GI Pathology: Colon Cancers and Polyps - USE THIS ONE

What are the 3 types of colonic polyps

inflammatory pseudopolyps

hamartomatous polyps

epithelial polyps

The following describes what type of polyp

-intraluminal projections of mucosa that are formed of a non-neoplastic mixture of stomal and epithelial components and inflammatory cells

Inflammatory pseudopolyps

What causes Inflammatory pseudopolyps

result from recurrent cycles of injury and healing

Inflammatory pseudopolyps usually develop in what diseases

Crohn's

UC

Ischemic colitis

Other inflammatory states

What polyps are associated with Peutz-Jeghers syndrome and juvenile polyposis

hamartomatous polyps

Large hamartomatous polyps can cause what

intussusception

The following describes what type of polyp

-polyps contain submucosa and have arborizing pattern

hamartomatous polyps

The following describes what type of hamartomatous polyps

-fairly large (up to 3 cm)

-pedunculated polyps

Juvenile polyps

Juvenile polyps (hamartomatous polyps) occur where

almost exclusively in the colon/rectum

-rectosigmoid most common

Juvenile Polyposis Syndromes carry an increased risk of

colorectal and upper GI tract carcinomas

Where is the most common place for Peutz-Jegher-type polyps to occur

can occur throughout GI tract, but small intestine most common

Describe Petuz-Jegher polyps

-similar to juvenile polyps

-exhibit distinctive arborizing pattern with smooth muscle present in the core of the polyp

The following describes what

-rare, autosomal dominant disorder

-multiple hamartomatous polyps

-mucocutaneous pigmentation (especially facial: lips, nostrils, buccal mucosa)

-finger clubbing

Peutz-Jegher syndrome

What is the inheritance pattern of Peutz-Jegher syndrome

autosomal dominant

What is Peutz-Jegher syndrome

autosomal dominant disorder characterized by

-multiple hamartomatous polyps

-mucocutaneous pigmentation (especially facial: lips, nostrils, buccal mucosa)

-finger clubbing

Up to 70-80% of patients with Peutz-Jegher syndrome have germline loss of function mutations of what

tumor suppressor gene STK11 (know this)

Loss of function mutations of tumor suppressor gene STK11 increases risk of what

several malignancies

-gut

-pancreas

-breast

-lung

-also seen in 70-80% pts with Peutz-Jegher syndrome

What are the 3 epithelial polyps? What is the malignant potential of each?

Hyperplastic polyp = no malignant potential

Serrated polyp = premalignant

Adenomatous = high risk premalignant

The following describes what type of epithelial polyp

-small (<5 mm) without malignant potential

-found in the left colon and rectum

Hyperplastic polyp

What is the most common type of polyp

Hyperplastic polyp

Where are hyperplastic polyps found

left colon and rectum

The following describes what type of epithelial polyp

-larger polyps

-typically in right colon

-have malignant potential

-can progress to cancer through the DNA mismatch repair pathway

Serrated polyps

Where are serrated polyps found

Right colon

How do serrated polyps progress to cancer

through the DNA mismatch repair pathway

-leading to microsatellite instability and BARF mutations

The following describes what type of epithelial polyp

-precursors to the majority of colorectal carcinomas

-progress to malignancy through the APC pawthway

Adenomatous polyps

What are malignancy risk factors for adenomatous polyps

-size (>4 cm = >40% risk of carcinoma)

-morphology (tubular vs. villous and pedunculate vs. sessile)

What are the 3 main morphologies of adenomatous polyps? What is the malignant potential of each?

Tubular = less of a malignant potential

Tubulovillous = medium

Villous = highest malignancy risk

What type of adenomatous polyp has the greatest risk for progression from ademona to carcinoma

Villous polyps

What polyps progress to malignancy through the APC pathway (chromosomal instability pathway)

adenomatous polyps

What polyps progress to malignancy through the DNA mismatch repair pathway

serrated polyps

The following describes what type of adenomatous polyp

-smaller

-pedunculated

-carry less of a malignant potential

Tubular polyp

The following describes what type of adenomatous polyp

-larger

-typically sessile

-have greatest risk for progression to carcinoma

villous polyp

The following describes what type of adenomatous polyp

-contain mixture of tubular and villous elements

tubulovillous polyp

What is Familial Adenomatous Polyposis (FAP)

autosomal dominant disorder caused by germ-line mutation of APC gene, so only 1 hit is required for the carcinoma to deveop

