GI cancers- First Aid and Class and pathoma – Flashcards

1. Adenomatous (most common) 2. Hyperplastic 3. Juvenile 4. Hamartomous (Peutz Jegher's) 5. Inflammatory (due to Ulcers)

Precancerous polyp Appearance: 1. Dysplasia (low or high grade)--> hyperchromatic, large nuclei/N:c ratio, less goblet cells 2. didn't invade submucosa (v. carcinoma) 3. Architecture: tubular vs. villous vs. tubulovillous 4. multiple Danger: Inc risk of progression to carcinoma when large and villous

Common non neoplastic tumor in the colon that has a "serrated" appearance. Usually located in rectosigmoid colon (left sided)

Definition: Sporadic hamartomous polyp that arises in children no malignant potential -Multiple: juvenile polyposis syndrome; increased risk of cancer.

AD disease of Hamartomous (excess normal tissue accumulation) polyps throughout GI tract; benign Danger: Benign but increased risk of colorectal cancer + breast+ gyno cancer Symptoms: 1) Perioral hyperpigmentation (freckle spots) on the lips, oral mucosa, genitals 2) polyps throughout the GI tract

1)Micro satellite pathway: (15%) - 2) Chromosomal instability: Adenoma carcinoma sequence aka APC/ Beta Catenin pathway.

Molecular progression from normal colonic mucosa to adenomatous polyp (low grade--> high grade dysplasia) to carcinoma (desmoplastic change and invasion of SM) 1) APC mutation puts colon @ risk -need 2 gene mutations to KO this [tumor suppressor] -KO= Unregulated expression of beta catenin= inc proliferation/ decreased cellular adhesion 2) K-ras mutation (proto-oncogene) leads to an adenoma -1 hit required (oncogene) -unregulated intracellular signal transduction = polyp 3) Loss of tumor suppressor P53 and DCC = carcinoma Order: AK53 2-1-2 (2 hits needed; 1 hit needed; 2 hits needed)

WNT signalling pathway: APC and beta catenin. (APC= Tumor suppressor) In the absence of a WNT signal, APC degrades Beta catenin to turn off transcription. If there is a WNT signal, this turns on to increase transcription. In cancer: mutated APC = can't degrade Beta catenin = Beta catenin is on even in the absence of a wnt signal.= can go into nucleus and turn on transcription= increased cell proliferation and reduced adhesion

DNA mismatch repair gene mutations; occurs with HNPCC (lynch syndrome) or spontaneous hypermethylation of the gene leads to MMR gene silencing = both pathways lead to silencing of MLH1/ BRAF = defect in mismatch repair= microsat instability -mutations accumulate but no defined morphologic correlates

In MSI, there are no morphologic correlates but in Chr instability, you get adenomas/ polyps

Adenoma: mucosa only Adenocarcinoma: invaded the submucosa to access lymphatics.

1. Familial Adenomatous Polyposis 2) Gardner syndrome 3) Turcot Syndrome 4) Juvenile polyposis syndrome 5) Hereditary non polyposis colorectal cancer (Lynch syndrome) 6) Peutz Jagher

Genetics: AD mut in APC gene on chr 5q -2 hit hypothesis (AD inheritance of risk only); 100% to progress to CRC Pathophysiology: WNT: APC/ Beta catenin pathway Location: Pancolonic, and always includes the rectum. Symptoms: 100-1000s of adenoma polyps starting at a young age (teens) and progression to CRC ; 40 years old. *always arises from polyps!* (vs. HNPCC) Screening: Early surveillance Treatment: prophylactic removal of colon @ age 40

Syndrome with following features: 1) Familial Adenomatous Polyposis (FAP) 2) Fibromatosis= non neoplastic proliferation of fibroblasts 3) Osteomas (bone tumors) on the skill and the face 4) Congenital hypertrophy or retinal pigment epithelium = increased risk of CRC

Familial Adenomatous Polyposis inaddition to malignant CNS tumors- medulloblastomas (Turcot= Turban)

Genetics: AD mutation in DNA mismatch repair genes= microsatelite instability Location: -Proximal colon is always involved, RIGHT SIDED tumor - increased risk for endometrial cancer and gyno cancer Symptoms/ clues 1. Fast growing tumors that arise denovo NOT from adenomas --> progress to CRC in 3 years (vs. 10 years in FAP) 2) Patient with a history of endometrial cancer or a FH of endometrial cancer

1) IBD (UC ; Crohn's) 2) Adenomas- Adenomatous(large and villous), Juvenile, or Peutz Jegher's 3) Lifestyle: Diet of High fat/ Low fiber, alcohol, obese, tobacco) 4) Infection- strep bovis

Rectosigmoid ; ascending colon ; descending colon. Right side bleeds; left side obstructs

Evaluate for colorectal cancer

(Right sided) 1. exophytic mass (raises outwards) 2. iron deficiency anemia (occult bleed), 3. weight loss suspect especially in an old adult with iron deficiency anemia

(left sided) Descending cancer, obstructive 1. Infiltrating mass (grows inwards, "napkin ring"), 2. partial obstruction with colicky pain in LLQ 3. Bright red blood per rectum (hematochezia/ bright bloody poop!) and decreased stool caliber (pencil thin stools)

investigate for right sided colon cancer (proximal)

Screening every 10 years at age 50; earlier if you have a predisposing dz -teens for FAP and 20s for HNPCC

CEA for recurrence and treatment response not screening

Tumor marker for monitoring treatment response or recurrence of CRC not useful for screening

COX-2; Implications: can treat cancer with NSAIDS

Familial adenomatous polyposis and Ulcerative colitis