Colorectal Adenocarcinoma

Radiologic-Pathologic Correlation

Abstract Introduction Etiologic and Growth Characteristics

Tumor Spread and Staging Role of Radiology Treatment and Follow-Up Prognosis

Conclusion Source Information References

Etiologic and Growth Characteristics

Etiologic Features

Virtually all carcinomas of the colon are adenocarcinomas. Almost all adenocarcinomas develop from a preexisting adenoma. The evolution from adenoma to carcinoma (the so-called adenoma-carcinoma sequence) has been well substantiated (Figure 1) (3). The most convincing data supporting this concept include the following: (a) the frequent existence of an adenoma within a carcinoma, (b) the similar distribution of adenomas and carcinomas within the colon, (c) the consistent proportional prevalence of adenomas and carcinomas in populations having varied magnitudes of colon cancer risk, (d) the increased frequency of carcinoma in patients with adenomas, (e) the reduction of the incidence of carcinomas in those patients who have undergone endoscopic removal of polyps, (f) the fact that all patients with familial adenomatous polyposis syndrome develop carcinoma if the colon is not removed, and (g) the similarity of the DNA and chromosomal constitution of adenomas and carcinomas.

Some adenocarcinomas of the colon, however, develop not from preexisting adenomas but from a premalignant condition within flat mucosa called dysplasia. This condition may be partially responsible for the carcinoma seen in patients with the hereditary nonpolyposis colon cancer syndrome.

Histologically, adenomas are classified as tubular, villous, or mixed (5,6,7,8,9). Tubular adenomas demonstrate glandular formation and contain nests of colonic epithelium within the lamina propria of the neoplasm. Tubular adenomas are usually less than 1 cm in diameter, and larger lesions are often pedunculated.

Villous adenomas demonstrate thin, frondlike projections from their surface; colonic epithelium lines the outer margins of these fingerlike projections. Villous adenomas are often greater than 2 cm in diameter and usually have a papillary appearance. The term villous is often used interchangeably to describe both the histologic frondlike projections and the macroscopic papillary features of this type of tumor. Villous adenomas are often broad-based sessile lesions, and, when coated with barium, the papillary projections and crevices may be seen (Figure 2a, Figure 2b). Capacious mucin may be secreted by villous adenomas and trapped within their network of papillary projections and crevices. This characteristic may result in heterogeneous low attenuation on computed tomographic (CT) scans (Figure 2c). Invasive carcinoma is more likely to be seen in villous adenomas than in polypoid tumors.

Adenomas are common and noted in 5%-10% of asymptomatic patients older than 40 years of age. The size of the adenoma is directly related to its prevalence of malignancy: Those less than 1 cm in diameter have an approximately 1% prevalence of carcinoma; 1-2 cm, approximately 10%; and greater than 2 cm, 30%-50% (8,9,10,11). Invasive carcinoma (which in the colon is defined as penetrating the muscularis mucosa) is rarely found in a pedunculated adenoma less than 1.5 cm. Conversely, approximately 30% of villous adenomas larger than 5 cm harbor invasive carcinoma (5).

The presence of adenomas heralds transformation of the colonic mucosa to a premalignant state. When an adenoma is detected, there is an approximately 50% chance that the patient is harboring another adenoma (a so-called synchronous adenoma) and a 30%-40% chance of developing a subsequent adenoma (a so-called metachronous adenoma). Of course, adenomas may be associated with adenocarcinomas (Figure 3). In the case of adenocarcinoma, the synchronous and metachronous rates for other adenocarcinomas are 1.5%-5% and 5%-10%, respectively (12).

The malignant potential of an adenoma is uncertain. Whether the adenomas are tubular or villous, however, it can be safely ascertained that they evolve relatively slowly, usually taking 5-15 years to develop into carcinoma (Figure 1) if they are without significant dysplasia (8). Most adenomas do not, in fact, become cancer. About one in 20 adenomas of 5 mm in diameter will evolve to carcinoma (13).

Growth Characteristics

Both adenomas and adenocarcinomas have a similar distribution. Although they may occur anywhere in the colon, they are most common in the left colon between the rectum and splenic flexure (approximately 50% of cases). This percentage was higher in the past, but there has been a "proximal migration" of adenocarcinoma in recent years.

In the left side of the colon, cancers are more commonly annular strictures and tend to obstruct. Annular lesions are the result of invasive carcinoma that has extended to at least the muscularis propria. The innermost layer of the muscularis propria is composed of the circular muscles, which surround the bowel lumen, and the lymphatic channels parallel the course of these muscle fibers. Invasive carcinoma tends to grow along these lymphatic pathways, resulting in an annular constricting lesion. Reactive fibrosis to the infiltrating tumor also contributes to the luminal narrowing. In most cases, the longitudinal growth of invasive carcinoma is limited and extends no more than several centimeters beyond the area of annular narrowing. The so-called apple core lesion is a direct result of the abrupt transition from normal colonic mucosa to neighboring adenocarcinoma and the limited longitudinal growth of the tumor (Figure 4). The exception to this growth pattern is witnessed in the submucosal growth seen in the infiltrating submucosal tumors.

On the right side of the colon, adenocarcinomas are more commonly polypoid and may be associated with chronic bleeding and intussusception (Figure 4). Lesions with growth characteristics between those of a polypoid mass and an annular constricting lesion are so-called saddle lesions. These may result from the direct transformation of a polypoid lesion into an annular constricting lesion as it grows along the circular muscular layer of the muscularis propria, or, alternatively, from an annular constricting lesion that has not yet grown completely circumferentially. At any point in their evolution, all adenocarcinomas may ulcerate and bleed (Figure 2).

