Search Results (460)

Background and Objectives: Uterine metastasis from breast carcinoma is rare but poses substantial diagnostic and therapeutic challenges. Invasive lobular carcinoma (ILC) demonstrates a documented predilection for unusual metastatic patterns including the female genital tract, while tamoxifen-associated endometrial pathology may complicate diagnosis in breast cancer survivors. Materials and Methods: We performed a structured PubMed/MEDLINE and Google Scholar search (1980–2025) for cases with histologically confirmed breast primary and uterine involvement; a pooled analysis of demographic, histological, molecular, and clinical variables was performed. Results: 105 individual cases were identified. ILC accounted for 58.0% of histologically classified cases despite representing only 10–15% of breast cancers. Endometrial involvement was present in 68.6%, myometrial in 25.7%, and cervical in 26.7%. Tamoxifen exposure was strongly associated with polyp-substrate metastasis (29.3% vs. 4.7%; Fisher’s exact p = 0.0009; OR 8.41, 95% CI 2.20–32.14). Abnormal uterine bleeding was the dominant presentation (68.1%); 19.8% were asymptomatic. Median latency was 36 months (range from 24 months before to 360 months after the breast cancer diagnosis). Conclusions: Uterine metastasis from breast carcinoma is dominated by invasive lobular histology and frequently involves tamoxifen-associated polyps. A combined immunohistochemical panel (GATA3, TRPS1, E-cadherin, hormone receptors, PAX8) is essential for distinguishing metastatic disease from primary uterine pathology. Endometrial sampling should be considered with a low threshold in breast cancer survivors with abnormal uterine bleeding, and breast imaging is warranted when discohesive cells are encountered without a known breast primary. These proportions describe the published case literature rather than population-based prevalence; because the evidence is limited to case reports and small series, they should not be read as the true frequency of uterine involvement among women with breast cancer. Full article

Human papillomavirus (HPV) infection is a major driver of anogenital disease and virus-related carcinogenesis. Although most infections resolve spontaneously, persistent infection with high-risk genotypes may progress to high-grade squamous intraepithelial lesions (HSILs) and cancer, particularly in the setting of impaired immune surveillance. Unlike previous HPV-related reviews focused primarily on cervical disease, vaccination, or isolated immunosuppressed populations, this narrative review comparatively examines the clinical expression, colposcopic findings, screening strategies, and therapeutic implications of HPV-related disease across the immunological spectrum. This narrative review provides an integrative synthesis of HPV-related disease in the female lower genital tract across the immunological spectrum. A structured, non-systematic search of PubMed/MEDLINE, Scopus, and Web of Science was conducted using terms related to “human papillomavirus”, “HPV”, “cervical intraepithelial neoplasia”, “colposcopy”, “immunosuppression”, “HIV”, and “vaccination”. Immunosuppressed populations, including individuals living with HIV, transplant recipients, and patients receiving immunosuppressive therapy, exhibit higher rates of persistent infection, multifocal disease, recurrence, and progression to HSIL and invasive malignancy. These patients also present greater diagnostic complexity, broader anatomical involvement, and reduced response to conventional treatment. Rather than representing a uniform condition, HPV-related disease reflects a biologically dynamic spectrum shaped by host immune competence. This review highlights the distinct clinical, colposcopic, and therapeutic challenges observed in immunosuppressed populations and reinforces the need for individualized, risk-adapted strategies integrating contemporary advances in screening, vaccination, and HPV-related disease management. Full article

Background and Clinical Significance: Placental site trophoblastic tumour (PSTT) is a malignant tumour of the implantation site intermediate trophoblasts. It has historically been described using terms such as atypical chorioepithelioma, atypical choriocarcinoma, syncytioma, and chorioepitheliosis. It belongs to one of the heterogeneous spectrums of gestational trophoblastic disease. It accounts for about 0.25 to 5% of all gestational trophoblastic neoplasia. The typical clinical presentation is alternating menorrhagia and amenorrhea, mildly elevated β-hCG, and radiological findings of a uterine mass. Case Presentation: A 32-year-old woman presented with a history of intermittent menorrhagia and amenorrhea, with a persistent mildly raised β-hCG level. Ultrasonography showed a hypoechoic lesion on the right side of the posterior wall of the uterus. She was diagnosed with a missed miscarriage, and an evacuation of the products of conception was performed. Histologically, the tissue fragments comprised cords and sheets of atypical intermediate trophoblast cells, with characteristic features of myometrial smooth muscle infiltration, vascular invasion, and vascular wall replaced by the neoplastic cells. Immunohistochemically, these cells are positive for β-hCG and GATA3, while negative for P63. Conclusions: PSTT is a rare form of gestational trophoblastic neoplasia. Early recognition of PSTT is essential because its clinical presentation may mimic benign pregnancy-related conditions, and diagnosis relies heavily on histopathological and immunohistochemical evaluation. Full article

