Upper Gastrointestinal Pathology Flashcards
What type of epithelium lines the oesophagus?
Where are the sphincters located?
It is a 25cm long muscular tube mostly lined by squamous epithelium
the cricopharyngeal sphincter is at the upper end
the gastro-oesophageal junction is at the lower end
where is the distal 1.5 - 2 cm of the oesophagus located?
what is significant about this part of the oesophagus?
Distal 1.5 - 2 cm are situated below the diaphragm and lined by glandular (columnar) mucosa
the squamo-columnar junction is usually located at 40 cm from the incisor teeth
What are the 3 layers of cells of normal oesophagus histology?
- Muscularis propria
- Submucosa
- Mucosa (lamina propria & epithelium)
the epithelium is stratified squamous
What is oesophagitis?
How can it be classified?
Inflammation of the oesophagus
it can be acute or chronic
What is the aetiology of oesophagitis?
Infectious:
- bacterial
- viral (HSV1, CMV)
- fungal (candida)
Chemical:
- ingestion of corrosive substances
- reflux of gastric contents
What is reflux oesophagitis caused by?
what is the leading clinical symptom?
It is the commonest form of oesophagitis
it is caused by reflux of gastric acid (gastro-oesophageal reflux) and / or bile (duodenal-gastric reflux)
the leading clinical symptom is heartburn
What are the risk factors for reflux oesophagitis?
- Defective lower oesophageal sphincter
- hiatus hernia
- increased intra-abdominal pressure
- increased gastric fluid volume due to gastric outflow stenosis
What is a hiatus hernia?
What are the 2 different types and the symptoms they produce?
An abnormal bulging of a portion of the stomach through the diaphragm
a sliding hiatus hernia leads to reflux symptoms
a paraoesophageal hiatus hernia leads to strangulation
How is the histology of the oesophagus changed in reflux oesophagitis?
Squamous epithelium:
- basal cell hyperplasia
- elongation of papillae
- increased cell desquamation
- inflammation
Lamina propria:
- inflammatory cell infiltration - neutrophils, eosinophils, lymphocytes
what is shown in this image?
Normal squamous mucosa transitioning into severe reflux oesophagitis
what are the complications of reflux oesophagitis?
- Ulceration
- perforation
- haemorrhage
- benign stricture (segmental narrowing)
- Barrett’s oesophagus
What is the cause and risk factors for Barrett’s oesophagus?
The cause is longstanding gastro-oesophageal reflux
The risk factors are the same as for acid reflux (male, Caucasian, overweight)
What is seen on macroscopy and histology in Barrett’s oesophagus?
Macroscopy:
- proximal extension of the squamo-columnar junction
Histology:
- squamous mucosa is replaced by columnar mucosa
- this is “glandular metaplasia”
How is the histology of the oesophagus changed in Barrett’s oesophagus?
Stratified squamous epithelium is replaced by columnar epithelium
there are goblet cells within the columnar mucosa
there are mucous secreting glands within the lamina propria and an increased number of inflammatory cells
What are the 3 different types of columnar mucosa in Barrett’s oesophagus?
- Gastric cardia type
- gastric body type
- intestinal type - “specialised Barrett’s mucosa”
What is Barrett’s oesophagus and what risks is it associated with?
what is recommended to minimise these risks?
It is a premalignant condition with an increased risk of developing adenocarcinoma
regular endoscopic surveillance is recommended for early detection of neoplasia
what are the stages in the disease progression of Barrett’s oesophagus?
- Barrett’s oesophagus
- low grade dysplasia
- High grade dysplasia
- Adenocarcinoma
what are the two main types of oesophageal cancer?
How common is it?
There are two main histological types of oesophageal carcinoma
- squamous cell carcinoma
- adenocarcinoma
It is the 8th most common cancer in the world
distribution varies around the world
- UK = 30% squamous
- China / Japan = >95% squamous
In which groups is adenocarcinoma of the oesophagus more common?:
Which part of the oesophagus tends to be affected and what causes it?
It mainly affects the lower oesophagus
- higher incidence in men (M:F ratio is 7:1)
- higher incidence amongst Caucasian populations
aetiology:
- Barrett’s oesophagus
- (tobacco, obesity)
What are the risk factors for squamous carcinoma of the oesophagus?
which groups have higher incidence?
