Hamartomatous polyposis syndromes

Abstract

Since the histologic description of the hamartomatous polyp in 1957 by Horrilleno and colleagues, descriptions have appeared of several different syndromes with the propensity to develop these polyps in the upper and lower gastrointestinal tracts. These syndromes include juvenile polyposis, Peutz-Jeghers syndrome, hereditary mixed polyposis syndrome, and the phosphatase and tensin homolog gene (PTEN) hamartoma tumor syndromes (Cowden and Bannayan-Riley-Ruvalcaba syndromes), which are autosomal-dominantly inherited, and Cronkhite-Canada syndrome, which is acquired. This article reviews the clinical aspects, the molecular pathogenesis, the affected organ systems, the risks of cancer, and the management of these hamartomatous polyposis syndromes. Although the incidence of these syndromes is low, it is important for clinicians to recognize these disorders to prevent morbidity and mortality in these patients, and to perform presymptomatic testing in patients at risk.

Figure 1

(A) A typical juvenile polyp with the three classic histological features that define a hamartomatous polyp, which are dilated cystic glands with retention of mucus and lined by tall columnar epithelium, a markedly expanded lamina propria, and diffuse chronic infiltration of inflammatory cells. (B) Gross picture of the colon in a JP patient that is carpeted with juvenile polyps (reprinted with permission from101).

Figure 2

Algorithm for the surveillance and management of JP patients, incorporating genetic testing (reprinted with permission from60).

Figure 3

Oral melanosis in a patient with Peutz-Jeghers syndrome (reprinted with permission from25).

Figure 4

Polyp from a Peutz-Jegher syndrome patient. In (A), note the arborizing smooth muscle that branches into the stroma to where the absorptive epithelium, goblet, and Paneth cells are located. In (B), one can see the smooth muscle fibers that make up a large part of the stroma, originating from the muscularis mucosae. In (C), an area with low-grade dysplasia can be seen (reprinted with permission14).

Figure 5

Cumulative risk (percent) and relative risk (RR) of the various organs predisposed to the development of cancer in JPS, PJS, and PTEN hamartoma tumor syndromes (data derived from9,40,49,59,138).

Figure 6

Some of the pathognomonic features of CS, which are facial trichilemmoma (solid black arrow), papillomatosis of the tongue (open arrow), and acral keratoses (reprinted with permission from77).