Journal: Histopathology
This publication outlines the major updates in the 6th Edition of the WHO Classification of Digestive System Tumours and how they refine diagnosis, taxonomy, and clinical relevance for GI neoplasms.
Key structural changes:
- Epithelial tumours are now organised strictly by anatomical site.
- Neuroendocrine, mesenchymal, and haematolymphoid tumours are moved into dedicated, cross-volume–aligned chapters.
- Genetic tumour syndromes are classified by mechanism, pathway, and gene.
- Metastatic disease is addressed comprehensively in a unified section on “other tumours and metastases.”
- Carcinoma of unknown primary is given its own section, classified by molecular and immunophenotypic patterns to aid treatment selection.
Important diagnostic and classification refinements:
- Gastric dysplasia categories are consolidated to simplify and standardise reporting.
- Duodenal/ampullary tumours are separated from jejuno-ileal tumours, reflecting distinct biology and clinical behaviour.
- Colorectal serrated polyps receive clearer categorisation; colorectal carcinoma grading is updated with novel criteria.
- Small-duct and large-duct intrahepatic cholangiocarcinoma are recognised as separate entities.
- Undifferentiated carcinoma is redefined to explicitly include “carcinoma with mesenchymal differentiation.”
New or newly recognised entities:
- Oesophageal epidermoid metaplasia.
- Colorectal intramucosal adenocarcinoma.
- Low-grade tubuloglandular adenocarcinoma and lymphoglandular complex-like adenocarcinoma in the colorectum.
- Intraductal tubulopapillary neoplasm and intraductal oncocytic papillary neoplasm of the bile ducts.
- Sonic hedgehog hepatocellular adenoma.
Neuroendocrine and mixed tumours:
- The concept of amphicrine-like carcinoma is separated from MiNEN, broadening the framework for tumours with dual neuroendocrine and non-neuroendocrine differentiation.
- Neuroendocrine tumour grading criteria are enhanced and clarified.
Grading and terminology:
- Precursor lesion grading is simplified to a two-tier (low/high grade) system across the digestive tract.
- Anal canal neoplasia terminology is harmonised with HPV-related LAST nomenclature.
- Terminology for mass-forming precursors in biliary and gallbladder cancer is aligned across sites.
Overall, the work emphasises molecularly informed, standardised diagnostic criteria that improve comparability of diagnoses, guide targeted therapy, and support consistent epidemiologic and clinical research across the full spectrum of digestive system tumours.