Stomach, IBD, Malabsorption syndromes, polyps and colon cancer Flashcards
1
Q
Zones of ulcer
A
- Necrosis
- Inflammatory cells
- Granulation tissue
- Fibrosis
2
Q
Stomach ulcer (compared to duodenal ulcer)
A
- the less common peptic ulcer
- lesser curvature near incisura angularis
- poorer prognosis
- perforations more common
- no night pain
3
Q
Duodenal ulcer (compared to stomach ulcer)
A
- the more common peptic ulcer
- D1 zone
- better prognosis
- bleeding is more common
- night pain (relieved by food) is present
4
Q
Causes of acute gastritis
A
- Smoking🚬
- Aspirin and other NSAID
- Alcohol🍺
- Uremia
- Stress
5
Q
Type B chronic gastritis
A
M/C H. pylori associated Usually affects antrum H&E: Intraepithelial neutrophils and sub-epithelial plasma cells H. pylori strained by different stains
6
Q
H. pylori virulence factor
A
Gram negative bacteria with tuft of flagella at one end Only host is humans Virulence factors: 1. Flagella 2. Urease against acid 3. cag A and Vac A toxins - carcinogenic
7
Q
Diseases caused by H. pylori
A
- Chronic gastritis
- Gastric adenocarcinoma
- MALToma
8
Q
Stains used for H. pylori
A
- Warthin Starry silver stain
- Non silver stain:
• Giemsa stain
• Acridine orange
9
Q
Type A chronic gastritis
A
Autoimmune gastritis
Affects fundus, body; spares antrum
Clinically:
1. Pernicious anaemia
2. Increased risk of other autoimmune diseases
Gross: loss of rugal folds
H&E: infiltrate of lymphocytes and plasma cells
10
Q
Pathogenesis of type A chronic gastritis
A
- Antibodies against parietal cells and IF
- Reduced production of HCl, IF
- Hypergastrinemia
Also:
• Vit B12 absorption decreases ➡️ megaloblastic anaemia
• Chief cell destruction ➡️ reduced serum pepsinogen
11
Q
Risk factors for gastric adenocarcinoma
A
- Smoking 🚬
- H. pylori - antral
- Japanese people
- High intake of smoked fish
- Food rich in preservatives
- Blood group A
12
Q
Site of occurrence of gastric adenocarcinoma
A
Most common to least common
- Antrum
- Lesser curvature
- Greater curvature
13
Q
Lauren’s classification
A
Of gastric adenocarcinoma 1. Intestinal: Bulky polypoidal lesions 2. Diffuse: Infiltrative lesions Both presents as dyspepsia and gastritis
14
Q
Intestinal gastric adenocarcinoma
A
Bulky polypoidal lesions H&E: glands lined by malignant cells Better prognosis Pathogenesis: 1. Mutation in WNT pathway 2. p53 mutation 3. Loss of function in APC
15
Q
Diffuse type of gastric adenocarcinoma
A
Infiltrative lesion
H&E: mucin secretion and signet ring cell
Poorer prognosis
Pathogenesis:
CDH-1 gene mutation ➡️ loss of E-cadherin
16
Q
Linitis plastica
A
Leather bottle
Diffusely infiltrate the entire gastric wall without an intraluminal mass
Wall of stomach is thickened UTI 2-3 cm
Leathery and elastic consistency
Develops into desmoplasia (extreme fibrosis)
17
Q
Virchow’s node
Irish node
A
Virchow’s node is when left supraclavicular lymph node is affected and swollen
Irish node is when left axillary lymph node is affected
18
Q
Sister Mary Joseph’s nodule
A
Periumbilical nodule affected by gastric adenocarcinoma
19
Q
Blumer shelf
A
Gastric adenocarcinoma or similar carcinoma metastasised to pouch of Douglas
20
Q
Most important prognostic factor of gastric carcinoma
A
Depth of invasion
21
Q
GIST Gastrointestinal stromal tumour
A
M/C mesenchymal tumour of stomach From interstitial cells of cajal Part of Carney’s triad Pathogenesis: 1. C-kit mutation 2. PDGF R-A mutation Gross - well circumscribed fleshy mass H&E: 1. Spindly cells M/C 2. Epitheloid cells
