA-3 but were negative for CD34, CD10, CK20, c-KIT, DOG-1, PAX-8, and calretinin. Morphological and immunohistochemical features of the tumor were the same as an ovarian Brenner tumor, and so it was diagnosed as an extraovarian Brenner tumor., Conclusions: Although the location of the tumor was very unusual, we could diagnose the tumor as an extraovarian Brenner tumor on the basis of the histologic and immunohistochemical findings. This is the first case of extraovarian Brenner tumor arising in the omentum near the stomach ever reported in the English literature.

Benign ovarian Brenner tumors often are associated with mucinous cystic neoplasms, which are hypothesized to share a histogenic origin and progression, however, supporting molecular characterization is limited. Our goal was to identify molecular mechanisms linking these tumors. DNA from six Brenner tumors with paired mucinous tumors, two Brenner tumors not associated with a mucinous neoplasm, and two atypical proliferative (borderline) Brenner tumors was extracted from formalin-fixed, paraffin-embedded tumor samples and sequenced using a 358-gene next-generation sequencing assay. Variant calls were compared within tumor groups to assess somatic mutation profiles. There was high concordance of the variants between paired samples (40% to 75%; P < 0.0001). Four of the six tumor pairs showed KRAS hotspot driver mutations specifically in the mucinous tumor. In the two paired samples that lacked KRAS mutations, MYC amplification was detected in both of the mucinous and the Brenner components; MYC amplification also was detected in a third Brenner tumor. Five of the Brenner tumors had no reportable potential driver alterations. The two atypical proliferative (borderline) Brenner tumors both had RAS mutations. The high degree of coordinate variants between paired Brenner and mucinous tumors supports a shared origin or progression. Differences observed in affected genes and pathways, particularly involving RAS and MYC, may point to molecular drivers of a divergent phenotype and progression of these tumors., (Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Borderline Brenner tumors represent quite a rare entity of ovarian tumors (about 2%) that develop from the surface ovarian epithelium. They are formed from papillary structures made of fibrovascular conjunctive axes covered by a transition epithelium, similar to the urinary bladder epithelium. According to the WHO classification, Brenner tumors present the following forms: benign, borderline and malignant. The benign ones are the most frequent, representing about 95%, the borderline represent about 5%, and the malignant ones less than 1%. We present the case of a 64-year patient who was diagnosed with right ovary cyst. The histopathological examination highlighted the presence of a borderline Brenner tumor at the same time with the cystic lesion, on the same ovary. The surgical treatment led to a complete cure of the patient, so that the yearly ultrasound reexamination did not trace the presence of any tumoral relapse.

Computed tomography obtained as part of a urinary tract assessment in a 68-year-old woman incidentally detected a solid adnexal mass. Bilateral salpingo-oophorectomy revealed a unilateral, 4-cm, white to tan-yellow colored, focally calcified, left ovarian mass. Microscopically, the tumor was composed of bland fibroblasts, abundant collagen, and areas of calcification with a minor component composed of nests of epithelial cells with nuclear clefts focally evident, some of which contained central lumens with eosinophilic secretions. The major considerations were fibromatous overgrowth in a Brenner tumor or ovarian fibroma with minor sex cord elements. Immunostains for cytokeratin 7 showed diffuse positivity in the epithelial nests, whereas cytokeratin 20 and inhibin were negative, further supporting the diagnosis of a Brenner tumor.

Background: Borderline Brenner tumor of the ovary is a rare entity characterized by papillary structures with a fibro-vascular core, covered by a transitional epithelium, and by the absence of stromal infiltration. It is associated, by definition, with a benign component of Brenner tumor., Case: We report a case of a 68-year-old woman, with a right ovarian mass, whose morphology and immuno-profile were consistent with the diagnosis of a borderline Brenner tumor. Immunohistochemistry carried out on selected markers may help to formulate the diagnosis, more than the molecular analyses.

Brenner tumor is a rare tumor that represents approximately 1.5% of the tumors of ovary. It is defined as a tumor of transitional cells composed by urothelial cells arranged in solid or cystic groups absorbed in a fibrous stroma. It classifies in benign Brenner tumor (95%), borderline (3-4%) and malignant (1%). Let's sense beforehand the clinical case of a 46-year-old patient who underwent surgery having an adnexal mass of which the pathological intraoperative report brought a benign Brenner tumor.

