BACKGROUND: Bromodomain and extra-terminal (BET) domain proteins that bind to acetylated lysine residues of histones serve as the \"readers\" of DNA acetylation. BRD4 is the most thoroughly studied member of the BET family and regulates the expression of key oncogenes. BRD4 gene amplification has been identified in ovarian cancer (~18-19%) according to The Cancer Genome Atlas (TCGA) analysis. BET inhibitors are novel small molecules that displace BET proteins from acetylated histones and are currently tested in Phase I/II trials. We here aim to explore the prognostic role of the BRD4 gene and protein expression in the ascitic fluid of patients with advanced FIGO III/IV high-grade serous ovarian carcinoma (HGSC).
METHODS: Ascitic fluid was obtained from 28 patients with advanced stage (FIGO III/IV) HGSC through diagnostic/therapeutic paracentesis or laparoscopy before the initiation of chemotherapy. An amount of ~200 mL of ascitic fluid was collected from each patient and peripheral blood mononuclear cells (PBMCs) were isolated. Each sample was evaluated for BRD4 and GAPDH gene expression through RT-qPCR and BRD4 protein levels through enzyme-linked immunosorbent assay (ELISA). The study protocol was approved by the Institutional Review Board of Alexandra University Hospital and the Committee on Ethics and Good Practice (CEGP) of the National and Kapodistrian University of Athens (NKUA).
RESULTS: Low BRD4 gene expression was associated with worse prognosis at 12 months compared to intermediate/high expression (95% CI; 1.75-30.49; p = 0.008). The same association was observed at 24 months although this association was not statistically significant (95% CI; 0.96-9.2; p = 0.065). Progression-free survival was shorter in patients with low BRD4 gene expression at 12 months (5.6 months; 95% CI; 2.6-8.6) compared to intermediate/high expression (9.8 months; 95% CI; 8.3-11.3) (95% CI; 1.2-16.5; p = 0.03). The same association was confirmed at 24 months (6.9 months vs. 13.1 months) (95% CI; 1.1-8.6; p = 0.048). There was a trend for worse prognosis in patients with high BRD4 protein levels versus intermediate/low BRD4 protein expression both at 12 months (9.8 months vs. 7.6 months; p = 0.3) and at 24 months (14.2 months vs. 16.6 months; p = 0.56) although not statistically significant. Again, there was a trend for shorter PFS in patients with high BRD4 protein expression although not statistically significant both at 12 months (p = 0.29) and at 24 months (p = 0.47).
CONCLUSIONS: There are contradictory data in the literature over the prognostic role of BRD4 gene expression in solid tumors. In our study, intermediate/high BRD4 gene expression was associated with a favorable prognosis in terms of overall survival and progression-free survival compared to low BRD4 gene expression.

BACKGROUND: Endometrial serous carcinoma (ESC) and tubo-ovarian high-grade serous carcinoma (HGSC) are characterized by late-stage presentation and high mortality. Current guidelines for prevention recommend risk-reducing salpingo-oophorectomy (RRSO) in patients with hereditary mutations in cancer susceptibility genes. However, HGSC displays extensive genetic heterogeneity with alterations in 168 genes identified in TCGA study, but current germline testing panels are often limited to the handful of recurrently mutated genes, leaving families with rare hereditary gene mutations potentially at-risk.
OBJECTIVE: To determine if there are rare germline mutations that may aid in early identification of more patients at-risk for ESC and/or HGSC by evaluating patients with concurrent ESC, HGSC or precursor lesions, and endometrial atypical hyperplasia (CAH) or low-grade endometrial endometrioid adenocarcinoma (LGEEA).
METHODS: We performed targeted next-generation sequencing using TSO 500, a 523 gene panel, on formalin-fixed paraffin-embedded tumor and matched benign non-tumor tissue blocks from 5 patients with concurrent ESC, HGSC or precursor lesions, and CAH or LGEEA.
RESULTS: We identified germline pathogenic, likely pathogenic or uncertain significance variants in cancer susceptibility genes in 4 of 5 patients - affected genes included GLI1, PIK3R1, FOXP1, FANCD2, INPP4B and H3F3C. Notably, none of these genes were included in the commercially available germline testing panels initially used to evaluate the patients at the time of their diagnoses.
CONCLUSIONS: Comprehensive germline testing of patients with concurrent LGEEA or CAH and ESC, HGSC or precursor lesions may aid in early identification of relatives at-risk for cancer who may be candidates for RRSO with hysterectomy.

