This

review article focuses on the histolopathology of colorectal carcinoma and its precursor lesions. Recent advances in molecular pathology and molecular tests are discussed. Their clinical relevance is emphasized. Histopathologic diagnosis of colorectal carcinoma More than 90% of colorectal carcinomas are adenocarcinomas originating from epithelial cells of the colorectal mucosa (3). Other rare types Inhibitors,research,lifescience,medical of colorectal carcinomas include neuroendocrine, squamous cell, adenosquamous, spindle cell and undifferentiated carcinomas. Conventional adenocarcinoma is characterized by glandular formation, which is the basis for histologic tumor grading. In well differentiated adenocarcinoma >95% of the tumor is gland forming. Moderately differentiated adenocarcinoma Inhibitors,research,lifescience,medical shows 50-95% gland formation. Poorly differentiated adenocarcinoma is mostly solid with <50% gland formation. In practice, most colorectal adenocarcinomas (~70%) are diagnosed as moderately differentiated (Figure 1). Well and poorly differentiated carcinomas account for 10% and 20%, respectively. Figure 1 An example of moderately differentiated adenocarcinoma showing complicated glandular structures in a desmoplastic stroma (original

magnification ×200) It is apparent that the determination Inhibitors,research,lifescience,medical of tumor grade is a subjective exercise. Many studies have demonstrated that a AUY-922 mouse 2-tiered grading system, Inhibitors,research,lifescience,medical which combines well and moderately differentiated to low grade (50% gland formation) and defines poorly differentiated as high grade (<50% gland formation), reduces interobserver variation and improves prognostic significance (4,5). Though controversial, tumor

grade is generally considered as a stage-independent prognostic variable, and high grade or poorly differentiated Inhibitors,research,lifescience,medical histology is associated with poor patient survival (6-8). It should be emphasized, however, that histologic grading should apply only to conventional adenocarcinoma. Some of the histologic variants, which will be discussed later, may show high grade morphology but behave as low of grade tumors because of their MSI status. The vast majority of colorectal carcinomas are initially diagnosed by endoscopic biopsy or polypectomy. The key aspect of microscopic examination is to look for evidence of invasion. However, this can be difficult when the biopsy is superficial or poorly oriented. If the muscularis mucosae can be identified, it is important to determine whether it is disrupted by neoplastic cells. Invasive carcinoma typically invades through the muscularis mucosae into the submucosa, and is sometimes seen in close proximity to submucosal blood vessels.