Brenner tumors are ovarian tumors, usually benign, containing epithelium that resembles transitional epithelium. As with other epithelial tumors there exist frankly malignant tumors and tumors that display greater proliferation than the benign Brenner tumors but lack destructive infiltrative growth, and these have been designated 'atypical proliferative' (borderline) Brenner tumors. There have been no well-documented cases of atypical proliferative Brenner tumors that have exhibited malignant behavior. Based on shared morphologic features it is generally believed that atypical proliferative Brenner tumors develop from benign Brenner tumors. The aim of the present study was to confirm this impression by investigating the immunohistochemical and molecular genetic features of benign and atypical proliferative Brenner tumors. Immunohistochemical staining for p16, fluorescence in-situ hybridization (FISH) for CDKN2A (p16-encoding gene) and mutational analysis of the genes commonly mutated in ovarian tumors were performed. p16 immunostaining was positive in the epithelial component of 12 (92%) of 13 benign Brenner tumors, but completely negative in all 7 atypical proliferative Brenner tumors. FISH identified homozygous deletion of CDKN2A in the epithelial component of all atypical proliferative Brenner tumors, but CDKN2A was retained in all benign Brenner tumors. Two PIK3CA somatic mutations were detected in the stromal component in 1 (5%) of 20 Brenner tumors and 3 somatic mutations (1 in KRAS and 2 in PIK3CA) were identified in the atypical epithelial component of 2 (29%) of 7 atypical proliferative Brenner tumors. In summary, our findings suggest that loss of CDKN2A and, to a lesser extent, KRAS and PIK3CA somatic mutations have a role in the progression of a benign to an atypical proliferative Brenner tumor.

Objectives: To describe clinical and ultrasound features of Brenner tumors of the ovary., Methods: In this retrospective study, the databases of the International Ovarian Tumor Analysis (IOTA) studies and one tertiary center were searched to identify patients who had undergone an ultrasound scan before surgery for an adnexal mass that proved to be a Brenner tumor. Twenty-eight patients with 29 Brenner tumors were included, most of which had been collected within the framework of the IOTA studies. An experienced ultrasound examiner reviewed available ultrasound images (available for 14 tumors), searching for a pattern specific to Brenner tumors., Results: Most patients were postmenopausal and asymptomatic. Twenty-four (83%) tumors were benign, two (7%) were borderline and three (10%) were malignant. Most benign tumors (17/24, 71%) contained solid components and manifested no or minimal blood flow on Doppler examination (19/24, 79%). Information about calcifications was available for 15 benign tumors, and in 13 (87%) calcifications were present. The five borderline and invasively malignant tumors contained solid components less often than did the benign ones (3/5, 60%) and were more richly vascularized on Doppler examination. Information about calcifications was available for four borderline or invasively malignant tumors, and in three (75%) calcifications were present., Conclusion: We failed to demonstrate ultrasound features specific to Brenner tumors. A prospective study is needed to determine if ultrasound features of calcifications can discriminate between Brenner tumors and other types of ovarian tumor., (Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.)

Ovarian tumor composed only of Brenner tumor and struma ovarii is very rare; only 6 cases have been reported in the English literature, to the best of the author's knowledge. A 66-year-old woman underwent right oophorectomy because of torsion of right ovarian cyst. Macroscopically, the ovarian cyst was hemorrhagic and red. Cystic content was hemorrhagic fluid. Microscopically, the cyst walls were composed only of Brenner tumor (50% in area) and struma ovarii (50% in area). Hemorrhage and ischemic changes were seen. Other elements were not recognized. No malignant transformation was noted. These two elements were separately present, and no mergers between them were recognized. Immunohistochemically, the Brenner tumor element was positive for cytokeratins (AE1/3 and CAM5.2) and Ki67 (labeling=3%), but negative for thyroglobulin, TTF-1, p53, CA125, and vimentin. The struma ovarii element was positive for cytokeratins (AE1/3 and CAM5.2), thyroglobulin, TTF-1 and Ki67 (labeling=5%), but negative for p53, CA125 and vimentin. The findings suggests that there were cases of ovarian cyst composed only of Brenner tumor and struma ovarii, that such a case may be monodermal mature cystic teratoma or the Brenner tumor element was derived from surface epithelium in the preexisting struma ovarii, and that such a tumor manifest as cystic torsion.

