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Flashcards in Jackson - Colon Polyps to Cancer Deck (66)
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1

What are the 7 types of colon polyps?

- Adenomatous (70%): pre-malignant (how most colon cancers start) 

1. Tubular 

2. Villous 

3. Tubulovillous 

4. Sessile serrated 

- Non-adenomatous (30%): 

1. Hyperplastic 

2. Hamartomatous 

3. Juvenile polyps 

2

What are these?

Hyperplastic polyps: most common non-neoplastic polyp

- Histology with saw tooth (star-shaped) pattern (some histo overlap with sessile serrated adenomas)

- Usually diminutive

- Location usually in rectum and sigmoid

- No malignant potential in small distal hyperplastic polyps

3

What do you see here? Describe the related syndrome.

Peutz-Jeghers Syn.: multiple GI hamartomatous polyps (sm. intestine) & mucocutaneous lesions (like freckles on buccal mucosa; may go away by age 20) 

- Auto dom (present around 11) -> germline hetero LOF mutations in the gene STK11

- Assoc w/markedly INC risk of several malignancies; lifetime risk approx 40%

- Regular surveillance recommended starting at birth:

1. Sex cord tumors of the testes

2. Late childhood gastric, sm. intestinal cancer

3. 2nd-3rd decades of life for colon, pancreatic, breast, lung, ovarian, and uterine cancers 

- Occasionally sporadic, or as components of various genetically determined/acquired syndromes 

4

What are juvenile polyps? Presentation? Morphogenesis?

- Focal malformations of epi and lamina propria

- Sporadic (usually solitary) or syndromic in kids <5

- Commonly in rectum; present with rectal bleeding 

1. Intussusception, intestinal obstruction, polyp prolapse (through anal sphincter) may occur

- Pts w/auto dom syndrome can have from 3-100 hamartomatous polyps, and a minority can undergo malignant transformation 

- Morphogenesis is incompletely understood, but proposed that mucosal hyperplasia is initiating event

1. Dysplasia is rare in sporadic juvenile polyps

2. 30-50% of pts w/juvenile polyposis syndrome develop colonic adenocarcinoma by age 45 

3. Most common mut, SMAD4

5

What is this? Risk factors? Types? Histo?

- Adenomatous polyp: prevalence 25-30% at age 50 

- RISK FACTORS: age, abdominal obesity, male sex, and AA race 

- Can be sessile (front image), pedunculated, flat, or depressed

- HISTO: tubular (80%), villous (5-15%), or mixed (tubulovillous adenoma)

6

What is the most common type of neoplastic polyp?

- Adenomatous

- Image of pedunculated attached here 

7

What are these?

Villous adenomas

8

What factors are most important in the prognosis of colon polyps?

- SIZE + villous component 

- Usually takes about 10 years for malignant transformation 

9

What do you see here?

- Sessile serrated adenoma: some histo features of hyperplastic polyps, but have malignant potential

- More prevalent in proximal colon

- Typically flat lesions

- May account for missed lesions on colonoscopy

- Have MSI-H or BRAF mutations

- May have mucous cap sitting on top of them 

10

What is going on here?

Polypectomy: removal of a stalked polyp with colonoscopy using cautery and a snare

- Sent to pathology next to check margins 

11

What is the epi of colorectal cancer?

- Most common GI malignancy; mortality 2nd only to lung cancer 

- Higher incidence in developed countries: thought to be 2o to high fat, low fiber diet

- Calcium and folate in diet may be protective

1. Folate may have anti-cancer benefit early in adenoma sequence

- Most colorectal tumors are adenocarcinomas 

- Incidence of CRC has declined 30% in last decade in patients >50-y/o

1. 5% of Americans will develop CRC and 40% of these will die of the disease

- NOTE: cancer of sm. intestine very rare

12

What are the risk factors for colorectal cancer?

- Age: >50 

- Colitis: may not develop colon polyps 

13

What is the most common risk factor for colon cancer?

- Age 

- Male = female 

- NOTE: AA's may have earlier age of onset

14

How does family hx affect colon cancer risk?

- Very young relatives, or more than one relative, start thinking about inherited syndromes 

15

What is the influence of tumor location on colon cancer presentation?

- LEFT: obstructive symptoms (smaller lumen), changes in bowel movements, overt bleeding 

- RIGHT: iron deficiency anemia or occult blood in stool

- NOTE: when an adult presents with iron deficiency anemia, think about colon or gastric cancer 

16

What is going on here?

Barium enema: apple-core lesion surrounding lumen of descending colon 

- Can be used to diagnose colorectal cancer: will show mass or constricting lesion 

17

What are 2 techniques for diagnosis of colorectal cancer?

- Barium enema: will show mass or constricting lesion 

Colonoscopy: locate & biopsy lesions, and remove polyps

18

What are some of the txs for colorectal cancer?

Endoscopic polypectomy can be curative if cancer is localized to head of polyp

- Pre-op CT to look for metastatic disease (mets usually to liver, lungs) 

- Surgery: mainstay of treatment -> involves removal of tumor and adjacent lymphatics

Chemo: adjuvant tx in pts with (+) nodes -> DEC recurrences and improves survival (see attached) 

19

What are the 2 goals and 4 barriers of colorectal cancer screening?

