The 2019 WHO Classification of Tumours of the Digestive System reflects significant advancements in understanding digestive system tumors, emphasizing both molecular and histological characteristics. The classification aims to be globally applicable, even in settings with limited resources. Key changes include: 1. **Oesophageal and Gastric Tumors**: Progress in understanding the development of glandular oesophageal neoplasia and gastric cancer, driven by gastro-oesophageal reflux disease and Helicobacter pylori infection, respectively. Molecular markers like TP53 and SMAD4 mutations are now recognized for diagnostic and prognostic purposes. 2. **Tumors of the Anus, Small and Large Intestines**: Improved understanding of adenocarcinomas and appendiceal tumors, with better-defined molecular pathways and precursor lesions. HPV infection is identified as a significant factor in some cases. 3. **Neuroendocrine Neoplasms (NENs)**: NENs are now classified within each organ-specific chapter, with a focus on distinguishing between well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs). Mixed NENs are categorized as 'mixed neuroendocrine–non-neuroendocrine neoplasms (MiNENs)'. 4. **Precursor Lesions**: Standardization of terminology for precursors to invasive carcinoma, with a two-tiered grading system for dysplasia and intra-epithelial neoplasia. 5. **Liver Tumors**: Refinements in the classification of liver tumors, including better-defined subtypes of hepatocellular carcinoma and intrahepatic cholangiocarcinoma, and clearer definitions of combined hepatocellular-cholangiocarcinoma. 6. **Pancreatic Tumors**: Classification of pancreatic neoplasms remains largely unchanged, with improvements in the classification of precursor lesions and neuroendocrine tumors. 7. **Mixed Tumors**: Uncertainty remains in the classification of mixed tumors, but improvements in pathological criteria are expected to standardize the diagnostic approach. 8. **Haematolymphoid and Mesenchymal Tumors**: Grouped together for consistency. 9. **Genetic Tumor Syndromes**: A new chapter provides detailed information on major syndromes, including Lynch syndrome, familial adenomatous polyposis, and Li-Fraumeni syndrome. The classification also includes format changes to enhance clarity and readability.The 2019 WHO Classification of Tumours of the Digestive System reflects significant advancements in understanding digestive system tumors, emphasizing both molecular and histological characteristics. The classification aims to be globally applicable, even in settings with limited resources. Key changes include: 1. **Oesophageal and Gastric Tumors**: Progress in understanding the development of glandular oesophageal neoplasia and gastric cancer, driven by gastro-oesophageal reflux disease and Helicobacter pylori infection, respectively. Molecular markers like TP53 and SMAD4 mutations are now recognized for diagnostic and prognostic purposes. 2. **Tumors of the Anus, Small and Large Intestines**: Improved understanding of adenocarcinomas and appendiceal tumors, with better-defined molecular pathways and precursor lesions. HPV infection is identified as a significant factor in some cases. 3. **Neuroendocrine Neoplasms (NENs)**: NENs are now classified within each organ-specific chapter, with a focus on distinguishing between well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs). Mixed NENs are categorized as 'mixed neuroendocrine–non-neuroendocrine neoplasms (MiNENs)'. 4. **Precursor Lesions**: Standardization of terminology for precursors to invasive carcinoma, with a two-tiered grading system for dysplasia and intra-epithelial neoplasia. 5. **Liver Tumors**: Refinements in the classification of liver tumors, including better-defined subtypes of hepatocellular carcinoma and intrahepatic cholangiocarcinoma, and clearer definitions of combined hepatocellular-cholangiocarcinoma. 6. **Pancreatic Tumors**: Classification of pancreatic neoplasms remains largely unchanged, with improvements in the classification of precursor lesions and neuroendocrine tumors. 7. **Mixed Tumors**: Uncertainty remains in the classification of mixed tumors, but improvements in pathological criteria are expected to standardize the diagnostic approach. 8. **Haematolymphoid and Mesenchymal Tumors**: Grouped together for consistency. 9. **Genetic Tumor Syndromes**: A new chapter provides detailed information on major syndromes, including Lynch syndrome, familial adenomatous polyposis, and Li-Fraumeni syndrome. The classification also includes format changes to enhance clarity and readability.