Module 2: Crohn's, Ulcerative colitis, Juvenile Polyp, Neoplastic, FAP, HNPCC, Carcinoid

Question 1

Now moving onto the inflammatory bowel diseases. The first disease to discuss is Crohn’s Disease/Terminal ileitis/Regional enteritis/Granulomatous Colitis. What is the etiology?

Answer 1

Etiology: Diagnosis of exclusion

• -most common is Ashkenazi Jews (due to imbreding in the past and Young Adults
• -Pre-disposing factors: genetic predisposition, abnormal host reactivity (autoimmune destruction by CD4 T cells) and microbial infections
• more common in women and has a bimodal distribution in terms of age (young adults and older females)

Question 2

What is the pathogenesis for Crohn’s?

Answer 2

Chronic, transmural inflammation with non-caseating granulomas which can affect anywhere from the mouth to the anus

• -Produces SKIP lesions (not continous therefore not able to be fixed by sx)
• –Most common location: terminal ileum and proximal colon (but can happen anywhere)
• -Typically spares the rectum

Question 3

What is the presentation for Crohn’s?

Answer 3

Fever 
Abdominal Pain 
Bloody/watery diarrhea 
--blood = colon 
---watery = small bowel 
Weight loss 
Malabsorption 
Steatorrhea

Question 4

What is seen on gross, barium enema and biopsy for Crohn’s patients? (pic 15a&b)?

Answer 4

Gross: Linear and serpentine ulcers with cobblestoning and creeping fat (due to fibrosis and the mesenteric fat coming over the serosa), skip lesions, transmural
Biopsy: pic to left: transmural so there is mucosal ulceration and lots of CD4 T cells within lamina propria all the blue dotted cells, PMNs, submucosa (fibrosis and fibroblasts), muscularia propria (thickening and fibrosis) and in serosa = non caseating granulomas
pic to right: blue dotted cells higher mag are lymphocytes aggregates of CD4 T cells, swallow and then deep ulcers (Also called fissures), blood vessels (angiogenesis and type III collagen)
Barium: See a string sign (that is due to luminal narrowing due to fibrosis) (pencil stools)
–note do the colonoscopy during remission not during an acute on chronic flare

Question 5

What extraintestinal manifestations are seen with Crohn’s patients?

Answer 5

Eyes (uveitis and iritis)
Skin (erythema nodusum and pyoderma gangrene)
Joints (Arthritis)
Kidney ( stones — oxilic)
Cholesterol gallstones ( bile salt absorption problems in terminal ileum)

Question 6

What are the complications of Crohn’s?

Answer 6

Colon Cancer — Adenocarcinoma
Colon Obstruction — due to strictures (Seen in pic), perforation
Malabsorption of iron, bile salts, water and B12 aka everything
Toxic Megacolon – exposing meisners and auerbach’s plexus
Perianal Abscesses: sterile abscess

Question 7

What is the treatment for Crohn’s Disease?

Answer 7

Immunosuppressive Therapy

–surgery does not work due to skipping and recurrence

Question 8

Now onto Ulcerative Colitis. What is the etiology for this?

Answer 8

Etiology: Idiopathic
–most common in Ashkenazi Jews
Pre-Disposing factors: Genetic, microbial infection, abnormal post reactivity (autoimmune destruction by CD4 T cells)
–bimodal distribution and more common in females
–associated with HLA-DRB1

Question 9

What is the pathogenesis for Ulcerative Colitis?

Answer 9

Starts in the rectum (proctitis) and moves proximally and goes to distal part of ileum (Backwash ilitis)

• –no skipped lesions (so curable)
• -spares the anus
• -not transmural just mural (First two layers)

Question 10

What is the presentation for patients with Ulcerative Colitis?

Answer 10

Fever 
Abdominal Pain 
Bloody Diarrhea 
Weight Loss 
Acute on chronic inflammation

Question 11

On histology and gross image slide 16a,b what is seen in Ulcerative Colitis ?

