Mira Kheil

Xanthogranulomatous oophoritis: malignant appearance, benign pathology

Xanthogranulomatous oophoritis (XO) is a rare inflammatory condition of the female genital tract that closely mimics malignancy due to its non-specific clinical presentation and mass-like appearance on imaging. It is histologically characterised by lipid-laden macrophages, chronic inflammatory cells and necrosis. We report the case of a woman in the late 60s referred to the gynaecologic oncology clinic for evaluation of a newly identified complex ovarian mass on CT. She underwent surgical intervention with histopathological examination confirming the diagnosis of XO with extension into the uterine wall and peri-appendicitis. Postoperative recovery was uneventful, and intraoperative cultures grew Bacteroides fragilis , suggesting a potential infectious aetiology. XO remains a diagnostic challenge due to its resemblance to ovarian malignancy. This case underscores the importance of considering XO in patients presenting with adnexal masses, particularly those with a history of chronic pelvic inflammation or infection. Awareness of this rare entity can help prevent unnecessary radical surgeries, improve patient outcomes, and guide future research into its pathogenesis and management strategies.

BRCA Status Dictates Wnt Responsiveness in Epithelial Ovarian Cancer

Abstract The association of BRCA1 and BRCA2 mutations with increased risk for developing epithelial ovarian cancer is well established. However, the observed clinical differences, particularly the improved therapy response and patient survival in BRCA2-mutant patients, are unexplained. Our objective is to identify molecular pathways that are differentially regulated upon the loss of BRCA1 and BRCA2 functions in ovarian cancer. Transcriptomic and pathway analyses comparing BRCA1-mutant, BRCA2-mutant, and homologous recombination wild-type ovarian tumors showed differential regulation of the Wnt/β-catenin pathway. Using Wnt3A-treated BRCA1/2 wild-type, BRCA1-null, and BRCA2-null mouse ovarian cancer cells, we observed preferential activation of canonical Wnt/β-catenin signaling in BRCA1/2 wild-type ovarian cancer cells, whereas noncanonical Wnt/β-catenin signaling was preferentially activated in the BRCA1-null ovarian cancer cells. Interestingly, BRCA2-null mouse ovarian cancer cells demonstrated a unique response to Wnt3A with the preferential upregulation of the Wnt signaling inhibitor Axin2. In addition, decreased phosphorylation and enhanced stability of β-catenin were observed in BRCA2-null mouse ovarian cancer cells, which correlated with increased inhibitory phosphorylation on GSK3β. These findings open venues for the translation of these molecular observations into modalities that can impact patient survival. Significance: We show that BRCA1 and BRCA2 mutation statuses differentially impact the regulation of the Wnt/β-catenin signaling pathway, a major effector of cancer initiation and progression. Our findings provide a better understanding of molecular mechanisms that promote the known differential clinical profile in these patient populations.