This article reports a case of an ovarian collision tumour consisting of an ovarian fibroma and a serous cystadenoma. A 60-year-old woman exhibited symptoms of post-menopausal bleeding and abdominal pain persisting for three months. Computerized tomography identified a solid mass with a cystic component in the right adnexa, and the patient underwent staging laparotomy. Gross examination of the right ovary revealed a cystic tumour with adjacent solid mass. The histopathological analysis identified a cystic mass that matched the characteristics of a serous cystadenoma, with an adjacent solid mass that matched the characteristics of a sex-cord stromal tumour, both located in the right ovary. Additionally, a small cyst that matched the characteristics of a serous cystadenoma was found in the left ovary. There have been only seven previously reported examples of this specific mix of ovarian tumours. Mostly affecting patients above 60 years of age, although tumour markers levels are normal, such cases may present with a complex clinical scenario, as in this case, and demand a comprehensive diagnostic and therapeutic approach.

OBJECTIVE: Accurate staging of ovarian cancer is critical to guide optimal management pathways. North American guidelines recommend contrast-enhanced CT as the primary work-up for staging ovarian cancer. This meta-analysis aims to compare the diagnostic accuracy of contrast-enhanced CT alone to PET/CT for detecting abdominal metastases in patients with a new or suspected diagnosis of ovarian cancer.
METHODS: A systematic review of MEDLINE, EMBASE, Scopus, the Cochrane Library, and the gray literature from inception to October 2022 was performed. Studies with a minimum of 5 patients evaluating the diagnostic accuracy of contrast-enhanced CT and/or PET/CT for detecting stage 3 ovarian cancer as defined by a surgical/histopathological reference standard ± clinical follow-up were included. Study, clinical, imaging, and accuracy data for eligible studies were independently acquired by two reviewers. Primary meta-analysis was performed in studies reporting accuracy on a per-patient basis using a bivariate mixed-effects regression model. Risk of bias was evaluated using QUADAS-2.
RESULTS: From 3701 citations, 15 studies (918 patients with mean age ranging from 51 to 65 years) were included in the systematic review. Twelve studies evaluated contrast-enhanced CT (6 using a per-patient assessment and 6 using a per-region assessment) and 11 studies evaluated PET/CT (7 using a per-patient assessment and 4 using a per-region assessment). All but one reporting study used consensus reading. Respective sensitivity and specificity values on a per-patient basis were 82% (67-91%, 95% CI) and 72% (59-82%) for contrast-enhanced CT and 87% (75-94%) and 90% (82-95%) for PET/CT. There was no significant difference in sensitivities between modalities (p = 0.29), but PET/CT was significantly more specific than CT (p < 0.01). Presumed variability could not be assessed in any single category due to limited studies using per-patient assessment. Studies were almost entirely low risk for bias and applicability concerns using QUADAS-2.
CONCLUSIONS: Contrast-enhanced CT demonstrates non-inferior sensitivity compared to PET/CT, although PET/CT may still serve as an alternative and/or supplement to CT alone prior to and/or in lieu of diagnostic laparoscopy in patients with ovarian cancer. Future revisions to existing guidelines should consider these results to further refine the individualized pretherapeutic diagnostic pathway.

Aim: To investigate the efficacy and safety of bevacizumab in patients with recurrent low-grade serous ovarian carcinoma. Materials & methods: The data of patients who received at least two cycles of bevacizumab in combination with chemotherapy were retrospectively recorded. Results: The median age of 51 patients was 56 (range: 33-75) years. The complete response rate was 10.4% and the partial response rate was 43.7%. The objective response rate was 54.1%. Median progression-free survival was 15.9 months (95% CI: 9.1-22.6) and median overall survival was 42.5 months (95% CI: 37.2-47.8). Conclusion: Bevacizumab with chemotherapy is an effective option for treating recurrent ovarian low-grade serous carcinoma.

Serous cystadenoma is a rare lesion in the para-testicular tissue, with even rarer reports of this entity occurring in the scrotum post-orchidopexy. We present such an occurrence, adding support for its existence as a distinct entity.