While the pathological impact of reactive oxygen species (ROS) in the aetiology of human infertility has received much attention, this review explores the counterproposal that these highly reactive metabolites play a positive role in mediating reproductive success. The physiological importance of ROS in biological systems can be distilled into three main categories of influence: (1) ROS can oxidize thiols to generate either the corresponding sulfenic acid or disulfide bridges. This oxidizing capacity is critical for several reproductive processes, including the cross linking of sperm chromatin during epididymal maturation, formation of the mitochondrial sheath, and the activation of proteolytic zymogens involved in such processes as ovulation, menstruation, implantation, and parturition. Thiol oxidation is also involved in the suppression of phosphatase activity and the resulting promotion of phosphorylation-dependent signal transduction pathways, which are involved in virtually every aspect of reproduction from sperm capacitation to parturition; (2) The destructive properties of ROS are also biologically significant in the defence against genital tract infections and in mediating such processes as autophagy, apoptosis, and ferroptosis, which are fundamental to the reproductive process; (3) Finally, ROS are involved in controlling the redox status of transition metals (particularly iron and copper) in the active site of many enzymes that are of fundamental importance to reproduction. Given the biological importance of ROS to procreation, we should use antioxidants with care in managing both male and female infertility and avoid the induction of reductive stress. Full article

Background and Clinical Significance: Postpartum hemorrhage (PPH) is a leading cause of maternal mortality worldwide. Among its various etiologies, uterine atony accounts for approximately 70% of cases, while other causes include genital tract trauma, pathologic placentation, and intrapelvic arterial injury. Uterine artery embolization (UAE) has emerged as a preferred management option for severe PPH due to its high success rates of 89–98% and fertility preservation benefit. Despite its efficacy, UAE can lead to complications, such as pain, re-bleeding, infection, persistent vaginal discharge, ovarian insufficiency, and uterine necrosis—a rare but serious complication occurring in 1.4–2.7% of cases. Case Presentation: We present three cases of uterine necrosis following UAE from a single center (CHA Bundang Medical Center) between 2003 and 2024. All patients developed persistent high-grade fever approximately two weeks after the procedure, despite an initial response to antibiotic therapy. Imaging studies, including contrast-enhanced CT and MRI, revealed uterine ischemia and necrosis, and all patients ultimately required total hysterectomy. Conclusions: Uterine necrosis is a rare but potentially life-threatening complication of UAE that should be suspected in patients with persistent high-grade fever beyond the typical post-procedural course. Early imaging evaluation, particularly with contrast-enhanced modalities, is essential for prompt diagnosis. Timely surgical intervention, including hysterectomy, may be required to prevent severe morbidity. Full article

Neuroendocrine differentiation in tumors of the female genital tract is an uncommon but diagnostically consequential finding. Its interpretation is challenging because neuroendocrine marker expression does not necessarily define a neuroendocrine neoplasm. Focal or aberrant staining for synaptophysin, chromogranin A, CD56 or INSM1 may occur in otherwise conventional gynecologic carcinomas, whereas true poorly differentiated neuroendocrine carcinomas represent aggressive tumors with distinct prognostic and therapeutic implications. This narrative review examines neuroendocrine differentiation across the cervix, endometrium, ovary, vagina and vulva from an integrated clinicopathologic perspective. We emphasize that neuroendocrine differentiation should be approached as a diagnostic and biological spectrum, ranging from incidental immunophenotypic expression to carcinoma with neuroendocrine differentiation, mixed neuroendocrine/non-neuroendocrine tumors, well-differentiated neuroendocrine tumors and poorly differentiated neuroendocrine carcinomas. Morphology remains the diagnostic anchor, while immunohistochemistry, molecular context and clinicoradiologic correlation refine classification and help exclude mimics or metastatic disease. Site-specific interpretation is essential: cervical neuroendocrine carcinoma is commonly HPV-associated and clinically aggressive; endometrial tumors require integration with p53, mismatch repair, POLE and SWI/SNF-related contexts; ovarian lesions demand distinction between primary well-differentiated neuroendocrine tumors, poorly differentiated carcinomas and metastases; and vaginal or vulvar tumors require careful exclusion of adjacent extension, cutaneous mimics and extragenital primaries. We propose a practical diagnostic framework that separates incidental marker expression from clinically meaningful neuroendocrine differentiation and links this distinction to reporting, prognosis and treatment. The central diagnostic question is not whether neuroendocrine markers are expressed but whether their expression defines a morphologically, biologically and clinically meaningful tumor category. Full article

