HistoPath - Upper GI Flashcards
What is the z-line in the oesophagus
the point at which epithelium transitions from being stratified squamous epithelium to columnar
What are the layers of the oeseophagus
Epithelium
Submucosa
Muscularis externa
What is the gross structure of the stomach
Inlet: cardia
Fundus → body → antrum → pylorus
What do the presence of goblet cells in the stomach suggest
goblet cells are NOT normally seen in the stomach
The presence of goblet cells in the stomach is a feature of intestinal metaplasia
What are the layers of the normal stomach body and antrum, and what is the difference between them
- Gastric mucosa columnar epithelium (foveolar, mucin secreting)
- Lamina propria
- Muscularis mucosa
Body: lamina propria has specialised glands
Antrum: non-specialised glands, lacks specialised cells
What is the villous:crypt ratio in the duodenum and what happens the villi and crypt during proliferation
2: 1 villous: crypt ratio
When the villi get damaged, the crypts will proliferate to replace the damage villi
The cells proliferate in the crypt and then migrate upwards to the tip of the villous and shed at the top
What type of epithelium is found in the duodenum
Glandular epithelium with goblet cells (intestinal type)
What are the histological features of acute oesophagitis
Neutrophils
gross: Redness and inflammation of the oesophagus
What are the complications of acute oesophagitis
Ulceration:
- Necrotic slough
- Inflammatory exudate
- Granulation tissue
Fibrosis
Haemorrhage
Perforation
Stricture
Barrett’s oesophagus
What is the difference between an ulcer and an erosion
Ulcer = depth of tissue loss goes past muscularis mucosa (into submucosa)
Erosion = depth of tissue loss stops before muscularis mucosa (not into submucosa)
What is Barrett’s oesophagus
columnar-lined oesophagus (CLO)
Metaplastic process where squamous epithelium of the lower oesophagus is replaced by columnar epithelium
Reversible process
What are the two main types of Barrett’s oesophagus
CLO (metaplasia WITHOUT goblet cells = gastric metaplasia (Columnar epithelium)
CLO with IM (metaplasia WITH goblet cells = intestinal metaplasia (IM) = higher cancer risk)
What are the pathways to cancer in the GI tract
Flat pathway
Upper GI
Metaplasia → dysplasia → cancer
Polyp pathway
Lower GI
Adenoma precursor common
Describe the flat pathway to cancer development
(0) Squamous epithelium
(1) Metaplasia = not pre-malignant because reversible (however, metaplasia can progress to dysplasia)
(2) Dysplasia = changes showing some of the cytological and histological features of malignancy but with no invasion through the basement membrane (this is the stage that screening identifies at)
1. Low grade
2. High grade
(3) Adenocarcinoma = abnormal cells invade through the basement membrane
Can spread underneath the columnar epithelium
Describe adenocarcinoma of the oesophagus (site, causes, histological features)
Most common oesophageal cancer in developed countries
Lower 1/3 of the oesophagus
Associated with GORD and Barrett’s
All adenocarcinomas make glands and secrete mucin
Histology: mucin | glandular epithelium
Describe squamous cell carcinoma of the oesophagus (site, causes, histological features)
Upper 2/3 most common mid-oesophagus)
Associated with smoking and alcohol
Histology: Invades submucosa | cells produce keratin | intercellular bridges
What is the prognosis for oesophageal carcinoma
Poor prognosis
Diagnosis at pre-invasive stage is important
What are the features of oesophageal varices
Portal HTN
Porto-systemic anastomoses
Haemorrhoids
High mortality from bleeding and rebleeding
What is gastritis
Inflammation of the gastric mucosa
What are the causes of acute gastritis and what type of cells are involved
Chemical = Aspirin/NSAIDs, Alcohol, Corrosives
Bacterial = H. pylori, other (CMV, strongyloides in immunocompromised people)
Neutrophils
What are the causes of chronic gastritis and what type of cells are involved
Autoimmune (atrophic) = autoantibodies (i.e. anti-parietal cell ABs) BODY
Bacterial (atrophic/ non-atrophic) = H. pylori, other (CMV, strongyloides) ANTRUM
Chemical (NSAIDs, bile reflux) ANTRUM
D = Inflammatory Bowel Disease (Crohn’s)
Lymphocytes (may have co-existent neutrophils due to co-existent acute inflammatory processes)
What is the link between H. pylori and gastric cancer
Whilst H. pylori can bind to epithelial cells and inject toxins into intercellular junctions, they do NOT directly invade the epithelium
Can lead to CLO-IM-dysplasia, adenocarcinoma or lymphoma (MALToma)
8x fold increase in risk of gastric cancer
Chronic infection → MALToma (Abx can reverse lymphoma before it transforms)
What cancers are associated with atrophic and non-atrophic disease of the stomach
Atrophic → adenocarcinoma
Antrum-predominant gastritis
duodenal ulcer