Context: The origin of and relationship between ovarian mucinous and transitional cell (Brenner) neoplasms are enigmatic. The reported association ranges from 1% to 16%, and whether there is an association with Walthard cell nests is unknown., Objective: To clarify the histologic relationship between mucinous and Brenner tumors., Design: A total of 40 mucinous cystadenomas, 67 Brenner tumors, and 13 combined tumors were studied. Peritoneal surfaces were examined for Walthard nests in 83 patients compared with 272 controls., Results: A total of 25% of tumors with a mucinous component contained a Brenner component, and 16% of tumors with a Brenner component contained a mucinous component. Most calcifications were spiculated (nonpsammomatous). In 6 combined tumors, the relative volume of the 2 components was less than 1:3000 (transitional-mucinous). Walthard nests were found in 50% of patients with Brenner tumors and 59% of patients with mucinous tumors. This was significantly higher than the 28% found in controls (P = .002 and P < .001, respectively). The number of fallopian tube blocks examined was correlated with the likelihood of finding Walthard nests, and accordingly, sampling accounted for 39% of the increase with Brenner tumors but strengthened the association with mucinous tumors., Conclusions: The strong association of mucinous and transitional cell components, similar type of calcification, complementary size distributions, and frequent identification of a transitional component in the face of an exceedingly small estimated proportion of that component suggest that this association has been underestimated. The association of Brenner tumors with Walthard nests, although significant, appears weak and not strongly supportive of a histogenetic relationship. The stronger association of Walthard nests with mucinous tumors remains unexplained.

A small percentage of ovarian neoplasms are transitional cell tumors, which proves to be a distinct group with various histological and immunohistochemical patterns. In this study, 13 archived formalin-fixed paraffin-embedded samples of transitional cell tumors of the ovary have been assessed using standard HE stain and the indirect tristadial ABC peroxidase IHC method for 11 antibodies (CA125, CK7, CEA, EMA, MNF116, CK20, Vim, ER, PgR, PCNA, Ki-67). More than 50% were malignant Brenner tumors. CA125 was positive in all malignant tumors (of Brenner type and transitional cell carcinomas), but not in benign and borderline tumors, while CK7 was positive in approximately 70% of all cases. These two antibodies have shown a high sensitivity and low specificity, but do not correlate to each other. PCNA was positive in the study batch with a mean value of 40% and Ki-67 with a mean value under 25%. A direct correlation statistically significant has been noted between the aforementioned proliferation factors and the tumor grade (r = 0.4, p = 0.05). The other markers were unspecific, with low sensitivity and independently of the histopathological type.

Matriptase is a type II transmembrane serine protease expressed by cells of surface epithelial origin, including epithelial ovarian tumor cells. Matriptase cleaves and activates proteins implicated in the progression of cancer and represents a potential prognostic and therapeutic target. The aim of this study was to examine the expression of matriptase in ovarian tumors and to assign clinicopathological correlations. Immunohistochemical analysis of matriptase was performed in tissue microarrays of 164 ovarian neoplasms including 84 serous adenocarcinomas, 23 mucinous adenocarcinomas, 10 endometrioid adenocarcinomas, six yolk sac tumors, 12 clear cell carcinomas, six dysgerminomas, eight granulosa cell tumors, four transitional cell carcinomas, five fibromas, and six Brenner tumors. All ovarian tumors except the fibromas and Brenner tumors showed significant expression of matriptase. The matriptase scores were significantly higher in the tumors than in their nontumor counterparts (304+/-26 for serous adenocarcinoma; 361+/-28 for mucinous adenocarcinoma; 254+/-17 for endometrioid adenocarcinoma; 205+/-19 for yolk sac tumor; 162+/-16 for clear cell carcinoma; 109+/-11 for dysgerminoma; 105+/-9 for granulosa cell tumor; and 226+/-18 for transitional cell carcinoma). Matriptase scores in serous adenocarcinoma were correlated with TNM stage and FIGO stage. Our findings demonstrate for the first time that matriptase is overexpressed in many malignant ovarian tumors. It may be a novel biomarker for diagnosis and treatment of malignant ovarian tumors.

Malignant Brenner tumour is a rare pathological entity. Apart from identification of typical benign, metaplastic and/or proliferating components, stromal invasion must be observed for diagnosis of Brenner tumour. A case of malignant Brenner tumour is described along with a brief review of strict criteria of diagnosis and its biological behaviour.