Answer 11

Gross: no skip lesions; pseudopolyps on gross (due to regenerating mucosa)
Colonoscopy with biopsy: Mucosa CD4 T cells, abnormal morphology of crypts, ulceration of mucosa, granulation tissue and fibrosis of submucosa. (no granulomas thats Crohns)
16b: crypt abscesses with neutrophil exudate in the lumen of the crypts
PSC: periductal onion skining fibrosis and beaded appearance of biliary tree

Question 12

On barium enema what do you see in Ulcerative Colitis?

Answer 12

Lead pipe appearance

–loss of hostra

Question 13

What are the extraintestinal manifestations of Ulcerative Colitis?

Answer 13

Crohn’s manifestions + Primary sclerosis cholangitis

• -in biliary tract they get PSC (fibrosis in the biliary tree of both the intra and extra hepatic bile ducts, so what backs up is conjugated bilirubin so you get jaundice)
• -only time you will see jaundice in Ulcerative Colitis
• -PSC also causes malabsorption and PANCA positive

Question 14

What are additional complications of Ulcerative Colitis besides Primary Sclerosis Cholangitis?

Answer 14

Colon Cancer (After about 10 years with dysplastic crypts as the precursor lesion)
Toxic Megacolon (damages meisners plexus) — peritonitis
Vit A,D,E,K deficiency due to malabsorption during PSC
PCS – malabsorption – osteomalacia
Liver Cancer — hepatocellular carcinoma

Question 15

Now moving onto GIT polyps, the most common in children is Juvenile Polyp or Retention Polyp. what is the etiology?

Answer 15

Seen in children under 5

• -Juvenile Polyposis syndrome (AD): leads to increased risk of malignancy in other areas
• -Single, sporadic poly however had no malignant potential (No dysplastic features): lobulated with stalk

Question 16

What is seen on histology for Juvenile Polyp?

Answer 16

Lamina Propria forms the bulk and encloses abundant cystically dilated glands
(+ or - inflammatory cells)

Question 17

The next GIT poly is Peutz Jegher’s Polyp or Hammartomatous Polyp. What is the etiology/pathogenesis for this?

Answer 17

Peutz Jegher (AD BLK1 mutation)

• -Multiple polyps in entire GI tract
• -Melanotic Pigmentation of lips (black), peri-oral areas, face, genitalia and uterus

Question 18

What is seen on histology for Peutz Jegher Polyp?

Answer 18

Arborizing network of smooth muscle extending into the polyp intermixed

• -glands are lined by non-dysplastic epithelium rich in goblet cells
• -no malignant potential in the colon, can have carcinomas in other places though

Question 19

Next topic is Carcinoid Tumors. Most commonly found where? And what are the origin in cells?

Answer 19

Submucosa of the small bowel and appendix
–Origin: enterochromaffin/Kuchitsky/neuroendocrine cells
–same origin as small cell carcinoma of the lung
Appendix tumors usually benign and Small bowl usually malignant (non specific abd pain/mass)
small bowel more common then appendix

Question 20

What are the three different types of Carcinoid Syndrome?

Answer 20

Type I: Autoimmune Chronic Gastritis and Achlorhydria (decreased acid)
—hypergastrinemia due to ECL cell hyperplasia
–Usually benign
Type II: Zollinger-Elison Syndrome: gastrinoma in the pancreas
—usually in men1
—Hypergastrinemia: due to increased acid and no negative feedback leading to multiple large duodenal ulcers (partial cells)
Type III: Malignant: very aggressive and sporadic
–mets to liver and will do carcinoid syndrome

Question 21

What is the best investigation for carcinoid tumor? (Slide 17)

Answer 21

Biopsy: sheets of uniform cells with stippled oval nuclei and salt and pepper appearance in the submucosa

Question 22

What is seen in the urine for Carcinoid tumor and what are the tumor markers?

Answer 22

Urine: 5-HIAA

Tumor Markers: synaptophysin, chromogranin and CD56 (All for confirmation)

Question 23

One complication of Carcinoid syndrome, explain the pathogenesis for this

Answer 23

Only happens when there is metastasis to the liver or cirrhosis of the liver b/c normal liver can metabolize serotonin but damaged liver can not.
–Present with: episodic flushing, diarrhea and wheezing

Question 24

What are additional complications of Carcinoid syndrome?

