GI Pathology Flashcards
Basic Histology of GI tract
Mucosa, Submucosa, Muscularis Propria and Serosa/Adventitia depending on peritoneal covering
Anatomical disorders of oesophagus: definitions (2), common sites, pathogenesis (1), presentations (3)
Atresia = congenital absence of lumen (most commonly at or near tracheal bifurcation) Fistula = abnormal connection between 2 structures (most tracheoesophageal fistula are congenital -- type III MC: connection of lower oesophagus to trachea)
- failure of foregut division (partitioning) in 4th week of gestation (1/3000 pregnancies, slight male predominance)
- atresia is a/w fistula
Presentation:
- aspiration
- regurgitation
- electrolyte or fluid imbalances
Motor disorder of oesophagus: definition and characteristics (3), aetiologies (2), presentations (3), complications (4)
Achalasia = rare neuromotor disease characterised by triad of:
- aperistalsis
- increased resting tone of LES
- incomplete LES relaxation during swallowing
Aetiologies:
- primary - idiopathic (failure of inhibitory neurons)
- secondary - Chagas disease (trypanosoma cruzi cause destruction of myenteric plexus; endemic in SA)
Presentations:
- progressive dysphagia
- nocturnal regurgitation
- aspiration
- Barium swallow: bird beak with proximal dilation at LES
Complications:
- candida oesophagitis
- lower oesophageal diverticulum
- aspiration pneumonia
- ESOPHAGEAL SCC
Mallory Weiss Syndrome: definition, aetiology, pathogenesis, prognosis, complication
= Longitudinal MUCOSAL tears of distal oesophagus +/- proximal stomach
- 5-10% UGIB, usually self-limiting
Aetiology:
- severe retching associated with excessive alcohol intake
Pathogenesis:
- failed reflex relaxation of gastro-oesophageal musculature during prolonged vomiting –> reflux of gastric contents –> stretch oesophageal wall and tear
Prognosis
- superficial tears heal quickly without surgical intervention
Boerhaave Syndrome = severe transmural form of MWS involving oesophageal rupture (leading to mediastinitis)
Oesophageal varices: definition, aetiology, presentation/prognosis, pathogenesis, pathology (2)
= dilated tortuous submucosal veins in lower oesophagus due to portal hypertension
- second most common cause is hepatic schistosomiasis
65-90% of cirrhotic patients (commonly AFLD)
- asymptomatic until rupture –> life-threatening massive UGIB (40% mortality; 50% rebleed within 1 year)
- death due to direct haemorrhage and hypovolemic shock or hepatic coma from massive protein load in bleeding
Pathogenesis:
- portal HT induces back flow of portal blood into caval system (via portosystemic shunts) –> enlargement of submucosal venous plexus in distal oesophagus –> massive haematemesis
Pathology:
- tortuous dilated veins within submucosa seen on endoscopy
- intact or ulcerated and necrotic overlying mucosa (especially if ruptured)
Oesophagitis: definition, aetiologies, most common?, manifestations of chemical esophagitis, clues to agent in viral esophagitis
= inflammation of the oesophagus
Wide variety of aetiologies:
(VITAMINCD)
- infection e.g. HSV, CMV, Candida (immunosuppressed)
- autoimmune (eosinophilic oesophagitis)
- metabolic e.g. renal failure
- iatrogenic e.g. doxycycline, bisphosphonates, chemo/RT
- chemical —> GASTROESOPHAGEAL REFLUX (MC cause), corrosive agents (alcohol, hot drinks, acids
Chemical oesophagitis usually causing odynophagia
- ulceration and acute inflammation
Viral esophagitis endoscopic/histological appearance gives clue for agent
- punched out ulcers with nuclear viral inclusions and rim of degenerating epithelial cells – HSV
- shallower ulcers with nuclear and cytoplasmic inclusions – CMV
Reflux oesophagitis (GERD): cause, prevalence, presentation (3), complications (3), risk factors (4), histology (3)
Most common type of oesophagitis affecting 3-4% of general population
- due to reflux of gastric contents into lower oesophagus
Presentation:
- heartburn
- dysphagia
- regurgitation
Complications:
- minor UGIB (haematemesis, melena)
- stricture
- BARRETT OESOPHAGUS
Risk factors:
- conditions that decrease LES tone or increase abdominal pressure
- — alcohol, smoking, obesity, CNS depressants, pregnancy, hiatal hernia etc.
