Theme 5: Gastrointestinal, Hepatobiliary and Pancreatic Pathology Flashcards
What is colorectal cancer?
A malignant neoplasm developing in the submucosa of the large bowel
In which section of bowel are colorectal cancers commonest?
Left side - sigmoid colon and rectum
The most common site of metastasis in bowel cancer is the ____.
liver
Over the past 40 years, have incidences of colorectal cancer increased or decreased? Is this the same for males and females?
Over the past 40 years, bowel cancer rates have increased for both males and females, though rates are higher in males.
What are the risk factors for bowel cancer?
Increased age More common in men Western populations Diet: high fat, red meat, low fibre Obesity Alcohol Smoking Ionising radiation exposure Genetics IBD
In the pathogenesis of colorectal cancer, what allows the advancement of the tumour from each stage to the next?
Genetic mutation/loss.
Vast majority of bowel cancers develop along the adenoma-carcinoma sequence, beginning as normal epithelium and advancing until it becomes metastatic disease.
At each stage, genomic events occur to allow progression. Not all event have to occur and not in a specific order, but multiple hits are required to develop into metastatic carcinoma.
Normal bowel mucosa contains regular, rounded glands.
Normal bowel mucosa contains regular, rounded glands. The nuclei are basally located and are roughly the same size and shape.
Adenomatous mucosa features irregularly-shaped glands. The nuclei are pseudostratified and much bigger, with varying sizes and shapes.
What are the two main ways in which colorectal cancer develops?
Adenoma-carcinoma sequence (85%)
Microsatellite instability (15%)
What allows microsatellite instability to occur?
Loss of function of the DNA-mismatch-repair genes.
DNA mismatch repair genes repair sporadic mutational damage throughout the genome.
What condition leads to increased susceptibility for developing colorectal cancer due to mutations in DNA mismatch
repair genes?
Lynch Syndrome
Also known as Hereditary Nonpolyposis Colorectal Cancer (HNPCC)
What histopathological clues indicate a tumour may be caused by microsatellite instability?
- Right-sided
- Mucinous
- Poorly differentiated
- Infiltration by immune cells
What are the key clinical implications associated with colorectal cancer?
- Ulceration: leading to bleeding. If on left side, this is normally noticed by patients. Blood from the right side changes colour during its bowel journey, and may not be noticed by patients. This is called occult bleeding (no signs/symptoms). Chronic bleeding leads to anaemia
- Stenosis: bowel obstruction, pain
- Weight loss and altered bowel habit
What is the normal treatment for operable colorectal cancer?
Surgery to remove tumour, along with a margin of normal tissue on either side. The two ends of bowel and then anastomosed to maintain normal intestinal continuity.
If cancer is in rectum, anal sphincters may need to be removed. This requires permanent colostomy.
+/- preoperative radiotherapy
+/- postoperative chemotherapy
What has happened to trends in UK colorectal mortality rates over the past 40 years?
Mortality rates have decreased
- improved diagnosis and treatment
- better MDT involvement
- screening programme tests for occult blood in faeces
Define gastric cancer
Malignant neoplasm developing in the stomach (between the gastroesophageal junction and gastroduodenal junction)
True or false: gastric cancer is relatively rare.
True. Gastric cancer is only the 16th commonest cancer in the UK (6,700 cases per year).
What risk factors are associated with gastric cancer?
- More common with age
- More common in men than women (2:1)
- Diet: smoked/cured meat and fish, pickled foods
- Alcohol
- Smoking
- Obesity
- H Pylori infection
- Bile reflux/ low levels of stomach acid
- Family history
True or false: H Pylori infection is associated with carcinoma of the gastroesophageal junction?
False. H Pylori is associated with carcinomas of the gastric body/antrum, but not the GOJ.
White males are associated with being most at risk of developing which type of gastric cancer?
Carcinoma of Gastroesophageal Junction
What are the key pathogenic factors associated with carcinoma of the gastroesophageal junction?
White Males
Gastroesophageal reflux
Obesity
What are the key pathogenic factors associated with carcinoma of the gastric body/antrum?
H Pylori infection
Diet (high salt, low fibre)
Why have incidences of gastroesophageal junction carcinoma increased in recent years?
Increased rates of obesity and GO reflux
Why have incidences of gastric body/antrum carcinoma decreased in recent years?
Eradication of helicobacter
What are the two histopathological classifications of gastric cancer?
Intestinal type:
- Appears similar to normal glands
- Well-moderately differentiated
- May undergo intestinal metaplasia and adenoma steps
Diffuse type:
- Poorly differentiated
- Scattered growth
- Does not form glandular structures
- Cadherin loss (mutation of E-Cadherin gene)
What key clinical features are associated with gastric cancer?
Dependent on type and site of tumour.
- Dysphagia (difficulty swallowing) if tumour obstructs gastroesophageal junction
- Weight loss
- Indigestion
- Feeling full after small amount of food
- Vomiting
- Bleeding: haematemesis/melaena
How is gastric cancer diagnosed?
