What's new in upper gastrointestinal pathology: Key updates and evolving challenges in 2026

Area of Science:

• Gastroenterology
• Oncology
• Pathology

Background:

• Diagnostic pathology of the upper gastrointestinal (GI) tract is rapidly evolving.
• Updates in molecular insights, clinical practices, and international standards are crucial for disease understanding.
• The 6th edition of the World Health Organization (WHO) classification for digestive system tumors introduces significant changes.

Purpose of the Study:

• To summarize key updates in the 6th edition of the WHO classification for upper GI tumors.
• To outline emerging therapy-related injuries associated with immunotherapies.
• To provide a practical guide for pathologists on navigating diagnostic challenges in upper GI pathology.

Main Methods:

• Review of the 6th edition of the WHO classification for digestive system tumors.
• Analysis of literature on therapy-related upper GI mucosal alterations.
• Focus on rituximab- and chimeric antigen receptor T-cell (CAR-T) therapy-associated changes.

Main Results:

• The 6th WHO edition incorporates esophageal epidermoid metaplasia as a distinct entity.
• Modified approaches to metaplastic and dysplastic gastric lesions are introduced.
• New patterns of upper GI injury associated with immunotherapies like rituximab and CAR-T therapy are identified.

Conclusions:

• Pathologists must recognize updated WHO classifications and new therapy-related injuries.
• Accurate histologic evaluation is essential to avoid misclassification of upper GI lesions.
• These updates aim to improve diagnostic consistency and patient care in upper GI pathology.