Tong Sun

The Evolving Molecular Landscape of Uterine Mesenchymal Tumors: Diagnostic and Therapeutic Implications

Uterine mesenchymal tumors encompass a diverse and diagnostically challenging group of neoplasms, including smooth muscle tumors, endometrial stromal tumors (ESS), perivascular epithelioid cell tumors (PEComas), inflammatory myofibroblastic tumors (IMTs), uterine tumor resembling ovarian sex cord tumor (UTROSCT), along with many other relatively rare entities. Traditionally classified by histomorphology and immunophenotype, these tumors are now increasingly defined by recurrent genetic alterations that refine diagnosis and elucidate tumorigenesis. For example, leiomyosarcomas display complex genomic instability with frequent TP53, RB1, and ATRX mutations. Low grade-ESS are characterized by JAZF1::SUZ12 and other related fusions, whereas high-grade tumors harbor YWHAE::NUTM2 or ZC3H7B::BCOR fusions, and BCOR internal tandem duplication (ITD) alterations. PEComas frequently contain TSC1 or TSC2 mutations, leading to aberrant activation of the mTOR pathway. Beyond their diagnostic utility, these molecular signatures increasingly inform prognosis and highlight potential therapeutic targets, including CDK4/6 inhibition, PI3K/AKT/mTOR blockade, and immunotherapy. This review summarizes the evolving molecular landscape of uterine mesenchymal tumors, underscoring the value of integrating molecular testing into clinical practice to enhance diagnostic precision and enable personalized management of these rare yet clinically significant neoplasms.

Prognostic significance of pelvic washing cytology in early stage endometrial cancer: A 10‐year matched cohort analysis from a large single institute

Abstract Background Pelvic washing (PW) cytology has been excluded from endometrial cancer staging by the 2009 International Federation of Gynecology and Obstetrics (FIGO) criteria, and its prognostic significance in early stage disease remains controversial. In this study, the authors evaluated the clinicopathologic correlates and prognostic impact of positive PW cytology in a large institutional cohort using a matched case–control design. Methods A retrospective case–control cohort was created by reviewing PWs for endometrial cancer from 2013 to 2023 in the authors' pathology database. Cases with positive PW were retrieved from consecutive patients who had FIGO 2009 stage I or II endometrial cancer. The control group was comprised of randomly selected patients with negative PWs who were matched to patients in the positive PW group on patient age, tumor histologic subtype, FIGO grade, and disease stage. Cox proportional hazards models and multivariable logistic regression analyses were used to correlate survival outcomes and to identify predictors of cytologic positivity. Results The cohort included 88 patients who had positive PW cytology and 223 matched controls. Positive PW cytology was independently associated with significantly worse disease‐free survival (hazard ratio, 4.33; p  < .001) and demonstrated borderline significance for overall survival (hazard ratio, 1.67; p  = .05). The presence of free‐floating tumor cells in the fallopian tubes was an independent predictor of positive PW cytology ( p  < .001). Conclusions The current study demonstrates that positive PW cytology is an independent adverse prognostic factor in patients with stage I/II endometrial cancer and suggests that PW cytology status should be considered for accurate risk stratification of patients who have early stage endometrial cancer although it is not part of the current FIGO staging criteria.

Human papillomavirus genotype distribution and its correlation with intraepithelial neoplasia, vaccination, and ethnicity

Cervical cancer is primarily attributed to high-risk human papillomavirus (HPV), specifically genotypes 16 and 18. The introduction of HPV vaccines aimed to reduce the incidence of cervical cancer. This study reviewed cases of High-Grade Squamous Intraepithelial Lesion (HSIL) and Atypical Squamous Cells Cannot Exclude HSIL (ASC-H) with positive high-risk HPV and HPV genotyping data. The prevalence of HPV genotypes 16/18 and non-16/18 was compared in cases with high-grade intraepithelial neoplasia (IN2+), across different ethnicities and with HPV vaccination status. A total of 274 patients (94 HSIL and 180 ASC-H) were evaluated. HPV non-16/18 was significantly more prevalent in ASC-H (68%) than in HSIL patients (50%); (P = 0.003). HPV non-16/18 was more common in cases without -IN2+ (69%), but a significant proportion of IN2+ cases were also positive for non-16/18 HPV genotypes (56%); (P = 0.04). Overall, HPV non-16/18 was more prevalent in all ethnic groups. There was a trend to a higher prevalence in non-white and vaccinated compared with white and nonvaccinated women respectively, but the difference was not significant. HPV non-16/18 genotypes are more prevalent than HPV 16/18, even in women with high-grade lesions with a greater shift towards non-16/18 genotypes in non-white and in vaccinated women. The study suggests the need for extended HPV genotyping and vaccines targeting a broader range of HPV types to include HPV non-16/18 to improve prevention, particularly in certain ethnic groups.

Diandric triploid partial mole versus digynic nonmolar triploidy: is morphological assessment sufficient for the diagnostic distinction?

AimsDiagnostic separation of diandric triploid gestation, i.e. partial mole from digynic triploid gestation, is clinically relevant, as the former may progress to postmolar gestational trophoblastic neoplasia. The aim of the study was to investigate if the combination of abnormal histology combined with ploidy analysis‐based triploidy is sufficient to accurately diagnose partial mole.Methods and ResultsA genotype–phenotype correlation study was undertaken to reappraise histological parameters among 20 diandric triploid gestations and 22 digynic triploid gestations of comparable patient age, gestational weeks, and clinical presentations. Two villous populations, irregular villous contours, pseudoinclusions, and syncytiotrophoblast knuckles, were common in both groups. Villous size ≥2.5 mm, cistern formation, trophoblastic hyperplasia, and syncytiotrophoblast lacunae were significantly more common in the partial hydatidiform mole. Cistern formation had the highest positive predictive value (PPV) (93%) and highest specificity (96%) for diandric triploid gestation, although the sensitivity was 70%. Cistern formation combined with villous size ≥2.5 mm or trophoblast hyperplasia or syncytiotrophoblast lacunae had 100% specificity and PPV, but a marginal sensitivity of 60%–65%. A moderate interobserver agreement (Kappa = 0.57, Gwet's AC1 = 0.59) was achieved among four observers who assigned diagnosis of diandric triploid gestation or digynic triploidy solely based on histology.ConclusionsNone of histological parameters are unique to either diandric triploid gestation or digynic triploid gestation. Cistern formation is the most powerful discriminator, with 93% PPV and 70% sensitivity for diandric triploid gestation. While cistern formation combined with either trophoblastic hyperplasia or villous size ≥2.5 mm or syncytiotrophoblast lacunae has 100% PPV and specificity for diandric triploid gestation, the sensitivity is only 60% to 65%. Therefore, in the presence of triploidy, histological assessment is unable to precisely classify 35% to 40% of diandric triploid gestations or partial moles.