Hamartomatous Polyps.

Juvenile polypsrepresent focal hamartomatous malformations of the mucosal epithelium and lamina propria. For the most part they are sporadic lesions, with the vast majority occurring

in children younger than age 5. Isolated hamartomatous polyps may be identified in the colon of adults; these incidental lesions are referred to as retention polyps. In both age groups,

nearly 80% of the polyps occur in the rectum, but they may be scattered throughout the colon. Juvenile polyps tend to be large (1 to 3 cm in diameter), rounded, smooth or slightly

lobulated lesions with stalks up to 2 cm in length; retention polyps tend to be smaller (<1 cm diameter). Histologically, lamina propria comprises the bulk of the polyp, enclosing abundant

cystically dilated glands. Inflammation is common, and the surface may be congested or ulcerated. In general they occur singly and being hamartomatous lesions have no malignant

potential. However, the rare autosomal dominant juvenile polyposis syndrome,in which there are multiple (50 to 100) juvenile polyps in the gastrointestinal tract, does carry a risk of

adenomas and hence adenocarcinoma. Mutations in the SMAD4/DPC4 gene (which encodes a TGF-b signaling intermediate) account for some cases of juvenile polyposis syndrome.[79]

Peutz-Jeghers polypsare hamartomatous polyps that involve the mucosal epithelium, lamina propria, and muscularis mucosa. These hamartomatous lesions may also occur singly or

multiply in the Peutz-Jeghers syndrome. This rare autosomal dominant syndrome is characterized by multiple hamartomatous polyps scattered throughout the entire gastrointestinal tract

and melanotic mucosal and cutaneous pigmentation around the lips, oral mucosa, face, genitalia, and palmar surfaces of the hands. Patients with this syndrome are at risk for

intussusception, which is a common cause of mortality. Peutz-Jeghers polyps tend to be large and pedunculated with a firm lobulated contour. Histologically, an arborizing network of

connective tissue and well-developed smooth muscle extends into the polyp and surrounds normal abundant

Figure 17-56Non-neoplastic colonic polyps. A, Hyperplastic polyp; high-power view showing the serrated profile of the epithelial layer. B, Peutz-Jeghers polyp; low-power view showing

the splaying of smooth muscle into the superficial portion of the pedunculated polyp.

Figure 17-57 A, Pedunculated adenoma showing a fibrovascular stalk lined by normal colonic mucosa and a head that contains abundant dysplastic epithelial glands, hence the blue color

with the H & E stain. B, A small focus of adenomatous epithelium in an otherwise normal (mucin-secreting, clear) colonic mucosa, showing how the dysplastic columnar epithelium

(deeply stained) can populate a colonic crypt and create a tubular architecture.

Figure 17-58 A, Sessile adenoma with villous architecture. Each frond is lined by dysplastic epithelium. B, Portion of a villous frond with dysplastic columnar epithelium on the left and

normal colonic columnar epithelium on the right.

Figure 17-59Familial adenomatous polyposis in an 18-year-old woman. The mucosal surface is carpeted by innumerable polypoid adenomas.

Figure 17-60Schematic of the morphologic and molecular changes in the adenoma-carcinoma sequence. It is postulated that loss of one normal copy of the tumor suppressor gatekeeper

gene APC occurs early. Indeed, individuals may be born with one mutant allele of APC, rendering them extremely likely to develop colon cancer. This is the "first hit," according to

Knudson's hypothesis. The loss of the normal copy of the APC gene follows ("second hit"). Mutations of the oncogene K-RAS seem to occur next. Additional mutations or losses of

heterozygosity inactivate the tumor suppressor gene p53 (on chromosome 17p) and SMAD2 and SMAD4 on chromosome 18q, leading finally to the emergence of carcinoma, in which

additional mutations occur. It is important to note that while there seems to be a temporal sequence of changes, as shown, the accumulation of mutations, rather than their occurrence in a

specific order, is more important.

Figure 17-61Carcinoma of the cecum. The fungating carcinoma projects into the lumen but has not caused obstruction.

Figure 17-62Carcinoma of the descending colon. This circumferential tumor has heaped-up edges and an ulcerated central portion. The arrows identify separate mucosal polyps.

Figure 17-63Invasive adenocarcinoma of colon, showing malignant glands infiltrating the muscle wall.

TABLE 17-14-- TNM Classification of Carcinoma of the Colon and Rectum

Date: 2016-04-22; view: 758