CHAPTER 35
Malignant tumors of the colon

Amin K. Soltani, Jay Luther, and Andrew T. Chan

Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

Despite improved screening modalities and therapeutic options, colorectal cancer remains a prevalent disease that carries significant morbidity and mortality. Globally, colorectal cancer is the second most common cancer; at current rates, one in five individuals will develop colorectal cancer during their lifetime. Our understanding of risk factors for the development of colorectal cancer is broadening. In addition to traditional risk factors such as age and sex, emerging data highlight the potential importance of lifestyle factors, such as diet, to cancer incidence. It is thought that diet and lifestyle factors may influence the gut microbiota, which in turn drives an increased risk for cancer development (Figure 35.1). The underlying mechanism for microbiota‐related carcinogenesis is not fully understood. The proximity of densely populated gut microbiota to the colorectal epithelium allows for direct (through attachment, invasion, and translocation) and indirect (via secreted molecules and metabolism products) influence on colorectal cancer development. These interactions modulate physiological and pathophysiological processes, such as metabolism, immune response, and colorectal cancer initiation and progression (Figure 35.2).

Genetic determinants of colorectal cancer development are also critical, perhaps best illustrated by hereditary colorectal cancer syndromes known to be associated with single‐gene mutations (Table 35.1), including familial adenomatous polyposis (Figure 35.3), serrated polyposis syndrome (Figure 35.4), Cowden syndrome (Figure 35.5), and Peutz–Jeghers syndrome (Figure 35.6). The most common hereditary colorectal cancer syndrome, Lynch syndrome, accounts for one in every 20 colorectal cancers and is characterized by tumors that exhibit loss of DNA mismatch repair proteins and regions of DNA microsatellite instability. Nonetheless, a significant proportion of sporadic colorectal cancers also arise through noninherited, epigenetic inactivation of mismatch repair proteins (Figure 35.7, Table 35.2).

The differential diagnosis of colonic lesions is broad and includes inflammatory masses and polyps (Figure 35.8), tumors metastatic to the colon (Figure 35.9), submucosal lesions (Figure 35.10), diverticulitis, lymphoma, infection, ischemia, endometriosis, and anatomical defects (such as a volvulus). Neuroendocrine tumors can also arise within the large bowel, most commonly as carcinoid tumors in the rectum (Figure 35.11). With the advent of more sophisticated endoscopic techniques, small neuroendocrine tumors can be resected endoscopically. In all cases, appropriate tissue sampling is critical to define the presence of malignancy and degree of differentiation, both of which are needed to plan appropriate therapy.

Improvements in endoscopic imaging techniques have also facilitated more accurate diagnosis and staging of other colorectal tumors. For example, endoscopic endosonographic characterization of depth of penetration has markedly improved staging of rectal adenocarcinoma, which has important implications for treatment (Figure 35.12). Furthermore, endosonography allows for better tissue sampling, especially in identifying less common causes of rectal disease, such as squamous cell carcinoma of the rectum (Figure 35.13).