Background/Objectives: Health outcome determinants affecting Human Papillomavirus (HPV) vaccination among the adult female population are scarce in Spain. This study aimed to describe the health outcomes and determinants of HPV vaccination in women 18–65 years attending lower genital tract outpatient clinics across regions of Spain. Methods: This was a cross-sectional, multicenter, non-interventional, descriptive, and comparative nationwide study. Sociodemographic characteristics and health outcomes included obstetric, gynecological and HPV vaccination antecedents, together with patient-reported outcomes related to HPV infection. Statistical analysis included multivariate logistic regression models. Results: Among 2004 adult women recruited, 1907 (95.2%) were eligible for analysis. Vaccine uptake was 48.8%; 81.6% among women who were ever HPV positive (adjusted OR = 2.16 [95% CI: 1.59–2.93], p < 0.001), but 65.9% among women with an active infection, which acted as a negative factor for vaccination (OR = 0.63 [0.45–0.87], p = 0.005), as did increasing age (OR = 0.92 [0.90–0.93], p < 0.001); the higher the age, the lower the adjusted likelihood of being vaccinated. HPV knowledge and adequate physician-provided information were weakly associated with vaccination likelihood. A history of conization (OR = 7.48 [5.34–10.47], p < 0.001), use of contraception (OR = 1.49 [1.13–1.96], p = 0.004), infection with high-risk or unknown-risk HPV genotypes (OR = 1.86 [1.23–2.82], p = 0.003 and OR = 1.68 [1.17–2.42], p = 0.006, respectively), and Spanish nationality (OR = 2.46 [1.68–3.61], p < 0.001) were identified as factors associated with a higher vaccination likelihood. Conclusions: This study found that HPV vaccination uptake is improvable. Previous HPV infection favored vaccination; however, active infection and increasing age acted against vaccination. HPV knowledge and adequate healthcare professional information appeared to favor vaccination, along with, most notably, a history of cervical surgery (conization), contraceptive use, or infection with high-risk or unknown-risk HPV genotypes. Spanish women had a higher likelihood of receiving HPV vaccination than foreign residents. Full article

HIV is primarily acquired in women at the female genital mucosa through heterosexual contact. Mucosal immune cells reside adjacent to, within, below, and distant from the epithelium that lines the surface of the female genital tract (FGT) mucosa. Innate immune cells play dual roles in HIV acquisition, both poised to rapidly recognize and respond to HIV, but are also capable of promoting HIV infection locally and distantly in the lymph nodes. In this review we emphasize recent human research on the roles of specific innate immune cells in HIV pathogenesis in the FGT, including dendritic cells, macrophages, neutrophils and innate lymphoid cells. We review how FGT mucosal dynamics, including anatomical compartmentalization, menstrual cycle regulation, reproductive history, menopause and chronological aging contribute to tissue conditioning of these cells and changes in HIV susceptibility in women throughout their lives. Full article

People affected by diabetes mellitus (DM), chronic kidney disease (CKD), or heart failure are often prescribed sodium–glucose cotransporter-2 inhibitors (SGLT2is) as a method of treatment. These drugs favorably affect glucose metabolism, as patients taking them have lower serum glucose levels. Another promising positive impact is protection against microvascular damage, cardiovascular disease, and chronic kidney disease. Nevertheless, fungal infections, urinary tract infections, and ketoacidosis are the adverse effects that might happen during the SGLT2i treatment. Fungal infections are more common among patients treated with these medications, including vulvovaginal Candidiasis in women and balanitis or balanoposthitis in men. Given the difficulty of treating fungal infections in patients with co-occurring diseases, we recommend that ongoing supervision of patients treated with SGLT2i include prevention and early detection of fungal infections. Full article

