Histopathology - Upper + Lower GI pathology

Question 1

Hirschsprung’s disease biopsy findings

Answer 1

Hypertrophied nerve fibres but no ganglia

Question 2

Where is volvulus more likely to occur in
children
eldelry

Answer 2

children - small bowel

elderly - sigmoid colon

Question 3

Where does diverticular disease occur more commonly?

Answer 3

90% occur in L colon

Question 4

How does diverticular disease present in endoscopy

Answer 4

empty spaces - look at photo in lecture

Question 5

Secretory diarrhoea vs exudative diarrhoea

Answer 5

secretory - toxin

exudative - invasion + mucosal damage

Question 6

Histology of pseudomembranous colitis

Answer 6

Volcanic eruption of pus coming from the surface of the bowel at the mucosa

Question 7

C. diff mx

Answer 7

Metronidazole (1)

Vancomycin (2)

Question 8

Where is ischaemic colitis more likely to occur?

Answer 8

In watershed zones

Splenic flexure (SMA + IMA)
Rectosigmoid (IMA + internal iliac artery)

Question 9

CD pathology

Answer 9

 Whole GIT can be affected (mouth to anus) – most common in terminal ileum + caecum (R side)

 Skip lesions  cobblestone appearance

 Transmural inflammation – entire thickness of the bowel wall

 Non-caseating granulomas – collections of macrophages but not necrotic or caseating (bottom L)
 Sinus/fistula/fissure formation common

Question 10

CD extra-intestinal manifestations

Answer 10

Arthritis
Uveitis
Stomatitis/ cheilitis

Skin

• Erythema nodosum
• Erythema multiforme
• Pyoderma gangrenosum

Question 11

UC

Answer 11

Slightly more common than CD

Superficial inflammation confined to the mucosa
Bowel wall normal thickness
No granulomas
No abscesses/fissures/fistulae

Shallow ulcers
Pseudopolyps (islands of regenerating mucosa bulge into the lumen - can fuse to form mucosal bridges)

May see backwash ileitis + appendiceal involvement

bloody diarrhoea + mucus
crampy abdo pain relieved by defecation

Question 12

Which conditions is UC associated with?

Answer 12

PSC

Adenocarcinoma

Toxic megacolon

Question 13

UC mx

o Mild
o Moderate
o Severe
o For remission

Answer 13

o Mild – prednisolone + mesalazine (5 ASA)

o Moderate – prednisolone + 5- ASA + steroid enema BD

o Severe – admit, NBM, IVF, IV hydrocortisone, rectal steroids

o For remission – all 5-ASA (1st line), azathioprine (2nd line)

Question 14

Carcinoid syndrome vs carcinoid crisis

Answer 14

Syndrome

• Bronchoconstriction
• Flushing
• Diarrhoea

Crisis

• Vasodilation
• Hypotension
• Tachycardia
• Bronchoconstriction
• Hyperglycaemia

caused by endochromaffin cell tumours which produce 5-HT commonly found in the bowel

Ix - 24h urine 5-HIAA (main metabolite of serotonin)
Mx - octreotide

Question 15

Adenomas - RF for cancer

Answer 15

• Large adenoma (most important RF)
• Increased villous component
• Dysplasia

Question 16

Tubular adenoma vs villous adenoma macroscopic appearance

Answer 16

Look at pics on ppt (week 15)

Villous adenoma looks like a line of test tubes

Question 17

How does an adenoma progress to a carcinoma?

Answer 17

o Normal colon  at risk mucosa after “first hit” mutation in 1st copy of APC (adenomatous polyposis coli) gene (those with FAP are born with this mutation)

o At risk  adenocarcinoma after “second hit” mutation remaining APC gene

o Progression to carcinoma follows activation of
KRAS
LOF
Mutations of p53

Question 18

Peutz Jeghers mutation

Answer 18

AD

LKB1

Question 19

Familial syndromes implicated in lower GI disease

Answer 19

• Peutz Jeghers

• FAP – Familial adenomatous polyposis
o Gardner’s
o Turcot

• HNPCC – hereditary non-polyposis colon cancer

Question 20

FAP buzzwords

Answer 20

• FAP – Familial adenomatous polyposis

Chr 5q21 APC tumour suppressor gene

At birth –> hypertrophy of the retinal pigment epithelium

Young people getting colorectal cancer

At least 100 polyps required for dx
Average - 1000 polyps –> will develop into adenocarcinoma if not resected

Prophylactic colectomy

increased risk of cancer elsewhere - ampulla of Vater, stomach

Question 21

What is Gardner’s syndrome?