22
Q
Carney’s triad
A
In young females
- Gastric GIST
- Pulmonary chondroma
- Paraganglioma
23
Q
Immunohistochemical markers for GIST (Gastrointestinal stromal tumour)
A
- DOG I - most specific
- CD-117 (C-KIT) - most sensitive
- CD-34
24
Q
Prognostic criteria of GIST (Gastrointestinal stromal tumour)
A
1. Tumour size: • <5 cm good • >10 cm bad 2. Location: • Gastric good • intestinal bad 3. Mitosis: >10/HPF bad prognosis
25
MALToma
Usually H. pylori associated
M/C stomach
Associated with t(11:18), t(14:18)
Usually DLBCL (diffuse large B cell lymphoma)
H&E: lymphoepithelial lesions (lymphocytes entering into a gland)
26
Carcinoid tumour
```
From enterochromaffin cells
Gross: pan brown/yellow colour
H&E: salt and pepper collation
e- microscopy: dense core neurosecretory granules
IHC markers:
1. MSE neuron specific enolase
2. Chomogranin
3. Synaptophysin
```
27
Inflammatory bowel disease
```
1. Crohn’s disease:
Any area of GIT, transmural
2. Ulcerative colitis:
Colon and rectum (Backwash ileitis)
Submucosal
3. Indeterminate colitis:
8-10 % of cases
```
28
Pathogenesis of IBD
1. Hygiene hypothesis:
Because of use of lot of preservatives and packed food, lack of development of mucosal immune response
2. Genetics
29
Genetic factors for IBD
1. NOD2 gene polymorphism ➡️ NFK-β pathway ➡️ increased cellular population ➡️ Crohn’s disease
2. ATG 16L1 - autophagy related
3. IRGM immune related GTPase M
• IL-23 receptor polymorphism is protective for both Crohn’s disease and ulcerative colitis
• HLA association:
Crohn’s disease HLA DR1
Ulcerative colitis HLA DR2
30
Crohn’s disease
Any area of GIT, but commonly in ileum, caecum, ileocaecal valve
• Transmural
• Bimodal (15-20 years and elderly) like Hodgkin lymphoma
• More common in females
• More common in Caucasians
• smoking 🚬 is a risk factor
Higher risk of CAN (colitis associated neoplasia)
Barium enema: string sign of Kantor
Anti saccharomyces cereviseae antibody is present
31
Crohn’s disease
| clinical manifestations
1. Intermittent diarrhoea attacks
2. Abdominal pain
3. Fever
4. Uveitis
5. Primary sclerosing cholangitis
6. Ankylosing spondylitis
7. Migratory polyarthritis
32
Crohn’s disease
| Gross features
1. Skip lesions
2. Deep knife like and serpentine ulcer
3. Rubbery thick intestinal wall
4. Cobblestone appearance
5. Creeping fat
6. Higher risk of structure, fissure, fossils and sinus
33
Microscopy of Crohn’s disease
1. Transmural involvement
2. CD4-TH1 cells increased: non caseating granuloma
3. Cryptitis
4. Crypt abscess
Last two are more prominent in ulcerative colitis
34
Ulcerative colitis
```
Site: colon, rectum submucosa
Smoking is protective
CD4 TH2 cells increased
Extra intestinal: primary sclerosis cholangitis
P-ANCA is present
Less risk of CAN
On barium enema - lead pipe appearance
```
35
Ulcerative colitis
| gross features
1. Continuous involvement
2. Superficial broad based ulcer
3. Pseudopolyps - islands of regenerating mucosa
4. Mucosal bridges from pseudopolyps
5. Toxic megacolon
36
Ulcerative colitis
| microscopy
1. Submucosal involvement
2. Cryptitis
3. Crypt abscess
37
Malabsorption syndromes
```
Clinically steatorrhea
Frothy, bulky and greasy stools
1. Celiac disease
2. Whipple’s disease
3. Tropical sprue
```
38
Celiac disease
```
Gluten sensitive enteropathy
Cannot have:
B. Barley
R. Rye
O. Oats
W. Wheat
Can have rice, maize
Usually affects 2nd part of duodenum
Marsh score for grading
```
39
Pathogenesis of celiac sprue
Ab mediated:
1. Anti-gliadin
