tbl 2 stomach pathology Flashcards
Gastritis – a form of inflammatory mucosal injury
- Seen on endoscopy usually as __________ – can be confirmed by biopsy
- Histologically, we can classify gastritis based on the type of inflammatory cells
Acute (active): ________ seen
Chronic Chronic inflammatory cells seen
Acute on chronic (chronic active) Both neutrophils and chronic inflammatory cells seen
Gastropathy: Mucosal injury with ______________ but
inflammatory cells are few or absent
erythema and redness; Neutrophils; regenerative epithelial changes
Aetiology of gastritis
- Normally – 1st line of defence against damaging forces is mucous secreted by ________ cells that are impermeable to acid and pepsin
o _______ supports the production of mucus and bicarbonate
o Mucosal blood flow helps remove acid that has infiltrated the mucosa and ________ helps to remove H+ ions from cells
- In injury – balance is disrupted, leading to mucosal damage
o There is a decreased or absent mucous layer with damaged epithelium and chronic inflammatory cells at the __________
o If insult persists, injuries can persist to ulcers
foveolar; Prostaglandin; epithelial ion pumps; lamina propria
Classification of gastritis
- Acute gastritis: Often temporary due to injurious insult
- Chronic gastritis: Typically H. Pylori with a small subset of autoimmune conditions
- ___________ – bile reflux or drug-related e.g. NSAIDs
- Hypertrophic gastritis (rare)
- Special types: Lymphocytic, eosinophilic and granulomatous gastritis
- Erosions – focal loss of _______ leading to a superficial mucosal defect
- Ulcers – mucosal defect extending into _______ or deeper
o All ulcers begin as erosions but not all erosions progress to ulcers
Chemical gastritis; epithelium; submucosa
Acute gastritis
- Due to sudden abrupt mucosal injury
- Ranges from mild inflammation to multiple
erosions and deeper ulcers affecting all parts of stomach
- Chemical injury – NSAID, alcohol
- Stress related (ischaemic injury) – shock (stress ulcers), severe burns (______ ulcers), raised intracranial pressure (________)
- Based on severity –
acute, acute erosive, acute erosive haemorrhagic gastritis - Symptoms – asymptomatic to dyspepsia/
_________ pain/ hematemesis - Healing occurs after removal of the injurious agent
Curling’s; Cushing ulcers; epigastric
Chronic gastritis
- Due to H.pylori or autoimmune conditions (a smaller subset)
- Location – antral, corpus, _____ gastritis
- Histology – chronic inflammatory cells, glandular atrophy and _____ metaplasia, fibrosis
- Infiltrates include lymphocytes and plasma cells
- Atrophy – loss of glands (specialised glands in the body and mucosal glands in the ______) with eventual replacement by metaplasia, commonly intestinal metaplasia
- Pattern of involvement can be diffuse or patchy or multifocal
pan; intestinal; antrum
Chronic H. Pylori gastritis
- Chronic active gastritis with chronic inflammatory infiltrate in the superficial mucosa consisting mainly of plasma cells and lymphocytes
o In addition, active inflammation can be seen with ____________ in lamina propria. - Lymphoid follicles may be present
- Curved H. Pylori organisms clustered in the surface mucus overlying ____________ and within gastric pits
- Antrum is always affected – may progress to __________ at a later stage
o Atrophy with intestinal metaplasia, multifocal in chronic inflammation - H. Pylori gastritis can progress to –
o Pangastritis, leading to eventual _______ and carcinoma
