Attenuated polyposis of the large bowel: a morphologic and molecular approach.

Maurizio Ponz De Leon,Giuseppina Rossi,Luca Reggiani Bonetti,Monica Pedroni,Federica Domati,Giulia Magnani,Annalisa Pezzi,Rossella Fante,Luca Roncucci

doi:10.1007/s10689-016-9938-9

Maurizio Ponz De Leon, Giuseppina Rossi + Show 7 more

Open Access

https://doi.org/10.1007/s10689-016-9938-9

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Abstract

Attenuated polyposis could be defined as a variant of familial adenomatous polyposis (FAP) in which synchronous polyps of the large bowel range between 10 and 99. We analysed all cases of attenuated polyposis observed over the last 30years with the objectives: (A) to classify the disease according to different type and proportion of polyps; (B) To ascertain the contribution of APC and MutYH genes; (C) to discover features which could arise the suspicion of mutations; (D) To obtain indications for management and follow-up. 84 individuals in 82 families were studied. Polyps were classified into four groups as adenoma, hyperplastic, other serrated lesions or others; APC and MutYH mutations were assessed. Mean age at diagnosis was 54±14years in men and 48±13 in women (P=0.005). Polyps were more numerous in women (37±26 vs 29±22). Sixty % of patients underwent bowel resection, mainly for cancer; the remaining were managed through endoscopy. A total of 2586 polyps were detected at diagnostic endoscopy: 2026 (80%) were removed and analysed. Adenomas were diagnosed in 1445 (70%), hyperplastic polyps in 541 (26%), other serrated lesions in 61 (2.9%). Adenomas and hyperplastic lesions were detected in the majority of patients. In 68 patients (81%) in whom studies were executed, APC mutations were found in 8 and MutYH mutations in 10. Genetic variants were more frequent in women (12 vs 6, P=0.039). Taking into consideration the prevalent (>50%) histology and presence of mutations, patients could be subdivided into four groups: (1) APC mutated polyposis (AFAP), when adenomas were >50% and APC mutations detected (no. 8, 10%); (2) MutYH mutated polyposis (MAP), adenomas >50% and biallelic MutYH mutations (no. 10, 12%); (1) attenuated polyposis without detectable mutations, prevalence of adenomas, 48 cases (57%); (1) hyperplastic-serrated polyposis, with prevalence (>50%) of hyperplastic/other serrated lesions and no constitutional mutation (no. 18, 21%). Aggregation of tumors, cancer in probands, distribution of polyps and other clinical characteristics showed no difference among the four groups. In conclusions, AFAP and MAP, the polyposis labeled by constitutional mutations, represented about 25% of all attenuated polyposis. Mutation-associated cases showed an earlier age of onset of polyps and were more frequent in the female sex.

Highlights

In a small fraction of cases (\1.0 %) colorectal malignancies develop in patients with familial adenomatous polyposis (FAP), a rare autosomal dominant condition in which the colon and rectum are usually carpeted by hundred or thousand polyps of various dimensions [1, 2]
Cancer was the main reason for surgery, though in 20 patients the approach was chosen because of polyposis not complicated by malignancy
The results of the present investigation can be summarized as follows: First, the clinical condition in which 10–99 synchronous colorectal polyps are detected at endoscopy can tentatively be classified into four main groups on the basis of histologic features of polyps and presence of constitutional mutations in either APC or MutYH genes

Summary

Introduction

In a small fraction of cases (\1.0 %) colorectal malignancies develop in patients with familial adenomatous polyposis (FAP), a rare autosomal dominant condition in which the colon and rectum are usually carpeted by hundred or thousand polyps of various dimensions [1, 2]. In most patients the FAP phenotype is associated with constitutional mutation in the APC gene, or, to a lesser fraction, in the MutYH gene [3, 4]. Attenuated polyposis (AFAP) is a phenotypic variant of FAP, in which, according to some authors, the number of polyps ranges between 10 and 99 [6, 7]. At variance with FAP, guidelines on diagnostic criteria, time and type of optimal treatment, search of lesions in other organs, extent of surveillance and use of prevention agents remain undefined [10,11,12]

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