Radiation necrosis is a rare but serious complication of pelvic chemoradiotherapy that may closely mimic tumor recurrence on both imaging and clinical examination. We describe the case of a 43-year-old woman with FIGO stage II vaginal squamous cell carcinoma and synchronous CIN3 who developed profuse vaginal discharge and necrotic cervical lesions five months after completing chemoradiation and brachytherapy. MRI revealed a necrotic cervical mass with suspicious features, while biopsies initially yielded inconclusive results. A multidisciplinary approach was adopted: the patient received empirical antibiotics, underwent necrotic tissue debridement, and repeat biopsies. Final histology showed no viable malignancy, confirming radiation necrosis. The patient was managed conservatively with symptomatic improvement. This case highlights the diagnostic challenge of distinguishing necrosis from recurrence, where early imaging, cytology, and even initial biopsies may be misleading. Thorough evaluation and repeated sampling are essential to avoid overtreatment. We provide a literature-informed comparison of distinguishing features to guide clinical decision-making.

Background/Objectives: Artificial intelligence (AI) is increasingly influencing oncological research by enabling precision medicine in ovarian cancer through enhanced prediction of therapy response and patient stratification. This systematic review and meta-analysis was conducted to assess the performance of AI-driven models across three key domains: genomics and molecular profiling, radiomics-based imaging analysis, and prediction of immunotherapy response. Methods: Relevant studies were identified through a systematic search across multiple databases (2020–2025), adhering to PRISMA guidelines. Results: Thirteen studies met the inclusion criteria, involving over 10,000 ovarian cancer patients and encompassing diverse AI models such as machine learning classifiers and deep learning architectures. Pooled AUCs indicated strong predictive performance for genomics-based (0.78), radiomics-based (0.88), and immunotherapy-based (0.77) models. Notably, radiogenomics-based AI integrating imaging and molecular data yielded the highest accuracy (AUC = 0.975), highlighting the potential of multi-modal approaches. Heterogeneity and risk of bias were assessed, and evidence certainty was graded. Conclusions: Overall, AI demonstrated promise in predicting therapeutic outcomes in ovarian cancer, with radiomics and integrated radiogenomics emerging as leading strategies. Future efforts should prioritize explainability, prospective multi-center validation, and integration of immune and spatial transcriptomic data to support clinical implementation and individualized treatment strategies. Unlike earlier reviews, this study synthesizes a broader range of AI applications in ovarian cancer and provides pooled performance metrics across diverse models. It examines the methodological soundness of the selected studies and highlights current gaps and opportunities for clinical translation, offering a comprehensive and forward-looking perspective in the field.

OBJECTIVE:To evaluate the prevalence and spectrum of occult invasive or preneoplastic lesions detected at risk-reducing salpingo-oophorectomy (RRSO) in BRCA1/2 carriers and to describe recurrent BRCA variants in a regional multicenter cohort. METHODS:This multicenter retrospective cohort study included 291 women with documented germline pathogenic BRCA1/2 alterations who underwent RRSO at three referral centers in Apulia, Italy, between 2020 and 2025. The primary endpoint was occult invasive or microinvasive tubo-ovarian malignancy at final histopathology. Secondary endpoints included serous tubal intraepithelial carcinoma (STIC), the distribution of histopathologic findings, distribution according to BRCA group, and recurrent annotated BRCA variants. RESULTS:After excluding one patient with ovarian metastasis, occult invasive or microinvasive tubo-ovarian malignancy was identified in 24/290 patients (8.3%), while STICs were identified in 5/290 (1.7%). STIL was observed in 3/291 patients (1.0%). Overall, 29/290 patients (10.0%; 95% confidence interval 7.1-14.0) met the composite endpoint of occult invasive or microinvasive primary tubo-ovarian malignancy or STIC. Among pathogenic variant carriers, the prevalence of the same endpoint was 20/159 (12.6%) in BRCA1 carriers and 9/131 (6.9%) in BRCA2 carriers (p = 0.119). Specific BRCA mutation was available for 154/291 patients (52.9%); BRCA1 c.5266dupC was the most frequent recurrent annotated variant, accounting for 43/154 (27.9%) annotated variants overall and 43/81 (53.1%) annotated BRCA1 variants. CONCLUSIONS:In this multicenter BRCA1/2 cohort, occult invasive or microinvasive primary tubo-ovarian malignancy and STIC were identified in approximately one in ten women undergoing RRSO. Most positive cases represented occult invasive or microinvasive malignancy, and BRCA1 c.5266dupC emerged as the dominant recurrent regional variant.

