Histopath of upper GI Flashcards
What stains can be used on tissue sections? What structures do they stain?
Haematoxylin and eosin (H&E)
H: purple blue basic stain, stains acidic macromolecules e.g DNA, RNA
E: Pink acidic stain, stains basic macromolecules e.g. cytoplasm, collagen
Periodic acid Schiff (PAS): detects glycogen
Alcian blue: detects mucin
Masson’s trichome: detects collagen etc
Perl’s: detects iron
What is epithelium?
type of tissue, of lots of closely packed cells with little or no ECM
Usually form membranes or gland lining
Epithelium is separated from connective tissue by basement membrane
Diverse functions: protection (skin), secretion/excretion
What are the different types of epithelium? What kind of epithelial cells exist?
Types:
simple = one cell layer, direct contact with basement membrane
Stratified = more than one cell layer. Most superficial cells, furthest away from basement epithelium, are squamous cells. Deeper layers are usually columnar or cuboidal cells
Pseudo-stratified = one cell layer but arranged so that it looks multi-layered
Cell types:
squamous
columnar
cuboidal
What is squamous epithelium?
Generally flat cells found in simple epithelium structures where there is direct contact between cells and the basement membrane
Squamous epithelium allow for the passage of small molecules either via filtration or diffusion
Found in capillaries, glomeruli and alveoli
What is columnar epithelium?
Lines most organs of the digestive tract e.g. small intestine, stomach etc
Also found in the uterus
Often narrow and slender in shape
They may contain microvilli on their apical surfaces
And secrete digestive enzymes to help absorb nutrients
Height of cells is usually ~4x its width
What is cuboidal epithelium?
cube-shaped cells
Found in lining of kidney tubules and respiratory bronchioles
main functions include absorption, secretion and excretion
can be arranged as either simple or stratified epithelium
What is transitional epithelium?
type of stratified epithelium
consists of multi-layered epithelium, which can contract and expand to adjust to function.
Lines organs of urinary system
e.g. urothelium
What is connective tissue?
Composed of ECM and a few cells
Provides structural and metabolic support
What is in extracellular matrix?
Fibres: collagen, elastin
Amorphous ground substance: a gel like substance
extracellular fluid
Which cells are present in connective tissue?
fibroblasts
adipocytes
macrophages
lymphoid cells (e.g. plasma cells, leukocytes)
What is cartilage?
Functions as supporting framework Types: hyaline (articular surfaces of bone) elastic (ear) fibrocartilage (intervertebral disks)
What is the function of bone?
support
protection
site for haematopoiesis
What are the different types of muscle?
Cardiac
Skeletal
Smooth
What is the nature of cardiac muscle?
striated
contains a centrally located nucleus
What is the nature of skeletal muscle?
attached to skeleton
striated
long cylindrical fibres with an eccentric nuclei
What is the nature of smooth muscle?
Present in hollow viscous organs
shorter cells with centrally placed nuclei
No striations
What is the nature of CNS nervous tissue?
neurons
supporting cells: microglia, Schwann cells
What is the nature of PNS nervous tissue?
bundles of parallel elongated nerve fibres (axons)
wavy, zig zag formation
oligodendroglia
astrocytes
What is pathology?
study of disease
What is histopathology?
study of cells and tissues at microscopic level to investigate disease
gold standard tests for diagnosis
What is metaplasia?
Reversible transformation of one differentiated cell type into another differentiated cell type
What is dysplasia?
Premalignant change within the epithelium
Dedifferentiation of a mature cell type
loss of maturation
Usually caused by a developmental abnormality not an acquired defect
What is neoplasia?
Abnormal or excessive cell growth
can be benign or malignant
What are the main tissue layers of the GI tract?
lumen Mucosa (epithelium, lamina propria, muscularis mucosae) submucosa muscularis propria subserosa serosa/adventitia
What sublayers are present in the muscularis propria layer of the GI tract?
towards lumen
circular muscle
longitudinal muscle
What kind of epithelium lines the oesophagus?
squamous epithelium
Describe the nature of the squamous epithelium that lines normal oesophagus
Superficial cells (near surface) flatten as they mature upwards Round Prickle cells exist deep into the epithelium near the basement membrane. These cells contain intercellular bridges
Basal layer adjacent to basement membrane contain stem cells
How does GORD/GERD affect squamous epithelium lining the oesophagus?
Damage to mucosa (erosive/non-erosive)
Infiltration of damaged mucosa (impaired barrier function) with neutrophil polymorphs and eosinophils
Basal cell hyperplasia following epithelium proliferation to replace damaged cells
What histopath changes can be observed for GORD/reflux oesophagitis?
erythema patches in lower oesophagus caused by inflammation secondary to acid reflux
Infiltration of epithelium lining with inflammatory immune cells
hyperplastic basal cell zone (layer immediately adjacent to basement membrane)
What are the main tissue complications of GORD?
