Colorectal carcinoma is the most common cancer of the digestive tract. It is the third most common cancer in men and women and the third leading cause of cancer death worldwide. Colorectal cancers are divided into three main anatomic areas: the right colon, left colon, and rectum. While the definition of the rectum varies, anatomically it is marked by the fusion of the tenia coli of the sigmoid to form a circumferential longitudinal muscle. As opposed to the sigmoid, which is intraperitoneal with a mesentery, the rectum has a partial or no peritoneal covering and no mesentery. The colon on the right side of the splenic flexure is considered the right colon and the colon on the left side of the splenic flexure is considered the left colon. The underlying molecular biology appears to be different between cancers of the right and left colon; right-sided colonic cancers are more likely to have high-frequency microsatellite instability (MSI-H) and harbor BRAF mutations. The clear majority (> 95%) of colorectal carcinomas are of glandular origin; rare types of carcinoma include adenosquamous, squamous, spindle cell, and undifferentiated carcinoma. The World Health Organization (WHO) classification of colorectal carcinomas includes six histologic subtypes of invasive adenocarcinoma, cribriform comedo-type adenocarcinoma, medullary carcinoma, micropapillary carcinoma, colloid carcinoma, serrated carcinoma, and signet ring cell carcinoma. Adenocarcinoma NOS is the most common type of colorectal adenocarcinoma, accounting for 80% of colorectal adenocarcinomas. The histologic subtype of the carcinoma gives prognostic information and different morphologies are associated with different underlying molecular changes. While immunohistochemistry is rarely needed for the diagnosis, colorectal carcinomas are typically positive for cytokeratin 20 (CK20), CDX2, special AT-rich sequence-binding protein 2 (SATB2), and villin, and are negative for cytokeratin 7 (CK7). CDX2 can be lost in high-grade colorectal adenocarcinoma and is associated with a worse prognosis. MSI-H colorectal carcinomas can have aberrant immunohistochemical expression, including loss of CK20 expression and CK7 positivity. The possibility of an MSI-H colorectal carcinoma should be considered with colorectal tumors with unusual morphologies and atypical immunohistochemical expression.
KeywordsAdenocarcinoma MSI Microsatellite Medullary Micropapillary Serrated Signet-ring Tubuloglandular
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