Flashcards in GI Pathology Deck (89):
How long should a normal oesophagus be?
25 cm long muscular tube mostly lined by squamous epithelium
What are the two oesophageal sphincters?
Sphincter at upper end (cricopharyngeal) and lower end (gastro-oesophageal junction)
What is distinct about the distal 1.5-2cm of the oesophagus?
Distal 1.5-2 cm are situated below the diaphragm and lined by glandular (columnar) mucosa.
Where is the squamo-columnar junction?
The squamo-columnar junction is usually located at 40 cm from the incisor teeth.
What are the causes of oesophageal inflammation?
Bacterial, viral (HSV1, CMV), fungal (candida)
Ingestion of corrosive substances
Reflux of gastric contents
What is the reflux of bile called?
What are the risk factors for reflux oesophagitis?
Defective lower oesophageal sphincter
Increased intra-abdominal pressure
Increased gastric fluid volume due to gastric outflow stenosis
What is a hiatus hernia?
Abnormal bulging of a portion of the stomach through the diaphragm
Histologically, what would be seen in reflux oesophagitis?
Basal cell hyperplasia, elongation of papillae, increased cell desquamation
Inflammatory cell infiltration (neutrophils, eosinophils, lymphocytes)
What can be the complications from reflux oesophagitis?
Benign stricture (segmental narrowing)
What is Barrett's oesophagus?
Same as for reflux (male, Caucasian, overweight)
Proximal extension of the squamo-columnar junction
Squamous mucosa replaced by columnar mucosa > “glandular metaplasia”
What are the types of columnar mucosa?
Gastric cardia type
Gastric body type
Intestinal type = “specialised Barrett’s mucosa”
Why is Barrett's oesophagus concerning?
Premalignant condition with an increased risk of developing adenocarcinoma
Regular endoscopic surveillance is recommended for early detection of neoplasia
How common is oesophageal carcinoma?
8th most common cancer in the world
What are the 2 histological types of oesophageal carcinoma?
Squamous cell carcinoma
Which gender is oesophageal adenocarcinoma more common in?
What is the aetiology for oesophageal adenocarcinoma?
Where are oesophageal adenocarcinomas usually found?
What does an oesophageal adenocarcinoma look like?
Plaque-like, nodular, fungating, ulcerated, depressed, infiltrating
What are the risk factors for squamous carcinoma?
Tobacco and alcohol
Nutrition (potential sources of nitrosamines)
Thermal injury (hot beverages)
Where are squamous carcinomas most common?
Iran, China, South Africa, Southern Brazil
How are oesophageal cancers staged?
How is the depth of invasion of the primary tumour scored?
pT1: tumour invades lamina propria, muscularis mucosae or
pT2: tumour invades muscularis propria
pT3: tumour invades adventitia
pT4: tumour invades adjacent structures
How are the regional lymph node involvements scored?
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
What are the 4 anatomical regions of the stomach?
What features normally protect the stomach from gastritis>?
- Balance of aggressive
(acid) and defensive
- Surface mucous
- Bicarbonate secretion
- Mucosal blood flow
- Regenerative capacity
What factors can cause increased aggression of gastritis?
- Heavy smoking
What factors can impair defences against gastritis?
- Delayed emptying
- Duodenal reflux
- Impaired regulation of
What are the pathogenic mechanisms of autoimmune gastritis?
Anti-parietal cell and anti-intrinsic factor antibodies
What are the pathogenic mechanisms of bacterial gastritis? (H.Pylori)
Liberation of chemokines
?Ammonia production by bacterial urease
Tissue damage by immune response
What is the pathogenic mechanisms of NSAID gastritis?
Disruption of the mucus layer
What is the pathogenic mechanisms of bile reflux gastritis?
Degranulation of mast cells
What is Helicobacter Pylori?
Gram negative spiral shaped bacterium
2.5-5.0 micrometres long
4 to 6 flagellae
Lives on the epithelial surface protected by the overlying mucus barrier
Where in the stomach is H.pylori most common?
What does h.pylori result in?
glandular atrophy, replacement fibrosis and intestinal metaplasia
What can be the complications of h.pylori infection?
pre-pyloric gastric ulcer
(however 85% patients have no complications)
What is peptic ulcer disease?
Localised defect extending at least into submucosa
What are the major sites of peptic ulcer disease?
First part of duodenum
Junction of antral and body mucosa
Distal oesophagus (GOJ)
What are the main etiological factors of peptic ulcer disease?
