HISTO: Upper GI pathology Flashcards
What is the junction between the squamous and columnar epithelium in upper GI called?
Squamous and columnar junction = Z line
Which parts of the stomach have the most specialised glands? Where does H pylori usually affect?
Body and fundus contain the most specialised glands (create acid + enzymes)
Antrum (+pyloric canal) are often where you find H. pylori associated gastritis
What cells are not usually seen in the stomach?
Goblet cells - their presence in the stomach is a feature of intestinal metaplasia
Which part of the upper GI tract is this? What are the labels?
Stomach body
Columnar epithelium, specialised glands in lamina propria, ,uscularis mucosa
Which part of the upper GI tract is this? What are the labels?
What is the sequence of histological layers of the oesophagus?
Mucosa (epithelium –> lamina propria –> muscularis mucosa) –>
submucosa –>
muscularis propria
How do cells in villi shed?
The cells proliferate in the crypt and then migrate upwards to the tip of the villous and shed at the top
When the villi get damaged, the crypts will proliferate to replace the damage villi
What type of cells make up the duodenum?
Length = ~2: 1 “villous: crypt ratio”
What is shown? What cells are present in the squamous epithelium?
Acute oesophagitis
Usually due to reflux or toxic substances
Neutrophils shown in squamous epithelium
What are the most common causes of acute oesophagitis?
GORD
What is the difference between erosion vs ulcer?
Ulcer = past muscularis mucosa (into submucosa)
Erosion = before muscularis mucosa (not into submucosa)
What are the complications of reflux oesophagitis?
- Perforation
- Ulceration
- Haemorrhage
- Stricture
- Barrett’s oesophagus
What are the histological signs of ulceration?
- Necrotic slough
- Inflammatory exudate
- Granulation tissue
What is Barrett’s oesophagus? What are the two types?
Columnal lined oesophagus (CLO) is AKA Barrett’s
Replacement of squamous by metaplastic columnar epithelium
2 types
- Without goblet cells: gastric metaplasia
- With goblet cells: intestinal type metaplasia
Which type has the higher risk of cancer in CLO?
Goblet cells present - CLO with intestinal metaplasia
What is the sequence that leads to formation of cancer in e.g. CLO?
- (1) Metaplasia = not pre-malignant because reversible
-
(2) Dysplasia = changes showing some of the cytological + histological features of malignancy but with no invasion through the BM
- Low grade
- High grade
- (3) Adenocarcinoma = abnormal cells invade through the BM
What is the difference between phenotype of progression to cancer between the lower and upper GI tract?
- Polyp pathway (lower GI pathway)
- Flat pathway (upper GI pathway; metaplasia (i.e. CLO ± IM) –> dysplasia –> cancer)
Where is adenocarcinoma of the oesophagus usually found?
- Lower oesophagus
- Developing countries most common
- Due to reflux
Below: gland formation + mucus secretion = most common
What are 2 associations/RFs for adenocarcinoma of the oesophagus?
GORD, Barrett’s oesophagus
What is seen histologically in adenocarcinoma of the oesophagus?
Glandular epithelium
Mucin
Where is SCC of oesophagus most common?
In developing countries
Alcohol smoking
Upper/mid oesophagus
Below: intercellular bridges + keratin production
What are 2 associations/RFs for SCC of the oesophagus?
Smoking and alcohol
What is seen histologically in SCC of the oesophagus?
Invasion of submucosa
Cells forming keratin (defining feature)
Cells that have intercellular bridges
What is the prognosis of oesophageal carcinoma?
- Poor prognosis
- Best to diagnose at pre-invasive stage (probably soon to be introduced in UK)
What is shown?
Oesophageal varices - most commonly due to portal HTN and cirrhosis; tortuous dilated vessels shown including a thrombosed vessel, there is a thin layer of mucosa which can cause bleeding easily
What is gastritis? What are the two types?
Inflammation of gastric mucosa
Acute and chronic can occur.
What are the causes of acute gastritis?
Chemical:
- Aspirin/NSAID
- Alcohol
- Corrosives
Infection e.g. H pylori
What are the causes of chronic gastritis?
- Autoimmune (antiparietal Abs etc against body) -additional one which does not cause acute
- Bacteria (H pylori affecting antrum)
- Chemical (NSAIDs, bile reflux into antrum)
- Remember the parts invovled*
- [D = IBD?]*
What type of cells infiltrate in acute vs chornic gastritis?
Neutrophils in acute
Lymphocytes in chronic (but may see coexisting neutrophils sye to acute inflammatory processes which may be ongoing)
What is the pattern and outcome/complications of H pylori associated gastritis?
H. pylori –> chronic gastritis +/- acute episodes
Outcomes/complications:
- CLO-IM-dysplasia,
- adenocarcinoma,
- lymphoma (MALToma)
What is shown?
H pylori
Where mouse is pointed there are H pylori which are said to look like seagulls
What is cag-A-positive H pylori associated with? What is its phenotype?
cag-A-positive H pylori have a needle-like appendage which injects toxin into intracellular junctions allowing the bacteria to attach more easily (H pyolori do not invade the epithelium)
These strains are associated with more chronic inflammation
What is the -fold change in risk of non-cardia gastric cancer in the presence of H pylori compared to absence?
x8
Treatment of the infection with antibiotics drastically reduces the risk of cancer
How does gastritis progress to cancer?
