Pathology of Polyps and Colon Cancer Flashcards
What are the 3 categories of NON-neoplastic polyps?
- inflammatory polyps
- hamartomatous polyps
- hyperplastic polyps
* polyp= raised protrusion of colonic mucosa
What is solitary rectal ulcer syndrome?
- associated with INFLAMMATORY polyps that causes rectal bleeding, mucus discharge, and an inflammatory lesion on the anterior rectal wall due to impaired relaxation of the anorectal sphincter. This causes a sharp angle at the rectal shelf leading to recurrent abrasion and ulceration of the mucosa.
What causes inflammatory polyps (non-neoplastic polyps)?
- repeated cycles of injury and healing.
What can happen to inflammatory polyps and what will you see histologically?
- the polyp may become entrapped, leading to mucosal prolapse.
- may see fibromuscular hyperplasia, mixed inflammatory infiltrates, erosion, and epithelial hyperplasia.
What causes hamartomatous polyps (non-neoplastic polyps)?
- occur sporadically and in some genetic and acquired syndromes.
What will you see histologically with hamartomatous polyps?
- tumor-like growths composed of mature tissues that are normally present in the organ.
- juvenile polyps
*** What syndromes are associated with hamartomatous polyps?
- Peutz-Jeghers syndrome
- Cowden syndrome
- Bannayan-Ruvalcaba-Riley syndrome
- Cronkhite-Canada syndrome
Where do juvenile polyps (type of hamartomatous polyp; non-neoplastic) occur most often?
- RECTUM and present as rectal bleeding and may protrude through the anal sphincter.
- sporadic juvenile polyps are usually solitary (pedunculated dilated gland with smooth surface).
*** What is juvenile polyposis?
- autosomal dominant disease (SMAD4, BMPR1A) that presents with 3-100 polyps, which may require colectomy due to the potential for sever hemorrhage.
- PULMONARY ARTERIOVENOUS MALFORMATIONS are extraintestinal manifestations marked by PROTEIN LOSS.
For what does juvenile polyposis increase your risk?
- colonic adenocarcinoma
*** What is Peutz-Jeghers syndrome?
- rare, autosomal dominant (LKB1/STK11) disease with multiple hamartomatous polyps (most common in SMALL INTESTINE) and mucocutaneous hyperpigmentation (PEDUNCULATED AND LOBULAR).
- maculoses form around mouth, palms, genitalia, and perianal areas.
- can initate INTUSSUSCEPTION (telescoping of bowel).
- associated with increased risk of malignancies (BREAST, COLON, LUNG, OVARIES, UTERUS OR TESTICLES) and sex cord tumor with annular tubules (SCAT).
What is Cowden syndrome?
- autosomal dominant hamartomatous polyp syndrome due to PTEN mutation, which encodes a lipid phosphatase that inhibits signaling through the P13K/AKT pathway.
- macrocephaly, benign skin lesions, trichilemmomas, papillomatous papules and acral keratoses.
- increased risk for GI malignancy, breast ca, follicular cancer, thyroid cancer, or endometrial cancer.
- REMEMBER: cows have big heads, cows have hair, cows have big necks so think follicular or thyroid cancer, and females cows have big uterus.
What is Bannayan-Ruvalcaba-Riley syndrome?
- similar to Cowden but has mental and developmental delays.
- Lower incidence of neoplasia than seen in Cowden.
What is Cronkite-Canda syndrome?
- nonhereditary disorder occuring in 50s where hamartomatous polyps occur in the stomach, small intestine, colon, and rectum.
- polyps resemble juvenile polyps histologically.
- nail splitting, hair loss, and cutaneous hyper or hypopigmentation can occur.
What are hyperplastic polyps (non-neoplastic)?
- common epithelial proliferations (most common in left colon) seen in 60s or 70s. No risk of malignancy! :)
- composed of goblet cells with a SERRATED surface.
- may be associated with a reaction adjacent to a more ominous lesion or inflammatory disorder.
What is the most common type of colonic polyp?
- hyperplastic polyps
What are Adenomatous polyps?
- neoplastic proliferation of glands; MOST COMMON type of NEOPLASTIC polyp and 2nd most common type of general colonic polyp.
- benign, but PREMALIGNANT; may progress to adenocarcinoma via the adenoma-carcinoma sequence.
- large nucleoli and eosinophilic cytoplasm with reduction in goblet cells (compared to hyperplastic polyps which have lots of goblet cells).
What is the adenoma-carcinoma sequence?
- the molecular progression from normal colonic mucosa to adenomatous polyp to carcinoma.
1. APC/beta-catenin (adenomatous polyposis coli gene) mutations increase risk for formation of polyp. Both copies of the APC gene must be inactivated. APC is a negative regulator of beta-catenin (component of WNT signaling).
