Search Results (338)

Background/Objectives: Lynch syndrome is an inherited autosomal dominant disease that predisposes to a broad spectrum of malignancies. This condition is driven by a germline pathogenic variant in one or more of the mismatch repair (MMR) genes (MLH1, MSH2, MSH6, PMS2, EPCAM) that results in genomic microsatellite instability (MSI-high). However, microsatellite-stable (MSS) tumors in Lynch syndrome patients may occur, but the relevant literature is scant. Our aim is to systematically identify, organize, and characterize the comprehensive available literature for Lynch syndrome-associated gynecological cancers (vulvar, vaginal, cervical, ovarian, endometrial) exhibiting a dMMR/MSS phenotype. Methods: Systematic review of the literature. Three medical databases, major related conferences and relevant oncology journals were scrutinized for relative evidence. Results: Eleven reports were identified comprising 2351 patients, 774 had confirmed Lynch syndrome (LS), of whom MSI results were available for 299 patients. In total, 130 patients developed LS-associated gynecological cancers, for whom MSI results were available. Among them, 36 tumors (27.7%) exhibited a dMMR/MSS molecular phenotype (23 endometrial, 12 ovarian, one synchronous endometrial–ovarian). No data for vulvar, vaginal, or cervical cancers were found. For dMMR/MSS endometrial cancers, the mean age at diagnosis was 50.5 years (range 36–62). dMMR/MSS tumors arose predominantly in MSH6 and, to a lesser extent, PMS2 carriers. No data on selective response to immune checkpoint inhibitors treatment were available. Conclusions: Lynch syndrome-associated gynecological cancers with dMMR/MSS phenotype are strongly underrepresented in the literature. Endometrial and ovarian cancers with dMMR/MSS phenotype are early onset and arise in a small proportion of patients. Better characterization is demanding to unearth whether response to immunotherapy treatment vary across Lynch dMMR/MSS and dMMR/MSI-High phenotypes. Full article

Patient embarrassment represents a significant yet often underrecognized barrier to effective gynecological care. This review integrates multidisciplinary evidence from Embase, PubMed, PsycINFO, and the Cochrane Library (2000–2025) to examine the relationship between embarrassment, shame, and modesty and their impact on care-seeking behaviors, clinical outcomes, and healthcare utilization. Available data indicate that embarrassment is consistently associated with reduced participation in preventive screening, with up to one-third of non-attenders citing modesty-related concerns. In symptomatic patients, these emotional barriers contribute to clinically meaningful diagnostic delays, particularly in conditions such as cervical cancer, vulvar cancer, and endometriosis. Embarrassment also affects in-consultation behavior, with a substantial proportion of patients reporting withheld concerns or incomplete disclosure of medically relevant information. The consequences extend beyond delayed diagnosis to include reduced treatment adherence, increased disease severity at presentation, and higher healthcare costs due to more complex and resource-intensive interventions. Contributing factors include cultural stigma, prior negative clinical experiences, fear of judgment, and aspects of the clinical environment that may heighten patient vulnerability. Full article

The postpartum period in beef cows is characterized by complex physiological and reproductive changes that may influence the postpartum reproductive changes and estrus expression. This exploratory pilot study evaluated postpartum reproductive responses in Angus cows receiving grape extract supplementation while investigating associations among thermographic, behavioral, hormonal, and reticulorumen temperature indicators associated with estrus expression. Nineteen Angus cows were assigned to a control group (C; n = 10) or a treatment group receiving slow-release grape extract boluses (T; n = 9). From calving until artificial insemination, ocular and vulvar thermographic images, blood samples, and physiological measurements were obtained weekly between 10:00 and 11:00 a.m. Reticulorumen temperature and activity data were continuously recorded using intraruminal sensors. Kaplan–Meier survival analysis demonstrated an earlier onset of postpartum estrus in supplemented cows compared with controls (p = 0.010). Mean time to first estrus was 23.88 ± 1.86 days in the T group and 39.82 ± 5.05 days in the C group. No significant differences were observed between groups for most individual physiological or hormonal variables. Exploratory correlation analysis revealed moderate associations among vulvar temperature, ocular temperature, activity, estrus index, and reticulorumen temperature indicators. However, because diagnostic accuracy was not evaluated, these findings should not be interpreted as validation of estrus detection performance. The results suggest that multimodal physiological monitoring may provide complementary information related to postpartum estrus expression in beef cows, while grape extract supplementation may be associated with earlier postpartum reproductive recovery. Due to the exploratory study design and limited sample size, further studies are required to validate these preliminary observations. Full article

