Carcinoma admixed with neuroendocrine carcinoma of the cervix is a rare malignant tumor with high malignancy and poor prognosis, of which large cell neuroendocrine carcinoma with adenocarcinoma are particularly rare, which have been reported limitedly in the literature. Currently, in most specimens, this disease is identified as a human papillomavirus (HPV)-related tumor. In the present study, we report a patient with mixed large cell neuroendocrine carcinoma and adenocarcinoma of the cervix, in which the molecular characterization of the lesion highlighted the ubiquitous presence of HPV18 DNA in both the adenocarcinomatous and neuroendocrine components, suggesting a potential pathogenic role of the virus. And 2 years later, the large cell neuroendocrine carcinoma component but not the adenocarcinoma component of the tumor progressed to cervical lymph node metastasis. Because large cell neuroendocrine carcinoma is known to exhibit early metastasis and extremely poor prognosis, it is important to carefully detect the large cell neuroendocrine carcinoma component in cervical cancer. Therefore, accurate diagnosis coupled with a comprehensive literature review is essential to supplement epidemiological data and facilitate the development of standardized treatment strategies.

To evaluate the diagnostic proficiency of well-established multimodal Large Language Models (LLMs)-specifically Gemini, Claude, and Copilot-in interpreting cervical cytopathology (PAP smears). This diagnostic accuracy study used 30 representative cases from the "Cytopathology of the Uterine Cervix-Digital Atlas," which represented the gold standard. The models were tested using a standardized, zero-shot prompt to distinguish between normal cells, benign modifications (infections), and cervical cell abnormalities. The models demonstrated significant variability. While Gemini and Copilot showed high proficiency (90%) in identifying normal physiological morphology, performance declined sharply for infectious pathogens and dysplastic/neoplastic lesions. Notably, all models misclassified several invasive carcinomas as benign or low-grade lesions. Claude exhibited a high rate of "diagnostic escalation," frequently misidentifying normal cells as having abnormalities. Current LLMs are inadequate for the definitive diagnosis of cervical dysplasia and malignancy due to significant rates of overdiagnosis and failure to detect invasive carcinomas. They should be viewed as emerging educational aids rather than autonomous diagnostic tools, requiring rigorous human oversight.

Background and Objectives: In women who are positive for high-risk human papillomavirus (hrHPV), abnormal cytology necessitates colposcopy and biopsy; however, cytology-histology concordance is variable and may differ by menopausal status. This study aimed to evaluate the concordance between cytologic findings and biopsy results in hrHPV-positive women with abnormal Pap tests and to compare outcomes by menopausal status. Materials and Methods: This retrospective, single-center study included 904 hrHPV-positive women with abnormal cytology who underwent colposcopy. Cytology findings [atypical squamous cells of undetermined significance (ASC-US), low-grade squamous intraepithelial lesion (LSIL), atypical squamous cells-cannot exclude high-grade squamous intraepithelial lesion (ASC-H), and high-grade squamous intraepithelial lesion (HSIL)] were compared with histological findings [normal, cervical intraepithelial neoplasia (CIN)-1, -2, -3]. Menopausal status was stratified as premenopausal (<48 years) and postmenopausal (≥48 years). Rates of cyto-histologic concordance, overestimation, and underestimation were calculated. Results: The predominant cytological result was ASC-US (61.7%), followed by LSIL (25.3%), whereas histologically, CIN was most common (66.5%; CIN-1: 42.8%, CIN-2: 11.5%, CIN-3: 12.2%). Cytology-biopsy concordance was 50.7%, with overestimation in 35.4% and underestimation in 13.9%. Overestimation was highest in ASC-US (43.9%) and ASC-H (37%), while underestimation was most frequently seen in LSIL cases (27.1%). HSIL cytology showed the highest agreement (85.7%). Conversely, LSIL cytology showed higher cyto-histologic concordance in postmenopausal women, whereas ASC-H and HSIL cytologies were more commonly overestimated in comparison to premenopausal women. Using ASC-H/HSIL as the positive cytology threshold for CIN-2+ detection, sensitivity was 41.1% and specificity was 95.8% [positive predictive value (PPV) 75.2%, negative predictive value (NPV) 84.0%; overall accuracy 82.9%]. The sensitivity and NPV were higher in postmenopausal women than in premenopausal women (50.0% vs. 39.9%; 91.3% vs. 82.3%, respectively). Conclusions: Cytology-histology concordance is moderate among women who are hrHPV-positive with abnormal cytology, characterized by notable underestimation in low-grade cytology and strong predictive value in HSIL cases. Menopausal status influences the outcomes; in postmenopausal women, high-grade lesions are less frequent, and diagnostic accuracy for detecting CIN-2+ is higher. These findings highlight the need for age- and menopause-sensitive diagnostic approaches.