Rheumatoid arthritis (RA) affects women during reproductive years, yet menstrual outcomes under disease-modifying antirheumatic drugs remain poorly investigated. Because the JAK–STAT pathway regulates both immunity and ovarian function, Janus kinase inhibitors (JAKi) might influence menstrual health. We performed a cross-sectional, retrospective study of reproductive-aged women with RA attending rheumatology and gynecology clinics. Eligible participants had been receiving stable therapy for at least three months. Treatment categories included JAKi, Tumor necrosis factor inhibitors (anti-TNF) agents, non-anti-TNF biologics, and methotrexate. A structured questionnaire retrospectively assessed menstrual characteristics prior to therapy and during treatment. Outcomes included amenorrhea, cycle frequency, flow, menorrhagia, and metrorrhagia. Standardized definitions were applied, and analyses included chi-square tests, McNemar’s test, and logistic regression adjusting for disease activity. The cohort included 100 women with RA. Amenorrhea occurred in 10

In recent years, liquid biopsy has emerged as a promising non-invasive strategy for the identification of tumor-derived biomarkers. Among circulating analytes, cell-free DNA (cfDNA), including both nuclear and mitochondrial fractions, has been extensively investigated in a variety of biological fluids for its potential applications in cancer diagnosis, disease monitoring, and prognostic stratification. Owing to its higher copy number per cell compared with nuclear DNA, mitochondrial DNA (mtDNA) is typically present at higher concentrations in body fluids and is therefore potentially detectable. Circulating cell-free mitochondrial DNA (cfmtDNA) is closely associated with pro-inflammatory signaling pathways and cellular damage responses, including apoptosis, necrosis, and neutrophil extracellular trap formation (NETosis). This review provides a comprehensive overview of the reported alterations of cfmtDNA in the most prevalent gynecological malignancies, namely ovarian and endometrial cancers, which are characterized by a chronic inflammatory microenvironment. We further critically assess the current evidence supporting cfmtDNA as a potential non-invasive biomarker in these malignancies, highlighting current limitations and future research directions.

BACKGROUND:Uterine smooth muscle tumors of uncertain malignant potential (STUMP) are rare neoplasms with unpredictable clinical behavior. Optimal management, particularly in reproductive-aged women, remains controversial, with limited data comparing the safety of fertility-sparing versus hysterectomy. METHODS:This multicentre retrospective cohort study included women aged 18-85 with histologically confirmed STUMP treated at 17 Italian gynecologic oncology centers from 2010 to 2023. Patients underwent either fertility-sparing surgery (myomectomy or hysteroscopic resection) or definitive surgery (hysterectomy ± salpingo-oophorectomy). Kaplan-Meier and Cox models were used to compare recurrence-free survival (RFS) and overall survival (OS). RESULTS:Median (range) follow-up was 51 (1-291) months. Among 401 women, 106 (26.4 %) received fertility-sparing treatment (mean [± SD] age: 35.3 ± 6.8 years) and 295 (73.6 %) underwent definitive surgery (mean [± SD] age: 47.7 ± 9.2). At total follow-up, recurrence occurred in 12.5 % of patients, predominantly within the pelvis. Median RFS was longer after definitive surgery than after fertility-sparing procedures (50.0 vs 42.5 months; HR 2.39 [95 % CI 1.36-4.19]), although this difference disappeared when benign (leiomyoma) recurrences were excluded (HR 1.74 [95 % CI 0.90-3.34]). At last available follow-up, 97.5 % of patients were alive, with no significant OS difference between treatment groups (HR 0.22 [95 % CI 0.27-1.79]). Outcomes were comparable across menopausal status and concurrent adnexal removal. CONCLUSION:Definitive surgery reduces recurrence risk, but long-term survival is similarly excellent after fertility-sparing surgery in appropriately selected women with STUMP. Conservative management represents a reasonable option for patients desiring fertility, provided they receive counseling regarding recurrence risk, diagnostic uncertainty, and the need for long-term surveillance.

