The new WHO classification of tumors of the digestive system not only redefines common diagnostic terms, such as intraepithelial neoplasia and dysplasia but also introduces changes in the nomenclature and diagnostics of colorectal tumors which will be important in daily practice. Changes in nomenclature and classification include the introduction of serrated adenocarcinoma, cribriform comedo type adenocarcinoma and micropapillary adenocarcinoma as new distinct histological subtypes of colorectal cancer. The grading of mucinous and signet ring carcinomas, which were previously invariably graded as G3/high grade, is now dependent on the microsatellite instability (MSI) status as a high MSI (MSI-H) indicates a better and low or no MSI (MSI-L/MSS) a worse prognosis. Thus, analysis of microsatellite instability via immunohistochemistry or fragment length analysis must be included in the pathological report of these tumors. Serrated polyps/adenomas and their potential of progression into colorectal cancer via the alternative pathway of colorectal carcinogenesis will be discussed as well as new insights into prognostic and predictive markers of colorectal cancer. This manuscript will give an overview of the most important changes within the new WHO classification of colorectal tumors.

Microscopic colitis (MC) is recognized to be a common cause of chronic, non-bloody diarrhea with rising incidence in the last decade. The diagnosis can only be made by histology and the specific histological findings define two subtypes of MC: lymphocytic (LC) or collagenous colitis (CC). The key histological feature of LC is an increased number of surface intraepithelial lymphocytes (IEL). In the literature, >20 IELs/100 epithelial cells are required to warrant the diagnosis of LC. IELs are mostly cytotoxic CD8+ T-lymphocytes. The key histological criterion for CC is a continuous subepithelial fibrous band underneath the surface epithelium (>10 µm). Other hallmarks of CC are chronic mucosal inflammation, and the collagen band can contain entrapped capillaries, red blood cells, and inflammatory cells. Damaged epithelial cells appear flattened, mucin depleted, and irregularly oriented. Focally, small strips of surface epithelium may lift off from their basement membrane. In both subtypes of MC, the lamina propria shows increased numbers of plasma cells and lymphocytes with loss of the normal gradient, even eosinophilic and neutrophilic granulocytes may be present. But these histological features alone do not warrant the diagnosis of MC even though they may be responsible for the clinical symptoms. The term MCi (MC incomplete) is suggested for the subgroup of patients with diarrhea and an increase in cellular infiltrate in the colonic lamina propria and either an abnormal collagenous layer and/or intraepithelial lymphocytes coming but not fulfilling the criteria for CC or LC.

Non-neoplastic and non-hamartomatous colorectal polyps or tumor-like lesions comprise a very heterogeneous group of changes in the colorectal mucosa or the colon wall. Mucosal prolapse-associated lesions and inflammatory polyps, which are predominantly associated with chronic inflammatory bowel disease, are the most prominent examples for polypoid lesions difficult to distinguish from neoplastic lesions such as adenomas, hyperplastic/serrated polyps/adenomas and invasive carcinomas. The considerably less frequent tumor-like lesions like heterotopias, endometriosis, amyloid tumors and pseudolipomatous changes are histologically often well defined and should be considered in the differential diagnosis of colorectal lesions. The etiology, endoscopic and histological appearance of these entities and their most important differential diagnoses are discussed.

Celiac disease is a relatively common immunological systemic disease triggered by the protein gluten in genetically predisposed individuals. Classical symptoms like chronic diarrhea, steatorrhea, weight loss and growth retardation are nowadays relatively uncommon. Diagnostic workup includes serological tests for IgA antibodies against tissue transglutaminase 2 (anti-TG2-IgA) and total IgA and histology of duodenal biopsies. Histomorphological classification should be done according to the modified Marsh-Oberhuber classification. Diagnosis of celiac disease should be based on serological, clinical, and histological findings. The only treatment is a life-long gluten-free diet. Unchanged or recurrent symptoms under gluten-free diet may indicate refractory celiac disease. Enteropathy-associated T-cell lymphoma and adenocarcinomas of the small intestine are known complications of celiac disease.