- Tobacco and alcohol
- nutrition (potentially sources of nitrosamines)
- thermal injury (hot beverages)
- human papilloma virus
- male
- ethnicity (black)
there is a wide geographical incidence
(high in Iran, China, South Africa, Southern Brazil)
which parts of the oesophagus tend to be affected by squamous carcinoma?
The middle and lower third of the oesophagus
(<15% in upper third of oesophagus)
What is squamous cell carcinoma of the oesophagus preceded by?
- Normal squamous epithelium
- High grade squamous dysplasia
- Invasive squamous cell carcinoma
squamous cell carcinoma is preceded by squamous dysplasia
what are the 3 different macroscopic appearances of oesophageal cancer?
- Polypoidal
- stricturing
- ulcerated
what system is used in the staging of oesophageal cancer?
The TNM system
What is “pT” when using the TNM system to stage an oesophageal cancer?
What are the 4 different stages?
pT = depth of invasion of the primary tumour
- pT1 - tumour invades lamina propria, muscularis mucosae or submucosa
- pT2 - tumour invades muscularis propria
- pT3 - tumour invades adventitia
- pT4 - tumour invades adjacent structures
what is meant by pN and M when using the TNM system to grade an oesophageal cancer?
what are the different stages?
pN = regional lymph nodes:
- pN0 - no regional lymph node metastasis
- pN1 - regional lymph node metastasis in 1 or 2 nodes
- pN2 - regional lymph node metastasis in 3 to 6 nodes
- pN3 - regional lymph node metastasis in 7 or more nodes
M = distant metastasis:
- cM0 - no distant metastasis
- pM1 - distant metastasis
What are the 4 anatomical and histological regions of the stomach?
Anatomic regions:
- cardia
- fundus
- body
- antrum
Histological regions:
- cardia
- body
- antrum
- each of these regions has a different function
What are the properties of the normal stomach like?
- Balance of aggressive (acid) and defensive forces
- surface mucous
- bicarbonate secretion
- mucosal blood flow
- regenerative capacity
- prostaglandins
What causes increased aggression that leads to development of gastritis?
- Excessive alcohol
- drugs
- heavy smoking
- corrosive
- radiation
- chemotherapy
- infection
What is the result of increased aggression in the development of gastritis?
Impaired defences
- ischaemia
- shock
- delayed emptying
- duodenal reflux
- impaired regulation of pepsin secretion
what usually causes acute gastritis?
What are the effects?
- It is usually due to chemical injury
- drugs e.g. NSAIDs
- alcohol
- initial response to Helicobacter pylori infection
- effects depend on the severity of the injury
- can get erosions and haemorrhage
- it generally heals quickly
What are the 3 main causes of chronic gastritis?
Autoimmune:
- anti-parietal and anti-intrinsic factor antibodies
Bacterial infection (Helicobacter pylori):
- majority have no disease
- 2-5% have gastric ulcers, 10-15% have duodenal ulcers
- increased risk of gastric cancer and MALT lymphoma
Chemical injury:
- NSAIDs, bile reflux, alcohol
- cause direct injury
what is Helicobacter pylori?
How big is it and where does it live?
It is a gram negative spiral shaped bacterium
2.5 - 5.0 micrometers long with 4 to 6 flagellae
it lives on the epithelial surface protected by the overlying mucus barrier
How does Helicobacter pylori cause damage?
what does this result in?
where is it most common?
It damages the epithelium leading to chronic inflammation of the mucosa
this results in glandular atrophy, replacement fibrosis and intestinal metaplasia
it is more common in the antrum than the body
What are the major sites affected by peptic ulcer disease?
It is a localised defect extending at least into the submucosa
major sites:
- first part of the duodenum
- junction of antral and body mucosa
- distal oesophagus (GOJ)
What are the main aetiological factors in peptic ulcer disease?
- Hyperacidity
- H. Pylori infection
- duodeno-gastric reflux
- drugs (NSAIDs)
- smoking
What is the histology like for an acute gastric ulcer?
- Full-thickness coagulative necrosis of mucosa (or deep layers)
- Covered with ulcer slough (necrotic debris + fibrin + neutrophils)
- granulation tissue at ulcer floor
what is the histology like for a chronic gastric ulcer?
- Clear-cut edges overhanging the base
- extensive granulation and scar tissue at ulcer floor
- scarring often throughout the entire gastric wall with breaching of the muscularis propria
- bleeding
What are the complications of peptic ulcers?