- cause not identified in most cases
Histology:
- doesn’t correlate with clinical symptoms
- unremarkable in mild cases
- basal zone hyperplasia (>20% full thickness)
- elongation of lamina propria papillae (>2/3 full thickness)
- leukocytic (neutrophilic, eosinophilic) exocytosis
Treatment with PPI
Barrett Oesophagus: definition, prevalence, appearance, histology, complications (2)
= replacement of distal oesophageal squamous epithelium with metaplastic columnar epithelium at least 1 cm above OGJ
- affecting 5-15% of patients with reflux oesophagitis
identified in:
- endoscopic exam - tongues/patches of “salmon-coloured” mucosa extending upward 1cm above OGJ alternating with pale areas of squamous mucosa
- histological exam - presence of goblet cells with distinct mucous vacuoles (intestinal metaplasia) and columnar cells
- presence of these 2 are required for diagnosis
Complications:
- risk factor (precursor lesion) for oesophageal glandular dysplasia and adenocarcinoma (30-100x); 0.5% dysplasia/year – but most don’t develop adenoCA
Management:
- surveillance endoscopy with biopsy for dysplasia –> early detection of cancer = better prognosis
Dysplasia: definition
Dysplasia = precursor of malignancy i.e. premalignant lesion with architectural and cytological abnormality but no stromal invasion
- can be classified into high grade or low grade depending on differentiation
Benign vs Malignant Neoplasms (4)
Recall features to distinguish (BAP)
- differentiation
- rapidness of growth (circumscription vs. necrosis/ haemorrhage)
- invasiveness (stromal/ desmoplastic, lymphovascular, perineural; adj organ, capsular invasion)
- distant metastases (LN, distant organs)
Oesophageal carcinoma: types, epidemiology, risk factors, common site of malignancy, presentations (6)
Malignant epithelial neoplasm
- SCC most common (90%), AdenoCA (10%)
- M:F 4:1
- 60-70 years old
Risk factors:
SCC
– lifestyle - tobacco smoking, alchohol, hot drinks, nutritional deficiency, nitrosamines
– oesophageal disease - achalasia, plummer-vinson syndrome (oesophageal web, anemia, atrophic gastritis)
– tylosis (hyperkeratosis of palms and soles)
AdenoCA
– Barrett oesophagus (30-100x) and GERD
Presentation:
- **SCC mostly in middle third, AdenoCA at distal third
- dysphagia (solid then liquid), odynophagia
- LOW
- dry cough, haemoptysis, pneumonia: tracheal invasion
- hoarseness: RLN invasion
- hyperCa (PTHrp in lung SCLC)
–> Sx usually appear at late stage with submucosal lymphatic invasion –> poor prognosis (5 year survival <25% for ADC and 9% for SCC)
Pathogenesis:
- AdenoCA –> chromosomal abnormalities and TP53 mutation
- SCC unclear
Oesophageal carcinoma pathology full details: gross appearance, histology, LN metastasis sites
Pathology:
- gross
- – SCC: whitish small plaque-like thickenings –> polypoid mass (may ulcerate, diffusely infiltrate - INTRAMURAL GROWTH in 11-17%, invade surrounding structures)
- – ADC: flat or raised patches –> large exophytic masses that infiltrate/ulcerate/invade
- histology
