Genomic analysis of spermatocytic tumors demonstrates recurrent molecular alterations in cases with malignant clinical behavior

: Spermatocytic tumor (ST) is a rare type of germ cell tumor that occurs exclusively in the postpubertal testis and typically affects elderly men. Most STs are benign, but rare cases exhibit aggressive clinical behavior, often in association with transition to sarcomatoid histology. Limited molecular analyses have been performed on STs; therefore, their genomic and epigenomic features remain incompletely described. Twenty-seven samples from 25 individual patients were analyzed with a combination of DNA sequencing panels, genomic methylation profiling, SNP array, isochromosome (12p) [i(12p)] FISH, and immunohistochemistry. The series included five metastasizing tumors (three with sarcomatoid transformation, one anaplastic, and one conventional) and 20 non-metastasizing tumors (14 anaplastic and six conventional). Anaplastic tumors comprised a monomorphic population of intermediate-sized neoplastic cells, as previously described. Multiomic analyses demonstrated that there were two genomic subgroups of STs: one with diploid genomes and hotspot RAS/RAF variants and the other with global ploidy shift and absence of recurrent mutations. Relative gain of chromosome 9 was a consistent finding in both subgroups. A comparison of metastasizing and non-metastasizing cases demonstrated that aggressive behavior was associated with the acquisition of pathogenic TP53 mutations and/or relative gains of 12p/i(12p). In cases with sarcomatoid transformation, TP53 mutations seem to underlie the transition to sarcomatoid histology. Genomic methylation analysis demonstrated that aggressive cases with gains of 12p cluster closer to pure seminomas than to STs without gains of 12p. In conclusion, STs include two genomic subgroups, characterized by global ploidy shifts without recurrent mutations and diploid genomes with RAS/RAF hotspot mutations, respectively. Biologic progression was associated with relative gains of 12p and TP53 mutations. The findings in STs with relative gains of 12p suggest that they may exhibit biologic characteristics akin to those seen in germ cell neoplasia in situ-related germ cell tumors rather than non-germ cell neoplasia in situ-derived STs. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland

Predictors of self-reported research productivity amongst medical students in the United Kingdom: a national cross-sectional survey

Abstract Background The number of academic clinicians in the UK is declining and there are demographic inequalities in the clinical-academic workforce. Increased research productivity by medical students is believed to reduce future attrition in the clinical-academic workforce. Thus, this study investigated the association between student demographics and research productivity amongst UK medical students. Methods This is a national multicentre cross-sectional study of UK medical students in the 2020/21 academic year. We appointed one student representative per medical school, and they disseminated a 42-item online questionnaire over nine weeks, through departmental emails and social media advertisements. The outcome measures were: (i) publications (yes/no) (ii) number of publications (iii) number of first-authored publications (iv) abstract presentation (yes/no). We utilised multiple logistic and zero-inflated Poisson regression analyses to test for associations between the outcome measures and predictor variables at a 5% significance level. Results There are 41 medical schools in the UK. We received 1573 responses from 36 UK medical schools. We failed to recruit student representatives from three newly formed medical schools, whilst two medical schools prohibited us from sending the survey to their students. Women had lower odds of having a publication (OR: 0.53, 95% CI: 0.33–0.85) and on average had fewer first-author publications than men (IRR: 0.57, 95% CI: 0.37–0.89). Compared to white students, mixed-ethnicity students had greater odds of having a publication (OR: 3.06, 95% CI: 1.67–5.59), an abstract presentation (OR: 2.12, 95% CI: 1.37–3.26), and on average had a greater number of publications (IRR: 1.87, 95% CI: 1.02–3.43). On average, students who attended independent UK secondary schools had a higher rate of first-author publications compared to those that attended state secondary schools (IRR: 1.97, 95% CI: 1.23–3.15). Conclusion Our data suggest that there are gender, ethnic and socioeconomic inequalities in research productivity among UK medical students. To tackle this, and potentially improve diversity in clinical academia, we recommend that medical schools should facilitate targeted high quality research mentorship, funding and training, especially for under-represented-in-medicine students

NCCN Guidelines® Insights: Palliative Care, Version 2.2021.

Palliative care has evolved to be an integral part of comprehensive cancer care with the goal of early intervention to improve quality of life and patient outcomes. The NCCN Guidelines for Palliative Care provide recommendations to help the primary oncology team promote the best quality of life possible throughout the illness trajectory for each patient with cancer. The NCCN Palliative Care Panel meets annually to evaluate and update recommendations based on panel members' clinical expertise and emerging scientific data. These NCCN Guidelines Insights summarize the panel's recent discussions and highlights updates on the importance of fostering adaptive coping strategies for patients and families, and on the role of pharmacologic and nonpharmacologic interventions to optimize symptom management

Genomic Classification of Cutaneous Melanoma

We describe the landscape of genomic alterations in cutaneous melanomas through DNA, RNA, and protein-based analysis of 333 primary and/or metastatic melanomas from 331 patients. We establish a framework for genomic classification into one of four sub-types based on the pattern of the most prevalent significantly mutated genes: mutant BRAF, mutant RAS, mutant NF1, and Triple-WT (wild-type). Integrative analysis reveals enrichment of KIT mutations and focal amplifications and complex structural rearrangements as a feature of the Triple-WT subtype. We found no significant outcome correlation with genomic classification, but samples assigned a transcriptomic subclass enriched for immune gene expression associated with lymphocyte infiltrate on pathology review and high LCK protein expression, a T cell marker, were associated with improved patient survival. This clinicopathological and multidimensional analysis suggests that the prognosis of melanoma patients with regional metastases is influenced by tumor stroma immunobiology, offering insights to further personalize therapeutic decision-makingclose3