Abortion in cattle entails substantial economic loss, and rapid identification of abortigenic pathogens is critical for timely on-farm response and reduction in human exposure risk. In 2024, two Holstein cows from a small farm in Inner Mongolia aborted in close succession without an obvious cause. Vulvar swabs from both cows, one afterbirth sample, and whole blood from one aborted fetus were collected. Shotgun metagenomic sequencing was performed, followed by host-read removal, taxonomic profiling with Kraken2, de novo assembly of Brucella-aligned reads, and whole-genome comparison. Serological tests, Gram-stained smears, and Brucella genus- and species-specific qPCR assays were used as orthogonal verification. Putative resistance and virulence determinants were screened against CARD and VFDB. Brucella reads were detected in all samples, with the highest relative abundance in the 138-afterbirth (96%). qPCR assays detected Brucella DNA and B. abortus-specific signals in all four samples. A draft Brucella genome was assembled from the 138-afterbirth sample and was phylogenetically placed within B. abortus, showing relatedness to previously circulating Chinese lineages. Cows 138 and 198 were RBT-positive with SAT titres of 1:100 (++). No acquired Brucella resistance genes were identified in CARD. Within 72 h of sample receipt, B. abortus was reported to the farm and local authorities and emergency biosecurity measures were implemented. This field investigation shows that metagenomic sequencing, when combined with conventional serology, microscopy, and targeted qPCR, can support rapid etiological investigation when culture is delayed, hazardous, or biosafety level 3 facilities are unavailable. 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

Vulvar squamous cell carcinoma (VSCC) and its precursor lesions are relatively rare malignancies of the gynecologic tract. In recent years, international organizations and pathologic reporting guidelines endorse the subdivision of VSCC into human papillomavirus (HPV)-associated and HPV-independent types. There is also growing evidence for the further separation of HPV-independent into p53 abnormal and p53 wild-type cancers. Although the diagnosis and subclassification of VSCC is often straightforward, using immunohistochemical markers such as p16 and p53 as surrogate markers for high-risk HPV infection and TP53 mutation respectively, rare and unusual scenarios exist that can complicate VSCC classification. Herein we discuss these challenging scenarios in VSCC classification, as well as emerging VSCC prognostic biomarkers such as cyclin D1. In addition, the pathologic diagnosis of VSCC precursor lesions, particularly those of HPV-independent type, are frequently challenging to distinguish from benign conditions of the vulva. We discuss the recent literature describing the added diagnostic value of immunohistochemical biomarkers p53, CK17, CK13, SOX2, GATA3, GLUT1 and others, which may be particularly helpful when morphology is inconclusive. It is anticipated that with improved VSCC classification and precursor recognition, avenues for more tailored therapeutic strategies and earlier therapeutic intervention can be achieved. Full article

Background/Objectives: This exploratory single-arm study evaluated the effects of non-ablative Erbium-doped Yttrium Aluminum Garnet (Er:YAG) laser therapy in a real-world healthcare setting. Methods: A prospective pre–post study was conducted in 47 postmenopausal women who received two sessions of non-ablative Er:YAG vaginal laser therapy (IncontiLase^®®/IntimaLase^®®). Assessments were performed at baseline and two follow-ups (FSFI, ICIQ-SF, I-QOL, and Oxford Scale). Wilcoxon signed-rank tests and Spearman correlations were used. Results: Vaginal hiatus was significantly reduced from 2.5 cm (IQR 2.0–3.0) to 2.0 cm (IQR 1.0–3.0) (p < 0.001). Vaginal length showed a small, non-significant increase, and pelvic floor strength was unchanged. Total FSFI scores remained stable; pain showed a non-significant upward trend, and arousal decreased transiently. ICIQ-SF scores did not significantly improve, although they correlated inversely with vulvar energy at second follow-up (r = −0.424; p = 0.016). I-QOL domains showed short-term improvements in social embarrassment (p = 0.002), psychosocial impact (p = 0.002), and behavioral limitations (p = 0.013) at first follow-up. Cystocele stage improved at second follow-up (p = 0.013). Conclusions: Non-ablative Er:YAG vaginal laser therapy was associated with reduced vaginal hiatus and produced short-term improvements in select quality-of-life domains and cystocele stage, while effects on sexual function and urinary symptoms were limited. Findings remain exploratory and inform the design of future controlled studies evaluating innovative outpatient care models for GSM. Given the absence of a control group and short follow-up, these findings should be interpreted as hypothesis-generating and may be influenced by placebo or expectation effects. Full article

