Histopathology 10 - Upper GI disease Flashcards
What is the “Z line” in the GI tract?
Normal appearance of squamo-columnar junction of the oesophagus
upper 2/3: squamous
lower 1/3: columnar
Where is the cardia portion of the stomach?
Junction between oesophagus and stomach
In a normal duodenum, what is the villous:crypt ratio?
>2:1
Where are goblet cells usually found?
Intestine
What is the most common cause of acute oesophagitis?
GORD
Less common- swallowing toxic substances
If reflux oesophagitis causes a perforation of the oesophagus, what will be the result?
Mediastinitis
What are the most common complications to remember of most GI pathologies?
Ulceration
Haemorrhage
Perforation
Stricture
How is Barrett’s oesophagus different from metaplasia?
Reversible
What is gastric metaplasia?
Metaplastic change in oesophagus without goblet cells
What is intestinal type metaplasia? and risk of this?
Replacement of squamous epithelium with metaplastic columnar epithelium WITH goblet cells present
note: No goblet cells naturally found in stomach
Associated with increased risk of cancer
What is the most common sequence of pathological progression to cancer in the upper GIT?
Metaplasia (reversible) –> dysplasia (hyperchromatic cells) –> Cancer (invasion of basement membrane
What is the most common type of oesophageal carcinoma in developed coutries?
Adenocarcinoma: form glands and secrete mucus
Where does adenocarcinoma of the oesophagus usually develop?
Lower oesophagus- reflux has its maximum effect here
as it’s associtaed with barret’s oesophagus
Which type of oesophageal cancer is most strongly associated with GORD?
Adenocarcinoma
What is the most common type of oesophageal cancer in developing coutries?
Squamous cell carcinoma
Which type of oesophageal cancer is most associated with smoking and alcohol?
Squamous cell carcinoma
Where in the oesophagus does squamous cell carcinoma tend to present?
Mid/lower oesophagus
middle 1/3 (50%). Upper 1/3 – 20%, Lower 1/3 – 30% oesophageal
Why is prognosis for oesophageal cancer particularly poor?
Most patients are not suitable for resection surgery
What other condition are oesophageal varices particularly associated with? **other than cirrhosis
what is the pathophysiology of this
Portal vein stenosis/thrombosis
Pathophysiology
- Blockage of flow of blood into the liver
- Has to find other ways of doing this
- Opens up at sites of porto-venous anastomoses for site of entry of blood
- Such as lower oesophagus and stomach
What are the morphological categories of gastric cancer?
Intestinal
Diffuse
What is a gastrointestinal stromal tumour? (GIST)
Tumour of the interstitial cells of Cajal in the stomach - a SARCOMA
What is the cause of gastric MALToma?
Chronic inflammation, usually due to H pylori
What are gastric MALTomas composed of?
B cells
What is gastric epithelial dysplasia and what may be seen on a cellular level
Abnormal epithelial pattern of growth
- Big nuclei
- Raised nucleocytoplasmic ratio- most important feature
- Increased mitoses
- Abnormal mitoses
What is the first-line treatment of gastric MALToma?
H pylori treatment
Which type of gastrointestinal tract ulcers are always benign?
Duodenal
What is cryptosporidiosis?
Protozoal GIT infection seen in immunosuppressed patients
Where does giardia lamblia infection cause pathology?
Villi of GIT
What is the route of transmission of giardia?
Faeco/oral route
How are the villi damaged in coeliac disease?
Cytotoxic T cells
In what condition are increased numbers of intraepithelial lymphocytes in the GIT seen?
Coeliac
What are the 3 main histological features of coeliac?
Crypt hyperplasia
Villous atrophy
Increased numbers of intraepithelial lymphocytes
Which two antibodies are required for diagnosis of coeliac disease?
Endomysial Tissue transglutaminase (TTG)
Where is EATL associated with coeliac likely to be located?
Duodenum
What is the type of MALToma as a result of coeliac disease called? and what are the microscopic features
Enteropathy associated T cell lymphoma:
lymphocytes are very big, with big nuclei and prominent nucleoli and lots of mitotic figures
WHat’s the most common cause of acute oeosphagitis?
Complications?
Most common cause: acid reflux (GORD)
Complications:
- Ulceration:
- Which produces
- necrotic slough,
- inflammatory exudate
- and granulation tissue
- Which produces
- Fibrosis
- Haemorrhage
- Perforation
- Stricture
- BARRETT’s OESOPHAGUS - long term complication of reflux oesophagitis
Barret’s oesophagus: definition
What are the two types of barret’s oesophagus?
Defition: metaplasia of squamous to columnar of oesohpageal epithelium (usually with goblet cells) , usually at lower end of the oesophagus which is most susceptibel to acid reflux
(also calleld columnar lined oesophagus)
Two types:
Gastric metaplasia: without goblet cells
Intestinal metaplasia: with goblet cells. (gastric metaplasia–> intestinal metaplasia). *much higher risk of dysplasia into cancer*
Which cancer can barret’s oeosphagus progress to and by which pathway?