Papillary immature metaplasia, originally described in the uterine cervix, is increasingly recognized as a distinctive squamous intraepithelial lesion rather than a true metaplastic process. Accordingly, the term papillary squamous intraepithelial lesion (PSIL) has been proposed. PSIL occurring outside the uterine cervix is exceedingly rare. In this study, we characterize the clinicopathologic, immunophenotypic, and virologic features of 25 cases of PSIL involving non-cervical sites (vagina, vulva, anus, and endometrium). All lesions demonstrated exophytic papillary architecture lined by uniform immature squamous cells with limited surface maturation. Mitotic figures were frequently identified in the lower half of the epithelium. Low-risk HPV E6/E7 mRNA was detected in 76% of cases, whereas none harbored high-risk HPV. HPV transcripts exhibited a distinctive punctate distribution throughout the epithelium, contrasting with the superficial clustered pattern seen in condyloma/LSIL. Non-block p16 immunostaining pattern was seen in all PSILs, while Ki-67 labeling indices were increased (median 50%), predominantly involving the lower half to two-thirds of the epithelium. Clinical follow-up (median 32 months) demonstrated recurrence in 43% of cases, most commonly with incomplete excision. Our study shows that non-cervical PSIL shares morphologic, immunophenotypic, and virologic features with cervical PSIL. Despite the absence of block-type p16 expression, PSIL demonstrates high proliferative activity, frequently leading to diagnostic confusion with HSIL. Given its distinctive papillary architecture, unusual HPV distribution pattern, and tendency for recurrence, PSIL represents a unique low-risk HPV-associated intraepithelial lesion distinct from conventional LSIL and HSIL. Adoption of the term papillary squamous intraepithelial lesion is recommended in accordance with LAST terminology.

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.

Cervical cancer screening in Germany was newly regulated as of January 1, 2020. Since then, an organized cancer screening guideline (oKFE-RL) for cervical cancer screening has been effective. From the age of 20, a cytological smear is taken once a year and from the age of 35 a co-test is carried out every three years. In the event of abnormalities, an algorithm regulates the procedure. This algorithm states that even so-called low-risk groups should have a diagnostic colposcopy at an early stage. This approach has been widely discussed and continues to serve as the basis of this registry study.

Epithelioid trophoblastic tumor (ETT) is a rare subtype of gestational trophoblastic neoplasia, most commonly arising in the cervix or lower uterine segment and often associated with mildly elevated serum human chorionic gonadotropin (hCG). Owing to its nonspecific clinical and imaging features, preoperative diagnosis remains challenging, particularly when the tumor exhibits hypervascular characteristics mimicking uterine arteriovenous malformation (AVM). We report the case of a 48-year-old perimenopausal woman who presented with sudden-onset massive vaginal bleeding following a short period of amenorrhea. Transvaginal color Doppler ultrasonography and contrast-enhanced computed tomography revealed a hypervascular cervical mass with multiple enlarged and tortuous vessels, raising strong suspicion of uterine AVM. Given the high risk of hemorrhage, preoperative uterine artery embolization was performed, followed by laparoscopic total hysterectomy with bilateral salpingo-oophorectomy. Histopathological and immunohistochemical examination confirmed the diagnosis of epithelioid trophoblastic tumor. Retrospective assessment revealed mildly elevated serum hCG levels. This case highlights the diagnostic challenge of epithelioid trophoblastic tumor presenting as a hypervascular cervical lesion mimicking uterine arteriovenous malformation. In perimenopausal women with acute vaginal bleeding and AVM-like imaging findings, ETT should be included in the differential diagnosis to avoid delayed recognition and to guide appropriate perioperative management.

Colorectal and cervical cancers represent an important public health problem worldwide, particularly in Brazil. Colorectal cancer is one of the most frequently diagnosed malignancies worldwide and the most common cancer in both men and woman in Brazil. Although cervical cancer also remains a significant public health concern in the female population due to its high incidence and mortality rates. Epstein-Barr virus (EBV), and Polyomaviruses (JCPyV and BKPyV) are considered as oncoviruses with a prevalence of 90% in the adult population. Studies suggest that coinfection with Human papillomavirus (HPV) and EBV, JCPyV and BKPyV can be associated with anal cancer, with HPV being the dominant viral cause. Although in cervical cancer, this coinfection is often observed, and it may enhance cervical oncogenic potential. These facts are particularly concerning in women living with HIV, who are more susceptible to persistent HPV infections and HPV-related cancers. This study aimed to investigate EBV, JCPyV and BKPyV presence in HPV-infected women living with HIV. This cross-sectional study collected 33 cervical and 30 anal scrapings samples, as well as 26 paired samples from both sites from HPV-positive women living with HIV. Viral detection and quantification for EBV, JCPyV and BKPyV were performed using real-time polymerase chain reaction (qPCR), while HPV detection and genotyping utilized the NovaplexTM assay. EBV was detected in 33.3% of anal scraping and 21.2% in cervical scraping. HPV 51 and HPV 56 were most frequently detected in anal and cervical scrapings, respectively. The EBV mean viral load was higher in cervical scraping (2.27 × 10^5 copies/mL) when compared to anal scraping (1.19 × 10^5 copies/mL) in relation of JCPyV and BKPyV viral loads. Regarding coinfections, it was found that EBV presented a high coinfection rate with high-risk HPV genotypes (hrHPV) (14.6%) with HPV 31 in both samples. This study provided valuable data about the frequency of EBV in anal and cervical HPV-positive women. The elevated viral load of EBV in cervical scrapings may suggest a potential role in modulating the local microenvironment and warrants further investigation into the synergistic effects of EBV and HPV in anogenital and cervical carcinogenesis. Overall, the results of this study emphasize the need for further investigation into the role of these viruses in the progression of cervical lesions.