Neoplastic Diseases Of Th Elarge And Small Bowel Flashcards
Colonic polyps
Most common in colon but can be anywhere in the GI
- sessile = no stalk
- pedunculated = has a stalk
- can be classified as non neoplastic or neoplastic*
- most common neoplastic is adenoma
- most common non neoplastic = inflammatory
Inflammatory polyps
Is associated with solitary rectal ulcer syndrome
- clinical triad of*
- rectal bleeding
- mucus discharge
- inflammatory lesions on anterior rectal wall
the underlying cause is impaired relaxation of the anorectal sphincter
- leads to recurrent abrasions and ulceration for he rectal mucosa
- chronic injury and healing = Polaroid mass of inflamed and reactive mucosal tissue
Haramartous polyps
Are sporadic or genetically acquired polyps related to syndromes
They are disorganized tumor-like growths composed of mature cell types
most common type is juvenile polyps
Juvenile polyps
most common type of harartomatous poly
May be sporadic or syndromic
Usually solitary but can be as many as 100 w/ the autosomal dominant syndrome of juvenile polyposis
- polyps are located in the rectum and almost always present with rectal bleeding
- ** small amount shows dysplasia which if present can increases chances of adenocarcinoma
Most common in children <5 years old
Peutz-jeghers syndrome
Rare autosomal dominant disorder that presents with multiple GU harartomatous polyps and mucocutaneous hyperpigmentation
Always carries an increased risk for developing other malignancies (usually colon/breast/lung/ovaries/testes)
**is associated with loss of function of LKB1/STK11 (gene produces a protein that suppression’s protein kinase activity)
Shows large pedunculated small intestine polyps
Colonic hyperplastic polyps
Common epithelial proliferation’s that are typically seen in 60-70s
Believed to be caused due to decreased epithelial cell turnover rates (leads to pileup of goblet cells and absorbed cells with jagged appearance)
- NO malignant potential (however must be distinguished from sessile serrated adenomas which look similar but can be malignant)
Most common in the left colon and are less than 5mm
Colonic adenomas
- most common and clinically important neoplastic polyps*
- are benign by themselves, however chronically can give rise to adenocarcinomas
Show epithelial dysplasia with pedunculated polyps with hyperchromatic nuclei
- should be excised even though they are benign
Show more common in >50yrs and there is no gender preference
- range from 0.3-10cm and can be sessile or pedunculated
**if sessile = right colon almost always
Familial adenomatous polposis (FAP)
Autosomal dominant disorder where there is a mutation in the adenomatous polyposis gene (APC)
- causes numerous colorectal adenomas to grow throughout colon
- **need at least 100 polyps present to diagnose (can be as high 2000 though)
They look identical to sporadic adenomas
- **100% of patients with untreated FAP will get colorectal adenocarcinoma without treatment
- treatment = prophylactic colectomy
What syndromes are associated with FAP?
Gardner syndrome
- produce osteoma, Desmoids/thyroid tumorsand skin cysts in addition to colorectal adenocarcinoma
- also shows supernumerary teeth
Turcot syndrome
- produces (2/3)CNS tumors and (1/3) medulloblastomas in addition to colorectal adenocarcinoma
Hereditary non polyposis colorectal cancer (HNPCC)
“Lynch syndrome”
Autosomal dominant disorder that results in at least 5 DNA mismatch repair in the MSH2/MLH1 genes
- usually one copy of the mutation is inherited and the second Copy is lost through mutation/silencing. Once the 2nd is lost = HNPCC
Affects right colon and other areas around the body more often and tends to occur at younger ages
- *not polyposis high numbers, but are excessive (<50)
- most are sessile serrated adenomas with prominent mucin production
Adenocarcinoma of the colon/rectum
most common malignancy of the GI tract worldwide, also most deadly
Kills roughly 600,000 annually with 1.2 mil new cases annually
- accounts for approx. 10% of all cancer deaths
- 2nd to only lung cancer
Peak age = 60-70 yrs
- dietary factors are closely associated (low fiber and high refined carbs/fat)
NSAIDs actually have a protective effect against colorectal carcinomas = inhibits COX-2 which produces PGE2 which in large doses promotes epithelial proliferation particularly after insults
What are the two pathways for adenocarcinoma pathogenesis
APC/B-catenin pathway
- most common (80%)
Micro-satellite instability pathway (defects in DNA mismatch repairing)
- less common
Steps in the APC/B-catenin pathway for adneocarcinoma
1) APC mutation at 5q21
- (usually inherited)
- mucosa is still okay at this point
2) methylation of B-catenin and APC genes occurs due to an external insult
- (usually acquired)
- mucosa is at risk now
3) proto-oncogene mutation in the K-RAS gene at 12p12 and TP53 occurs = over expression of COX-2
- (always acquired)
- develops adenoma
4) telemerase and numerous other genes start to mutate
- (always acquired)
- develops carcinoma
APC relationship for B-catenin
APC is key negative regulator of B-catenin
- normally binds to and degrades B-catenin
*without APC function, B-catenin accumulates and translocates to nucleus where it increases MYC and cyclin D1 transcription and promote proliferation
Additional mutation that follow APC mutations
KRAS: promote growth and prevent apoptosis
SMAD2/4: encodes for effectors of TGF-B-signaling
*TP53 often is mutated in 70-80% of cancers as well but is late stage only