Endoscopy to visualise/biopsy neoplasm
How is gastric cancer treated?
Local excision
- Small, early staged tumours can be dissected out
Gastrectomy
- for advanced tumours
- partial or total gastrectomy
Chemotherapy
What are the mortality rates like for gastric cancer?
20% 5-year survival from diagnosis
- Diagnosis occurring too late
What epithelium normally covers the lumen of the oesophagus?
Non-keratinised stratified squamous
What is oesophagitis?
Inflammation of the oesophagus.
May be acute or chronic.
What are the main causes of oesophagitis?
Infection: bacterial, viral (HSV1, CMV), fungal (candida)
Chemicals:
- Ingestions of corrosive substance
- Gastric reflux
What is the commonest cause of oesophagitis?
Reflux
Gastric acid and/or bile irritates mucosa
What are the risk factors for reflux oesophagitis?
Defective lower oesophageal sphincter
Hiatus hernia
Increased intra-abdominal pressure
- e.g. tumour, ascites
Stenosis of gastric outflow (e.g. duodenal tumour), leading to increased gastric acid volume
What is the main clinical symptom associated with reflux oesophagitis?
Heartburn
What are the two types of hiatus hernia?
Which type can lead to reflux oesophagitis?
- Sliding hernia
- Para-oesophageal hernia
Can result in strangulation and ischaemia of stomach
BOTH types can lead to reflux oesophagitis.
What histology might be seen in reflux oesophagitis?
- Basal cell hyperplasia
- Elongated papillae
- Increased cell desquamation
- Inflammatory cells (esp. lymphocytes)
- May see signs of ulceration (e.g. erosion, granulation tissue)
What complications can occur with reflux oesophagitis?
- Ulceration
- Haemorrhage
- Perforation
- Stricture (healing of ulcer can result in fibrosis, may lead to dysphagia)
- Barrett’s oesophagus
What causes Barrett’s Oesophagus?
Chronic gastroesophageal reflux
What are the risk factors associated with Barrett’s Oesophagus?
Male, caucasian, overweight
What is Barrett’s Oesophagus?
Replacement of the normal squamous epithelium by columnar epithelium (glandular metaplasia) in response to chronic reflux oesophagitis.
Squamo-columnar junction migrates proximally
In the normal oesophagus, roughly how far from the incisors does the squamo-columnar junction lie?
40cm
This distance is reduced in Barrett’s oesophagus
Which condition is considered to be premalignant with an increased risk of developing adenocarcinoma of the oesophagus?
Barrett’s oesophagus
Regular endoscopic surveillance is recommended for early detection of neoplasia
What types of columnar mucosa may be present in Barrett’s Oesophagus?
- Gastric cardia type
- Gastric body type
- Intestinal type
Presence of rounded goblet cells that are not found in stomach
What stages are undergone for Barrett’s Oesophagus to develop into adenocarcinoma?
- Barrett’s Oesophagus
- Non-neoplastic
- Columnar lining with goblet cells - Low-grade dysplasia
- Cells disorganised
- Large nuclei
- Less cytoplasm - High-grade dysplasia
- Nuclei atypia
- Glands are disorganised - Adenocarcinoma
- Invasive cancer
What are the two main histological types of oesophageal carcinoma?
Which one is caused by Barrett’s oesophagus?
- Squamous cell carcinoma
- Adenocarcinoma
Barrett’s oesophagus causes adenocarcinoma
Which type of oesophageal carcinoma is commonest in the UK?
Adenocarcinoma (70%)
In China and Japan, more than 95% of cases are squamous cell carcinoma. They also have much lower incidence of reflux and obesity.
In which part of the oesophagus is adenocarcinoma most commonly found?
Lower oesophagus - where Barrett’s oesophagus occurs
What are the risk factors for developing oesophageal squamous cell carcinoma?
Smoking
Alcohol
Diet - nitrosamines
Thermal injury (hot drinks)
HPV
Male
Ethnicity (black)
In which part of the oesophagus is squamous cell carcinoma most common?
Middle and lower thirds
Squamous cell carcinoma is preceded by a low grade and then high grade ____ phase.
dysplastic
How is oesophageal cancer staged?
TNM system
- Depth of TUMOUR
- Spread to regional lymph NODE
- Distant METS
The area of the stomach around the gastroesophageal junction is known as the ____
cardia
The area of the stomach around the pylorus is known as the ____
Antrum
What is the commonest cause of acute gastritis?
Chemical injury
Drugs (e.g. NSAIDs), alcohol, early response to H Pylori
What are some causes of chronic gastritis?
Autoimmune
H Pylori infection
Persistent chemical injury
Which of the following statement regarding H Pylori is FALSE?
A) It is gram negative
B) It is non flagellated
C) It is spiral shaped
D) More commonly found in the antrum than the body of the stomach
B) It is non flagellated
Helicobacter pylori are gram negative spiral bacteria. The have 4-6 flagella.
