Deep Learning for Grading Endometrial Cancer.

Endometrial cancer is the fourth most common cancer in women in the United States, with a lifetime risk of approximately 2.8%. Precise histologic evaluation and molecular classification of endometrial cancer are important for effective patient management and determining the best treatment options. This study introduces EndoNet, which uses convolutional neural networks for extracting histologic features and a vision transformer for aggregating these features and classifying slides into high- and low-grade cases. The model was trained on 929 digitized hematoxylin and eosin-stained whole-slide images of endometrial cancer from hysterectomy cases at Dartmouth-Health. It classifies these slides into low-grade (endometrioid grades 1 and 2) and high-grade (endometrioid carcinoma International Federation of Gynecology and Obstetrics grade 3, uterine serous carcinoma, or carcinosarcoma) categories. EndoNet was evaluated on an internal test set of 110 patients and an external test set of 100 patients from The Cancer Genome Atlas database. The model achieved a weighted average F1 score of 0.91 (95% CI, 0.86 to 0.95) and an area under the curve of 0.95 (95% CI, 0.89 to 0.99) on the internal test, and 0.86 (95% CI, 0.80 to 0.94) for F1 score and 0.86 (95% CI, 0.75 to 0.93) for area under the curve on the external test. Pending further validation, EndoNet has the potential to support pathologists without the need of manual annotations in classifying the grades of gynecologic pathology tumors.

Recurrent pembrolizumab-induced mechanical small bowel obstruction in a patient with metastatic cervical cancer.

•Adverse events of pembrolizumab have been documented, but more severe gastrointestinal effects are not as well described.•We report a case of a patient with cervical cancer treated with pembrolizumab who developed small bowel obstruction (SBO)•Histological analysis and gastrointestinal workup points to pembrolizumab as likely cause of SBO.

Correlation of histopathologic findings with clinical predictors of disease recurrence and progression to vulvar carcinoma in patients with differentiated vulvar intraepithelial neoplasia (dVIN).

Objective: To evaluate predictors of recurrence and the risk of progression to carcinoma in patients with dVIN. Methods: 36 self-identified White patients with dVIN from 2011 to 2022 were identified. Demographics, treatment and clinical course were abstracted. Histopathologic features and IHC stains were reviewed by 2 subspecialty pathologists. Standard statistical analyses were applied. Results: Median cohort age was 70 years (range 39-91). Median follow-up was 29.5 months (range 1-123). All patients were Caucasian. 67% had lichen sclerosus (LS) adjacent to dVIN. 56% of patients had recurrent dVIN a median of 11 months from diagnosis. 14 patients had invasive squamous cell carcinoma of the vulva (SCCV) during the study period: 9 (25%) with synchronous dVIN, 5 (14%) developed SCCV after a median of 21.5 months (range 8-57). Patients treated with surgery were more likely to have recurrent/persistent dVIN (p = 0.04) and synchronous or progression to SCCV (p = 0.02) than patients treated with topical therapy. Excluding 9 women with synchronous SCCV, no initial treatment (observation, topical therapy, surgery) was superior at preventing recurrent/ progressive disease in isolated dVIN. Mutation-type p53 expression was identified in 18 (64%) and aberrant GATA3 staining/expression in 20 (56%) of cases. Aberrant GATA3 expression was associated with a higher frequency of synchronous/progression to SCCV (p < 0.05). Conclusion: dVIN has an aggressive clinical course in white patients with a high risk of recurrence/persistence and synchronous/progression to SCCV despite treatment. Close surveillance with a low threshold for additional biopsies is warranted. P53 and GATA3 IHC stains may be useful markers of disease outcome.

Maternal glucose levels and late pregnancy circulating extracellular vesicle and particle miRNAs in the MADRES pregnancy cohort.

Maternal hyperglycemia during pregnancy adversely affects maternal and child outcomes. While mechanisms are not fully understood, maternal circulating miRNAs may play a role. We examined whether continuous glucose levels and hyperglycemia subtypes (gestational diabetes, type 2 diabetes, and glucose intolerance) were associated with circulating miRNAs during late pregnancy. Seven miRNAs (hsa-miR-107, hsa-let-7b-5p, hsa-miR-126-3p, hsa-miR-181a-5p, hsa-miR-374a-5p, hsa-miR-382-5p, and hsa-miR-337-5p) were associated (p < 0.05) with either hyperglycemia or continuous glucose levels prior to multiple testing correction. These miRNAs target genes involved in pathways relevant to maternal and child health, including insulin signaling, placental development, energy balance, and appetite regulation.

High-Risk HPV Screening Initiative in Kosovo-A Way to Optimize HPV Vaccination for Cervical Cancer.

Nearly all cervical cancers are caused by persistent high-risk human papillomavirus (hrHPV) infection. There are 14 recognized hrHPV genotypes (HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68), and hrHPV genotypes 16 and 18 comprise approximately 66% of all cases worldwide. An additional 15% of cervical cancers are caused by hrHPV genotypes 31, 33, 45, 52, and 58. Screening patients for hrHPV as a mechanism for implementation of early treatment is a proven strategy for decreasing the incidence of HPV-related neoplasia, cervical cancer in particular. Here, we present population data from an HPV screening initiative in Kosovo designed to better understand the prevalence of the country's HPV burden and local incidence of cervical cancer by hrHPV genotype. Nearly 2000 women were screened for hrHPV using a real-time polymerase chain reaction (real-time PCR) assay followed by melt curve analysis to establish the prevalence of hrHPV in Kosovo. Additionally, DNA was extracted from 200 formalin-fixed, paraffin embedded cervical tumors and tested for hrHPV using the same method. Cervical screening samples revealed a high prevalence of hrHPV genotypes 16 and 51, while cervical cancer specimens predominantly harbored genotypes 16, 18, and 45. This is the first comprehensive screening study for evaluating the prevalence of hrHPV genotypes in Kosovo on screening cervical brush samples and cervical neoplasms. Given the geographic distribution of hrHPV genotypes and the WHO's global initiative to eliminate cervical cancer, this study can support and direct vaccination efforts to cover highly prevalent hrHPV genotypes in Kosovo's at-risk population.