Bridging Anatomy, Histology, and Pathology: A Novel Curriculum Component Incorporating Self-directed Learning for First-Year Medical Students.

During cadaveric dissection or prosection, medical students frequently encounter pathology that can be a springboard to further learning. We designed a novel educational activity linking anatomy, histology, and pathology that incorporated self-directed learning and teamwork, followed by feedback and instruction from pathologists. Post-activity, more than 97% of students rated the activity as useful (Likert scale of 1 to 5), indicating this activity should be continued in the future. Strengths included self-directed learning, content and design, and teamwork, peer, and faculty interactions. Clarity of assignment expectations, range of pathologies, and virtual presentation format remained areas for improvement.

Adaptive transcriptomic and immune infiltrate responses in the tumor immune microenvironment following neoadjuvant chemotherapy in high grade serous ovarian cancer reveal novel prognostic associations and activation of pro-tumorigenic pathways.

The high rate of ovarian cancer recurrence and chemoresistance necessitates further research into how chemotherapy affects the tumor immune microenvironment (TIME). While studies have shown that immune infiltrate increases following neoadjuvant (NACT) chemotherapy, there lacks a comprehensive understanding of chemotherapy-induced effects on immunotranscriptomics and cancer-related pathways and their relationship with immune infiltrate and patient responses. In this study, we performed NanoString nCounter® PanCancer IO360 analysis of 31 high grade serous ovarian cancer (HGSOC) patients with matched pre-treatment biopsy and post-NACT tumor. We observed increases in pro-tumorigenic and immunoregulatory pathways and immune infiltrate following NACT, with striking increases in a cohort of genes centered on the transcription factors ATF3 and EGR1. Using quantitative PCR, we analyzed several of the top upregulated genes in HGSOC cell lines, noting that two of them, ATF3 and AREG, were consistently upregulated with chemotherapy exposure and significantly increased in platinum resistant cells compared to their sensitive counterparts. Furthermore, we observed that pre-NACT immune infiltrate and pathway scores were not strikingly related to platinum free interval (PFI), but post-NACT immune infiltrate, pathway scores, and gene expression were. Finally, we found that higher levels of a cohort of proliferative and DNA damage-related genes was related to shorter PFI. This study underscores the complex alterations in the ovarian TIME following chemotherapy exposure and begins to untangle how immunologic factors are involved in mediating chemotherapy response, which will allow for the future development of novel immunologic therapies to combat chemoresistance.

Yolk Sac Tumor Arising in Uterine Carcinosarcoma With Endometrioid and Serous Components: A Case Report With Immunohistochemical Analysis.

Yolk sac tumor of the endometrium is an uncommon neoplasm. Here we report a case of yolk sac tumor arising in a uterine carcinosarcoma, with the carcinomatous component showing both endometrioid and serous components, and the sarcomatous component showing homologous (spindled) differentiation. The yolk sac tumor showed predominant glandular configuration and was present admixed with the epithelial components. Extensive immunostaining was performed to narrow the differential diagnosis, including potentially therapeutic testing for HER-2. To our knowledge, this is the first case of carcinosarcoma with this mix of epithelial components and corresponding reporting of these immune and therapeutic markers.

Comparison of PAX8 Expression in Breast Carcinoma Using MRQ50 and BC12 Monoclonal Antibodies.

PAX8 is a specific marker for kidney, ovarian, and thyroid tissue. Antibody-dependent cross-reactivity for PAX8 has been reported in mesothelial, pancreatic, and B-cell proliferations. We recently described antibody clone-dependent aberrant PAX8 expression in breast cancer. In this study we systematically analyze PAX8 expression in breast cancer on whole tissue sections, using MRQ50 and BC12 PAX8 monoclonal antibodies. Immunohistochemistry was performed on formalin-fixed paraffin-embedded whole tissue sections from 85 invasive mammary carcinomas. Immunostaining was evaluated at ×10 objective; extent (intervals of 10%, 0% to 100%) and intensity (weak, moderate, and strong) of nuclear staining was evaluated in the tumor, benign breast tissue, and lymphocytes. With MRQ50 variable PAX8 nuclear positivity was identified in tumor cells in 35/85 (41%) cases. Of 35 PAX8 cases, 23 (66%) showed only weak expression in 1% to 10% cells, 8 (23%) were weakly (5/8) or moderately (3/8) PAX8 in 11% to 50% cells, and 4 (11%) showed weak PAX8 positivity in >50% tumor cells. All 3 (3.5%) cases that showed moderate nuclear PAX8 staining with MRQ50 were histologic grade 3. No PAX8 expression was noted in benign lobules/ducts with either antibody. Breast carcinomas can show nuclear immunostaining with MRQ50 PAX8 antibody with up to 3.5% cases showing moderately intense expression. The BC12 PAX8 antibody does not cross-react with breast carcinoma and lymphocytes. During workup of metastatic carcinoma, weak to moderate PAX8 nuclear expression with MRQ50 clone should be interpreted with caution.