The following describes what disorder

-usually manifests in adolescence with more than 100 colonic adenomatous polyps (carpet of polyps)

Familial Adenomatous Polyposis (FAP)

disorder caused by germ-line mutation of APC gene

Familial Adenomatous Polyposis (FAP)

What is the treatment for Familial Adenomatous Polyposis (FAP)

prophylactic colectomy (will 100% develop colon cancer)

What is Gardner syndrome

a subset of Familial Adenomatous Polyposis (FAP)

-colonic ademonas

-pts may develop multiple osteomas, epidermal cysts, fibromatosis, abnormal dentition, and increased incidence of duodenal and thyroud cancers

The following describes what syndrome

besides adenomas, pts. may develop the following

-multiple osteomas

-epidermal cysts

-fibromatosis

-abnormal dentition

-increased incidence of duodenal and thyroid cancers

Gardner syndrome

What is Hereditary Non-Polyposis Colorectal Cancer (HNPCC; Lynch syndrome)

autosomal dominant disease caused by mutations in genes encoding proteins responsible for DNA repair

The majority of Hereditary Non-Polyposis Colorectal Cancer (HNPCC; Lynch syndrome) cases involve what genes

MSH2 and MLH1 (know these)

-pt will inherit one defective copy. losing copy leads to micro satellite instability

What is the most common form of hereditary colon cancer

Hereditary Non-Polyposis Colorectal Cancer (HNPCC; Lynch syndrome)

Hereditary Non-Polyposis Colorectal Cancer (HNPCC; Lynch syndrome) has a predominance for cancers on what side of the colon

Right sided cancers

The following describes what

-characterized by the development of colon cancer at an early age

-predominance of right-sided cancers

-cancers are often poorly differentiated

-extracolonic malignancies also occur in a subset of patients

Hereditary Non-Polyposis Colorectal Cancer (HNPCC; Lynch syndrome)

What is Turcot syndrome

Variant of Hereditary Non-Polyposis Colorectal Cancer (HNPCC; Lynch syndrome)

Characterized by

-adenomas

-predisposition to the development of brain tumors

-associated with Lynch syndrome or FAP

The following describes what

-Characterized by

-adenomas

-predisposition to the development of brain tumors

-associated with Lynch syndrome or FAP

Turcot syndrome (variant of HNPCC)

What is the most common GI malignancy

adenocarcinoma

What is the 3rd leading cause of cancer death in men and women

adenocarcinoma

What are risk factors for adenocarcinoma

-diets high in fats and refined carbs

-low in vegetable fiber and antioxidants

-alterations in GI flora

-inherited syndromes (FAP and HNPCC)

-IBD

All adenocarcinomas arise from

neoplastic polyps

What are the 2 major pathways for the development of colorectal adenocarcinomas

chromosomal instability pathway

microsatellite instability pathway

The following describes what

-pathway involving APC gene mutations affecting the Wnt signaling pathway

-accounts for 80% of sporadic colon carcinomas

-type occurs more frequently on the left colon and rectum

-pts typically present with LLQ pain, rectal bleeding, and decreased stool caliber (napkin ring lesion - "apple core" sign on x-ray)

chromosomal instability pathway

What is the chromosomal instability pathway

pathway involving APC gene mutations

affects the Wnt signaling pathway

accounts for 80% sporadic colon carcinomas

chromosomal instability pathway carcinomas typically occur where in the colon

left colon and rectum

The following describes the presentation of a colon carcinoma made by what pathway

-LLQ pain

-rectal bleeding

-decreased stool caliber

chromosomal instability pathway

Napkin ring lesion aka apple core sign on x-ray is indicative of what

colon carcinoma caused by the chromosomal instability pathway (APC pathway)

Describe the progression of genes affected in the chromosomal instability pathway

1. Loss of APC (requires 2 hits)

-beta-catenin accumulates, translocated to the nucleus, and activates a set of genes that promote proliferation of epi cells

2. Late KRAS (proto-oncogene) mutation

-promote cell growth and division

3. P53 (tumor suppressor) + DCC (deleted in colorectal cancer)

-P53 prevent apoptosis

-DCC (tumor suppressor) disrupt apoptosis pathway

What pathway accounts mostly for tumors arising from sessile serrated polyps, particularly those occurring in the right colon

Microsatellite instability pathway

The microsatellite instability pathway accounts mostly for what type of tumors that occur where