2. K-ras mutation leads to formation of polyp.
3. p53 mutation and increased exression of COX allow for progression to carcinoma.
*** What will impede the progression of adenoma to carcinoma?
- aspirin because it inhibits COX (which is required for progression to carcinoma).
How do we screen for polyps?
- colonoscopy and testing for fecal occult blood.
* polyps are usually clinically silent, but can bleed.
What is the goal when screening for polyps?
remove adenomatous polyps before progression to carcinoma.
What do adenomatous and hyperplastic polyps look like on colonoscopy?
identical!
*thus, all polyps are removed to be examined microscopically.
What is the risk of an adenomatous polyp progressing to carcinoma?
- size greater than 2 cm
- sessile growth= flat (rather than pedunculated= has a stalk) and can resemble hyperplastic polyps.
- villous histology (think villous is the villain). These may secrete protein and potassium causing hypoproteinemia and hypokalemia.
Do the majority of adenomas progress to adenocarcinoma?
NO
What is familial adenomatous polyposis (FAP)?
- autosomal dominant disorder characterized by 100s to 1000s of adenomatous colonic polyps.
- due to inherited APC mutation (chromosome 5).
What is done prophylactically for pts with FAP?
- colon and rectum are removed bc otherwise, almost all pts will develop carcinoma by age 40.
What is Gardner syndrome?
- FAP with FIBROMATOSIS (non-neoplastic proliferation of fibroblasts arising in retroperitoneum; desmoid and destructive) and OSTEOMAS (benign tumors of bone that usually arise in the skull).
- often THYROID cancer is associated
What is Turcot syndrome?
- FAP with CNS tumors (medulloblastoma and glioblastoma). Almost inverably fatal
What is intramucosal carcinoma?
- occurs when dysplastic epithelial cells penetrate the basement membrane to invade the lamina propria or muscularis mucosa. Once in breeches the muscularis mucosa it can metastasize.
What is colorectal carcinoma?
- adenocarcinoma arising from colonic or rectal mucosa; 3rd most common cause of cancer-related death.
- most commonly arises from adenoma-carcinoma sequence.
Aside from the adenoma-carcinoma sequence, what is a second molecular pathway by which colorectal carcinoma can arise?
- microsatellite instability (MSI). Microsatellites are repeating sequences of noncoding DNA; integrity of sequence (stability) is maintained during cell division. However, instability indicates defective DNA copy mechanisms (DNA mismatch repair enzymes).
- specifically TGF-B and PRO-APOPTOTIC BAX (remember BAL AND BAX; inhibiting this causes uncontrolled cell growth).
What is Hereditary nonpolyposis colorectal carcinoma (HNPCC) or “Lynch Syndrome”?
- inherited mutations in DNA mismatch repair enzymes (micosatellite instability).
- nonpolyposis= carcinoma arises de novo (not from adenomatous polyps) at a relatively early age; usually right sided.
*** What is often associated with HNPCC or “Lynch Syndrome”?
- ovarian and endometrial carcinoma
Are patients with ulcerative colitis at an increased risk for colorectal carcinoma?
YES
At what age does screening for colorectal carcinoma begin?
age 50
Can colorectal carcinoma develop anywhere along the length of the colon?
YES
How does a left-sided (distal) carcinoma usually grow?
- as a “napkin-ring” lesion that decreased the lumen diameter, presenting with DECREASED STOOL CALIBER, LLQ pain, and blood-streaked stool.
How does a right-sided (proximal) carcinoma usually grow?
- as a raised lesion presenting with iron-deficiency anemia (occult bleeding) and vague pain.
- An older adult with iron-deficiency anemia has colorectal carcinoma until proven otherwise.
What pathway of colorectal carcinoma is most common for the right-colon?
microsatellite instability pathway
*** If a patient presents with Steptococcus bovi endocarditis, what test should you always do next?
- colonoscopy bc it is HIGHLY associated with colonic carcinoma
How do we stage colorectal carcinoma?
- T= depth of tumor invasion (tumors limited to the mucosa generally do not spread due to lack of lymphatics in the mucosa).
- N= spread to regional lymph nodes.
- M= distant spread; most commonly involves LIVER.
What is an important serum tumor marker for assessing treatment response or detecting recurrence of colorectal carcinoma?
CEA
Is CEA useful for screening for colorectal carcinoma?
NO just for assessing treatment response or detecting recurrence.
Does mucin production by adenocarcinomas have a better or worse prognosis?
worse
With what are pure squamous cell cancers of the anal canal often associated?
HPV
Can tumors of the anal canal have a basaloid pattern?
YES (mixed glandular, squamous, or mucinous patterns)