Background: Treatment options for vulvar lichen sclerosus (VLS) remain limited; therefore, therapies that improve quality of life and reduce neoplastic risk are needed. Photodynamic therapy (PDT) is a potential option. This study aimed to evaluate quality of life and sexual function in patients treated according to the protocol used at our institution. Methods: Forty patients with refractory VLS underwent PDT using a 10% 5-aminolevulinic acid nanoemulsion (Ameluz^®) applied to lesions under an occlusive aluminum foil dressing. Patients received 1–6 sessions of 10 min illumination (LED: 37 J/cm², ~77 mW/cm²) at 4–6-week intervals. The Dermatology Life Quality Index (DLQI) and Female Sexual Function Index (FSFI) were used for assessment. Results: Thirty-seven participants answered DLQI, while 20 declared themselves to be sexually active and were included in the analysis. Greater number of PDT sessions was associated with a lower DLQI score (τ = −0.583; adjusted p < 0.001). The number of PDT sessions and the total FSFI score (p = 0.014), as well as desire (p = 0.016), arousal (p = 0.020), orgasm (p = 0.020), and satisfaction (p = 0.016) domains were significantly correlated. Age correlated positively with DLQI scores (p = 0.016), indicating greater disease burden in older patients. Longer disease duration was also associated with poorer quality of life (p = 0.020). Conclusions: PDT can be considered an effective treatment for patients with VLS refractory to standard topical corticosteroid and calcineurin inhibitor therapies when delivered using a refined, patient-centered protocol. This optimized approach used in our institution is based on short irradiation time and precise light delivery, providing a favorable balance between therapeutic efficacy, patient comfort, and treatment feasibility. Our findings also suggest that the cumulative number of PDT sessions is a key factor for clinical response. Further studies should address long-term outcomes. 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

Objectives: This systematic review aimed to evaluate malignant transformation (MT) in extraoral lichen planus to help contextualize the debated malignant potential of oral lichen planus in a mucocutaneous disease model. Methods: A comprehensive literature search was conducted across five databases and gray literature sources, without date restrictions. Observational studies reporting MT in cutaneous or genital LP were included. Data extraction, risk of bias assessment using Joanna Briggs Institute (JBI), and meta-analysis of proportions were performed. Subgroup analyses by anatomical site were conducted where possible. Results: Ten studies (15,829 patients) were included, with a predominance of women (93.1%). The pooled MT rate of extraoral LP was 1% (95% CI: 0.00–0.03). Subgroup analysis revealed a significantly higher rate in vulvar LP (2%; 95% CI: 0.02–0.03) compared to cutaneous LP (0%; 95% CI: 0.00–0.01) (p < 0.0001). Squamous cell carcinoma was the most frequent malignancy. The erosive and hypertrophic subtypes of LP were more commonly associated with cancer development. Conclusions: MT of extraoral LP appears to be rare, particularly in cutaneous forms. However, the risks observed in the genital mucosa reinforce the need for accurate diagnosis and long-term follow-up, especially in erosive presentations. Full article