Epithelial ovarian cancers (EOCs) histotypes are characterized by marked molecular heterogeneity and limited effectiveness of current screening and monitoring strategies. Earlier identification of tumor-associated alterations may support timely intervention, especially in genetically predisposed or early-onset patient populations. While liquid biopsy approaches have primarily focused on circulating DNA, RNA, and proteins, increasing evidence indicates that cancer-associated metabolic reprogramming generates measurable informative signals in peripheral biofluids. This review summarizes recent progress in liquid biopsy-derived metabolomics in EOCs, covering analytical platforms applied to serum, plasma, urine, and ascites. Recurrent metabolic signatures linked to tumor burden, disease stage, treatment response, and clinical outcome are described, and their significance in discriminating malignant and non-malignant conditions is critically discussed. Collectively, these findings suggest that metabolomics may provide complementary functional information alongside genomic and histopathological profiling. Although its clinical implementation still requires further validation and methodological standardization, ongoing advances in analytical technologies and the integration of high-dimensional metabolic data into machine learning-based frameworks may progressively support the identification of early tumor-associated alterations and contribute to more accurate disease stratification and biologically informed clinical management.

PURPOSE:Malignant ovarian germ cell tumors (MOGCTs) are rare, aggressive malignancies predominantly affecting young women. Unlike testicular germ cell tumors, prognostic factors are poorly understood, with small studies suggesting advanced stage as an adverse factor. Here, we examine a large international series to identify relevant prognostic factors. METHODS:We analyzed data from 254 patients with International Federation of Gynecology and Obstetrics stage IC-IV MOGCT, requiring surgery and chemotherapy between 1971 and 2018 at two UK and the Multicenter Italian Trials in Ovarian Cancer centers. RESULTS:The median age was 27 years (IQR, 21-31). Initial treatment was surgery in 87.8% of patients (50.4% fertility sparing, 37.4% nonsparing) or neoadjuvant chemotherapy. Most underwent BEP or POMB/ACE chemotherapy, with 32.5% receiving high-dose chemotherapy (HDCT) at relapse. First-line treatment resulted in a complete response in 84.6% (n = 215) and partial response or stable disease in 7.9% (n = 20), while 4.7% (n = 12) progressed. Overall, 37 patients (14.6%) died of disease. Ten-year progression-free survival and cancer-specific survival (CSS) was 82.8% (95% CI, 77.2 to 87.2) and 83.2% (95% CI, 77.3 to 87.7), respectively. CSS for stage IV disease was 79.4% (95% CI, 69.5 to 86.4). Age ≥35 years (hazard ratio [HR], 2.8 [95% CI, 1.5 to 5.4]; P = .003), stage III/IV disease (HR, 1.4 [95% CI, 1,0.2 to 1.9]; P = .035), and nondysgerminoma histology (HR, 7.3 [95% CI, 1.9 to 64.8]; P = .01) had worse CSS on multivariable analysis. By contrast, CSS of immature grade 2/3 MOGCT mirrored dysgerminomas. HDCT appeared to improve survival in first but not later relapses. CONCLUSION:Advanced stage (III/IV), age >35 years, and nondysgerminoma (excluding grade 2/3 immature teratomas) are adverse prognostic factors. Stage IV disease can achieve 80% long-term survival rates, and HDCT improves survival in first but not second relapse.