o Antral-predominant gastritis, leading to ___________ due to hyperacidity
intraepithelial neutrophils; surface foveolar cells; pangastritis; dysplasia; duodenal ulcers
Helicobacter Pylori – adapted to colonise in the harsh acidic environment of the stomach
- Present on the surface of foveolar cells, residing on the thin layer of mucous
- ________ on the outer layer, flagella for motility in mucus
- Produces urease that produce ammonia, increases pH, increases ____________ (damages the DNA) – urease is implicated in the development of neoplasias
- Adhesins – adhere to foveolar cells
- Toxins and CagA – cytotoxic associated gene A that damages cells leading to gastritis
Lipopolysaccharides; nitrosated compounds
Chronic autoimmune gastritis
- Diffuse damage of oxyntic mucosa of the body and fundus due to chronic inflammatory infiltrate in the lamina propria especially in the deeper parts of the mucosa
- Leading to diffuse atrophy, intestinal metaplasia mainly affecting the ___________ (antrum is not affected)
- Hyperplasia of __________- cells
Atrophy – multifocal and diffuse
- Normal body fundus – surface foveolar epithelium and __________ secretory glands
- Body atrophy and intestinal metaplasia – expanded lamina propria and chronic inflammatory cells, less specialised gastric glands, surviving glandular tissue shows intestinal metaplasia
o Chronic atrophic gastritis of body mucosa with intestinal metaplasia
- Both H. Pylori infection and autoimmune gastritis can lead to atrophy
body and fundus; neuroendocrine; tightly packed
Comparison of H. Pylori and autoimmune gastritis
- H.pylori is located at the _____ while autoimmune is located at the ____________
- Acid in the H.pylori is increased to slightly decreased while acid is decreased in autoimmune
- Inflammatory cells in H.pylori are ____, ____ while those in autoimmune are ____, _____
- H. pylori vs antibodies vs ______ cells antibodies
- atrophy in H.pylori is ____ while that in autoimmune is ____
- sequelae: ulcer, Intestinal Metaplasia, adenocarcinoma, MALT, MALToma for H.pylori and atrophi, vitamin B12 deficiency, pernicious anaemia, IM, adenocarcinoma, endocrine cell hyperplasia, carcinoid in autoimmune.
antrum, body & fundus;
neutrophils and plasma cells; lymphocytes & macrophages;
parietal cells
multifocal; diffused
Hypertrophic gastropathy
- Giant gastric rugal folds on endoscopy, with no inflammation
- Hyperplasia of
o Foveolar cells – Menetrier’s disease (present with _____________), risk of adenocarcinoma
o Specialised gland layer – Zollinger Ellison syndrome – multiple intractable peptic ulcers, hyperacidity, gastrinomas, MEN
§ Gastrinomas – gastrin-secreting gastrinomas at the ______________
Protein losing enteropathy;
pancreas and the small intestine
Special types of chronic gastritis
- Lymphocytic gastritis (intraepithelial lymphocytes) – associations with _______
o Similar patterns can be seen in some cases of H. Pylori infection
- Granulomatous gastritis – idiopathic or systemic, isolated granulomas of the stomach
o Infectious causes such as ______ needs to be excluded
- Eosinophilic gastritis (eosinophilic infiltrate) – allergic, food intolerances; part of eosinophilic enteritis
celiac disease; Crohn’s
Cases of long standing gastritis
Chronic gastritis with intestinal metaplasia: Tall, pale columnar mucous containing foveolar cells replaced by columnar cells with _________ cytoplasm (enterocyte-like) with interspersed ______. Lamina propria shows chronic inflammatory infiltrate.
