The Silva pattern-based classification for HPV-associated endocervical adenocarcinoma: A single institution concordance study of trainees and gynecologic pathologists.

The Silva pattern-based classification of HPV-associated endocervical adenocarcinoma has become an integral part of the histologic assessment of these tumors. Unfortunately, the Silva system reproducibility has had mixed results in past studies, and clinical practice still favors the FIGO stage assessment in directing therapeutic interventions for patients. In our study, we aimed to assess our institution's concordance including not only gynecologic pathologists, but also pathology trainees through a series of 69 cases. The grouped total kappa concordance from all participants was 0.439 (Moderate), with an overall trainee kappa of 0.417 (moderate) and an overall pathologist kappa of 0.460 (moderate). Perfect concordance among all 10 study participants was seen in 8/69 cases (11.6 %), corresponding to 5/22 Pattern A cases (22.7 %), 0/16 Pattern B cases (0 %), and 3/31 Pattern C cases (9.7 %), with similar findings between trainees and pathologists when compared within their own cohorts. Recurrence was identified in 2 Pattern A cases, indicating a potential issue with limited excisional specimens which may not fully appreciate the true biologic aggressiveness of the lesions.

From principles to practice: Implementation of entrustable professional activities (EPAs) for surgical pathology residency education in a large academic hospital.

Over the past decade, competency-based medical education (CBME) has gained momentum in the United States to develop trainees into independent and confident physicians by the end of their training. Entrustable professional activities (EPAs) are an established methodology for assessing trainee development through an outcomes-driven rather than a time-based model. While EPAs have been utilized as an assessment tool for CBME in Europe and Canada, their validation and implementation in some medical specialties has occurred more recently in the United States. Pediatrics was the first specialty in the US to conduct a large-scale UME-GME pilot. Pathology Residency EPAs were published in 2018; however, implementation in training programs has been slow. We have piloted EPAs in our residency program's surgical pathology rotation and propose a unique set of 4 surgical pathology EPAs to track trainee preparedness for independent practice.

A novel 6-day cycle surgical pathology rotation improves resident satisfaction and maintains Accreditation Council for Graduate Medical Education (ACGME) milestone performance.

Surgical pathology residency training in the United States lags behind other specialties in quality control and graduated responsibility to train independent pathologists capable of seamlessly entering practice after training. We observed that our traditional 3-day-cycle surgical pathology cycle (day 1-grossing; day 2 -biopsies/frozens/preview; day 3 - sign-out) consistently and negatively impacted resident education by reducing preview time, case follow-up, immunohistochemical stain (IHC) interpretation, and molecular study integration. We aimed to create a modern surgical pathology rotation that improved performance and outcomes. We innovated our rotation to enhance resident education and ensure graduated responsibility. A novel 6-day cycle was created composed of 2 grossing days, 1 frozens/biopsies/preview days, 2 dedicated sign-out days, and 1 frozens/biopsies/case completion day. Residents completed surveys before implementing the new rotation and 6 months after implementation to track self-assessment of Accreditation Council for Graduate Medical Education (ACGME) milestone performance and internal quality control metrics. Clinical Competency Committee (CCC) annual evaluations were assessed in paired PGY levels pre- and post-intervention. After implementation, there was a statistically significant improvement in self-assessment of levels 4 and 5 of ACGME milestones and improved satisfaction of quality metrics, including time for previewing, reviewing IHC, graduated responsibility, and perceived readiness for independent practice. CCC evaluations showed overall maintained performance levels, with trends towards improvements in junior resident classes. Our 6-day cycle adequately fulfills the current demands of our sizeable academic center's surgical pathology training and can be a model for pathology residencies looking to modernize their surgical pathology rotations and resident education.

The role of PRAME and NY-ESO-1 as potential therapeutic and prognostic biomarkers in triple-negative breast carcinomas.

PRAME and NY-ESO-1 are cancer-testis antigens (CTAs) reported to be highly enriched in triple-negative breast cancers (TNBCs), against which vaccines and immunotherapies are currently being developed. This study aims to analyze PRAME and NY-ESO-1 expression in TNBCs and their correlation with clinical outcomes. This is a retrospective cohort study of TNBC patients who have undergone neoadjuvant chemotherapy. PRAME and NY-ESO-1 expression were assessed on pre-therapy biopsies as H-scores (percentage x intensity) with final H scores of 2-3 considered as positive. Association between expression and pathologic complete response (pCR), metastasis, and residual cancer burden (RCB) were assessed via logistic regression. Cox proportional hazards models were used to assess the association with progression-free survival. P-values < 0.05 were considered statistically significant. Sixty-three percent of 76 patients were positive for PRAME. In contrast, only 5 % were positive for NY-ESO-1. PRAME positivity was significantly associated with a lower likelihood of early metastatic disease (OR = 0.24, 95 % CI 0.08-0.62; P = 0.005). However, it was not significantly associated with pCR, RCB category, or progression-free survival. NY-ESO1 score was not significantly associated with early metastatic disease, pCR, RCB category, or progression-free survival. Our results suggest that PRAME positivity may be associated with a lower risk of early metastasis in TNBCs, but not with response to neoadjuvant chemotherapy or progression-free survival. The high expression of PRAME in TNBCs makes it a potential therapeutic target, while NY-ESO1 appears to be a less useful marker. However, further larger studies are needed to ascertain the utility of these markers.

Hormone exposure and its suppressive effect on risk of high-grade gliomas among patients with breast cancer.

BACKGROUND: Prior reports demonstrate the expression of estrogen and progesterone receptors in high-grade gliomas (HGGs), but the relationship between hormone receptor-positive disease and risk of HHGs in patients with breast cancer (BC) remains uncharacterized. METHODS: Using the SEER 18 registries (2000-2017), we examined the temporal trend of the incidence of HGGs and BC. The standardized incidence ratio was calculated to assess the risk of subsequent HGG in BC patients. RESULTS: During the study period, the incidence of BC and HGGs remained comparable for men and women. Among 976,134 patients with BC, we found a decreased incidence of HGGs in females, but not in males. Female BC patients with hormone receptor-positive disease were at a lower risk of developing glioblastoma and anaplastic astrocytoma. CONCLUSION: Our study findings allude to the protective role of hormone exposure in the development of HGGs, which may lead to the development of therapies targeting hormonal pathways.

Glioblastoma in natalizumab-treated multiple sclerosis patients.

We present two natalizumab-treated multiple sclerosis patients who developed glioblastoma multiforme (GBM) with variable outcomes. One patient had an isocitrate dehydrogenase (IDH)-wildtype GBM with aggressive behavior, who declined treatment and died 13 weeks after symptoms onset. The other patient underwent resection of an IDH-mutant secondary GBM that arose from a previously diagnosed grade II astrocytoma. He is still alive 5 years after the diagnosis of GBM. JC virus was not detected in either case. Whether natalizumab played a role in the development of GBM in those patients deserves further investigation.