Background: Vascular malformations are congenital structural abnormalities of the blood vessels that may present at any age. In the vulvovaginal region, these lesions are uncommon and frequently misdiagnosed because their clinical appearance overlaps with common gynecologic conditions, particularly Bartholin’s gland cyst or abscess. Inappropriate surgical intervention without prior vascular evaluation may result in hemorrhage, incomplete treatment, and recurrence. Methods: A structured narrative review of the literature was performed using PubMed/MEDLINE and EMBASE databases (January 2000–April 2024) to summarize the classification, pathophysiology, clinical presentation, imaging characteristics, differential diagnosis, and management of vulvovaginal vascular malformations. Publications addressing vascular anomalies in other anatomical locations were also included when clinically relevant. A representative clinical case confirmed by histopathologic and molecular analysis is presented to illustrate the diagnostic pitfalls. Results: Vulvovaginal vascular malformations are predominantly low-flow venous lesions but may include high-flow arteriovenous malformations. A clinical examination alone is insufficient for diagnosis. Doppler ultrasonography is the recommended initial imaging modality, followed by magnetic resonance imaging to define the lesion extent and flow characteristics. Misdiagnosis most commonly occurs when lesions are treated as Bartholin’s gland pathology without prior imaging. Low-flow lesions are generally managed with sclerotherapy or planned surgical excision, whereas high-flow lesions require embolization and multidisciplinary care. Hormonal and hemodynamic changes, including pregnancy, may precipitate enlargement or thrombosis. Conclusions: Vascular malformations should be considered in the differential diagnosis of atypical vulvar masses. Preoperative imaging is essential in order to avoid inappropriate surgical procedures. A structured diagnostic approach combining clinical assessment and imaging enables correct classification and guides treatment. The presented case demonstrates a typical diagnostic pitfall and emphasizes the importance of recognizing vascular lesions in gynecologic practice. Full article

Vulvodynia is a chronic gynecological condition characterized by unexplained vulvar pain, which may significantly impact every aspect of women’s quality of life, encompassing physical, psychological, and social well-being. Due to its heterogeneous clinical presentation and associated comorbidities, vulvodynia is often misdiagnosed and/or not adequately treated. This descriptive observational study was conducted using an anonymous questionnaire, which was distributed through social media channels and included 29 questions (25 multiple-choice and four open-ended questions) and aimed to investigate participants’ most frequent symptoms, comorbidities, impact on quality of life, and treatment efficacy and costs. Analyzing a total of 221 answers, we found that burning (85%) and abrasion/irritation sensation (73%) are the most common symptoms, and they are most frequently localized in the vestibular area, while irritable bowel syndrome (35%) is the most common comorbidity. A significant negative effect on individual functioning was confirmed, also due to a noticeable diagnostic delay (4.5 years on average) and treatments’ prohibitive costs potentially impairing participants’ compliance. Our study provides valuable insights into self-reported aspects of women affected by vulvodynia, raising healthcare professionals’ awareness of this issue. Better knowledge of peculiar aspects of vulvodynia may help improve its diagnosis and promote a more personalized and efficient therapeutic approach. Full article

Background: The labia minora are cutaneous folds richly innervated along their entire edge and are important for the protection of internal structures. Several studies have emphasized the wide interindividual variability in labia minora appearance. Aim: We aimed to conduct a systematic review and meta-analysis of research that has quantitatively described labia minora in healthy premenopausal adult women. Methods: Following Joanna Briggs Institute (JBI) and Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 (PRISMA 2020) guidelines, we searched PubMed, Scopus, and Web of Science without date or language restrictions using the following terms and Boolean operators: (“labia minora” OR “vulva”) AND (anatom*) AND (measure* OR morphometr*). The search was last conducted on 27 October 2025. Observational studies reporting clinical measurements of labia minora length and/or width in women undergoing routine gynecological care were included. Results: The total number of records identified was 567. Seven cross-sectional studies comprising 991 women met the inclusion criteria. All studies collected measurements in hospital or outpatient clinical settings in Europe, Asia and the Middle East. All the measurements were conducted in the lithotomy position using standardized instruments. The range of labia minora length across studies varied from 36.5 mm to 60.6 mm. The labia minora width ranged from 14.7 mm to 21.8 mm. All studies described marked interindividual variability, with wide, overlapping ranges between samples. An important limitation concerns the incomplete assessment of measurement reliability in two of the included studies. A total of three studies, encompassing 307 women, provided the necessary data to permit meta-analysis. The pooled mean labia minora length was 53.23 mm (95% CI: 43.50–62.96), while the pooled mean labia minora width was 18.28 mm (95% CI: 14.93–21.64). The analysis of between-study variability revealed statistically significant heterogeneity (Cochran’s Q test, p < 0.001) and considerable heterogeneity (I² > 75%) for both outcomes, i.e., labia minora length and width. Conclusions: The findings demonstrate substantial variability in labia minora dimensions. The integration of these data into medical education and clinical guidelines may be useful to reduce unnecessary interventions. Register: PROSPERO (registration number: CRD420251174590). Full article