A less common growth pattern is a diffusely infiltrating adenocarcinoma (signet-ring type), which can grow submucosally and cause a long-segment stricture similar to linitis plastica seen in the stomach (Figure 5). This pattern results from invasive carcinoma spreading in the loose submucosal tissue between the muscularis mucosa and the muscularis propria. These long-segment strictures may not demonstrate significant mucosal abnormality, since the tumor growth is limited to the submucosa in most places.

A subtype of adenocarcinoma that warrants elucidation is mucinous adenocarcinoma. Mucinous adenocarcinomas are diagnosed when more than 50% of the tumor is composed of extracellular mucin. These pools of mucin may contain calcification, allowing a histologic diagnosis of mucinous adenocarcinoma to be suspected from radiographic findings. Although such cases are quite dramatic, in our experience calcification is very rare. Much more commonly, mucinous adenocarcinomas can be recognized by their low attenuation (approximately that of water) on CT scans (Figure 6). Mucinous adenocarcinomas are more commonly seen in younger patients, are more likely to seed the peritoneal cavity, have an aggressive behavior, and are probably associated with a worse prognosis (14).

Associated Environmental and Genetic Factors

The development of adenomas and adenocarcinomas is strongly linked to both environmental and genetic factors. Diet is particularly important in the development of colorectal carcinoma. High fiber diets produce rapid intestinal transit and decreased contact time between potential toxins and the colonic mucosa. Conversely, low fiber diets prevent rapid transit time. Increased ingestion of fat and animal protein raises the incidence of colon carcinoma.

Among the genetic disorders associated with colorectal carcinoma are the familial adenomatous polyposis syndrome, certain hamartomatous polyposis syndromes, and the hereditary nonpolyposis colon cancer syndrome (10,15,16,17,18). Collectively, these syndromes account for approximately 6% of the cases of colorectal carcinoma. More common conditions associated with an increased risk of developing colon carcinoma include a personal history of colorectal carcinoma or adenoma; a personal history of ovarian, endometrial, or breast cancer; and a history of colon cancer or adenoma in a first-degree relative. In fact, first-degree relatives of patients who have a single colorectal carcinoma have a threefold greater risk of developing colorectal carcinoma than the average population (15,19). Together, these high-risk groups account for approximately 30% of all cases of colorectal adenocarcinoma (20).

Patients with familial adenomatous polyposis syndrome (the term we use to include familial polyposis, Gardner syndrome, and Turcot syndrome) develop numerous adenomas (sometimes thousands) at an early age; it is, therefore, understandable that they in turn develop adenocarcinoma of the colon. In these patients, the cancer appears around age 40 years, approximately 20 years before colon cancer develops in the general population. This disorder has been traced to an abnormality in chromosome 5 (21). Colon cancer may develop before the polyposis becomes symptomatic; therefore, early screening for the disease is important for all family members at risk for this autosomal dominant trait. In certain of the hamartomatous polyposis syndromes (including Peutz-Jeghers syndrome, juvenile polyposis, and Cowden disease), there is also an increased prevalence of adenomas. Although the hamartomatous polyps are not necessarily premalignant themselves, the coexisting adenomas lead to definite increased prevalence of adenocarcinoma.

The hereditary nonpolyposis colon cancer syndrome is also know as the Lynch syndrome (22). In this disorder, which is associated with an abnormality of chromosome 2 and a defect in the DNA replication-repair process (17), adenocarcinomas probably develop in two ways, either from an accelerated transition from adenoma to carcinoma or from dysplasia arising from flat mucosa without the intermediate step of polypoid adenoma (23). The colonic epithelial cells lack the ability to appropriately repair injured or defective DNA, which leads to the evolution of abnormal cells that progress from dysplasia to carcinoma. The resulting cancers tend to be more proximal (70% of the cases occur before the splenic flexure), be of a less advanced stage at diagnosis, and have a better prognosis stage for stage than cancers seen in the general population (23).

The Lynch syndrome is divided into two types: (a) Lynch I, with no associated extracolonic cancers, and (b) Lynch II, associated with extracolonic malignancy especially of the endometrium and other organs. These other malignancies include transitional cell carcinoma of the ureter and renal pelvis; adenocarcinoma of the stomach, small bowel, pancreas, and biliary tract; hematologic malignancies; and carcinoma of the skin and larynx (23). The Lynch syndromes are five times more common than the familial adenomatous polyposis syndrome, and they are autosomal dominant in inheritance. Colon cancer is seen in younger patients (mean, about 45 years old) than in the general population.

Dysplasia within flat mucosa and the eventual development of adenocarcinoma is not seen solely in patients with the Lynch syndrome. The dysplasia produced by chronic inflammation accounts for the increased prevalence of adenocarcinoma seen in patients with ulcerative colitis and, less commonly, granulomatous colitis (24,25). There are probably many other genetic disorders that predispose the colon to dysplasia (26). Early detection (with either barium enema examination or colonoscopy) of adenocarcinomas arising from dysplasia within flat mucosa is much more difficult than it is for the more common cancers that arise from polypoid adenomas.

Abstract Introduction Etiologic and Growth Characteristics

Tumor Spread and Staging Role of Radiology Treatment and Follow-Up Prognosis

Conclusion Source Information References