2. Anti tissue transglutaminase IgA (most sensitive)
3. Anti endomysial antibody IgA (most specific)
Gluten contains α-gliadin, can’t be broken by digestive enzyme
Increased CD8+ T lymphocytes
Associated with HLA-DQ2, DQ8
40
Clinical features of celiac sprue
1. Steatorrhea
2. Diarrhoea
3. Abdominal pain
4. Increased risk of dermatitis herpetiformis
5. Increased risk of enteropathy associated T cell lymphoma
41
Celiac sprue microscopy
1. Villous atrophy
2. Crypt hyperplasia
3. Increased intraepithelial lymphocytes
42
Whipple’s disease
```
Caused by Actinomycete whipplei
Gram positive organism
Rare
Multisystem:
1. GIT
2. Lymph node
3. Joints
4. CNS
```
43
Whipple’s disease
| microscopy
Lamina propria is stuffed with foamy macrophages, PAS diastase resistant organisms
Differential diagnosis for giant macrophages on intestinal biopsy:
• TB - AFB positive
• Whipple’s disease - AFB negative
44
Tropical sprue
```
Caused by E. coli
Can effect:
• duodenum-iron deficiency
• jejunum-FA deficiency
• ileum-Vit B12 deficiency
Microscopy:
• Villous atrophy
• Regional arthritis
```
45
Ulcers of intestine
```
1. Typhoid:
• ileocaecal junction
• longitudinal ulcer ➡️ low chance of stricture
• microscopy: erythrophagocytosis
2. TB:
• transverse ulcer
• stricture
3. Amoebiasis:
• caecum M/C, liver
• flask shaped ulcer limited to submucosa
• microscopy: erythrophagocytosis
```
46
Polyps and their classification
```
Polyps are protrusion of mucosa
Classification of polyps
1. Sessile: more malignant
2. Pedunculated: less malignant
Classification:
1. Neoplasia- adenoma
2. Non-neoplastic:
• inflammatory
• hyperplastic
• hamartomatous
```
47
Microscopic classification of adenoma
```
1. Tubular polyp:
Has tubules
Also known as adenomatous polyp
2. Villous polyp:
Has villous projections
3. Tubulovillous polyp:
Has both tubules and villous architecture
Has highest malignant potential
```
48
Peutz-Jeghers syndrome
Jejunum M/C
Loss of function of LKB1/ STK11 gene
Features:
1. Multiple hamartomatous polyp
2. Perioral/ mucocutaneous hyperpigmentation
3. Increased risk of carcinoma colon, breast, thyroid, lung,...
49
Familial Adenomatous Polyp (FAP)
| pathogenesis
APC is a negative regulator of β-catenin ➡️ degrades β-catenin
1. APC mutation
2. β-catenin not degraded
3. β-catenin enters nucleus
4. Proliferation
5. FAP
50
Familial Adenomatous Polyp (FAP)
* Autosomal dominant
* APC (Adenomatous polyposis coli) gene mutation on chromosome 5q21
* Diagnosis: >100 polyps
* If left untreated, colon cancer is 100%
* Congenital hypertrophy of retinal pigment epithelium
51
Gardner syndrome
| Turcot syndrome
```
Gardner syndrome:
FAP + osteoma, epidermal cyst, abnormal dentition
Turcot syndrome:
FAP + brain 🧠 tumours
(Medulloblastoma > glioblastoma)
```
52
Colon cancer risk factors
1. FAP - APC gene mutation on chromosome 5q21
2. HNPCC - mismatch gene defect of HMPH1, MSH-1,2,6
3. Smoking, alcohol
4. High fat diet and highly processed food
5. Less fibre diet
6. IBD (ulcerative colitis > Crohn’s disease)
Fish 🎣 intake is protective
53
Adenocarcinoma sequence
```
1. APC gene
Normal epithelium ➡️ epithelium at risk
2. K-RAS
Epithelium at risk ➡️ Adenoma
3. p53
Adenoma ➡️ carcinoma
AK-53 🔫
```
54
Mismatch repair (microsatellite instability) pathway
Hereditary non-polyposis colon cancer
1. Mismatch repair gene mutation
Normal colon ➡️ sessile serrated adenoma
2. TGF-β, BAX, TCF-4, IGF2R gene mutations:
Sessile serrated adenoma ➡️ carcinoma
55
Mismatch repair genes
MLH-1
MSH-2
(MSH-6, PMS-1, 2)