Answer 21

o Same clinical/pathological/etiologic features as FAP with high cancer risk

o Distinctive extra-intestinal manifestations
 Multiple osteomas of skull + mandible
 Epidermoid cysts
 Desmoid tumours
 Dental caries, unerupted supernumerary teeth
 Post-surgical mesenteric fibromatoses

Question 22

Most common hereditary colon cancer syndrome

Answer 22

HNPCC (hereditary non-polyposis colorectal cancer) / Lynch syndrome

Question 23

HNPCC vs FAP

Answer 23

HNPCC is more common

In HNPCC there are few polyps, in FAP there are at least 100

In HNPCC there are multiple synchronous cancers (endometrium, ovary, small bowel, prostate, breast)

In HNPCC the mutation is in the DNA mismatch repair genes, in FAP the mutation is in the APC tumour suppressor gene

Both syndromes –> onset of colorectal cancer at an early age

Question 24

Where are the carcinomas in HNPCC usually found?

Answer 24

R colon

proximal to the splenic flexure

Question 25

Where is the mutation HNPCC ?

Answer 25

DNA mismatch repair genes

Question 26

Which staging system is used to stage colorectal cancer? ``` A B1 B2 C1 C2 D ```

Answer 26

Duke's staging system A Limited to mucosa B1 Extends into muscularis propria, no lymph node involvement B2 Transmural extension, no lymph node involvement C1 Extends into muscularis propria + lymph node involvement C2 Transmural extension + lymph node involvement D Distant mets

Question 27

Colorectal cancer mx o Caecum, ascending colon, proximal transverse o Transverse colon o Descending colon + distal transverse o Sigmoid cancer o Rectal cancer/low sigmoid cancer  <1-2cm above anal sphincter (lower 1/3 of rectum)  >1-2cm above anal sphincter • If it’s a transmural invasion

Answer 27

o Caecum, ascending colon, proximal transverse  R hemicolectomy o Transverse colon  extended R hemicolectomy o Descending colon + distal transverse  L hemicolectomy o Sigmoid cancer  sigmoid colectomy o Rectal cancer/low sigmoid cancer  <1-2cm above anal sphincter (lower 1/3 of rectum)  abdomino-perineal resection  >1-2cm above anal sphincter  anterior resection • If it’s a transmural invasion you will likely get radiotherapy, chemotherapy + excision

Question 28

• What sort of colon polyps most commonly predispose to adenocarcinoma of the colon?

Answer 28

Adenomas

Question 29

What is the z line?

Answer 29

the point at which the epithelium of the oesophagus transitions from being squamous (proximal 2/3) to being columnar (distal 1/3)

Question 30

Where is H pylori gastritis usually found?

Answer 30

Antrum of the stomach + pyloric canal

Question 31

Difference between the body and the antrum of the stomach

Answer 31

glands in lamina propria body - specialised (secrete acid + enzyme, produce IF) No goblet cells* antrum - non-specialised, produce gastrin * goblet cells are present in the intestine therefore presence of goblet cells in the stomach is a feature of intestinal metaplasia

Question 32

Normal villus: crypt ratio

Answer 32

>2:1

Question 33

Layers of the oesophagus

Answer 33

o Epithelium  muscularis mucosa  submucosa with connective tissue + fat  muscularis externa (muscularis propria)

Question 34

Layers of the stomach

Answer 34

Mucosa (epithelium  lamina propria  muscularis mucosa)  submucosa  muscularis propria

Question 35

How would you describe the epithelium of the normal duodenum?

Answer 35

Glandular epithelium with goblet cells Villous: crypt ratio --> >2:1

Question 36

Ulcer vs erosion

Answer 36

Ulcer = through muscularis mucosa (into submucosa) Erosion = before muscularis mucosa, not past lamina propria (not into submucosa)

Question 37

What is Barret's oesophagus?

Answer 37

The same as columnar lined oesophagus (CLO) • Replacement of squamous epithelium by metaplastic columnar epithelium without goblet cells: gastric metaplasia (CLO) with goblet cells: intestinal type metaplasia (CLO with IM) Risk: can lead to adenocarcinoma (metaplasia -> dysplasia -> cancer)

Question 38

# Define metaplasia dysplasia cancer

Answer 38

1) Metaplasia = not pre-malignant because reversible (can progress to dysplasia)  (2) Dysplasia = changes showing some of the cytological and histological features of malignancy but with NO invasion through the BM (this is the stage that screening identifies at)  (3) Adenocarcinoma = abnormal cells invade through the BM

Question 39

2 pathways to development of GI cancer

Answer 39

 Adenoma-carcinoma pathway o Lower GI o Polyp pathway - adenomas becoming malignant  Metaplasia-Dysplasia patway o upper GI pathway o Oesophagitis/ chronic gastritis --.> Metaplasia (i.e. CLO ± IM) --> dysplasia --> cancer

Question 40

Defining feature of SCC of the oesophagus

Answer 40

cells from keratin (other histological features include: Invasion of the submucosa Cells have intracellular bridges)

Question 41

SCC vs adenocarcinoma of the oesophagus

Answer 41

SCC - Upper 2/3 of oesophagus (middle > lower > upper) - Developing countries - Smoking, Alcohol, HPV (16,18) Adenocarcinoma - lower 1/3 of oesophagus - Developed countries - GORD, Barrett's

Question 42

Histology of acute vs chronic gastritis

Answer 42

Acute = neutrophils Chronic = lymphocytes, plasma cells

Question 43

Causes of acute vs chronic gastritis

Answer 43

Acute Chemicals Infection ``` Chronic ABCD Autoimmune [body] Bacterial [antrum] Chemicals [antrum] IBD ```

Question 44

What does presence of lymphoid follicles in a stomach biopsy indicate?