- Haemorrhage (acute and/or chronic –> anaemia)
- perforation –> peritonitis
- penetration into an adjacent organ (liver, pancreas)
- stricturing –> hour-glass deformity
Complete the table comparing gastric and duodenal ulcers
what are the more frequent and less frequent forms of gastric cancer?
More frequently:
- adenocarcinoma
less frequently:
- endocrine tumours
- MALT lymphomas
- stromal tumours (GIST)
How common is gastric adenocarcinoma?
What is the incidence like?
- 5th most common cancer in the world
- wide geographical variation (high rates in Eastern Asia, Andean regions of South America, Eastern Europe)
- steady decline over the past decades
what is the aetiology of gastric adenocarcinoma like?
- Diet (smoked/cured meat or fish, pickled vegetables)
- Helicobacter pylori infection
- bile reflux (e.g. post Billroth II operation)
- hypochlorhydria (allows bacterial growth)
- 1% cases are hereditary
Who is more likely to get carcinoma of the GOJ?
What is this associated with?
Most common in white males
associated with gastro-oesophageal reflux, but no association with H. Pylori / diet
increased incidence in recent years
What is carcinoma of the gastric body / antrum associated with?
- Association with H pylori
- association with diet (salt, low fruit & vegetables)
- no association with GO reflux
- decreased incidence in recent years
What are the following macroscopic subtypes?
What are the different microscopic subtypes?
Intestinal type:
- well or moderately differentiated
- may undergo intestinal metaplasia and adenoma steps
Diffuse type:
- poorly differentiated
- scattered growth
- cadherin loss / mutation
what causes hereditary diffuse type gastric cancer (HDGC)?
- Germline CDH1/E-cadherin mutation
- increased risk for other cancers
what are the pT stages in the TNM staging system?
- pT1 - intramucosal or submucosal
- pT2 - into muscularis propria
- pT3 - through muscularis propria and into subserosa
- pT4 - through serosa (peritoneum) or into adjacent organs
What are other names for coeliac disease?
what is it and how common is it?
- Also known as coeliac sprue or gluten sensitive enteropathy
- immune mediated enteropathy
- ingestion of gluten containing cereals
- wheat, barley or rye
- geneticall predisposed individuals
- fairly common - estimated prevalence is 0.5% to 1%
What is gliadin and how is it implicated in coeliac disease?
It is an alcohol soluble component of gluten
it contains most of the disease-producing components
it induces epithelial cells to express IL-15
what is the consequence of epithelial cells expressing IL-15 in coeliac disease?
- IL15 produced by the epithelium leads to activation/proliferation of CD8+ intraepithelial lymphocytes (IELs)
- these are cytotoxic and kill enterocytes
- CD8+ IELs do not recognise gliadin directly
- gliadin-induced IL15 secretion by epithelium is the mechanism
Why is diagnosis of coeliac disease difficult?
Who does it commonly affect?
Commonly affects adults between 30 and 60 years
- atypical presentations / non specific symptoms
- silent disease (positive serology / villous atrophy but no symptoms)
- latent disease (positive serology but no villous atrophy)
What types of symptoms will patients with coeliac disease present with?
Symptomatic patients present with:
- anaemia
- chronic diarrhoea
- bloating
- chronic fatigue
What are the clinical features and associations of coeliac disease?
- No gender preference
other disease associations:
- dermatitis herpetiformis in 10% of patients
- lymphocytic gastritis and lymphocytic colitis
coeliac Disease & cancer:
- enteropathy-associated T cell lymphoma
- small intestinal adenocarcinoma
- BEWARE - symptoms despite gluten free diet!!!!!
What is involved in the diagnosis of coeliac disease?
- Non-invasive serology tests usually performed before biopsy
- IgA antibodies to tissue transglutaminase (TTG)
- IgA or IgG antibodies to deamidated gliadin
- anti-endomysial antibodies - highly specific but less sensitive
- tissue biopsy is diagnostic (2nd biopsy after GFD)
what is involved in the treatment for coeliac disease?
- Gluten free diet leads to symptomatic improvement in most patients
- reduces risk of long term complications including anaemia, female infertility, osteoporosis & cancer
what is the morphology of coeliac disease like?
- Villous atrophy
- crypt elongation
- increased IELs
- increased lamina propria inflammation