Adenocarcinoma of the oeosphagus
Via flat metaplasia–>dysplasia pathway
what are the two types of oesophageal carcinoma and risk factors?
1. Adenocarcinoma
- more common in developed countries
- RF: barret’s oeosphagus
Other risk factors incl: smoking, obesity, prior radiation therapy Adenocarcinoma
Most common in Caucasians, M>>F
2. Squaous cell carcinoma
- more common in developing countries
- RF: alcohol and smoking
Other RF: achalasia of cardia, Plummer-Vinson syndrome, nutritional deficiencies, nitrosamines, HPV (in high prevalence areas)
6x more common in Afro-Carribeans, M>F
Histology of squamous cell carcinoma of the oesophagus (x2)
Normally the oeosphageal squamous epithelium is non-keratinised
Cancer cells are keratinised
You also see inter-cellular bridges
How do H pylori inject toxin into the mucosa?
Via cag-A needle appendage
Risk factors for oesophageal varices
Cirrhosis
Portal vein thrombosis
What are the 3 layers of the stomach wall?
Gastric mucosa (columnar) Lamina propria (containing glands) Muscularis mucosae
nb: difference between mucosa and mucosae
Difference in histology of gastric body vs gastric antrum
Body: specialised glands in lamina propria
Antrum: non-specialised glands in lamina propria
**body is SPECIAL
What are the 3 main causes of acute gastritis?
chemical:
Aspirin/NSAIDs
Alcohol- especially in combination with aspirin
infection
H pylori
What are the 3 major causes of chronic gastritis?
ABC
Autoimmune (antiparietal cell Ig) >> affects body of stomach
Bacterial (H pylori, affects antrum)
Chemical (NSAIDs, bile reflux from duodenum into stomach, affects antrum)
key cells are lymphocytes as this is chronic inflammation
But presence of co-existing acute processes can mean you may also get a lot of neutrophils.
Which types of gastric neoplasm does H pylor associated chronic gastritis predispose to?
1) B cell Lymphoma (MALToma)
It induces lymphoid tissue in the stomach- particularly lymphoid follicles in germinal centres.
CLO >>> IM >>>Dysplasia >>> MALToma (Mucosal associated lymphoid tissue)
2) gastric adenocarcinoma
chronic gastritis–>gastric adenocarcinoma
Which strain of H pylori is associated with more aggressive chronic gastritis?
cag-A positive
strain is associated with more chronic inflammation and increases the risk of cancer
What will be the result of a perforated gastric ulcer?
Peritonitis
Which part of the stomach does H Pylori affecr?
Antrum but can also affect pylorus
How do you treat gastric MALToma?
Treat H pylori infection with 2 antibiotics and a PPI
What pathology can H pylori cause in the oesophagus?
Barret’s oesophagus –> oesophageal adenocarcinoma
What are the cells associated with chronic gastritis? And what would make you suspect B cell lymphoma?
Lymphocytes as this is a chronic process
eg you would see proliferation of lymphoid follicles
If you see neutrophils- can be sign of gastric MALToma
(acute process within a chronic process)
Definition of ulcer- how is it different to an erosion?
Complications of ulcers
Ulcer: when inflammation invades the muscularis mucosae into the submuocsal layer: Through the full thickness of the mucosa and into the submucosa
Erosion: loss of superficial tissue - does not invade into the submucosae
Complications: bleeding(iron deificnecy anaemia) , perforation (peritonitis), malignancy
Why might you biopsy a gastric ulcer and indicate what might be seen/not seen
ALL gastric ulcers should be biopsied to exclude malignancy
Ulcers with smooth non-rolled edges are unlikely to be cancer
What is intestinal metaplasia of the stomach and what is its significance?
When you see goblet cells in the intestine
Higher risk of developing into cancer
What are the two cancer pathways in the upper GI tract?
- Flat pathway: metaplasia-dysplasia pathway : oesophageal and gastric cancer (upper GI)
- polyp pathway: adenoma-carcinoma pathway: colon cancer (lower GI)
What is the key cytological feature of gastric epithelial dysplasia?
High nuclear cytoplasmic ratio
What is the difference between gastic dysplasia and gastric Ca?
Invasion of basement membrane
What type of carcinoma is the most common type of gastric cancer?
Adenocarcinoma- 95%
Other 5%:
- squamous cell carcinoma
- gastric maltoma
- gastrointestinal stromal tumour
- neuroendocrine tumours: GIT is one of the richest sites of neuroendocrine cells
Where is gastric cancer most common?
Japan, by far
What are the two types of gastric adenocarcinoma?
1. intestinal: intestinal metaplasia. well-differentiated glands: Form big glands and secrete mucus
2. diffuse: undifferentiated. more aggressive = poor prognosis
- linitis plastica
- signet ring cell carcinoma
What is linitis plastica?