Answer 44

 Highly suggestive that the patient has had an H. pylori infection (i.e. the presence of lymphoid follicles is not part of the normal stomach mucosa) H. pylori infection induces the development of lymphoid follicles in germinal centres --> MALT --> lymphoma o If someone has H. pylori as well as lymphoma, you will see crypts that are full of neutrophils  good because if you treat H. pylori, the lymphoma could be reversed

Question 45

Helicobacter strain associated with chronic inflammation + cancer

Answer 45

cag-A-positive H.pylori Needle like appendage --> injects toxin into intercellular junctions --> bacteria attach more easily

Question 46

2 types of cancer that arise from chronic stimulation by H pylori

Answer 46

* CLO-IM-Dysplasia in the stomach  Adenocarcinoma (atrophic) * Chronic infection  Lymphoma (MALToma) (non-atrophic)

Question 47

Types of ulcers in * Antrum-predominant gastritis * Body-predominant atrophic gastritis

Answer 47

* Antrum-predominant gastritis  duodenal ulcer | * Body-predominant atrophic gastritis  gastric ulcer

Question 48

Gastric ulcer mx

Answer 48

All ulcers should be biopsied to exclude malignancy

Question 49

Gastric vs duodenal ulcer

Answer 49

Gastric --> body of stomach, worse with food Most are caused by H. pylori Duodenal --> antrum of stomach, relieved with food Almost all are cause by H. pylori Duodenal ulcer 4x more common than gastric ulcer

Question 50

Why does gastric intestinal metaplasia happen?

Answer 50

In response to long term damage isn't cancerous/pre-cancerous but can lead to dysplasia + is associated with an increased risk of cancer in intestinal metaplasia there will be goblet cells

Question 51

Commonest type of gastric cancer

Answer 51

Adenocarcinoma

Question 52

Treatment of H pylori

Answer 52

CAP (Clarithromycin, Amoxicillin, PPI)

Question 53

What are the two types of gastric adenocarcinomas?

Answer 53

• Intestinal o Well-differentiated o Mucin-containing big glands o Big well-formed glands • Diffuse o Poorly differentiated o Individual cancerous cells spread throughout the stomach o Single cells with no attempt at gland formation o Types = Linitis plastica, Signet ring cell carcinoma (spreads all over stomach)

Question 54

What type of lymphoma is MALT

Answer 54

B cell NHL

Question 55

How does H. pylori cause duodenal ulcers?

Answer 55

Almost all duodenal ulcers are caused by H. pylori antrum predominant gastritis causes duodenal ulcers H pylori --> antral infection --> increased stomach acid production --> acid spills over into duodenum --> chronic inflammation --> gastric metaplasia of the duodenal epithelium --> gastric epithelium in the duodenum can now become infected with H. pylori --> duodenitis + ulcer

Question 56

Normal range of intraepithelial lymphocytes

Answer 56

<20 lymphocytes per 100 enterocytes

Question 57

Coeliac disease classic histology findings

Answer 57

Villous atrophy (flattening/flat) Normal villous: crypt ratio >2:1 Crypt hyperplasia Increased intraepithelial lymphocytes commonest cause = malabsorption o Lymphocytes in coeliac disease are the cells that are causing damage to the villi

Question 58

What is coeliac disease?

Answer 58

T cell mediated autoimmune disease Abnormal T cell response to gliadin DQ2 DQ8 HLA associations young children, Irish women

Question 59

Typical rash seen in coeliac disease

Answer 59

Dermatitis herpetiformis

Question 60

How do you diagnose coeliac disease?

Answer 60

Antibodies + imaging + biopsy Antibodies - Anti-Endomysial (best sensitivity + specificity) - Anti - TTG (also check IgA since these are IgA ab and IgA deficiency might give you a false negative result) - Anti-gliadin ab duodenal biopsy ON gluten free diet showing Villous atrophy (flattening/flat) Crypt hyperplasia Increased intraepithelial lymphocytes OFF gluten --> normal villi

Question 61

Most serious complication of coeliac disease

Answer 61

Enteropathy associated T cell lymphoma (EATL) type of NHL found in the duodenum (n.b. lymphomas in the stomach are due to H. pylori and are B cell lymphomas)

Question 62

• Most oesophageal and gastric cancers arise from pre-existing adenomas – yes or no

Answer 62

o No – most gastric + oesophageal gastric cancers arise from a flat dysplasia pathway – chronic inflammation  metaplasia  dysplasia  cancer o This statement would be true for colonic tumours (adenoma-carcinoma pathway)