— architecturally, composed of proliferation of tumour cells with squamous/ glandular differentiation in a desmoplastic stroma
with tumour cells in sheets and nests with keratinisation for SCC
or infiltrative irregular and complex glands for ADC
— cytologically, malignant with hyperchromasia, high N:C ratio, prominent nucleoli, pleomorphism and frequent mitosis
with intercellular bridging for SCC
or
mucin secretion for ADC
– may also comment: infiltration into muscularis propria, lymphovascular invasion
- LN metastasis
- middle third –> mediastinal, paratracheal, tracheobronchial nodes
- lower third –> gastric and celiac nodes
Important elements of pathology report (3)
Diagnosis
Prognosis
- stage, grade, resection margin clearance, lymphovascular/perineural invasion, background tissue status
Therapeutic prediction
- e.g. HER2 over expression in 15% patients with gastric adenoCA using IHC and FISH techniques
Basic anatomy and physiology of the stomach
Cardia - mucus secreting glands lined by foveolar cells
Fundus - parietal and chief cells
Body - mucus secreting glands, parietal cells (acid), chief cells (pepsin)
Antrum - mucus secreting glands, endocrine cells (G cells produce gastrin)
Balance of destruction (acid, peptic enzymes) and protection (mucus layer, bicarbonate, rich blood flow, PGs, regenerative capacity)
Other structures include inflammatory cells, stromal and soft tissue cells
- Gastropathy = cell injury and regeneration but inflammatory cells rare/ absent
Acute Gastritis: definition, consequences (3), manifestations (6), aetiology (5), Cushing vs Curling ulcer, pathogenesis of common causes (3)
= Transient mucosal inflammation (destruction>protection)
- may lead to mucosal erosion (epithelium of mucosa), ulceration (breach whole mucosa and extend deeper) and haemorrhage
Clinical manifestations:
- asymptomatic in mild cases
- epigastric pain, nausea, vomiting
- bleeding –> haematemesis, melon, massive blood loss (rare)
- acute gastric ulcers (Curling or Cushing)
- —> Curling in proximal duodenum
- —> Cushing in stomach, duodenum or oesophagus; higher risk of perforation
Aetiology:
- Drug - NSAID (most common), aspirin, chemotherapy
- Metabolic - alcohol, chemical, uraemia
- Traumatic e.g. NG tube
- Severe stress e.g. severe burns, trauma (Curling ulcer)
- CNS injury (Cushing ulcer with high incidence of perforation) – direct stimulation of vagal nucleus increasing acid secretion
Pathogenesis:
- NSAID –> inhibit COX dependent synthesis of PG E2 and I2 –> loss of stimulation of all defence mechanisms of stomach (mucus, bicarbonate, blood flow, regeneration) — COX-1 larger role than COX-2 but both involved (higher risk with aspirin/ ibuprofen but celecoxib also has risk)
- uremia –> inhibition of gastric bicarbonate transportors by ammonium ions
- chemicals/ alcohol/ radiation/ NSAID –> direct cellular damage
- chemo –> insufficient epithelial renewal
- stress related mucosal injury –> local ischemia (hypotension, vasoconstriction)
Pathology: acute/active!! neutrophils!!
