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Kirsten rat sarcoma viral oncogene homolog (KRAS) somatic mutations occur in 30% to 40% of patients with colorectal cancer (CRC). These were thought to equally affect prognosis and resistance to anti-epidermal growth factor receptor agents; however, recent data show the activity of KRAS-G12C and pan-RAS inhibitors. The effects of uncommon KRAS (uKRAS) variants are largely unexplored. The distribution and pathogenicity of uKRAS mutations and their relationship with patients' clinicopathologic features were assessed. A total of 2427 CRCs were profiled for KRAS using next-generation sequencing (NGS). The study and control groups included patients with uKRAS (<1% frequency in CRC data sets on cBioPortal) and canonical KRAS mutations, respectively. In silico protein structure modifications and prediction analyses were performed by using PyMOL, trRosetta, and PolyPhen-2. uKRAS mutations affected 35 cases (1.5%), with G13C (28.6%), G12R (20%), and V14I (8.6%) being most common. Missense mutations (D33E, G12W, G12F, Q22H, Q61L, and L19F) occurred in nine cases (25.7%). Duplications (G10dup and L52&#95;G60dup) affected two cases. Pathogenicity analyses showed that G12W, Q22R, L56V, and A130I mutations are probably damaging, with scores between 0.928 and 1.000. No differences were seen in clinicopathologic features. uKRAS mutants had lower event-free survival but no difference in overall survival compared with controls. Although these data are hypothesis generating and need further confirmation, they highlight the importance of NGS-based profiling to identify CRC patients with uKRAS mutations as candidates for personalized therapy., (Copyright © 2025 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Background : Neuroendocrine neoplasms (NENs) are a heterogeneous group of tumors with unique biological characteristics and complications, including thromboembolism. This systematic review evaluates the incidence, types, and clinical outcomes of venous thromboembolic events (VTEs) in NEN patients. Methods : A systematic search of PubMed, Scopus, and Embase was conducted to identify studies on TEs in NENs. Eligible studies included case reports, case series, and retrospective cohort studies reporting VTEs, including deep vein thrombosis (DVT), pulmonary embolism (PE), and visceral vein thrombosis (VVT). Data were extracted on tumor site, functionality, differentiation grade, and VTE type. Results : In total, 33 studies were included, comprising 26 case reports, 2 case series, and 5 retrospective cohort studies. VTE prevalence ranged from 7.5% to 33% across studies. The most common VTEs were DVT, PE, and portal vein thrombosis (PVT). A meta-analysis revealed a pooled VTE prevalence of 11.1% (95% CI: 9.07-13.53%). Pancreatic NENs exhibited the highest thrombotic burden, particularly in poorly differentiated and advanced-stage tumors. Functioning tumors, including glucagonomas and ACTH-secreting NENs, were strongly associated with VTEs, potentially related to their systemic effects on coagulation and inflammation. Conclusions : Venous thromboembolism is a significant complication in NEN patients, especially in advanced or poorly differentiated tumors. Early detection and targeted management are critical for improving outcomes. Further investigations are required to clarify the mechanisms underlying thromboembolism in NENs and to develop optimized prophylactic and therapeutic strategies tailored to this patient population.