Answer 24

Metastasis: regional lymph nodes, liver, ovaries, peritoneum and spleen
Fibrosis (Due to increased collagen) of the right sided heart valves (tricupsid and pulmonary)
–not on left side due to lack of bio-amines on left side

Question 25

Next topic to discuss is Neoplastic Polyps (adenomas). What are the two types?

Answer 25

Pedunculated: stalk (pic on right 18) and sessile (pic to left 18) (Described as cauliflower)

Question 26

What is the most common location of these Neoplastic Polyps?

Answer 26

Colon (Can be left or right sided)

Question 27

Describe some features of the Neoplastic Masses

Answer 27

Both are Benign but have dysplastic lining the glands
–lined by tall, hyperchromatic and disordered epithelium
Pedunculated: tubular adenoma (has a stalk and can cause obstruction)
Sessile: villous adenoma (flat and therefore more dangerous) (Secretes mucus)

Question 28

How does a patient present with Neoplastic Polyps?

Answer 28

Asymptomatic commonly

• -incidental finding on colonoscopy
• -Rarely: bleeding, obstruction, bloody diarrhea, and mucoid diarrhea

Question 29

what do you see on biopsy for Neoplastic Polyps? slide 18b

Answer 29

Tubular Adenoma (pedunculated): on left: adenoma means benign tumor of glands and is lined by dysplastic glands and thats why it becomes cancer (Not yet cancer in pic because its still on mucosal surface) 
Sessile Polyp (on right): finger like projections (Villous adenoma) lined by dysplastic cells but again still benign

Question 30

What are complications of these Neoplastic Polyps?

Answer 30

Intestinal obstruction 
Bloody diarrhea ( iron deficiency anemia) 
mucoid diarrhea (hypokalemia and hypoalbuminemia)

Question 31

What are the three factors that lead to increased malignant potential?

Answer 31

Size: greater than 2cm
Villous Architecture (aka sessile)
Degree of Dysplasia

Question 32

The last topic dealing with multiple polyps (polyposis) is FAP. what is the etiology for FAP?

Answer 32

Genetic AD

• -2 hits on APC gene (tumor suppressor gene) only born with one hit and later in life you get the second hit and this second hit leads to multiple polyps.
• -mutation in KRAS — mutation in p53 — adenocarcinoma

Question 33

What are some features of FAP?

Answer 33

Left side of colon
Asymptomatic
Start screening at age of 12 if there is a family history of left sided colon cancer at a young age
–later stages: bright red blood and mucoid diarrhea (intestinal obstruction and LLQ pain)

Question 34

What kind of polyps are present in FAP?

Answer 34

Pedunculated, benign polyps (tubular adenoma on histology)

• -100% chance of becoming malignant with KRAS (proto oncogene so 1 hit) or p53 mutation (tumor suppressor gene)
• -follows the beta catenin pathway

Question 35

What are the complications for FAP?

Answer 35

Diameter of left colon is smaller — napkin ring constriction – intestinal obstruction

Question 36

What is Gardner’s Syndrome?

Answer 36

FAP + multiple osteomas + desmoid tumors and epidermal cysts

Question 37

What is Turcot’s Syndrome?

Answer 37

FAP + CNS glioma (medullablastoma in kids)

Question 38

Finally lets finish this section with a discuss on HNPCC/Lynch Syndrome. What are some features?

Answer 38

Few polyps but on the right side
Gross: sessile serrated morphology —- villous adenocarcinoma because it goes straight to cancer (no benign polyps) (invades submucosa and muscularis propria)
–Exophytic mass
–DNA mismatch repair genes (MLH1,MSH2,MSH6,PMS2)
–microsatellite instability: start screening at 25

Question 39

What do patients present with who have HNPCC?

Answer 39

Initially no symptoms because of occult bleeding, fatigue and iron deficiency anemia due to chronic blood loss
—Older male and post menopausal women think right sided colon cancer

Question 40

What is the spread of HNPCC?

Answer 40

Lymph nodes, liver, and then lungs