Discussion

Diagnosis

Familial Adenomatous Polyposis (FAP). 

Discussion

Familial adenomatous polyposis (FAP), also known as familial polyposis coli or adenomatous polyposis coli, is an autosomal dominant polyposis syndrome due to a germline mutation in the APC tumor suppressor gene (5q21-22). This patient was previously diagnosed with a heterozygous germline mutation in the APC gene.

FAP is defined by the presence of a germline mutation in the APC gene, the presence of greater than 100 colorectal adenomatous polyps, or a family history of FAP with varying degrees of adenomatous polyps or extra-intestinal tumors. As seen in this case, the majority of the colorectal polyps in FAP are small and sessile.

A germline APC mutation confers a nearly 100% risk of colorectal cancer if left untreated, with mean age of cancer diagnosis of 39 years. Treatment is prophylactic total colectomy. FAP accounts for about 1% of all colorectal cancers, however up to 80% of all colorectal cancers display a sporadic-type APC deletion, a core component of the adenoma-carcinoma sequence, responsible for the transformation from “normal” to “early adenoma.”

Patients with FAP may develop extracolonic tumors as well. Within the GI tract, this include gastric and small bowel polyps which may develop overt malignancy. Outside the GI tract, patients with FAP are also at increased risk for developing desmoid tumors, which are seen in 10-25% of patients with FAP, as well as bony osteomas and epidermal inclusion cysts, among other lesions.    

Variants of FAP included attenuated FAP (aFAP), Gardner syndrome, and Turcot syndrome, with phenotypic differences that can be attributed to the location of the mutation within the APC gene. Attenuated FAP has fewer than 100 colorectal polyps in the setting of a germline APC mutation. The risk of developing colorectal cancer in aFAP is a decreased compared to FAP, but still high, with a 70% risk of developing colorectal cancer by age 80. Gardner syndrome refers to FAP with extraintestinal tumors and includes an increased risk of thyroid cancer, especially in women. Turcot syndrome refers to FAP with concurrent brain tumors, which are typically medulloblastomas. The differential for familial polyposis syndromes also includes MUTYH-associated polyposis (MAP), which is an autosomal recessive polyposis syndrome caused by homozygous mutations in a base excision repair gene. These patients have a similar polyp burden to aFAP patients and typically present at age 50.

References

Armaghany, T., Wilson, J. D., Chu, Q., & Mills, G. (2012). Genetic Alterations in Colorectal Cancer. Gastrointestinal Cancer Research: GCR, 5(1), 19–27.

Chung, D. C. (2017, November 28). Clinical manifestations and diagnosis of familial adenomatous polyposis. Retrieved September 01, 2018, from https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-familial-adenomatous-polyposis?search=familial adenomatous polyposis§ionRank=2&usage_type=default&anchor=H1251987977&source=machineLearning&selectedTitle=1~135&display_rank=1#H11752503​

Punatar, S. B., Noronha, V., Joshi, A., & Prabhash, K. (2012). Thyroid cancer in Gardner’s syndrome: Case report and review of literature. South Asian Journal of Cancer, 1(1), 43–47. http://doi.org/10.4103/2278-330X.96510

Talseth-Palmer, B. A. (2017). The genetic basis of colonic adenomatous polyposis syndromes. Hereditary Cancer in Clinical Practice, 15(1). doi:10.1186/s13053-017-0065-x​

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