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Intestinal Polyps & Colorectal Cancer

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Intestinal Polyps & Colorectal Cancer

Sections






Here we'll learn about neoplastic and nonneoplastic intestinal polyps and colorectal cancer.

Polyps are nodules of tissue that project above the mucosa; they can occur throughout the GI tract, but are most common in the colon.

Colon polyp on a stalk:

Polyps are usually asymptomatic, but can cause bleeding or other GI issues, depending on their size.

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.

Diagnosis: 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), inflammatory 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

Morphology: Pedunculated (with a stalk) or sessile (flat).

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.

Villous adenomas are characterized by long, finger-like projections; some authors report that villous adenomas are more likely to be malignant.

Tubular adenomas are characterized by disorganized and irregular tubular glands.

Tubular adenoma of the colon:

Tubulovillous adenomas comprise a combination of villous and tubular structures.

Tubulovillous adenoma of the colon:

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.

The apical crypts of hyperplastic polyps have a serrated or sawtooth appearance, with goblet cells and mucin droplets.

Hyperplastic polyp:

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.

Mucosal polyps, which are clinically insignificant, and submucosal polyps, which are rare (these include lipomas, leiomyomas, fibromas, etc.).

Inflammatory polyps and pseudopolyps are associated with inflammatory bowel disorders; they comprise inflammatory cells mixed with epithelial and stromal components.

Polyposis syndromes

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.

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.

Board Review

Colorectal Cancer

Getting ready for boards? Review these concise, bulleted high yield reviews for your exam.

USMLE & COMLEX-USA

Nurse Practitioner (NP)

Physician Assistant (PA)

Internal Medicine (ABIM)

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Images:

  • Tubulovillous adenoma: https://en.wikipedia.org/wiki/Colorectal_adenoma#/media/File:Tubulovillous_adenoma.jpg
  • Tubular adenoma colon: https://en.wikipedia.org/wiki/Colorectal_adenoma#/media/File:Tubulovillous_adenoma.jpg
  • Peutz Jegher syndrome: https://commons.wikimedia.org/wiki/File:Peutz_jegher_syndrome_new_photo_for_diagnosis.jpg
  • Colon polyp on a stalk: Stephen Holland, M.D., Naperville Gastroenterology, Naperville, IL, USA
  • Hyperplastic polyp: https://en.wikipedia.org/wiki/Hyperplastic_polyp#/media/File:Hyperplastic_Polyp_of_the_Rectum_(14060044206).jpg