Adenoma Development in a Patient with MUTYH-Associated Polyposis (MAP): New Insights into the Natural Course of Polyp Development

Abstract

This course of the disease, with a strong subsequent acceleration of polyp development, may explain the wide range of polyp numbers counted in newly diagnosed MAP patients as a result of the time of observation. Therefore, MAP should also be considered in younger patients (35-55 years) with only few adenomas or colorectal cancer. The high frequency of medium and severe dysplasia in the patient's preferential small adenomas suggests accelerated progression from adenoma to carcinoma in MAP, but this observation must be confirmed by further studies.

Evidence for accelerated colorectal adenoma–carcinoma progression inMUTYH-associated polyposis?

“…This risk is even higher than the risk of developing CRC under surveillance reported for Lynch syndrome, which was 6% at 10 years of follow-up 18. Along with our observation of an advanced stage (regional metastases) in one third of the screen-detected CRCs, these findings may indicate the presence of an accelerated carcinogenesis in MAP that has also been reported for Lynch syndrome 19. There are parallels between MAP and Lynch syndrome as defects in DNA repair function are involved in both syndromes, that is, base excision repair and DNA mismatch repair, respectively.…”

MUTYHhotspot mutations in unselected colonoscopy patients

“…Another patient with atypical MAP (#H022), which in comparison to typical MAP [3,4,13,23] was characterized by later onset (67 years) and lower polyp burden, was a compound heterozygous carrier of the pathogenic p.Y179C mutation and the p.Q338H variant. The predominant localization of adenomas in the proximal colon and the presence of high grade intraepithelial neoplasia in an adenoma smaller than 5 mm, found in this patient, are features that have also been described in typical MAP [3,4,7,8,24]. In general, p.Q338H has been thought to be a variant without clinical impact [2,21,25].…”

“…During the past 14 years, 107 colonic adenomas and four hyperplastic polyps were removed. This peculiar course of disease and the implications for understanding MAP have been published previously [8].…”

“…MAP is usually suspected in patients who present with 15-200 colorectal adenomas at an age between 35 and 65 years [3][4][5], although there is evidence that MAP should also be considered in younger patients (35 to 55 years) presenting with few adenomas or colorectal cancer (CRC) without typical polyposis phenotype [6][7][8]. Several extracolonic manifestations, for example bladder, breast and skin cancers and, especially, upper gastrointestinal tract lesions (duodenal adenomas and cancer, gastric cancer, fundic gland polyps), have also been reported in some studies, but seem to occur less frequently than in classic familial adenomatous polyposis (FAP) [9,10].…”

Biallelic MUTYH mutations can mimic Lynch syndrome

“…12,22,29 As MAP can manifest in an extremely variable phenotype, MUTYH mutation analysis should also be considered in patients with a low number of adenomas, early-onset or synchronous or metachronous CRC and in patients with MSS tumours. 30,31 With an incidence of only 1.18% in MMR-deficient CRC patients with typical histological features of LS and several adenomas MAP can mimic LS. These patients need different surveillance and due to the different pattern of inheritance a different risk annotation for family members.…”