- Chronic gastritis –>
- Intestinal metaplasia –>
- Dysplasia –>
- Cancer
What is shown?
Gastric ulcer - always requires biopsies to exclude malignancy.
How many layers do gastric ulcers infiltrate?
Depth of the loss of tissue goes beyond the muscularis mucosa (into the submucosa)
What are the complications of ulcers?
- Bleeding –> anaemia, shock (massive haemorrhage)
- Perforation –> peritonitis
What is shown in this gastric slice?
Gastric intestinal metaplasia (because goblet cells are present)
What is shown in this gastric slice in terms of the pathway to progression to cancer?
Gastric epithelial dysplasia- abnormal epithelial pattern of growth shown; some cytological / histological features of malignancy but no invasion through the basement membrane
What is shown in this gastric slide?
Gastric epithelial dysplasia
No invasion of BM
Abnormal epithelial pattern of growth
How common is gastric cancer in males vs females? Which regions globally?
- High incidence in Japan, Chile, Italy, China, Portugal and Russia
- M: F ratio = 1.8: 1 (more common in men)
What are the risk factors for gastric cancer?
- Host genetic factors
- Bacterial virulence factors (i.e. Cag-A)
- Environmental factors
- Gastric cancer phenotypes
What are the two types of gastric adenocarcinomas (gastric cancers)?
-
Intestinal - well-differentiated
- Mucin-containing big glands
-
Diffuse - poorly differentiated
- Composed of single cells with no attempt at gland formation
- Types = Linitis plastica, Signet ring cell carcinoma (spreads all over stomach)
What is the prognosis with gastric cancers?
Prognosis: overall survival rate = 15%
What is a characteristic histological feature of H pylori?
Lymphoid follicles
These shoud not be seen in the stomach otherwise. Crypts full of neutrophils coexisting would also mean MALToma which can be treated with Abx in this case.
Apart from adenocarcinomas, what are the other gastric cancers?
- Squamous cell carcinoma
- Lymphoma (MALToma – a B-cell NHL):
- Gastrointestinal stromal tumour (GIST)
- Neuroendocrine tumours (i.e. Zollinger-Ellison syndrome)
Adenocarcinomas make up 95%, these make up the remaining 5%
What are the causes of gastric MALToma? How can they be cured early on?
- Driven by chronic inflammation (chronic immune stimulation)
- B cell (marginal zone) lymphocytes
- You should not see lymphoid follicles in the stomach (if you do, patient has H. pylori)
If someone has H. pylori as well as lymphoma, you will see crypts that are full of neutrophils = good because if you treat H. pylori, the lymphoma could be reversed
Treatment = CAP (Clarithromycin, Amoxicillin, PPI)
What are the causes of duodenitis/duodenal ulcer?
Increased acid production in stomach (pre-antral) can spill into stomach and less duodenal HCO3-
Most still caused by H pylori
(NB: H pylori leads to many gastric ulcers but it causes virtually all of duodenal ulcers)
Duodenitis and Duodenal ulcers have a good correlation between endoscopy and biopsy
What are the other causes of duodenal ulcer?
- Immunosuppression
- CMV
- Cryptosporidium
- Giardia lamblia
- Whipple’s disease (Tropheryma whippelii) / parasites
What is shown in this malabsorption disorder?
- Flattening i.e. villous atrophy (normal villous:crypt ratio is >2:1)
- Crypt hyperplasia
- Increased intraepithelial lymphocytes (normal range is <20 per 100 epithelial cells)
Malabsorption –> partial vilous atrophy
What is the diagnosis and what other factors are important for diagnosis?
Coeliac disease
Diagnosis required:
- Endomysial antibodies - anti-EMAs
- Tissue transglutaminase antibodies - anti-TTG
- Duodenal biopsy (on diet containing gluten)
What does a duodenal biopsy in Coeliac patients look like when on a diet not containing gluten?
Normal
What other condition can mimic the duodenal histology in Coeliac disease?
Tropical sprue - another type of malabsorption disorder
What is the difference between Coeliac disease and lymphocytic duodenitis histology?
Coeliac’s Disease -
- architectural changes (loss of villi and crypt hyperplasia)
- inflammatory changes (increased intraepithelial lymphocytes)
Lymphocytic Duodenitis -
- inflammatory changes (increased intraepithelial lymphocytes)
- without architectural changes*
*many people with this either have Coeliac’s or are going to develop Coeliac’s
What are the complications of Coeliac disease? Where does this occur and which type?
Duodenal MALToma/lymphoma
This is usually:
- In the duodenum
- T cell origin lymphoma (called EATL- Enteropathy-associated T-cell lymphoma)
True or false: most oesophageal and gastric cancers arise from pre-existing adenomas.
False
Flat dysplasia pathway - not from adenomas
3
4 - metabolic disease
(ABC acronym for causes of chronic gastritis)