Non-atrophic → MALToma
Non-atrophic pan-gastritis
MALToma
How does the site of gastritis within the stomach affect the outcome
Antrum predominant (atrophic) → duodenal ulcer
Body-predominant (atrophic) → gastric ulcer, adenocarcinoma (flat pathway)
Pan-gastritis (non-atrophic) → MALToma
What are the two pathways that lead to GI cancer development
Metaplasia-Dysplasia Pathway (Upper GI: i.e. oesophageal cancer)
Adenoma-Carcinoma Pathway (lower GI: i.e. colon cancer)
What is the difference between acute and chronic ulcers
Fibrosis is present in chronic ulcers
IN acute ulcers (no fibrosis), they can heal
What are the complications of ulcers
Bleeding → anaemia, shock (massive haemorrhage)
Perforation → peritonitis
What investigation must be done if someone presents with a gastric ulcer
All ulcers should be biopsied to exclude malignancy
What is gastric intestinal metaplasia, what is it caused by and what is it associated with
Presence of goblet cells in the mucosa of the stomach
Occurs in response to long term damage
Isn’t itself cancerous/pre-cancerous but can lead to dysplasia and is associated with an increased risk of cancer
What is gastric epithelial dysplasia
Abnormal epithelial pattern of growth - pre-invasive stage of gastric cancer
Some cytological / histological features of malignancy but no invasion through the basement membrane (therefore non-cancerous)
What are the risk factors for Gastric cancer
Host genetic factors
Bacterial virulence factors (i.e. Cag-A)
Environmental factors
Gastric cancer phenotypes
(Japanese ethnicity, male sex)
What are the types of gastric cancer
Adenocarcinoma (>95%)
Squamous cell carcinoma
Lymphoma
Gastrointestinal stromal tumour (GIST)
Neuroendocrine tumours e.g. Zollinger-Ellison syndrome
What are the types of adenocarcinoma of the stomach and their histological features
Intestinal (L): well-differentiated
Mucin-containing big glands
Diffuse (R): poorly differentiated
Composed of single cells with no attempt at gland formation - no architecture
Types = Linitis plastica, Signet ring cell carcinoma (spreads all over stomach)
Describe lymphoma of the stomach and its histological features
MALToma - B-cell Non-hodgkin’s
Driven by chronic inflammation (associated with H. pylori)
→ development of lymphoid follicles in germinal centres
→ B cell (marginal zone) lymphocytes
What is the prognosis for gastric cancers
15% survival rate
What do lymphoid follicles on biopsy of the stomach suggest and what is the treatment
Suggests that there is H. pylori infection (Lymphoid follicles are NOT present in normal mucosa)
The lymphoma can reverse with Abx treatment if there is H. pylori infection (neutrophils in crypts)
Treatment = CAP (Clarithromycin, Amoxicillin, PPI)
How does H. pylori infection impact the duodenum
Increased acid in the antral-predominant strain that spills into duodenum + less duodenal HCO3-
Chronic inflammation leads to gastric metaplasia with H. pylori (intestinal epithelium will change to look more like gastric epithelium because gastric epithelium is well designed to deal with acid)
Chronic inflammation can also lead to duodenal ulceration
What other pathogens can cause duodenal ulcers
Giardia lamblia (Traveller’s diarrhoea)
CMV
Cryptosporidium (issue for pets)
Whipple’s disease (Tropheryma whippelii)
What are the histological features of malabsorption (partial villous atrophy)
Villous atrophy (i.e. flat villi)
Crypt hyperplasia (occurs in an attempt to regenerate the damage villi)
Increased intraepithelial lymphocytes [Normal range: <20 per 100 epithelial cells]
What are the histological features of coeliac disease
architectural changes (loss of villi and crypt hyperplasia) with co-existent inflammatory changes (increased intraepithelial lymphocytes)
T-cell resonse to gliadin
What is 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 investigations are done for coeliac disease
AEndomysial Antibodies (anti-EMAs)
Tissue Transglutaminase Antibodies (anti-TTG ABs)
Duodenal biopsy (villous atrophy if on gluten diet, normal villi if gluten-free)
What do the following histological features suggest for coeliac disease:
Villous atrophy with increase in intra-epithelial lymphocytes -
Villous atrophy with no increase in intra-epithelial lymphocytes
No villous atrophy with increase in intra-epithelial lymphocytes
Villous atrophy with increase in intra-epithelial lymphocytes - coeliac
Villous atrophy with no increase in intra-epithelial lymphocytes - Recently stopped the gluten-rich diet
No villous atrophy with increase in intra-epithelial lymphocytes - Early coeliac disease
What infection gives a similar histological picture to coeliac disease
tropical sprue
What type of lymphoma are duodenal lymphoma/MALToma and what are they associated with
T cell lymphomas (EATL)
Associated with coeliac disease
