Intestinal Polyps & Colorectal Cancer
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Intestinal Polyps & Colorectal Cancer
Here we'll learn about neoplastic and nonneoplastic intestinal polyps and colorectal cancer.
Overview
- Polyps are nodules of tissue that project above the mucosa; they can occur throughout the GI tract, but are most common in the colon.
- Polyps are usually asymptomatic, but can cause bleeding or other GI issues, depending on their size.
- Denote that colorectal cancer is a leading cause of cancer in the U.S.
- Most arise from adenomas (adenocarcinoma).
- Screening should begin at age 45, or earlier if a patient has family members with colorectal cancer, or if there is an expectation of early onset.
- We use colonoscopy or flexible sigmoidoscopy to diagnose cancer; for staging, we can use CT scans and physical exams to look for metastasis. The liver is the most common site for distant metastasis in colorectal cancer.
- Risk factors include adenomatous polyps, age (over 50 is higher risk), irritable bowel disease, and family history.
- Signs and symptoms include blood in the stool, abdominal pain, and iron deficiency anemia.
- Treatment relies on surgical resection; adjuvant chemotherapy and radiation may be recommended.
- Unfortunately, recurrence of colorectal cancer is common, especially cancers of the rectum.
Intestinal Polyps
- Pedunculated (with a stalk) or sessile (flat).
- To show this, we'll use adenomas as an example.
- Pedunculated adenomas have a stalk that comprises an outgrowth of submucosa covered in muscularis mucosae and adenomatous epithelium – show that the epithelium is thicker, i.e., overgrown, at the top of the polyp.
- Sessile polyp are characterized by overgrown epithelia that raises above the normal tissue but in a flat, shelf-like way (sessile means fixed at the base without a stalk).
- Polyps can be neoplastic or nonneoplastic.
- Neoplastic Polyps
- Adenomatous polyps (aka, adenomas) are very common. As we mentioned in the intro, most colorectal cancers arise from adenomas.
- Adenomas can range in size from small to large; larger polyps are more often malignant.
- The histology is glandular, and can be categorized as villous, tubulovillous, or tubular.
- We show that villous adenomas are characterized by long, finger-like projections; some authors report that villous adenomas are more likely to be malignant.
- We show that tubular adenomas are characterized by disorganized and irregular tubular glands.
- Common features of the histological subtypes are elongated, crowded nuclei and loss of goblet cells.
- Neoplastic subtypes of serrated polyps
- Sessile serrated lesions are flat, variable in size, and have a mucinous cap; these are often found in the proximal colon.
- Sessile serrated lesions have irregular crypts that are dilated and branching with a "T" or "boot-shaped" bottom.
- Traditional serrated adenomas are larger and have villous architectures; these are more often found in the distal colon.
- Be aware that the nomenclature used for serrated polyps has undergone changes as our understanding of them has evolved.
- Nonneoplastic polyps
- Hyperplastic are a third subtype of serrated polyps.
- As opposed to the dilated crypts of the neoplastic subtypes we just learned, hyperplastic polyp serration tends to be concentrated towards the upper region of the crypts.
- Hyperplastic polyps are the most common polyp, and that they are often found co-existing with adenomas.
- They are small (5 mm or less), with a flat or oval shape; they are often found in the distal colon.
- Two subtypes are goblet rich and micro-vesicular; the clinical significance of these subtypes is uncertain.
- We show that the apical crypts of hyperplastic polyps have a serrated or sawtooth appearance, with goblet cells and mucin droplets.
- Unfortunately, it can be very difficult to tell hyperplastic polyps from sessile serrated polyps based on histology alone; researchers are working on molecular methods to distinguish the nonneoplastic from neoplastic polyps.
- Hamartomatous polyps comprise normal tissues with abnormal distributions.
- Though rare overall, they are the most common polyp found in children, and are typically solitary and benign.
- Later, we'll learn about polyposis syndromes characterized by multiple hamartomatous polyps.
- There are two histological subtypes:
- Peutz-Jeghers polyps are characterized by ribbons of arborizing smooth muscle (notice the tree-like appearance).
- Juvenile polyps comprise large dilated cystic glands. Be aware that "juvenile" refers to the histopathology, not the age of onset.
- Others:
- Inherited disorders characterized by multiple polyps and increased cancer risk.
- Familial adenomatous polyposis (FAP) is the most common polyposis syndrome.
- Caused by mutations in the APC tumor suppressor gene.
- Penetrance varies, and patients develop 100s-1000s of adenomas ("attenuated familial adenomatous polyposis" is characterized by fewer than 100 polyps).
- If untreated, FAP is associated with a 100% chance of developing colorectal cancer by age 40.
- Extracolonic manifestations, including desmoid tumors and gastric polyps are common, and two variants of FAP are recognized by their propensity for specific manifestations:
- Gardner syndrome is FAP with osteomas, often of the mandible or skull, and skin/soft tissue tumors.
- Turcot syndrome is FAP with CNS tumors, often medulloblastomas.
- Hamartomatous polyposis syndromes are inherited autosomal disorders; two of the syndromes are named for their polyp subtypes.
- Peutz-Jeghers polyposis syndrome is characterized by pigmented macules on mucous membranes and skin (often in/around the mouth and nose).
- Complications in children tend to directly result from mechanical issues related to the polyps, such as intussusception, torsion, and obstruction.
- In adults, complications include reproductive and GI cancers.
- Be aware that Peutz-Jeghers polyps are often found in the small intestine and stomach, whereas we've focused on colon polyps for most this tutorial.
- Juvenile polyposis syndrome is characterized by cutaneous and skeletal manifestations (for example, telangiectasia).
- Other hamartomatous polyposis syndromes include PTEN-Hamartoma syndromes and hereditary mixed polyposis syndrome.
Colorectal cancer
- Occurs when polyps invade the submucosa or deeper layers.
- We show this by re-drawing our pedunculated and sessile adenoma examples and indicating that the cancerous cells have invaded the deeper layers.
- As we stated earlier, most colorectal cancers arise from adenomas.
- Thus, they follow the classic adenocarcinoma pathway, in which mutations accumulate over 10-15 years and facilitate progression from adenoma to carcinoma.
- Serrated pathway carcinomas, on the other hand, are associated with mutations in BRAF or KRAS genes and hypermethylation.
- Lastly, indicate that Lynch Syndrome, aka, Hereditary Nonpolyposis CRC is the most common cause of hereditary colorectal cancer.
- It is the result of mismatch repair and microsatellite instability cancer pathways.
- Lynch syndrome is associated with early cancer onset, and patients are more likely to develop other cancers, especially of the endometrium, liver, and brain.