Image Description
Molecular Pathogenesis: Familial adenomatous polyposis (FAP) is caused by germline loss-of-function mutations in the tumor suppressor gene APC (on 5q22.2) which are passed on to the offspring. Colonic adenomas develop when the second allele acquired from the unaffected parent is mutated or lost (second hit). One of more of the adenomas subsequently undergo malignant transformation following acquisition of additional mutations, such as activation of KRAS and disruption of p53. In FAP, the number of polyps and their time-frame to malignant transformation depends upon specific mutations within the APC gene. Mutations in APC gene are also found in 70% to 80% of non-hereditary colon cancers as well as sporadic adenomas.
The image is a higher magnification of the previous slide showing a small microscopic adenoma consisting of several dysplastic crypts from a colon with FAP.
About the Disease
Introduction: A gastrointestinal polyp is any discrete mass of tissue protruding into the lumen. They can occur anywhere in the GI tract but are most common in the colo-rectal region. They may be pedunculated (with a well-defined stalk) or sessile (broad-based with no stalk). Colonic polyps are subdivided into two major groups: non-neoplastic and neoplastic. Non-neoplastic group includes hyperplastic polyps, hamartomatous polyps (juvenile polyps, Peutz-Jeghers polyps), inflammatory polyps and mucosal polyps. Hamartomatous polyps in syndromic settings can show germline mutations in tumor suppressor genes or oncogenes and carry malignant potential. Submucosal lesions may also lift the mucosa giving it a polypoid appearance. Neoplastic polyps show epithelial dysplasia by definition and include adenomas and carcinomas. Adenomas can be tubular, tubulovillous, or villous based on the glandular architecture. Serrated adenomas, which are related to hyperplastic polyps, have malignant potential and are now considered neoplastic. References: 1. Feldman, M., Friedman, L. S., & Brandt, L. J. (2016). Sleisenger & Fordtrans Gastrointestinal & Liver Disease; 10th Edition. Philadelphia, PA. Elsevier Saunders. 2. Goldblum, J. R. et al (2018). Rosai and Ackermans Surgical Pathology; Eleventh Edition. Philadelphia, PA. Elsevier. 3. Kumar, V., Abbas, A. K., & Aster, J. C. (2015). Robbins and Cotran Pathologic Basis of Disease; Ninth Edition. Philadelphia, PA. Elsevier.