- GOALS:

1. DEC mortality by detecting lesions earlier

2. Prevention by removing adenomatous polyps

- BARRIERS: 

1. Limited access to medical care/colonoscopy

2. Pt preference: bowel prep, time off from work for colonoscopy

3. Risk and expense of screening tests: best test for individual patient is test that gets done

- NOTE: only 65% of patients currently get screening between age of 50 and 75

20

What are the colorectal cancer screening recommendations based on risk category?

- Average risk: asymptomatic, age >50

1. US Task Force recommended to stop screening at age 75

- High risk: asymptomatic + 1 of the below; always require a colonoscopy 

1. Personal history of adenomas or cancer

2. Family history of adenomas or cancer

3. Hereditary cancer (FAP, HNPCC)

4. IBD colitis

- If any of these screening tests (+), recommended pt have colonoscopy (last 3 are stool sample tests)

- NOTE: if you have symptoms, no longer screening, but rather diagnostic colonoscopy 

21

What is the FOBT?

Fecal occult blood test (FOBT): stool-based colo-rectal screening test 

- (+) test = 20% chance of having lg polyp or cancer 

- 80% false positive rate: affected by meds, diet 

1. Can also have false negatives b/c pt may not always be bleeding 

- Requires 3 stool samples 

- Low sensitivity for detecting CRC 

NOTE: FIT is a better test 

22

What is FIT?

Fecal immunochemistry test: stool-based colo-rectal cancer screening test 

- Responds to only human hemoglobin: no dietary restrictions 

- Does NOT detect UGI bleeding

- Requires 1 or 2 stool samples, and may detect as little as 0.3gmHb/gm stool

- More expensive than Guiac (FOBT), but also more sensitive and specific

- Can use for low-risk, asymptomatic patients 

23

What is virtual colonoscopy?

- Helical CT reconstructed into 3D images

- Requires bowel prep: most pts dislike this

- Exposure to radiation

- Not widely available, and studies on sensitivity and specificity have been variable

- Role in screening unclear: not paid for by most insurance

1. Positive test requires colonoscopy

24

Is sporadic or familial colorectal cancer more common? 1difference?

- Majority of cases SPORADIC (see attached image) 

- Cumulative incidence much higher at younger ages in FAP, then HNPCC -> genetic syndromes, as compared with the general public 

25

What is the genetic etiology of FAP?

- Auto dom: one allele of APC gene inherited in a mutated form (germ line mutation) 

- Mutation present in every cell of the colon 

- Polyp growth begins when 2nd allele is somatically mutated, causing loss of gene function 

1. Normally, during teen years 

26

What is FAP?

- Mucosal surface of colon a "carpet" of small, adenomatous polyps (see attached image) 

- Typically, total colectomy before age 20 (post-pubertal) 

- Polyps look like tubular adenomas histologically 

1. Don’t look any different than sporadic, and no higher risk of change, but so many that risk of colon cancer is high 

- Adenocarcinoma in 100% of these pts if untreated, often before age 30, and always by age 50 

- NOTE: adenomas may devo elsewhere in GI tract, esp. adjacent to ampulla of Vater (union of pancreatic and common bile duct) and in the stomach

27

What are the two syndromic variants of FAP?

- Gardner's: multiple colon polyps, osteomas, thyroid cancer, desmoid fibromas, epidermal inclusion cysts

- Turcot's (autosomal recessive): polyps with glioblastoma or medulloblastoma

28

What is HNPCC?

- Hereditary non-polyposis colon carcinoma/Lynch syn: auto dom -> faulty DNA mismatch repair gene

- Most HNPCC tumors have microsatellite instability (variations in dinucleotide repeat sequences)

1. Compared to APC, in HNPCC, there are fewer polyps and an older age for devo of carcinoma

- 2-4% of all colorectal cancers, making it the most common syndromic form of colon cancer 

- Tend to occur at younger ages than sporadic colon cancers, and are often located in the right (proximal) colon

29

What are the Bethesda Criteria for the dx of HNPCC?

1. CRC diagnosed in individual < 50 

2. Presence of other HNPCC-assoc. tumors (small bowel, endometrial, ovarian, gastric, hepatobiliary, transitional cell carcinoma of renal pelvis or ureter), regardless of age

3. CRC w/MSI-H histology, in patient <60 

4. CRC in >1 1st-degree relative w/HNPCC-related tumor, w/1 cancer diagnosed <50

5. CRC dx'd in 2 or more 1st or 2nd degree relatives with HNPCC-related tumors, regardless of age 

- NOTE: this is a clinical dx that can be confirmed by histology -> currently most GI pathology leaders are screening every colorectal adenocarcinoma for MSI

30

Briefly describe the histology of the benign CRC polyps (image too).

- A: normal 

- B: hyperplastic, with sawtooth (serrated, star-shaped) lumens 

- C: hamartoma = mass of mature, but disorganized tissue indigenous to site (feature of Peutz-Jeghers syndrome) 

- D: juvenile -> called "retention polyps" in adults