More commonly found in the antrum than the body, they damage the epithelium leading to chronic inflammation of the mucosa.
This damage leads to glandular atrophy, replacement fibrosis and intestinal metaplasia.
What is the difference between an erosion and an ulcer?
An erosion is when only part of the mucosa has disappeared.
It is classified as an ulcer if the full thickness of mucosa has disappeared.
In peptic ulcer disease, there is the presence of a localised defect that extends at least into the ____
submucosa
Which major sites are commonly affected by peptic ulcer disease?
Distal oesophagus
Junction of antral and body mucosa
First part of duodenum
What are the main aetiological factors leading to peptic ulcer disease?
Hyperacidity H. Pylori Duodenogastric reflux Drugs (NSAIDs) Smoking
Endoscopy shows a poorly defined full-thickness, coagulative necrosis of the mucosa and some of the submucosa in the stomach. At the base of the lesion is granulation tissue. What is the diagnosis?
This is an acute gastric ulcer, as the lesion has eroded through the full thickness of the mucosa.
It is likely to be acute as it is poorly defined and hasn’t eroded very far through the gastric wall. Chronic gastric ulcers tend to have clear-cut edges.
On the surface you would expect to see ulcer slough (necrotic debris, fibrin, neutrophils)
What complications are associated with peptic ulcers?
- Haemorrhage (anaemia, haematemesis)
Acute if large vessel
Chronic if small vessel - Perforation (peritonitis)
- Penetration into adjacent organs
- Stricture (hour-glass deformity)
Chronic; narrowing of stomach due to healing of ulcer. Divides stomach into parts
Which is more common: gastric or duodenal ulcers?
Duodenal (3:1)
True or false: your blood group may be associated with your relative risk of developing gastric or duodenal ulcers
True
Gastric ulcers are more common in group A
Duodenal ulcers are more common in group O
What is the most common type of gastric cancer?
Adenocarcinoma (stomach lining is columnar)
Less common types:
Endocrine tumours
MALT lymphomas
Stromal tumours
Gastric adenocarcinoma is the 5th most common cancer in the world. What are the key aetiological differences between carcinoma of the gastroesophageal junction and carcinoma of the gastric body/antrum?
GOJ:
- White males
- Gastroesophageal reflux
- NOT associated with H. Pylori or diet
- Incidence increasing (increased obesity and reflux)
Body/antrum:
- H Pylori infection
- Diet: salt, low fibre
- NOT associated with GO reflux
- Incidence decreasing (eradication of h. pylori)
A gastric cancer that is raised above the surface of the epithelium is classified as:
A) Exophytic
B) Linitis plastica
C) Depressed
D) Polypoidal
A and D
Exophytic and polypoidal are both correct when describing a neoplasm that is raised above the surface of the epithelium.
There are two main microscopic subtypes of gastric cancer. What are they?
Intestinal type
- most common
- glandular formations
- well or moderately differentiated
Diffuse type
- Poorly differentiated
- Scattered growth
- Cadherin loss/mutation
Germline CDH1/E-cadherin mutation may be responsible for which type of gastric cancer?
Hereditary diffuse type gastric cancer (HDGC)
Which condition presents as an immune-mediated enteropathic reaction to gliadin?
Coeliac disease
How does the presence of gliadin lead to enteropathy in coeliac disease?
Gliadin induces expression of IL-15 in epithelial cells. There is also an increased presence of CD8+ intraepithelial lymphocytes (IELs).
IL-15 activates CD8+ IELs, which are cytotoxic and kill enterocytes.
CD8 IELs do not recognise gliadin directly, must have IL-15. Gliadin-induced secretion of IL-15 by the epithelium is the mechanism.
Which age group is most commonly affected by coeliac disease?
Adults 30-60
How is a diagnosis of coeliac disease made?
History
Serology
- IgA to tissue transglutaminase (TTG)
- IgA or IgG to deamidated gliadin
- Anti-endomysial antibodies
Biopsy before and after gluten-free diet
- check villous atrophy
What other conditions are closely associated with coeliac?
Dermatitis herpetiformis
- Blistering rash on rump
Lymphocytic gastritis/colitis
- CD8+ IELs extend into stomach and colon
Enteropathy-associated T-cell lymphoma
Small intestinal adenocarcinoma
Which of the following are signs of coeliac disease?
- Villous atrophy
- Crypt elongation
- Increased IELs
- Increased inflammation of lamina propria
All of these are signs of coeliac disease
Blind-ended sac-like protrusions from the bowel wall in communication with the bowel lumen
Diverticula
What is the difference between true/congenital diverticulum and acquired/false diverticulum?
True/congenital:
- Less common
- Outpouches that involve all the layers of the bowel wall
- e.g. Meckel’s diverticulum
Acquired/false:
- More common
- Outpouches of mucosa and submucosa, not all layers
Where is diverticulosis most commonly found?
Sigmoid colon
Diverticulosis is common in which parts of the world?
Common in developed (western) world.
Rare in Africa, Asia and S. America. Increasing with diet change.
