Context.— The 5th edition of the World Health Organization classification of digestive system tumors discusses several advancements and developments in understanding the etiology, pathogenesis, and diagnosis of several digestive tract tumors. Objective.— To provide a summary of the updates with a focus on neuroendocrine neoplasms, appendiceal tumors, and the molecular advances in tumors of the digestive system. Data Sources.— English literature and personal experiences. Conclusions.— Some of the particularly important updates in the 5th edition are the alterations made in the classification of neuroendocrine neoplasms, understanding of pathogenesis of appendiceal tumors and their precursor lesions, and the expanded role of molecular pathology in establishing an accurate diagnosis or predicting prognosis and response to treatment.

Immune checkpoint inhibitors block the co-inhibitory receptors on T cells to activate their cytotoxic immune function and are rapidly being explored for the treatment of various advanced-stage malignancies. These novel drugs have already significantly increased survival rates. The first available immune checkpoint inhibitors were cytotoxic T lymphocyte antigen 4 (CTLA-4) inhibitors (such as ipilimumab), followed by programmed cell death protein 1 (PD-1) and programmed cell death protein ligand 1 (PD-L1) inhibitors (such as pembrolizumab and nivolumab). Anti-PD-1 and anti-PD-L1 therapies have demonstrated better efficacy and tolerability and less severe adverse effects compared to anti-CTLA-4 agents. Idelalisib, a PI3Kδ isoform inhibitor, is another immunotherapeutic agent that is often classified separately and is currently used in treatment of chronic lymphocytic leukemia and non-Hodgkin lymphomas. Despite successful therapeutic responses, immune-related adverse events have been reported with the use of these agents. The gastrointestinal side effects, particularly diarrhea, are among the most commonly reported symptoms. The histologic features of immune checkpoint inhibitor-associated colitis show a spectrum of patterns of injury among various drug classes. There is significant overlap between immune checkpoint inhibitor-associated colitis and other colitides, making the differential diagnosis difficult-especially in the absence of clinical history. The histopathology data on immune checkpoint inhibitor-associated colitis are limited. Here we review clinical features as well as various histologic patterns of colitis associated with these groups of medications.

Despite an anticipated increase in sensitivity for EMVI detection by histopathologic analysis using elastin compared with H and E staining, MRI maintains a high specificity and moderate sensitivity for the detection of EMVI.