Lower Gastrointestinal Tract and Microsatellite Instability (MSI)

By conventional definition, the lower gastrointestinal (GI) tract includes the appendix, entire colon, and anus. Diseases involving these organs are traditionally classified into nonneoplastic and neoplastic categories. Clinical application of immunohistochemistry (IHC) is most useful in the diagnosis of neoplastic lesions, with a few exceptions such as to identify of viral pathogens in infectious colitis and to facilitate diagnosis of Hirschsprung’s disease. For diagnosis of neoplasm, IHC is particularly useful in several aspects: (1) to help confirm glandular dysplasia associated with inflammatory bowel disease (IBD) and to differentiate it from sporadic adenoma in challenging cases; (2) to confirm diagnosis and grade of neuroendocrine tumors; (3) to confirm diagnosis of a poorly differentiated or undifferentiated colonic adenocarcinoma variant, such as medullary carcinoma; (4) to help differentiate commonly encountered benign and malignant primary mesenchymal tumors; (5) to differentiate primary carcinomas from various morphological mimickers from other organ systems, such as carcinomas of the gynecological and genitourinary systems; and, (6) to initiate Lynch syndrome screening in patients with diagnosed colorectal cancer. In this chapter, we provide an overview of the most useful markers in the diagnosis of lower GI tract diseases, albeit many of them are shared with the upper GI chapter. The content is organized into 19 diagnostic issues frequently encountered in daily practice. The use of both individual markers and other relevant markers to form effective panels to address specific diagnostic challenges are illustrated in a tabular format. Concise notes with representative microscopic pictures are included whenever deemed necessary.