H. pylori infection
What is the histology of an acute gastric ulcer?
Full-thickness coagulative necrosis of mucosa (or deeper layers)
Covered with ulcer slough (necrotic debris + fibrin + neutrophils)
Granulation tissue at ulcer floor
What is the histology of 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
What are the complications possible with peptic ulcers?
Haemorrhage (acute and/or chronic anaemia)
Penetration into an adjacent organ (liver, pancreas)
Stricturing hour-glass deformity
What are the main causes of gastric cancer?
Stromal tumours (GIST)
What is the incidence of gastric adenocarcinoma?
5th most common cancer in the World
(951,594 new cases/year)
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?
Diet (smoked/cured meat or fish, pickled vegetables)
Helicobacter pylori infection
Bile reflux (e.g. post Billroth II operation)
Hypochlorhydria (allows bacterial growth)
What are the features of carcinoma of GOJ?
- White males
- Association with GO reflux
- No association with H. pylori / diet
- Increased incidence in recent years
What are the risk features of carcinoma of gastric body/antrum?
- Association with H. pylori
- Association with diet (salt, low fruit
- No association with GO reflux
- Decreased incidence in recent years
What are the 2 main histological subtypes of gastric adenocarcinoma?
- Diffuse type
- (signet ring cell ca)
What is coeliac disease?
Also known as Coeliac sprue or gluten sensitive enteropathy
Immune mediated enteropathy
How common is coeliac disease?
Fairly common, estimated prevalence of 0.5% to 1%
What is GLIADIN?
Alcohol soluble component of gluten
Contains most of the disease-producing components
Induces epithelial cells to express IL-15
What are CD8+ Intraepithelial lymphocytes (IELs)?
IL15 produced by the epithelium activation / proliferation of CD8+ 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 often difficult?
Atypical presentations / non specific symptoms
Positive serology / villous atrophy but no symptoms
Positive serology but no villous atrophy
Anaemia, chronic diarrhoea, bloating, or chronic fatigue
What are the clinical features and associations of coeliac disease?
No gender preference
Other disease associations
Dermatitis herpetiformis - 10% of patients
Lymphocytic gastritis and lymphocytic colitis
Coeliac disease and cancer
Enteropathy-associated T-cell lymphoma
Small intestinal adenocarcinoma
BEWARE!!!! Symptoms despite GFD
How is coeliac disease diagnosed?
Non-invasive serologic tests usually performed before biopsy
The most sensitive tests
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)
How is coeliac disease treated?
Gluten-free diet symptomatic improvement for most patients
Reduces risk of long-term complications including anaemia, female infertility, osteoporosis, and cancer
What are the types of IDIOPATHIC INFLAMMATORY BOWEL DISEASE?
INDETERMINATE COLITIS ( 10 – 15 % )
What is the epidemiology of IBD?
UC 5 – 15 cases per 100,000 p.a.
CD 5 – 10 cases per 100,000 p.a.
Incidence highest in Scandinavia, UK, Northern Europe, USA
Lower in Japan, Southern Europe, Africa
Peak age incidence 20 – 40 years of age
CD more common in females 1.3 : 1
UC equally common in males and females
Incidence of UC is increased in urban areas
What are other risk factors for IBD?
Cigarette smoking UC 0.5 x
CD 2 x
Oral Contraceptive UC 1.4 x
CD 1.6 x
Others eg. Childhood infections
What is the clinical presentation of ulcerative colitis?
Diarrhoea ( > 66 % ) with urgency/tenesmus
Constipation (2 %)
Rectal bleeding (> 90%)
Abdominal pain (30 – 60 %)
Weight loss (15 – 40 %)
What are the complications of ulcerative colitis?
Toxic megacolon and perforation
Stricture ( rare )
What are the clinical features of Chrohn's disease?
Chronic relapsing disease
Affects all levels of GIT from mouth to anus
Diarrhoea ( may be bloody )
Colicky abdominal pain
Palpable abdominal mass
Weight loss / failure to thrive
Peri – anal disease
What is the distribution of Crohn's disease throughout the GI tract?
Ileocolic 30 – 55 %
Small bowel 25 – 35 %
Colonic 15 – 25 %
Peri-anal / ano-rectal 2 – 3 %
Gastro – duodenal 1 – 2 %
What complications can arise from Crohn's disease?
Short bowel syndrome (repeated resection)
What are some hepatic manifestations of IBD?
Bile duct carcinoma
What are some skeletal manifestations of IBD?