High grade dysplasia
- Complex, crowded
glands lined by __________ nuclei and loss of ______. Both cytological and architectural changes are seen
Low grade dysplasia
- Atypical glands,
cells with hyperchromatic
basal nuclei
eosinophilic; goblet cells
hyperchromatic; polarity
Complications of chronic gastritis
- Peptic ulcer disease – especially with H. pylori or _______
- Intestinal metaplasia
- Dysplasia – low / high grade
- Adenocarcinoma
- Induced mucosa associated lymphoid tissue (MALT) (with H. pylori) later turning malignant which is ________
hyperacidity; lymphomas
Peptic ulcer disease
- Stomach or first part of duodenum or distal oesophagus – mucosa exposed to potentially injurious effects of acid and _______
- Causes – hyperacidity (important for development of
duodenal ulcers), H. pylori (PUD can also develop in
cases with low acid levels), infection, drugs (NSAID) or
smoking, reflux (_________ appears to be an important factor for gastric ulcerations)
- Peptic ulcers – clean and sharply punched out with radiating ___________, usually solitary (if multiple, may be indicative of ZES)
o ________ ulcers are more common than gastric ulcers (4:1) – H. Pylori accounts for >90%in duodenal and 70% in gastric ulcers
o Microscopy – ulceration with underlying granulation tissue and fibrosis, thick walled blood vessels with ____________ (erosion of these vessels may lead to haemorrhages)
- Mucosal defect extending into the submucosa with necrotic debris at the base,
underlying an acute infection
o Granulation tissue merging into fibrosis lying below
- Complications of PUD –
o Bleeding – 20%, commonest complication (25% of deaths)
o Penetrate full thickness
§ Can erode into pancreas or liver
§ Perforation of free wall of stomach – 5% (30% of deaths)
o Obstruction – rare 2%, in chronic ulcers with fibrosis, pylorus
§ Especially in the duodenum and pylorus – healing by fibrosis leads to
strictures resulting in gastric outlet syndrome
pepsin; bile reflux; rugal folds
Duodenal; endarteritis obliterans
Peptic ulcer disease
- Stomach or first part of duodenum or distal oesophagus – mucosa exposed to potentially injurious effects of acid and _______
- Causes – hyperacidity (important for development of
duodenal ulcers), H. pylori (PUD can also develop in
cases with low acid levels), infection, drugs (NSAID) or
smoking, reflux (_________ appears to be an important factor for gastric ulcerations)
- Peptic ulcers – clean and sharply punched out with radiating ___________, usually solitary (if multiple, may be indicative of ZES)
o ________ ulcers are more common than gastric ulcers (4:1) – H. Pylori accounts for >90%in duodenal and 70% in gastric ulcers
o Microscopy – ulceration with underlying granulation tissue and fibrosis, thick walled blood vessels with ____________ (erosion of these vessels may lead to haemorrhages)
- Mucosal defect extending into the submucosa with necrotic debris at the base, underlying an acute infection
o Granulation tissue merging into fibrosis lying below
- Complications of PUD –
o Bleeding – 20%, commonest complication (25% of deaths)
o Penetrate full thickness
§ Can erode into pancreas or liver
§ Perforation of free wall of stomach – 5% (30% of deaths)
o Obstruction – rare 2%, in chronic ulcers with fibrosis, pylorus
§ Especially in the duodenum and pylorus – healing by fibrosis leads to strictures resulting in ________________
pepsin; bile reflux; rugal folds
Duodenal; endarteritis obliterans
gastric outlet syndrome
Gastric dysplasia
- Dysplasia is a direct precursor of adenocarcinoma
o Marker of risk of gastric carcinoma elsewhere in stomach (12% according to a study in Japan)
- Increased severity of atrophy and extent of intestinal metaplasia is associated with an increased risk of cancer
o High grade dysplasia carries a significant risk of progression to __________ - Gastric biopsies are reported for dysplasia as – negative, indefinite, low and high grade (if present)
- Differentiation between high grade dysplasia and gastric tumours
o High grade dysplasia – invasion of the ___________
o In epithelial dysplasia, anaplasia (dedifferentiation) can be mild, moderate or severe
o Malignant neoplasia is a tumoral condition wherein dysplastic epithelium breaches the basement membrane and invade the underlying __________________
gastric adenocarcinoma; epithelial layer; connective tissue stroma
Gastric polyps
- Hyperplastic or regenerative polyps: Commonest (75%) –
elongation of _____________ - Fundic gland polyps: In gastric body or fundus – long-standing
____ therapy - Adenomatous polyps: risk of carcinoma
foveolae; PPI
Gastric tumours morphology:
- Large ________ nodular masses bulging into the lumen
- Ulcerative lesions and irregular ulcers surrounded by ______