Peptic ulceration (acid-induced benign ulceration)
Replacement of squamous mucosa by glandular mucosa
Columnar metaplasia = Barrett’s oesophagus
Development of dysplasia in Barrett’s oesophagus
Development of adenocarcinoma in Barrett’s oesophagus
What are the structural indicators of peptic ulcerations in GORD?
overhanging ulcer edges of mucosa layer (adj to lumen)
inflammatory slough within fibrin on surface of ulcer
granulation tissue at base of ulcer
granulation = fibrosis and angiogenesis
How can peptic ulcers in GORD heal leading to further complications?
Formation of benign peptic stricture at gastro-oesophageal junction due to scar tissue
This may complicate reflux oesophagitis
How does an ulcer look in histopathology?
Well-defined margins
Clean base
What histopathological change is defined by Barrett’s oesophagus?
metaplasia from squamous mucosa to columnar mucosa
The latter is found normally in small and large intestine lining
There may also be abnormal interspersed goblet cells found in Barrett’s oesophagus, but this is not a structural requirement for Dx according to british guidelines
Under which condition can metaplasia be reversible?
If stimulus causing damage/metaplasia is removed
e.g. gastric acid can be suppressed using PPIs
What is dysplasia characterised by?
impaired cell differentiation: disorganised often failure to mature towards surface
atypical nuclear features: pleomorphism
increased or abnormal number of mitosis reactions
Describe the dysplasia that occurs in Barrett’s oesophagus
Nuclei multilayering in surface epithelium
hyperchromatism (excess chromatin)
pleomorphism (variable cell size and shape)
increased mitoses
Why does adenocarcinoma resulting from GORD present with dysphagia?
Luminal narrowing
Infiltration of oesophageal walls with tumour cells
These inhibit peristalsis
What is the classic histopathological signature for adenocarcinoma of the oesophagus?
Diffuse signet-ring cell type
This type of cell has a large vacuole which is seen as a marker of malignancy in carcinomas
Where is squamous cell carcinoma of the oesophagus most commonly found?
Mid or upper oesophagus
~40% incidence in west
Where does adenocarcinoma of the oesophagus most commonly found?
Just above or below the gastro-oesophageal junction
~60% incidence in west
Globally, which type of oesophageal cancer is more common?
Squamous cell carcinoma
What are the main tissue layers of the stomach?
lumen mucosa submucosa muscularis propria serosa
The body and fundus of the stomach have specialised gastric mucosa function. What is the nature of this?
Mucous neck cells secrete mucus blanket over the mucosal surface: protection from digestive enzymes and acid
Deeper specialised body-type glands
What 2 cell types are present in the specialised gastric mucosa of the gastric fundus and body?
Parietal cells: pink staining following H&E, secrete acid
Chief cells: purple staining following H&E stain, secrete pepsinogen
The gastric antrum and pylorus contain non-specialised gastric mucosa. What are the main features of this?
Mucus blanket present over luminal surface
Mucus secreted and made by mucous neck cells in crypts
Mucous glands are found deeper in tissue
And even deeper to that are endocrine cells (e.g. S and G cells) not seen on routine H&E staining
What are the main normal protective mechanisms found in the stomach?
Pepsin secreted as inactive zymogen (pepsinogen), only activated at low pH
Mucus blanket continuously secreted and maintained by mucous neck cells
Bicarbonate buffer secreted by epithelial cells in gastric neck/isthmus
What may interfere with the normal protective mechanism found in the stomach?
H. pylori infection
Drugs e.g. aspirin, NSAIDs
Alcohol
Impaired mucin neck cells can result from excessive inflammatory stimulation -> impaired mucus blanket
Bicarbonate secretion is stimulated by prostaglandins
NSAIDs therefore will block PG synthesis and therefore bicarbonate secretion
What are the main complications of peptic ulcers in the stomach or duodenum?
iron deficiency anaemia (occult bleeding from small damaged vessels) Haematemesis or malaena (erosion of a major blood vessel, can cause shock or death) Perforation into peritoneal cavity (can cause chemical peritonitis, shock and death) erosion into adjacent organ/structures (e.g. pancreas) Scar formation (contraction of scar may cause stricture or obstruction or hourglass stomach)
What is the ‘hourglass stomach’ complication of peptic ulcers?
Deformity in the waist of the stomach such that it is constricted by fibrosis or scar formation
Produced upper and lower cavity separated by a narrow channel in between
Can cause early satiation and occasionally projectile vomiting
What are two histopathological types of adenocarcinoma in upper GI tract?
Intestinal type (metaplasia to columnar epithelium) Diffuse signet ring cell type
How do intestinal type adenocarcinomas usually present?
As ulcers or polypoid tumours
Ulcerated adenocarcinomas have a ‘rolled’ everted edge not as distinct at the edge of a peptic ulcer
How do peptic ulcers and adenocarcinomas differ on a slide?
peptic ulcers: no epithelial cells in submucosa
Adenocarcinoma: invasion if the mucosa and submucosa
How do diffuse signet-ring cell carcinomas affect the integrity of the stomach?
Stomach can be shrunken, thickened and non-distensile
Patient may present with early satiety
