Background/Objectives: Atypical cytological findings in cervical screening, such as ASC-US, ASC-H, and AGC, present a clinical challenge due to their variable risk of underlying high-grade lesions. The precise stratification of this risk is crucial for effective patient management. This study aimed to correlate Bethesda cytology categories with HPV genotyping, including viral load, and histological follow-up to improve risk prediction for cervical intraepithelial neoplasia grade 2 or worse (CIN2+). Materials and Methods: In this retrospective single-center study, we analyzed 407 patients with cytological reports of ASC-US, ASC-H, or AGC. All patients underwent HPV DNA testing with genotyping for 21 types, with viral load quantification for HPV16/18, and subsequent histological verification. Statistical analyses included non-parametric tests, correlation analysis, and multivariate logistic regression to identify independent predictors of CIN2+. Results: The prevalence of CIN2+ differed significantly among the cytological categories: 23.2% in ASC-US, 47.3% in ASC-H, and 19.5% in AGC. ASC-H and a high HPV16 viral load were identified as independent predictors of CIN2+ in the multivariate analysis. An ASC-H result increased the probability of CIN2+ by 2.5 times (aOR = 2.51; 95% CI: 1.28–4.94). For each 1 log10 increase in HPV16 viral load, the risk of CIN2+ increased by 30% (aOR = 1.30; 95% CI: 1.16–1.46). Stratification of ASC-US cases by HPV16 status revealed a dramatically higher positive predictive value (PPV) for CIN2+ in HPV16-positive patients (66%) compared to HPV16-negative patients (12.6%). The AGC category showed the strongest association with glandular pathology, including adenocarcinoma in situ. Conclusions: The combination of cytological findings and HPV16 viral load provides a powerful model for risk stratification. An ASC-H result is a strong independent risk marker, while the clinical significance of ASC-US is fundamentally determined by HPV16 status. These findings advocate for a risk-based management algorithm that integrates liquid-based cytology with extended HPV genotyping and viral load assessments to optimize patient triage and follow-up.

Background/Objectives: Fumarate hydratase-deficient leiomyomas (dFH-LMs) are a rare subtype of uterine smooth muscle tumors (USMTs) with implications for hereditary leiomatosis and renal cell carcinoma (HLRCC). Although several morphologic clues have been proposed, their diagnostic reproducibility is poorly defined. We aimed to determine the diagnostic significance of histopathologic features associated with fumarase deficiency and the reproducibility of key morphologic criteria for defining dFH-LMs. Methods: A retrospective analysis was performed on 45 USMTs that were initially classified as atypical leiomyomas (ALMs). The cohort comprised patients aged 21 to 75 years who had surgery at one tertiary medical care center from 2016 to 2025. Hematoxylin–eosin (H&E) slides were independently examined by three pathologists for features associated with FH deficiency, including eosinophilic globules, staghorn-like vessels, diffuse nuclear atypia, “bizarre” nuclei, and prominent nucleoli with halos. Molecular status was determined by immunohistochemistry (IHC) for fumarate hydratase (FH) and S-(2-succino)-cysteine (2SC). Interobserver agreement was quantified using Fleiss’s κ and Cohen’s κ. Results: Loss of FH expression was detected in 26/45 tumors (57.7%). Eosinophilic globules occurred in 88.5% of dFH-LMs, but only in 15.8% of ALMs (p < 0.001). By majority consensus (≥2 of 3 reviewers), the eosinophilic globules predicted FH deficiency with a sensitivity of 88.0% and a specificity of 85.0%; interobserver reproducibility was substantial (κ = 0.63). Staghorn-like vessels occurred in 73.1% of dFH-LMs vs. 26.3% of ALMs (p = 0.02) and diffuse nuclear atypia (84.6%) was also more frequent in dFH-LMs (p = 0.01). Patients with dFH-LMs were significantly younger than those with ALMs (Median, 34 vs. 41 years). Conclusions: Eosinophilic globules, staghorn-like vessels and diffuse nuclear atypia have been shown to have high diagnostic value and could be considered morphologic indicators of dFH-LMs. The substantial interobserver reproducibility of eosinophilic globules makes this feature particularly promising for routine clinical practice.

