Large Intestine I Flashcards
What is this?
what are the characteristic features?
What is it caused by?
Inflammatory Polyp
characteristic features of the polyp include mixed inflammatory infiltrates, erosion, and epithelial hyperplasia with lamina propria fibromuscular hyperplasia
Inflammatory polyps are caused by cycles of injury and healing
the clinical triad of presentation:
rectal bleeding
mucosal discharge
anterior rectal wall lesions
Inflammatory Polyps
what is this?
what are the histological characteristics?
Peutz-Jegher polyp
the polyp surface overlies stroma composed of smooth muscle bundles cutting through lamina propria with a complex glandular architecture
Peutz-Jegher Syndrom
age at onset:
Mutated genes
extra GI manifestations:
Peutz-Jegher Syndrom
age at onset: 10-15
Mutated genes: AD of LKB1/STK11
extra GI manifestations: mucocutaneous hyperpigmentation and an increased risk of pancretic, breast, lung, ovarian, uterus, testicle, and sex-cord stromal tumors
What is this?
What are the characteristic histological findings?
Juvenile Polyps
Surface erosion and cystically dilated crypts
Inspissated mucus, neutrophils, and inflammatory debris can accumulate within the dilated crypts (bottom pic)
Juvenile Polyp
age at onset:
mutated gene:
extra GI manifestations:
What layers of the GI does the polyp affect?
Juvenile Polyp
age at onset: <5 yo
mutated gene: SMAD4, BMPR1A
extra GI manifestations: Pullmonary AV malformations and digital clubbing
The polyp is a focal malformation of the mucosal epithelium and the lamina propria
Cowden Syndrome
mutation:
what type of cancers are associated with Cowden Syndrome?
Cowden Syndrome
PTEN
25-50% increased risk for Breast CA
10% Thyroid
5-10% endometrial
PTEN mutation plus mental deficiencies
Bannaya-Ruvalcaba Syndrome
What is this?
Age at presentation?
significance?
Mutation?
Hyperplastic Polyp
usually benign and only discovered in the 6th decade of life. They are a result of decreased cell turnover and delayed shedding of surface epithelial cells leading to a piling up of goblet cells.
You must distinguish them from sessile serrated adenomas
BRAF (+)
What is the definition of an Adenoma?
An adenoma is a benign tumor formed from glandular structures in the epithelium
HNPCC
what pathway does it follow?
where does the cancer occur in the colon?
HNPCC
MSI pathway- mutations in the MMR
cancer is usually on the right side of the colon
Diagnosis is clinical based on family history and clinical information
Lynch Syndrome
how is the diagnosis made?
Lynch Syndrome is a genetic diagnosis based on the findings of defective MMR in the tumor and a germline mutation in one of the MMR genes
What tests can we do in the molecular diagnosing of Lynch Syndrome?
DNA- sequencing or PCR of microsatellites
Protein Levels- immunohistochemistry
What is the significance of finding microsatellite instability?
- identifies other family members at risk
- changes the surveilance strategy
- colon cancer- begin colonoscopy at 20-15 yrs
- look for endometrial and ovarian cancers
- prophylatic hysterectomy and BSO is a risk reducing option
Visceral malignancy (GI or GU)
AND
sebaceous neoplasm of the skin
Variant of the HNPCC called Muir-Torre Syndrome
Combination of colorectal cancer
and
GLIOBLASTOMA
Variant of HNPCC
Turcot syndrome
Familial Adenomatous Polyposis follows what pathway?
what is the inheritance pattern?
what is mutated?
FAP follows the Adenoma- Carcinoma sequence (Chromosomal instability Pathway)
the inheritance is AD
APC gene is mutated
sometimes the MUTYH gene
Colorectal Cancer
plus
Medulloblastoma
Turcot Syndrome but its a varient of FAP
colorectal cancer, and desmoid tumors, and lipomas, epidermoid cysts, osteomas, gastric polyps, nasopharyngeal angiofibromas
Gardner syndrome
a varient of FAP
What is the mutation is associated with the MSI pathway?
an aquired or inherited mutation of the mismatch repair genes
this will change the number of microsatellites produced in the cell.
The mutations accumulate in genes that regulate cell growth, proliferation, and differentiation including TGFß and BAX
The picture on the right is what?
It occurs in what pathway?
this type of cancer is usually found on what side of the colon?
The picture on the right is of signet rings in the extracellular mucin
they appear in the MSI pathway
Cancers associated with the MSI pathway usually occur on the right side of the colon
The MSI pathway usually affects what side of the colon?
what are some signs and symptoms of these types of cancers?
MSI pathway usually affects the right side of the colon.
Pts will often complain of fatigue and weakness due to iron deficiency anemia
In sporadic forms of Colon Canccer with Microsatellite instabaility, what is silenced and how?
CpG islands are silenced by hypermethylation in the promotor regions of the MMR genes in sporadic forms of colon cancer with MSI
The adenoma-carcinoma (chromosomal instability pathway) usually affects what side of the colon?
what are some signs and symptoms of this type of cancer?
The adenoma-carcinoma pathway (APC mutations) usually affects the Left side of the colon.
patients will complain that their stool is thinner (decreased caliber) secondary to “napkin-ring” constriction. They may experience cramping in the LLQ. The pt may also have occult bleeding