Background: There is a need for intraoperative image guidance in gynecologic oncologic surgery to provide accurate identification of malignant tissue and ensure negative resection margins. Emerging imaging technologies can complement standard histopathology and reshape intraoperative decision-making. Spectral imaging can extract information on tissue composition and physiological status in real time, without the need for tissue contact, contrast agents, staining, or freezing. This systematic review synthesizes its current clinical applications in gynecologic oncology, decision support utility, and diagnostic performance with data processing frameworks for tissue classification. Materials and Methods: This systematic review (PROSPERO: CRD420251032899) adhered to PRISMA guidelines. PubMed, Google Scholar, Embase, ClinicalTrials.gov, and Scopus databases were searched until September 2025. Manuscripts reporting data on spectral imaging in gynecologic oncology were included in the analysis. Results: Twenty-nine studies and two clinical trials met the inclusion criteria. Most of them focused on cervical neoplasia (n = 17, 58.6%) and ovarian cancer (n = 7, 24.1%) detection, followed by assessment of the fallopian tubes (n = 2, 6.9%), endometrium (n = 1, 3.4%), and vulvar skin (n = 2, 6.9%). Using final pathology as the gold standard, overall specificity ranged from 30 to 99%, and overall sensitivity from 75 to 100%, with particularly high sensitivity for cervical lesions (79–100%) and ovarian cancer (81–100%). Among the included studies, thirteen (44.8%) used data interpretation algorithms, of which eleven (84.6%) applied machine learning, one (7.7%) deep learning, and one (7.7%) combined both. Conclusions: Spectral imaging, supported by computational methods, has shown promising results in the diagnostic evaluation of gynecologic disease by providing functional and molecular information beyond the capacities of standard visual assessment. Full article

Background/Objectives: The authors hypothesize that some vulvar varicosities are due to and can be treated by addressing underlying pelvic venous disorders (PeVDs). The purpose of this single center retrospective study is to evaluate vulvar varicosity resolution following treatment of an underlying PeVD. Methods: This study is a single center, retrospective case series from 2010 to 2025 of all patients evaluated in a single vein clinic with vulvar varicosities confirmed by examination and/or imaging, most commonly CT abdomen and pelvis with contrast. Inclusion criteria were presence of vulvar varicosities, evidence of an underlying PeVD, treatment with either left ovarian vein embolization or left iliac stenting, and at least one month of follow-up. PeVD was defined as a combination of suggestive imaging findings (left ovarian vein dilation or left common iliac compression) combined with associated symptoms including pelvic pain and pelvic fullness. Exclusion criteria included prior intervention for PeVDs, other vascular pathologies such as vascular malformations, incomplete documentation, and inaccessible imaging. Results: A total of 18 women with an average of 44 years of age met inclusion and exclusion criteria for the study. Thirteen patients (72.2%) presented with lower extremity varicosities at the same visit. Fifteen patients were multiparous at the time of presentation with a para status averaging 2.5. Ten patients (55.6%) had left ovarian reflux confirmed venographically and received ovarian vein embolization. Preoperative or intraoperative left ovarian venous diameter averaged 7.8 mm. Seven patients (38.9%) had left common iliac vein compression and received self-expandable left common iliac venous stenting. Preoperative CT suggested compression and all patients had intraoperative intravascular ultrasound (IVUS) prior to stenting with an average stenosis of 75.9%. One patient had both pathologies and received both treatments. No patients underwent right ovarian vein embolization nor had venographic evidence of right ovarian reflux. A total of 16 out of 18 patients (88.9%) had complete resolution of PeVDs. One patient had partial response for pelvic pain at one month of follow-up. Another patient had recurrence of pelvic pain symptoms and is being worked up for Nutcracker syndrome. All patients had resolution of their vulvar varicosities on follow-up examination. Conclusions: Vulvar varicosities may be indicative of an underlying PeVD. Vulvar varicosity resolution is associated with PeVD treatment in this case series. Therefore, vulvar varicosities are an important physical exam finding in pelvic examination and referral to a vein specialist should be considered. Additional higher powered, prospective, and randomized studies are indicated to further evaluate this relationship. Full article