Background. A comprehensive understanding of the relationship between uterine scars and the blood flow in adjacent myometrial tissue is crucial for the early identification of risk groups, which can significantly reduce the incidence of complications, facilitate differential diagnosis, and inform effective treatment strategies for patients with uterine scar defects (USD). Aim. To study the histoarchitectural features, area and percentage of collagen fibers in excised scar tissue from the uterus, contingent upon the blood flow status in the adjacent myometrium. Materials and methods. Laparoscopic metroplasty was performed on patients diagnosed with USD, categorized into two groups based on blood flow assessment via functional magnetic resonance imaging (fMRI): preserved blood flow (n = 6) and impaired blood flow (n = 6). A histochemical examination was performed on samples of excised fibrous tissue from the scars, focusing on morphometric analysis, area, and the percentage of collagen fibers contingent upon the blood flow characteristics in the adjacent myometrium. Results. The mean age of the participants was 35.17 ± 3.35 years. The predominant complaints included postmenstrual spotting in 8 of 12 patients (66.7%), heavy menstruation in 3 patients (25%), pain in 2 patients (16.7%), and infertility in 3 patients (25%). According to fMRI, the average scar thickness was 2.16 ± 0.74 mm. Scar samples with impaired blood flow demonstrated a statistically significant reduction in both the area and percentage of collagen fibers by 2.2 times (p = 0.03) and 1.9 times (p = 0.01), respectively, when compared to samples without circulatory disorders. Conclusions. The state of blood flow in the adjacent myometrium significantly influences the development of the connective tissue component in scar tissue. Assessment of perfusion blood flow in the adjacent myometrium using fMRI could serve as an indicator of the morphological integrity of the uterine scar following cesarean section. Consequently, fMRI may serve as an additional diagnostic tool and assist in formulating management strategies for patients with USD.

This article presents a comprehensive analysis of clinicopathological features, molecular characteristics, and diagnostic challenges of high-grade endometrial stromal sarcoma (HG-ESS). This rare and highly aggressive mesenchymal neoplasm is characterized by nonspecific clinical symptoms. The prognosis remains poor, with 5-year survival rates not exceeding 30–35 % and median progression-free survival ranging from 7 to 11 months. Three molecular subtypes of HG-ESS have been identified, each with distinct histopathological and immunohistochemical features: YWHAE-NUTM2A / B gene fusion, BCOR-rearranged, BCOR internal tandem duplication. The identification of these molecular subtypes carries significant diagnostic implications and opens new avenues for personalized targeted therapies. However, HG-ESS diagnosis remains challenging due to morphological variability, histological overlap with other uterine mesenchymal neoplasms, and technical limitations in biopsy specimen evaluation. Given the tumor’s aggressive behavior and diagnostic complexities, a multidisciplinary approach involving pathologists, clinicians, and experts in molecular diagnostics is crucial for accurate diagnosis and development of optimal treatment strategy.

Sclerosing stromal tumor is a rare benign ovarian neoplasm that occurs predominantly in young women. This article presents a clinical case of such a tumor, demonstrating its characteristic macroscopic, microscopic, and immunohistochemical features. The importance of comprehensive morphological evaluation in establishing an accurate diagnosis is emphasized. Differential diagnosis was performed considering the most common ovarian stromal tumors, as well as metastatic lesions. Key aspects of management and prognosis of this pathology are also discussed.

The presence of nervous tissue is a key characteristic of mature and immature ovarian teratomas, therefore, differential diagnosis between ependymal tubules and neuroectodermal rosettes is of fundamental diagnostic and prognostic importance. Ependymal tubules are differentiated glial tissue characteristic of mature teratomas and indicate a favorable prognosis. In contrast, neuroectodermal rosettes reflect primitive neuroepithelial differentiation and are a pathognomonic sign of an immature teratoma. Their number directly determines the degree of malignancy of the tumor and the patient’s treatment strategy. Thus, a thorough morphological analysis combined with immunohistochemical examination underlies accurate diagnosis and optimal management of patients with ovarian teratomas.