Challenge in The Differentiation Between Attenuated Familial Adenomatous Polyposis and Hereditary Nonpolyposis Colorectal Cancer: Case Report With Review of The Literature

Abstract

The clinical differentiation between hereditary nonpolyposis colorectal cancer (HNPCC) and attenuated familial adenomatous polyposis (AFAP) is very difficult. The 62-yr-old proband presented with duodenal adenocarcinoma. His history of subtotal colectomy for colon cancer, the rarity of duodenal adenocarcinoma in the general population, and his family history of colon cancer made us suspect that he might have FAP. We investigated this family by obtaining medical records and performing gene analysis. The proband had only 10 adenomatous colon polyps when he underwent subtotal colectomy for the cancer, so classic FAP was excluded. His family history included rectal cancer in his brother at 69 yr of age, colon cancer in his mother at 75 yr, and colon cancer in one maternal cousin at 42 yr. Three months after we started to study this family, the proband's 32-yr-old son presented with rectal cancer. His family fulfilled the Amsterdam criteria for HNPCC, but AFAP could not be excluded. Upon gene testing, the proband was negative for APC gene germline mutation, which made AFAP highly unlikely. Moreover, high microsatellite instability (MSI) was detected in his adenomas and cancer tissues. The fulfillment of Amsterdam criteria, the exclusion of FAP and AFAP, and the high MSI established the diagnosis of HNPCC in this family. We also summarize the differences between FAP, AFAP, and HNPCC; extend the graphic description of the MSI mechanism; and propose a diagnostic strategy for HNPCC.

Hereditary colorectal cancer syndromes: molecular genetics, genetic counseling, diagnosis and management

“…These include FAP, the hamartomatous polyposis syndromes, and hereditary mixed polyposis syndrome (HMPS). FAP and, in particular, FAP's attenuated variant, AFAP, are high on the differential diagnosis when there is consideration for Lynch syndrome [41,42]. Patients with the FAP phenotype and the APC germline mutation show close to 100% lifetime risk for CRC should they fail to undergo prophylactic total colectomy.…”

Hereditary nonpolyposis colon cancer: Revised Bethesda criteria, immunohistochemistry, microsatellite instability, germline analysis, and emerging issues in genetic testing

“…Additionally, there is overlap in the phenotype of families with HNPCC and attenuated familial adenomatous polyposis, which is caused by germline adenomatous polyposis coli mutations. Both syndromes can present with multiple colonic adenomas and extracolonic cancers [67]. A clinical finding that would suggest attenuated familial adenomatous polyposis over HNPCC is fundic gland polyposis of the stomach.…”

Cancer screening guidelines and prevention factors for high-risk patients with a family history of colorectal cancer

“…Historically, family history consideration were paramount, as evidenced by the so-called Amsterdam and Amsterdam II criteria for HNPCC, namely three or more cases of CRC (Amsterdam II guidelines allow substitution of extracolonic tumors) over two or more generations, with one case diagnosed prior to age 50 [30,31]. In recognition of the possibility of attenuated FAP being mistaken for HNPCC, an additional criterion was the exclusion of FAP [32]. As noted below, family history, although still a helpful clue when present, does not necessarily carry the diagnostic weight in individual cases that it once did, for the reasons cited below [33].…”