What are some muco-cutaneous manifestations of IBD?
Oral apthoid ulcers
What are some haematological manifestations of IBD?
What are some renal and systemic manifestations of IBD?
kidney and bladder stones
amyloid and vasculitis
Risk factors for colo-rectal cancer in ulcerative colitis?
Early age of onset
Duration of disease > 8-10 years
Total or extensive colitis
Family History of CRC
? Severity of inflammation ( pseudopolyps )
Presence of dysplasia
What are colorectal polyps?
A “mucosal protrusion”
Solitary or multiple ( polyposis )
Pedunculated , sessile or “flat”
Small or large
Due to mucosal or submucosal pathology or a lesion deeper in the bowel wall
What are the types of colorectal polyps?
Neoplastic , hamartomatous , inflammatory or reactive
Benign or Malignant
Epithelial or Mesenchymal
What are the features of a hyperplastic polyp?
1 – 5 mm in size
located in rectum and sigmoid colon
small distal HPs have NO malignant potential
NB some large right sided “hyperplastic polyps” ( sessile serrated lesions ) may give rise to microsatellite unstable carcinoma ( 10 – 15 % all colorectal cancer )
What are the features of a juvenile polyp?
often spherical and pedunculated
10 – 30 mm
commonest type of polyp in children
typically occur in rectum & distal colon
sporadic polyps have no malignant potential
NB juvenile polyposis associated with increased risk of colorectal and gastric cancer
What is PEUTZ-JEGHERS SYNDROME?
Autosomal dominant condition ( mutation in STK11 gene on chromosome 19 )
Prevalence : 1 in 50,000 – 1 in 120,000 births
Present clinically in teens or 20s with abdominal pain ( intussusception ), gastro-intestinal bleeding & anaemia
Multiple gastro-intestinal tract polyps ( predominantly small bowel )
( 1 – 5mm macules peri-oral , lips , buccal mucosa , fingers and toes )
What is the distribution of polyps in Peutz-Jeghers Syndrome?
Small bowel 96 %
Colon 27 %
Rectum 24 %
Stomach 24 %
NB polyps also described in gallbladder, urinary bladder and nasopharynx
What are some examples of benign neoplastic polyps?
What are some examples of malignant neoplastic polyps?
What are the features of colorectal adenomas?
Benign epithelial tumours
Commonly polypoid but may be “flat”
Precursor of colorectal cancer (at least 80%)
Present 25% - 35% population > 50 years
Multiple in 20 – 30 % patients
Evenly distributed around colon BUT larger in recto-sigmoid and caecum
A small % of adenomas progress to adenocarcinoma over an average of 10 – 15 years. What are some specific risk factors for this?
Size ( most malignant polyps > 10 mm )
Villous & Tubulo-Villous
Severe ( high grade ) dysplasia
HNPCC associated adenomas
What are the statistics of colorectal cancer in the UK?
2nd or 3rd commonest cancer (mortality) after bronchus, breast and prostate
Lifetime risk 1 in 18 to 1 in 20
Estimated prevalence in UK 77,000
Incidence in UK 35,300
Mortality in UK 16,220
What are the risk factors for colorectal cancer?
- Dietary fibre, fat, red meat, folate, calcium
Obesity / Physical Activity
HRT and oral contraceptives
Ulcerative colitis and Crohns disease
What is FAP?
inherited gene that increases susceptibility to colorectal cancer
What is HNPCC?
inherited gene that increases susceptibility to colorectal cancer
1 – 2 % all colorectal cancer
50 - 70 % lifetime risk of large bowel cancer
Increased risk of endometrial, ovarian, gastric, small bowel, urinary tract and biliary tract cancer
Due to mutations in DNA mismatch repair genes
What is the most common type of colorectal cancer?
What are the ways colorectal cancer can spread?
Direct invasion of adjacent tissues
Lymphatic metastasis (lymph nodes)
Haematogenous metastasis (liver & lung)
Transcoelomic ( peritoneal ) metastasis
Iatrogenic spread eg. needle track recurrence or port site recurrence
How are colorectal cancers staged?
May be clinical ( imaging ) or pathological
Describes extent of local and distant tumour spread
What are Duke's stages?
Stage A : adenocarcinoma confined to the bowel wall with no lymph node metastasis
Stage B : adenocarcinoma invading through the bowel wall with no lymph node metastasis
Stage C : adenocarcinoma with regional lymph node metastasis regardless of depth of invasion
Stage D : distant metastasis present