Type of diffuse gastric adenocarcinoma
spreads to stomach wall muscles and makes it thicker and more rigid → leather bottle stomach
→ trouble digesting food
What is signet ring cell carcinoma and how do they spread
Type of diffuse gastric adenocarcinoma
Signel ring cell: single cells with holes in them - no attempt of gland formation
What is the normal villous:crypt ratio in the duodenum?
>2:1
Effect of H pylori on duodenum
Chornic inflammation of the antrum of the stomach
Acid production
Spills over into the duodenum *i.e. H pylori doesn’t infect the duodenum itself*
This then causes GASTRIC METAPLASIA- adaptation to deal with increased acid production (As gastric epithelium is more well suited to deal with stomach acid)
Which other pathogens infect the duodenum?
- cryptosporidium - protozoa
- CMV
- giardia lamblia - very common parasite which exists in immunocompetent people
- whipple’s disease: Infective disease via Tropheryma whippelii >>>>Infection of macrophages which involves the duodenum >>>malabsorption
Which HLA molecules are associtaed with Coeliac disease?
HLA-DQ2 and HLA-DQ8
I 8 2 much
Pathophysiogy of coeliac disease
- T cell response
- gliadin in gluten is deamidated by TTG enzyme
- deamidated gliadin is presented by APC to cytotoxic T cells which then activate intra-epithelial lymphocytes leading to duodenal epithelial damage - antibody response
- gliadin presented by APC–> T cells
- T cells –> B cells
- B cells produce high affinity isotype switched antibodies following germinal centre reaction
Gold standard for serological testing of coeliac disease
IgA anti-TTG antibodies
IgA is more sensitive than IgG
*but not as useful in IgA deficient individuals*
*can also use anti endomysial antibodies*
Gold standard for diagnosis of coeliac disease
Distal duodenal biopsy
*must be distal because brunner’s glands in proximal duodenum distort the arhcitecture*
Findings:
- villous atrophy: smaller + flatter
- crypt hyperplasia: proliferating to regeneratre the damaged Villi
–> decrease in villous:crypt ratio
-high intraepithelial lymphocytes
NB: must be on gluten rich diet at the time of the biopsy
marker of intestinal metaplasia
goblet cells in the stomach, they should normally have no goblet cells in the stomach
Complications of coeliac disease
Nutritional deficiencies
- iron
- vitamin B12
- folate
- vitamin D and vitamin K
MALToma
- enteropathy associated T cell lymphoma (=/= B cell lymphoma)
Conditions similar to coeliac disease
- lymphocytic duodenitis
- similar to coeliac- increased intraepithelial lymphocytes
- but no change in villous: crypt architecture - tropical sprue
- similar histology but different cause - in tropical regions
Spread of squamous cell carcinoma of the oesophagus
Rapid growth and early spread (to LNs, liver and directly to proximal structures) –> palliative care
Complications of chronic gastritis
1) gastric ulcer
2) cancer (metaplasia–>dysplasia)
Gastric vs duodenal ulcer
Gastric: worse with food, responds to PPIs. can be malignant. more common in elderly.
Duodenal: better with food. not malignant. more common in young adults.
duodenal is more common than gastric
Description of H pylori gastric ulcer
Punched out lesion with rolled margins.
what will happen if there is atrophy and inflammation of the body of the stomach
inflammation and atrophy of the body will produce hypochlorhydria and blocks Interferon production
- Intrinsic factor secretion also occurs from body of stomach
- marker for intestinal type epithelium
glandular epithelium with goblet cell
what does lymphoid follicles in the stomach indicate
past or current has H. pylori infection
Normally you do NOT see lymphoid follicles in the normal stomach
marginal zone lymphocytes (which are around the follicles) proliferatre to cause MAlToma
what are oesophageal varices
dilated varicose veins in the submucosa
other causes of gastritis:
Infection
- Stronglyoides – immunosuppressed patients
- Candida is the most common in the oesophagus
- Occurs especially in the immunosuppressed (H. pylori oesophagitis is very common)
- CMV is the commonest opportunistic viral infection
Inflammatory bowel disease
- Crohn’s disease
- (lips to anus)
- See granulomas and focal inflammation
difference between acure ulcer vs chronic ulcer
chronic ulcer- scarring + fibrosis = irreversible + lymphocyte predominant
acute ulcers- reversible + neutrophil predominant
epidemiology of gastric cancer
- High incidence in Japan, Chile, Italy, China, Portugal, Russia
- More common in men than women (1.8 M: 1 F)
most common cause of gastric and duodenal ulcerations:
H. pylori
Palpable lymph node in supraclavicular fossa
troissier’s sign
The stomach mucosa is normally lined with which cell type?
simple columnar
What type of epithelium is oesophagus made of?
stratified squamous epithelium with glands in submucosa