Hypospadias is a congenital malformation of the male external genitalia resulting from incomplete fusion of the urethral folds during embryonic development. The perineal form represents the most severe phenotype and is frequently associated with abnormalities such as cryptorchidism and penile hypoplasia. Although surgical correction is generally recommended in young dogs, the long-term clinical course of severe hypospadias under conservative management remains poorly documented. In this study, we describe an unusual canine case of severe perineal hypospadias that survived to geriatric age under conservative management and subsequently developed bilateral testicular tumors arising from cryptorchid testes. Despite recurrent urinary tract infections during early life, the patient maintained an acceptable quality of life with long-term supportive care, providing a rare clinical example of extended survival without surgical correction. Because no molecular material was available from the patient, publicly available mouse transcriptomic datasets related to genital tubercle development and Leydig cell differentiation were consulted only as contextual reference. These datasets illustrate established developmental regulators and steroidogenic pathways relevant to genital formation and testicular function but do not represent direct molecular findings from the reported case. This report primarily highlights the clinical course and management of severe hypospadias in a dog, while using existing transcriptomic knowledge solely to provide biological context. The findings should therefore be interpreted as descriptive and hypothesis-generating rather than as evidence of a direct mechanistic link between developmental abnormalities and endocrine tumorigenesis. Full article

Background and Objectives: Synchronous cervical and vulvar squamous intraepithelial lesions are rarely reported. In most cases, these lesions are associated with high-risk human papillomavirus (HPV) infection and follow the conventional HPV-related pathway. Rarely, vulvar lesions may show an unusual immunohistochemical profile, with block-type p16 expression accompanied by aberrant p53 staining, creating diagnostic and etiopathogenetic challenges. Case Presentation: We report the case of an 83-year-old woman who presented with metrorrhagia and a symptomatic vulvar lesion. Histopathological evaluation revealed synchronous high-grade squamous intraepithelial lesion of the cervix and vulvar high-grade squamous intraepithelial lesion (VIN 3). Immunohistochemically, the cervical lesion showed block-type p16 positivity and a wild-type p53 pattern, supporting a conventional HPV-associated profile. In contrast, the vulvar lesion also demonstrated block-type p16 positivity, but with aberrant p53 overexpression, representing an unusual double-positive immunophenotype. Conclusions: This case highlights a rare presentation of synchronous lower genital tract squamous intraepithelial lesions with divergent immunophenotypic features. Accurate interpretation requires integration of morphology and immunohistochemistry, while the absence of direct HPV testing and TP53 molecular analysis limits definitive etiopathogenetic classification. Reporting such cases may broaden awareness of unusual vulvar precursor lesions and potential diagnostic pitfalls in routine practice. Full article

Biliverdin (BV) and bilirubin (BR) are established endogenous antioxidants and immune modulators in other organ systems; however, their roles in the male genital tract remain undefined. The aim of this study was to quantify both bile pigments in human seminal plasma using a fluorescent protein biosensor and to examine their associations with basic semen parameters. We analyzed forty-two semen samples from men undergoing infertility evaluation. Biliverdin predominated over bilirubin in 88.1% of samples. Biliverdin concentration ranged from 51.8 to 611.2 nM, whereas bilirubin ranged from 19.7 to 240.7 nM. The mean total amounts per ejaculate were 1054 pmol for biliverdin and 280 pmol for bilirubin. The total amount of bilirubin in the ejaculate was positively correlated with total sperm count (Rs = 0.47; p = 0.028), whereas biliverdin showed no significant association (Rs = 0.21; p = 0.723). Oligozoospermic samples had significantly lower bilirubin concentrations (p < 0.001) and lower total bilirubin amounts (p < 0.005). Teratozoospermic samples exhibited significantly higher biliverdin concentrations (p < 0.05). This study provides the first simultaneous quantification of biliverdin and unconjugated bilirubin in human seminal plasma and identifies distinct associations with sperm quality. These findings suggest that bile pigments may reflect localized redox-related processes in the male genital tract and may influence male fertility potential. Full article