Uterine perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal neoplasm whose sonographic profile has not been systematically characterized. We describe an index case of malignant uterine PEComa and present a PRISMA 2020-compliant systematic review (PubMed, Scopus, Cochrane Library; search 1 March 2026) of studies reporting original ultrasound data of histologically confirmed uterine PEComa. Sonographic features were coded with MUSA/IETA terminology; Clopper–Pearson 95% confidence intervals (CI) were calculated for key proportions, and malignancy subgroups were summarized descriptively. Thirty-one cases were pooled (30 from 18 studies plus our index case; median age 41 years). The profile comprised absent acoustic shadowing in all documented cases (10/10; 95% CI 69.2–100%), moderate-to-abundant vascularisation (Color Score 3–4, 91.7%), variable echogenicity (heterogeneous 56.0%) and predominantly regular margins (69.6%). Preoperative misdiagnosis occurred in 100% of cases, most often as leiomyoma (41.4%). In cases with known malignancy status (n = 17), irregular margins and cystic areas appeared more often in malignant lesions, but subgroups were too small for testing. Only 4/18 studies applied standardized terminology. Uterine PEComa shows a recurrent pattern of absent shadowing, high vascularisation and solid consistency with regular margins that may aid differential diagnosis; systematic adoption of MUSA/IETA terminology in future reports is strongly advocated.

ABSTRACT:This study aimed to assess whether co-treatment with gonadotropin-releasing hormone agonists during cyclophosphamide therapy protects ovarian function and preserves fertility in women with systemic lupus erythematosus. We performed a systematic review and meta-analysis of comparative cohort studies including premenopausal women with systemic lupus erythematosus treated with intravenous cyclophosphamide with or without gonadotropin-releasing hormone agonists. The primary outcome was primary ovarian insufficiency, with pregnancy and serious adverse events as secondary outcomes. Two reviewers independently selected studies, extracted data, and assessed risk of bias. Pooled risk ratios with 95% confidence intervals were calculated using fixed-effect models. Five cohort studies including 162 women (93 with gonadotropin-releasing hormone agonists and 69 controls) met the inclusion criteria; no randomized controlled trials were available. Premature ovarian insufficiency occurred in 5 of 93 women receiving gonadotropin-releasing hormone agonists and in 28 of 69 controls, corresponding to a risk ratio of 0.16 (95% confidence interval (CI): 0.07-0.37). Pregnancy was more frequent after gonadotropin-releasing hormone agonist co-treatment (19 of 87 versus 6 of 60 women; risk ratio: 1.82, 95% CI: 0.86-3.86), although this difference did not reach statistical significance. The incidence of serious adverse events was similar between groups (10 of 36 versus 10 of 34 women; risk ratio: 0.99; 95% CI: 0.50-1.93). In premenopausal women with systemic lupus erythematosus receiving cyclophosphamide, co-treatment with gonadotropin-releasing hormone agonists markedly reduces the risk of primary ovarian insufficiency without evidence of added serious toxicity and may increase subsequent pregnancy. However, the absence of randomized controlled trials represents a major limitation, and larger prospective randomized or well-controlled studies with a standardized long-term reproductive follow-up are needed to confirm these findings. LAY SUMMARY:Systemic lupus erythematosus is an autoimmune disease that often affects young women. When the disease is severe, the drug cyclophosphamide, which can damage the ovaries and cause early menopause and infertility, may be used. With our study, we wanted to assess whether adding injections of gonadotropin-releasing hormone agonists, drugs that temporarily switch off the ovaries, can protect fertility. We combined results from five studies including 162 women with systemic lupus erythematosus who received cyclophosphamide with or without these hormone injections. Early permanent loss of ovarian function occurred in 5 of 93 women who received the injections, compared with 28 of 69 women who did not. More women in the injection group later became pregnant (19 of 87 versus 6 of 60). Serious side effects were similar in both groups. These findings suggest that temporary ovarian suppression during cyclophosphamide treatment can reduce the risk of losing fertility in young women with systemic lupus erythematosus.