Wk 6 Colorectal Cancer Flashcards
Peak incidence of CRC?
60-70 years
What are the 2 major pathways for CRC to arise?
- adenoma-carcinoma sequence (~80%)
- microsatellite (repeats of non-coding DNA) instability (MSI)
What is HNPCC?
= Heriditary non-polyposis colorectal carcinoma
-inherited mutation in DNA mistmatch repair enzymes (in all cells)
-increased risk for colorectal, ovarian and endometrial cancers
-colorectal carcinoma arises de novo at a relatively early age, usually right sided
What are 2 mechanisms for colorectal carcinoma screening?
- colonoscopy
- fecal occult blood testing
How does left-sided CRC grow?
Napkin-ring lesion / apple core
-> decreased stool caliber (thin poop),
LLQ pain,
blood-streaked stool
-more common than right sided
-more associated w/ adenoma-carcinoma sequence
How does right-sided CRC grow?
As a raised lesion/ bump of colonic mucosa
-> IDA due to small amounts of bleeding and vague pain
-more associated w/ microsatellite instability
What do patients w/ CRC have an increased risk for?
Streptococcus bovis endocarditis
Describe CRC staging
T: depth of invasion
N: spread to regional lymph nodes
M: distant spread - most commonly involves the liver
What are 3 things tumor markers are used to assess?
- screening
- assess tx response
- assess/detect recurrence
What is a CRC serum tumor marker?
CEA = carcinoembryonic antigen
-useful for assessing tx response and recurrence
-not useful for screening
What is a colonic polyp?
Raised protrusions of colonic mucosa
What are the 2 most common types of polyp in the colon?
- hyperplastic polyps
- adenomatous polyps
Characteristics of hyperplastic polyps
- “serrated” appearance due to hyperplasia of glands
- most common type
- usually arise in left colon (rectosigmoid)
- benign w/ no malignant potential
Characteristics of adenomatous polyps
- neoplastic proliferation of glands
- 2nd most common colonic polyp
- benign but premalignant - may progress to adenocarcinoma via the adenoma-carcinoma sequence
What are 3 mutations in the adenoma-carcinoma sequence
- APC (TS) mutations (sporadic or germline - FAP) increase risk for polyp formation
- K-RAS mutations ->polyp formation
- p53 mutation and increased COX expression -> progression to carcinoma
APC mutation = risk
K-RAS mutation = formation of polyps
p53 mutation & increased COX = progression
What can protect against adenoma-carcinoma sequence?
aspirin b/c it’s a COX inhibitor
How are polyps treated during a colonoscopy?
All polyps are removed and examined microscopically
What are 3 factors in the risk of progression from adenoma to carcinoma?
- related to size, >2 cm
- sessile growth (flat vs pedunculated like a mushroom, flat is worse) sessile serrated covering entire depth of crypt
- villous history (villi seen in histology vs tubular adenoma, villous is worse/the villan)
What is FAP?
=familial adenomatous polyposis
1. autosomal dominant
2. 100s-1000s of adenomatous colonic polyps
3. due to inherited APC mutation on chromosome 5
What is tx for FAP?
Remove colon and rectum
otherwise almost all patients develop carcinoma by 40 yo
What is Gardner syndrome?
=FAP w/ fibromatosis and osteomas
-fibromatosis = non-neoplastic proliferation of fibroblasts, usually in retroperitoneum, locally destructive
-osteomas = usually benign tumor of bone, usually arises in skull
What is Turcot syndrome?
=FAP w/ CNS tumors (medulloblastoma and glial tumors)
What is a juvenile polyp?
=sporadic hamartomatous (benign) polyp that arises in children (<5)
-usually presents as solitary rectal polyp that prolapses and bleeds
What is a hamartoma?
A tumor that arises w/ normal (for the area) but disorganized tissue
What is juvenile poylposis?
=multiple juvenile polyps in the stomach and colon
-large numbers increases the risk of progression to carcinoma
What is Peutz-Heghers Syndrome?
=hamartomatous polyps throughout GI tract
-mucocutaneous hyperpigmentation on lips, oral mucosa, and genital skin
-autosomal dominant disorder
-increased risk for colorectal, breast and GYN cancer
Inflammatory polyps
1
Solitary rectal ulcer
-a type of inflammatory polyp
-not actually solitary
-if sphincter cannot relax completely, physical trauma from passing of stool -> mucosa can become pedunculated
-> hemoptasis
3 signs of epithelial dysplasia
- nuclear hyperchromasia
- elongation of nuclei
- nuclear stratification
-adenoma implies dysplasia is present
Sessile vs pedunculated
Villous vs tubular adenoma
Name this adenoma
Tubulovillous adenoma
What adenomous pattern is associated w/ increased Ca risk?
villous pattern
Views of adenocarcinoma of colon
Pedunculated tubular adenoma
Hyperplastic polyp
adenocarcinoma
4 colon Ca comorbidities
- IBD
- Type 2 Diabetes
- Prior Cancer
- Hx of polyp
Hereditary/genetic colon Ca
- FAP
- HNPC/ Lynch Sydrome
- 1st degree relative w/ CRC
7 Modifiable Colon Ca Risk Factors
- heavy EtOH
- Obesity (BMI>30)
- Hyperlipidemia
- red meat (100g/day)
- Processed meat (50g/day)
- Smoking
- High sucrose diet
What gene mutation -> 80% of all CRC?
APC gene
-inherited and acquired
Clincal presentation of CRC
- hematochezia
- change in bowel habits & stool shape
- abd discomfort (gas pain, bloating, cramps)
- unexplained weight loss
- constant fatigue - IDA
R vs L-sided CRC
R - midgut: cecum, ascending transverse
-flatter polyps, harder to detect
L- descending, sigmoid
What are the 2 stool-based tests for CRC?
- gFOBT = guaiac fecal-occult blood test
2.Fecal immunochemical test = FIT
What does gFOBT test?
Indirect measurement of blood in stool: peroxidase activity
-not meant to rule out GI bleed
-requires 3 stool tests
-avoid specific foods and meds prior
-sensitivity: 62-79%
-specificity: 87-96%
What is the FIT?
=fecal immunochemical test
-direct measurement of Hb in stool
-1 stool sample
-no dietary or med restrictions
-sensitivity: 73-92%
-specificity: 91-97%
2 CRC test modalities besides stool tests
- CT colonography
- colonoscopy (gold standard)
Where might you find an applecore lesion?
in the colon
-circumferential, large and deeply invasive
-usually very advanced colon cancer
How is colon cancer staged?
- how deeply does it penetrate the wall - deeper is much worse px
- has it spread to the lymph nodes? Has it gone past the lymph nodes? Most often to liver b/c of portal vein
What does metastatic colon cancer look like in a lymph node?
What is an osteoma?
Benign bony growth
What does mucin look like?
The white
-mucin made b/c colon cancer from adenocarcinoma