-sessile serrate polyps

-right colon

Polyps that come from what pathway grow as raised lesion that is non-obstructive

microsatellie instability pathway

Polyps that come from the microsatellite instability pathway grow as what

raised lesions that are non-obstructive

Pts. with polyps that come from the microsatellite instability pathway typically present how

with iron deficiency

-no fresh blood in the stool

The underlying genetic defect in the microsatellie instability pathway is

a mutation in one of 5 mismatch repair genes

-MSH2

-MLH1

The following describe what? Name 2

-are responsible for fixing errors in base pair mismatches anywhere in our DNA

-if these are mutated or non-functional, this failure to correct base pair mismatches leads to malignant proliferation of colonic epithelium

Mismatch repair genes

-MSH2

-MLH1

Iron deficiency anemia in a post-menopausal female or adult male without any eating disorder or malabsorption syndrome is what until proven otherwise

colon cancer

Colonic carcinoma is associated with an increased risk for

Streptococcus bovis endocarditis/bacteremia

What is the most common site of metastasis of colonic cancer

liver

Neuroendocrine tumors of the GI tract are derived from

enteroendocrine cells

Neuroendocrine cells typically form

rosettes

What tumors stain positively for chromogranin and synaptophysin

Neuroendocrine tumors

Neuroendocrine tumors stain positively for

chromogranin and synaptophysin

Electron microscopy shows what when looking at neuroendocrine tumors

dense-core granules

The following describes what

-low-grade malignancy that produces serotonin

-most common location is small intestine, but can arise anywhere in the intestine and lung

Carcinoid tumor

What is a Carcinoid tumor

a type of neuroendocrine tumor

-low grade malignancy that produces serotonin

-most common location is small intestine, but can arise anywhere in the intestine and lung

-serotonin produced by the tumor is normally metabolized in the liver by monoamine oxidase (MAO)

-metastasis of the tumor to the liver allows serotonin to bypass liver leak into systemic circulation in carcinoid syndrome

The following describes what? What causes the symptoms discussed

-characterized by bronchospasm, diarrhea, and flushing of skin

-symptoms can be triggered by alcohol or emotional stress

Carcinoid syndrome

Symptoms can be triggered by alcohol or emotional stress, which stimulate serotonin release from the tumor

What causes carcinoid syndrome

Metastasis of a carcinoid tumor to the liver

-allows serotonin to bypass the liver (which has MAO that metabolized serotonin) and leak into systemic circulation causing the syndrome

The following describes what

-characterized by RIGHT-sided valvular fibrosis (increased collagen)

-leads to tricuspid regurgitation and pulmonary valve stenosis

-left sided valvular lesions are not seen

Carcinoid heart disease

Why are left sided valvular lesions not seen in carcinoid heart disease?

monoamine oxidase (metab serotonin) is found in the lungs

the serotonin is sent from the right heart to the lungs, where serotonin is metabolized, and then the blood returns with metabolized serotonin to the left heart --> no left sided symptoms

Carcinoid heart disease is characterized by ______-sided valvular fibrosis

right

What is zollinger-ellison syndrome? What is the presentation of ZE?

results from a gastrin-secreting (G cell) tumor (gastrinoma) in either the pancreas or small intestine

presentation

-peptic ulcer disease

-ulcers in duodenum and JEJUNUM

Zollinger-Ellison syndrome may be associated with

MEN 1 (multiple endocrine neoplasia I)

Where to peptic ulcers present in pts with ZE

JEJUNUM and duodenum

What is an insulinoma

tumor of the pancreatic B cells. Overproduction of insulin results in hypoglycemia

What is a glucagonoma

tumor of pancreatic A cells. Overproduction of glucagon causes diabetes. Patients also present with dermatitis (necrolytic migratory erythema) and DVT

What dermatitis do pts with a glucagonoma present with?

Necrolyticc migratory erythema

What dermatitis do people with Crohn's present with

erythema nodosum

What dermatitis do people with UC present with

pyoderma gangrenosum

What is a somatostatinoma

tumor of pancreatic D cells. Overproduction of somatostatin causes decreased production of

-secretin

-CCK

-glucagon

-insulin

-gastrin

May present with diabetes/glucose intolerance, steatorrhea, gallstones, and achlorhydria

People with an insulinoma present with what

hypoglycemia

People with a glucagonoma present with what

diabetes

also dermatitis (necrolytic migratory erythema)