Background and Clinical Significance: Cirrhosis-associated immune dysfunction (CAID) is characterized by impaired innate and adaptive immune responses, gut dysbiosis, and increased bacterial translocation, predisposing patients to severe and atypical infections. While spontaneous bacterial peritonitis and other intra-abdominal infections are well-recognized complications of cirrhosis, extraintestinal infectious manifestations related to bacterial translocation are less commonly described. A tubo-ovarian abscess (TOA) typically arises from ascending pelvic infections associated with pelvic inflammatory disease and is rarely reported in patients with cirrhosis without gynecologic risk factors. Thus, recognizing unusual infectious presentations in cirrhotic patients is important given their functionally immunocompromised state. Case Presentation: We report a 46-year-old woman with previously undiagnosed alcohol-related cirrhosis who presented with sepsis and abdominal pain. She had no prior gynecologic history or known risk factors for pelvic inflammatory disease. Contrast-enhanced computed tomography (CT) demonstrated bilateral tubo-ovarian abscesses. Image-guided percutaneous drainage was performed, and cultures from both ascitic fluid and bilateral adnexal collections grew Enterococcus faecium, supporting a shared intra-abdominal source of infection and suggesting transperitoneal dissemination via infected ascitic fluid as a plausible mechanism, although an ascending genital tract source cannot be fully excluded. The patient was treated with targeted intravenous antibiotics and drainage with subsequent clinical improvement. Conclusions: This case highlights bilateral tubo-ovarian abscesses as a rare infectious complication of cirrhosis-associated immune dysfunction. In cirrhotic patients presenting with sepsis and intra-abdominal pathology, clinicians should consider atypical infection pathways related to bacterial translocation among the differential mechanisms of spread. Thus, recognizing cirrhosis as a functionally immunocompromised state is essential for the timely diagnosis and management of unusual infections. Full article

Background: Obstructed hemivagina and ipsilateral renal anomaly (OHVIRA) syndrome, also known as Herlyn–Werner–Wunderlich syndrome (HWWS), is a rare Müllerian malformation. Gynaecologic malignancies reported in association with OHVIRA syndrome/HWWS are exceptional and scattered across isolated case reports and small case series, leading to significant challenges for screening, early diagnosis, and optimal management. The primary aim of this study was to comprehensively review and synthesize the clinicopathologic features, treatment approaches, and reported outcomes of patients with OHVIRA-associated gynaecologic neoplasms. Methods: A systematic review of published cases of gynecologic malignancies in OHVIRA/HWWS was conducted using PubMed/MEDLINE and Scopus from database inception through January 2026. To expand the current evidence, an illustrative novel institutional case is also presented and integrated into the analysis. Results: A total of 21 cases were identified and analysed; reported tumours predominantly involved the lower genital tract (vagina/cervix), with a recurrent representation of adenocarcinoma, particularly clear cell histology, and a frequent origin from the obstructed or non-visible compartment when side was described. Endometrial and ovarian involvement was uncommon. Conclusions: The anatomical complexity of OHVIRA syndrome creates a diagnostic blind spot that warrants heightened clinical suspicion, rigorous MRI-based anatomic delineation, and side-specific evaluation in symptomatic patients. By synthesizing the available literature, this review underscores the necessity for tailored, multidisciplinary management and proactive surveillance strategies in this rare population. Full article

Background: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a bothersome condition characterized by pelvic pain and lower urinary tract symptoms (LUTS). Phytotherapy can be used to treat this challenging condition. The aim of this study was to investigate the role of an oral combination of bovine colostrum, Serenoa repens extract and other anti-inflammatory elements in the treatment of CP/CPPS patients. Methods: Our study was a prospective, observational, single-arm study that enrolled patients > 18 years with a history consistent with CP/CPPS, a Chronic Prostatitis Symptom Index (CPSI) pain domain score ≥ 5 and a Meares–Stamey microbiological test negative for bacterial infection. Pelvic or genital pain was measured via the Numeric Pain Rating Scale (NPRS) and validated questionnaires. All patients were treated with an oral combination of colostrum, Serenoa repens extract and other anti-inflammatory elements for 6 months. Follow-up visits were scheduled at 3 and 6 months. Pre- and post-treatment variables were compared by means of the Wilcoxon signed-rank nonparametric test. Results: We included 42 patients in our analysis. The median (Inter-Quartile Range, IQR) age was 42 (28–51) years. Compared with baseline, after 3 months we observed a significant reduction in pain: total CPSI score of 16 (12–21) vs. 22 (17–26), p < 0.001, −6 points (−27.3%); CPSI score of “pain” domain 7 (5–9) vs. 8 (7–11), p < 0.001, −1 point (−12.5%). Moreover, quality of life improved: CPSI “quality of life” domain 6 (4–9) vs. 8 (7–10), p < 0.001. After 6 months, a significant reduction in pain was maintained: total CPSI score 19 (10–23), p < 0.001, −3 points (−13.65%); and CPSI “pain” domain 7 (4–9), p < 0.001, −1 point (−12.5%). After 6 months, a mild reduction in urinary symptoms was also reported. During the observation period, five patients discontinued treatment, two of them because of gastrointestinal intolerance. Conclusions: The daily oral administration of bovine colostrum, Serenoa repens and other anti-inflammatory elements showed a potential in improving pain and other urinary symptoms and was generally well tolerated by patients affected by CP/CPPS. Full article