Transitional cell tumours or Brenner tumours of ovary are uncommon neoplasms. Out of all the Brenner tumours less than 2% are either proliferating or malignant type. Borderline or malignant tumours occur in women who are on an average 10 years older than those with benign tumours. It is essential to categorise these tumours as benign, borderline or malignant type as the biologic behaviour and choice of surgery differs in all of the three categories. The gross and microscopic findings of a proliferating brenner tumour are reported here.

We investigated the tumor marker for malignant Brenner tumors, which had not been established because of the rarity and variable histological criteria. Representative areas of two cases of malignant Brenner tumor were investigated by means of the peroxidase-antiperoxidase method using monoclonal antibody to CA125 and CA72-4 antigen and the streptavidin-biotin immunoperoxidase complex method using monoclonal antibody to SCC antigen. Based on clinical course and immunohistochemical studies, serum CA125 and CA72-4 for Case 1 and SCC and CA72-4 for Case 2 were appropriate tumor markers for the establishment of the extent of tumor burden before treatment and to monitor the response to therapy. The discrepancy of the tumor markers of the two present cases is considered to be a reflection of the difference in the malignant component of these cases. However, serum CA72-4 was an appropriate tumor marker for both malignant Brenner tumors.

Polyps of the vagina are rare and are either of inflammatory/reactive or neoplastic origin. A case of extraovarian Brenner tumour of the vagina in a postmenopausal woman, who presented with a vaginal polyp, is described. The polyp was excised and on histological examination, had the triphasic pattern (transitional, glandular and stromal) characteristic of Brenner tumour. The histogenesis of Brenner tumour is discussed in the context of this unusual location and the controversy of its origin.

We present the case of a 62-year-old man with a malignant Brenner tumor of the testis and epididymis. The neoplasm showed the distinctive histologic features of Brenner tumors of the ovary, including the presence of nests of transitional epithelium with focal mucinous differentiation, surrounded by septae of dense fibrous tissue. In addition to areas of typical Brenner epithelium, the tumor displayed a component of transitional and squamous carcinoma that invaded the testicular parenchyma, epididymis, and vas deferens, and metastasized to periaortic lymph nodes. To our knowledge, there are only four previously described instances of testicular Brenner tumors. Our case appears to represent the first description of a malignant Brenner tumor of the testis and epididymis.

In a clinicopathological study of 70 Brenner tumours in 61 patients seen at Groote Schuur Hospital during the 30-year period 1956-1985, 68 were benign, 1 malignant and 1 proliferating. Fifty-seven were pure tumours and the remainder were mixed with other ovarian neoplasms. The age range of patients was 26-71 years (median 49 years). Most of the Brenner tumours were incidental findings and probably not responsible for the symptoms or signs, which were most commonly a pelvic mass (28 patients) and abnormal vaginal bleeding (15).

Argentaffin cells were searched for in the epithelial nests of 30 Brenner's tumors, with the Fontana-Masson stain for the screening. Although these cells were found in five tumors, ultrastructural examination of one case, in which the argentaffin cells were multiple, identified the cytoplasmic granules as lysosomes and not as amine precursor uptake and decarboxylation (APUD)-type granules. We conclude that the epithelial component of Brenner's tumors consists of urothelium only and does not include the cells containing argentaffin APUD-type granules.

The classification of ovarian neoplasms on a histogenetic basis according to presentday concepts of development and structure of the ovary is considered. There are four histogenetic categories of primary ovarian tumours: neoplasms of germ cell origin, neoplasms of celomic (germinal) epithelium and its derivatives, neoplasms of specialized gonadal stroma (sex cords and mesenchyme), and neoplasms of non-specialized gonadal stromal and heterotopic elements. In patients of all ages, 70% of ovarian neoplasms were of celomic epithelial origin, 16% of germ-cell origin, 5% of specialized gonadal stromal origin, and 9% arose from the non-specialized stroma and heterotopic elements. Before 20 years of age, 59% of ovarian neoplasms were of germ cell origin and before puberty they accounted for 90% of all ovarian tumours. The different structural types of neoplasms within the four categories are described. Accurate classification of ovarian neoplasms on a histogenetic basis is stressed if proper treatment is to be given and intelligent assessment of end results is to be made.