Ovarian lesions represent a diagnostic challenge for the radiologist and should be approached according to the patient\'s age, menstrual cycle, and imaging characteristics. These lesions can be cystic, mixed, or solid-predominant structures. Generally, the occurrence of benign lesions surpasses that of malignant ones at a ratio of 3:1. However, within infantile and juvenile age groups, this becomes an infrequent occurrence, making up only about 5% of ovarian tumor cases. This case report sheds light on a unique scenario involving a pediatric patient who harbored 2 benign tumors simultaneously: a mature cystic teratoma and a serous cystadenoma.

Tumors of the ovarian epithelial type of testis are an infrequent entity. We report a case of borderline serous tumor in an 18-year-old male who presented with a right testicular mass, clinically suspicious of carcinoma. After right inguinal exploration, two pedunculated para-testicular masses were identified in the appendix of the right testis and epididymis. The histological features were as complex papillary structures lined by columnar cells with mild to moderate pleomorphism. Microscopically, features of borderline serous testicular tumors are identical to the morphology of the same tumors encountered in the ovarian counterparts. These tumors usually reveal papillae with fibrovascular cores lined by stratified cuboidal to columnar epithelium. This case highlights a need for clinicians and pathologists to be aware of this infrequent entity and improve the best patient management attitude. Serous epithelial tumors are common ovary tumors but are very rare entities in the testis. These tumors originate from the remnant of Mullerian ducts or Mullerian metaplasia of tunica vaginalis and are nonaggressive, even associated with extra ovarian spread, and have outstanding prognosis. A review of the literature has shown nearly fifty reported cases worldwide, and most of the cases occur in young to middle-aged adults.

Mesonephric-like adenocarcinoma (MLA) of the female genital tract is an uncommon histotype that can arise in both the endometrium and the ovary. The exact cell of origin and histogenesis currently remain unknown. Here, we investigated whole genome DNA methylation patterns and copy number variations (CNVs) in a series of MLAs in the context of a large cohort of various gynaecological carcinoma types. CNV analysis of 19 MLAs uncovered gains of chromosomes 1q (18/19, 95%), 10 (15/19, 79%), 12 (14/19, 74%), and 2 (10/19, 53%), as well as loss of chromosome 1p (7/19, 37%). Gains of chromosomes 1q, 10, and 12 were also identified in the majority of mesonephric adenocarcinomas of the uterine cervix (MAs) as well as subsets of endometrioid carcinomas (ECs) and low-grade serous carcinomas of the ovary (LGSCs) but only in a minority of serous carcinomas of the uterine corpus (USCs), clear cell carcinomas (CCCs), and tubo-ovarian high-grade serous carcinomas (HGSCs). While losses of chromosome 1p together with gains of chromosome 1q were also identified in both MA and LGSC, gains of chromosome 2 were almost exclusively identified in MLA and MA. Unsupervised hierarchical clustering and t-SNE analysis of DNA methylation data (Illumina EPIC array) identified a co-clustering for MLAs and MAs, which was distinct from clusters of ECs, USCs, CCCs, LGSCs, and HGSCs. Group-wise comparisons confirmed a close epigenetic relationship between MLA and MA. These findings, in conjunction with the established histological and immunophenotypical overlap, suggest bona fide mesonephric differentiation, and support a more precise terminology of mesonephric-type adenocarcinoma instead of MLA in these tumours. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Mixed endometrial carcinoma (MEEC) refers to rare endometrial tumours that are composed of two or more distinct histotypes, at least one of which is serous or clear cell. The aim of this study was to evaluate the epidemiology, treatment outcomes and survival rates of patients with mixed endometrial carcinoma. The medical records of 34 patients diagnosed with MEEC between March 2010 and January 2020 were reviewed retrospectively. Clinicopathological variables and treatment strategies were assessed, and overall survival and disease-free survival rates were evaluated. The histology of endometrioid and serous component was found in 26 (76.5%) patients, followed by serous and clear-cell components (5/34, 14.5%) and mixed endometrioid serous and clear-cell components (3/34, 8.8%). The median age at diagnosis was 70 years (range 52-84), and the median follow-up time was 55 months. The 5-year disease-free survival and the 5-year overall survival were 50.4% and 52.4%, respectively. Advanced disease stage was identified as an independent predictor of inferior disease-free (<0.003) and overall survival (p < 0.001). Except for stage, none of the traditional prognostic factors was associated with disease recurrence or death from disease. MEECs represent rare high-risk endometrial carcinomas with significant diagnostic and treatment challenges. Undoubtedly, the implementation of a molecular analysis can offer further diagnostic and management insights.