- Linitis plastica – diffused thickening in the gastric wall by an infiltrating tumour. No polypoidal mass or ulcer but ________ are prominent
exophytic; rugae; mucosal folds
Gastric tumours microscopy:
- _________ of tumour cells
- Dyscohesive infiltrative tumour cells with ________ – each cell have globules of mucin pushing the nucleus to the periphery
Glandular pattern; signet cell rings
Classification of tumours
- Lauren Classification
- intestinal: Bulky masses or ____________. Glandular pattern Precursor – dysplasia oradenoma
- diffuse: Thick stiff wall (___________). Infiltrative pattern
Dyscohesive signet ring cells. Mutation of _________ is a diagnostic marker. No definite precursor lesions are identified
- WHO classification – standardised reporting of tumours
- Gastric adenocarcinomas –
o Papillary, tubular, mucinous (intestinal type in Lauren’s)
o Signet ring carcinoma (poorly cohesive)
o Commonly mixed
ulcerative lesions; linitis plastica; e-cadherin
Malignant ulcers – usually adenocarcinomas
- Heaped up irregular borders – chronic gastric ulcers have more
________ and radiating rugae folds
- However, all gastric ulcers must be regarded as potentially malignant and biopsied
punched appearances
Gastric carcinoma
- More common in males in their 5th to 7th decade, presenting with dyspepsia, weight loss
- Geographical variations – higher incidence in countries such as Japan and Korea
o H.pylori – lower socio-economic groups, multifocal atrophy and intestinal metaplasia, previous partial gastrectomy
- Gastric antral cancers are decreasing but cardia cancers are increasing due to GERD, obesity and Barrett’s
Pathogenesis
o Mutations are mostly sporadic, but there are rare germline ____ mutations (e-cadherin that present as diffuse-type histology
o Infections – H. pylori leads to chronic gastritis (Correa’s cascade of precancerous lesions to gastric neoplasia), _____
§ __________ gastritis can give rise to PUD but not an increased risk of cancer
§ For multifocal atrophic gastritis – development of atrophy is the first step in the progression of cancer
CDH1; EBV; Non-atrophic;
Gastric carcinomas
- Staging and prognosis – depth of local invasion (T), extent of nodal and distant metastasis (N and M)
o ______ type cancer has the worst prognosis
o The 5-year survival for advanced gastric cancers is 20% (tumours with locally advanced tumour or metastasis) but early gastric cancers fare well (90%)
o Her2 test in AGC (Herceptin therapy) if there is HER2 overexpression
Early gastric cancer (T1) – confined to the ________, regardless of nodal involvement, with 5-year survival > 90%
o Grossly flat, depressed and elevated lesions
o >50% in Japan – due to high incidence and screening
- Spread of gastric cancer – via 4 routes
o Direct invasion – to adjacent regions such as the retroperitoneum and the _______
o Lymphatic spread (main route) – regional nodes or Virchow’s node (_______ node)
o Hematogenous spread (liver, lung) – portal vein
o __________ spread through the peritoneum – leading to malignant ascites often involving the ovaries
Diffuse;
mucosa and submucosa;
pancreas;
left supraclavicular;
Transcelomic
Kurkenburg tumour of ovary
- Metastatic, (likely) transcoelomic spread to ovaries – bilateral ovarian masses originating from the gastric area (primarily)
o Histology – _______ tumour cells, signet rings
decohesive
Gastrointestinal stromal tumour (GIST)
- Most common mesenchymal tumour in the abdomen, >50% in stomach
- Mutations in ______ (80%) and ________ genes
- Cancer of ____________ (pacemaker cells) – present in the myenteric layer
- Mural tumours – histologically _____ to epithelioid cells at the muscularis propria and submucosa, overlying a normal mucosa
o Elongated spindle cells arranged in loose fascicles
o Good prognosis with only 20% turning malignant
- Indolent to malignant behaviour – [prediction on the risk of malignancy is based on the size and site of tumour in the GI tract, mitotic rate
c-kit; PDGFRA;
interstitial cells of Cajal; spindle
Lymphoma
- MALT – normally, there are no inflammatory cells in the gastric mucosa
o Chronic gastritis due to H. Pylori infection or autoimmune causes induce an inflammatory response and mucosal-associated lymphoid tissue develops (MALT)
- Stomach is a common site for extranodal marginal zone Bcell lymphoma or MALT lymphoma
- Dense lymphoid infiltrate which infiltrate the glands – lymphoepithelial lesion
o Histologically – ___________ cells infiltrate, expanding to the mucosa and submucosa with destruction of glands or atypical cells present in the glands
- H. Pylori association, very good prognosis – regresses
following H. Pylori treatment – a small subset progresses to high grade B cell lymphoma
dense cryptical lymphoid