- moderate edema and slight vascular congestion
- hyperplasia of foveolar mucous cells
- may have erosions and haemorrhage in severe cases (acute erosive haemorrhagic gastritis)
- stress ulcers (brown to black base with sharply demarcated margins)
Chronic Gastritis: definition, clinical severity, aetiology (3)
Chronic inflammation of the gastric mucosa
- clinically usually less severe but more persistent than acute gastritis
Aetiology;
- H.pylori (>80%)
- Autoimmune (<10%)
- NSAID
H. Pylori-associated Chronic Gastritis: pattern of gastritis, pathogenesis (4), associated diseases, complications, histopathology (3), diagnosis, treatment
Major cause of chronic gastritis
Pattern of gastritis:
- antral predominant with increased acid secretion
- pangastritis affecting both antrum and body if severe (reduced parietal cell mass and reduced acid secretion)
Pathogenesis:
Features of virulence
– flagella: motility
– urease: break down urea and generate ammonia to neutralise gastric acid
– adhesins: enhance adherence to foveolar cells of gastric mucosa
– toxins (CagA): carcinogenesis
Associated diseases:
- gastric ulcer
- duodenal ulcer (account for almost 100% of cases)
Complications:
- increase risk of gastric adenoCA and gastric lymphoma
Histopathology:
- HP concentrated within overlying mucus layer with tropism for gastric foveolar epithelium (antrum)
- chronic +/- active inflammation –> lymphoplasmacytic + macrophages +/- neutrophils at superficial lamina propria
- glandular atrophy
- intestinal metaplasia –> may progress to glandular dysplasia and adenoCA
- may see lymphoid aggregates with induced MALT
Diagnosis:
- serological, stool, urea breath test
- specimens –> rapid urease, culture, PCR
Treatment: triple therapy (amoxicillin, clarithromycin + PPI)
Autoimmune Gastritis: pattern of gastritis, pathogenesis (2), associated disease, complication, histopathology (4)
Slight female predominance, median 60yrs old
Accounts for <10% gastritis
Pattern:
- body (parietal and chief cells) predominant
Pathogenesis:
- antibodies to parietal cells –> loss of H+/K+ ATPase (atrophic gastritis) –> defective gastric acid secretion (achlorydia) –> hypergastrinemia with antral G cell hyperplasia
- antibodies to intrinsic factor –> disable ileal vitamin B12 absorption –> B12 deficiency –> pernicious anaemia (megaloblastic)
- chief cell damage can cause increase in serum pepsinogen I levels
Associated diseases:
- pernicious anemia (minority of patients)
- neurological changes
Complications:
- risk of gastric adenoCA
Histopathology:
- chronic inflammation (lymphoplasmacytic and macrophages) –> deep and centred on gastric glands
- diffuse gastric glandular atrophy (of oxyntic acid producing mucosa in body and fundus) –> parietal and chief cell loss –> intestinal metaplasia
- endocrine G cell hyperplasia
NSAID-associated gastritis
Chronic use suppresses mucosal prostaglandin synthesis
Histopathology:
- reactive gastritis
- foveolar hyperplasia, proliferation of smooth muscle cells in lamina propria, lamina propria oedema, vascular ectasia
–> ulcer
Peptic Ulcer Disease: risk factors (5), pathogenesis (5), locations, gross morphology (4), histology (4)
Risk factors for injury:
- increase damage – H.pylori (MC, >70%), NSAID (MC), Aspirin, smoking (decrease blood flow and impair healing), alcohol
- decrease defence – ischemia, shock, high dose steroids (decrease PGs and impair healing)
Pathogenesis:
- imbalance of mucosal defences (mucus, bicarbonate, blood flow, PGs, regenerative capacity) and damaging forces –> chronic gastritis background –> peptic ulcer
- hyperacidity from H. pylori, parietal cell hyperplasia, excessive secretion, insufficient inhibition of gastrin, gastrin releasing tumour/ hyperCa stimulate gastrin production
- decreased blood flow and impaired healing due to smoking
- steroid suppress PGs and regeneration
Locations:
- can occur at any part of the GIT that is exposed to acid injury
- —> H. Pylori: gastric antrum and D1 of duodenum (MC)
- —> GERD: lower oesophagus
- —> Gastric heterotopia: Meckel diverticulum
- —> Zollinger Ellison syndrome (gastrin tumour): multiple ulcers
Gross morphology:
- round to oval solitary lesions
- sharply punched out
- fibrosis causing puckering of surrounding mucosal folds
- clear and smooth base (peptic digestion of exudate); bleeding possible
Histology: 4 layers
- necrotic debris
- acute inflammation
- granulation tissue (richly vascular)
- fibrosis
