Large Intestine I

Question 1

What is this?

what are the characteristic features?

What is it caused by?

Answer 1

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

Question 2

the clinical triad of presentation:

rectal bleeding

mucosal discharge

anterior rectal wall lesions

Answer 2

Inflammatory Polyps

Question 3

what is this?

what are the histological characteristics?

Answer 3

Peutz-Jegher polyp

the polyp surface overlies stroma composed of smooth muscle bundles cutting through lamina propria with a complex glandular architecture

Question 4

Peutz-Jegher Syndrom

age at onset:

Mutated genes

extra GI manifestations:

Answer 4

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

Question 5

What is this?

What are the characteristic histological findings?

Answer 5

Juvenile Polyps

Surface erosion and cystically dilated crypts

Inspissated mucus, neutrophils, and inflammatory debris can accumulate within the dilated crypts (bottom pic)

Question 6

Juvenile Polyp

age at onset:

mutated gene:

extra GI manifestations:

What layers of the GI does the polyp affect?

Answer 6

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

Question 7

Cowden Syndrome

mutation:

what type of cancers are associated with Cowden Syndrome?

Answer 7

Cowden Syndrome

PTEN

25-50% increased risk for Breast CA

10% Thyroid

5-10% endometrial

Question 8

PTEN mutation plus mental deficiencies

Answer 8

Bannaya-Ruvalcaba Syndrome

Question 9

What is this?

Age at presentation?

significance?

Mutation?

Answer 9

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 (+)

Question 10

What is the definition of an Adenoma?

Answer 10

An adenoma is a benign tumor formed from glandular structures in the epithelium

Question 11

HNPCC

what pathway does it follow?

where does the cancer occur in the colon?

Answer 11

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

Question 12

Lynch Syndrome

how is the diagnosis made?

Answer 12

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

Question 13

What tests can we do in the molecular diagnosing of Lynch Syndrome?

Answer 13

DNA- sequencing or PCR of microsatellites

Protein Levels- immunohistochemistry

Question 14

What is the significance of finding microsatellite instability?

Answer 14

1. identifies other family members at risk
2. changes the surveilance strategy
   
   1. colon cancer- begin colonoscopy at 20-15 yrs
3. look for endometrial and ovarian cancers
   
   1. prophylatic hysterectomy and BSO is a risk reducing option

Question 15

Visceral malignancy (GI or GU)

AND
sebaceous neoplasm of the skin

Answer 15

Variant of the HNPCC called Muir-Torre Syndrome

Question 16

Combination of colorectal cancer

and

GLIOBLASTOMA

Answer 16

Variant of HNPCC

Turcot syndrome

Question 17

Familial Adenomatous Polyposis follows what pathway?

what is the inheritance pattern?

what is mutated?

Answer 17

FAP follows the Adenoma- Carcinoma sequence (Chromosomal instability Pathway)

the inheritance is AD

APC gene is mutated

sometimes the MUTYH gene

Question 18

Colorectal Cancer

plus

Medulloblastoma

Answer 18

Turcot Syndrome but its a varient of FAP

Question 19

colorectal cancer, and desmoid tumors, and lipomas, epidermoid cysts, osteomas, gastric polyps, nasopharyngeal angiofibromas

Answer 19

Gardner syndrome

a varient of FAP

Question 20

What is the mutation is associated with the MSI pathway?

Answer 20

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

Question 21

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?

Answer 21

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

Question 22

The MSI pathway usually affects what side of the colon?

what are some signs and symptoms of these types of cancers?

Answer 22

MSI pathway usually affects the right side of the colon.

Pts will often complain of fatigue and weakness due to iron deficiency anemia

Question 23

In sporadic forms of Colon Canccer with Microsatellite instabaility, what is silenced and how?

Answer 23

CpG islands are silenced by hypermethylation in the promotor regions of the MMR genes in sporadic forms of colon cancer with MSI

Question 24

The adenoma-carcinoma (chromosomal instability pathway) usually affects what side of the colon?

what are some signs and symptoms of this type of cancer?

Answer 24

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

Question 25

A squamous cell carcinoma of the anal canal will be located ______ the pectinate (dentate) line?

Answer 25

A squamous cell carcinoma of the anal canal will be located below the pectinate (dentate) line?

Below the pectinate line the epithelium is squamous cell.

Above the pectinate line the epithelium is columnar epithelium so the tumor will be called

Question 26

HPV is frequently associated with what type of tumor?

Answer 26

Pure squamous cell carcinomas of the anal canal are frequently associated with HPV