Pathology of upper GI tract tumors Flashcards
oesophagus?
Typical length 23-25cm
•Stratified squamous epithelium
•Submucosa, Muscularis propria and Adventitia
•Native oesophageal submucosal glands secreting mucus
•At gastro-oesophageal junction transition to glandular (columnar) gastric cardia mucosa
Carcinoma of the oesophagus?
Squamous cell carcinoma
•Adenocarcinoma
•Other rarer malignant tumours
squmour cell carcinoma?
Upper or middle thirds of oesophagus largely
•Marked geographical variations
•Commonest type worldwide oesophageal cancer
•Becoming less common in the Western world
•Numbers in UK stable/slight decrease
•„Asian belt‟ – Turkey->China
RISK FACTORS
Smoking, spirits, dietary carcinogens
Chronic oesophagitis
HPV 16 & 18
Plummor-Vinson Syndrome
Post-menopausal women, Oesophageal webbing, glossitis and Fe-deficiency anaemia
10% multifocal
SIGNS AND SYMPTOMS
Dysphagia – often initial presentation
Fluids/Soft food ok – bread and meat difficulty
Weight loss – direct consequence and ? Metastases
Retrosternal pain
Hoarse cough (recurrent laryngeal nerve)
Regurgitation of food – aspiration pneumonia
•Haematemesis
•Fistula between oesophagus and trachea
•Most present advance stage
what is plummor vinson syndrome?
Plummer–Vinson syndrome (PVS), also called Paterson–Brown–Kelly syndrome or sideropenic dysphagia, presents as a triad of dysphagia (due to esophageal webs), glossitis, and iron deficiency anemia.[1] It most usually occurs in postmenopausal women.
presents with:
PVS sufferers often complain of a burning sensation with the tongue and oral mucosa, and atrophy of lingual papillae produces a smooth, shiny, red dorsum of the tongue.
Symptoms include:
Dysphagia (difficulty in swallowing)
Pain
Weakness
Odynophagia (Painful swallowing)
Atrophic glossitis
Angular stomatitis
increased risk of carcinoma
Serial contrasted gastrointestinal radiography or upper gastrointestinal endoscopy may reveal the web in the esophagus. Blood tests show a hypochromic microcytic anemia that is consistent with an iron-deficiency anemia. Biopsy of involved mucosa typically reveals epithelial atrophy (shrinking) and varying amounts of submucosal chronic inflammation. Epithelial atypia or dysplasia may be present.
molecules involved in squamous cell carcinoma?
EGFR overexpression
•Cyclin D1 amplification
•p53 and MTS1 mutation
•Allele loss p53, Rb, APC
•LOH at 3p, 9q, 10p, 17q, 18q, 19q, 21q
adenocarcinoma?
Lower oesophagus (bottom third) / GOJ
•Increasing in frequency - sharply
•On current trends may become dominant histology in world
•Males > females
•Smoking, alcohol, obesity
•GORD
In UK it‟s dominant type
One of highest incidence in world
barrett’s oesophagus?
Glandular metaplasia in the lower 3cm
(or more) of the native oesophagus,
usually induced by (duodeno-) gastro-oesophageal reflux
Prevalence inversely related to that of H pylori
•? H pylori gastritis and hypoacidity protective
surveillance i barrett’s?
- Goal is the detection of dysplasia
- Age and co-morbidity are important: only patients fit for surgery should be surveyed
- 2-3 year intervals
- Biopsy any endoscopic abnormality, especially polyps, erosions, masses
- Quadrantic biopsies every 2 cms
- LGD - 6 monthly x2 and then yearly
- HGD - resection or ablation
other oesophageal malignancies?
Small cell neuroendocrine carcinoma
•Malignant melanoma
•Leiomyosarcoma
•Rhabdomyosarcoma
•Lymphoma
•Others
TNM staging?
T1 Tumour invades lamina propria or submucosa
T2 Tumour invades muscularis propria
T3 Tumour invades adventitia
T4 Tumour invades adjacent structures
N0 No lymph node metastases
N1 Regional lymph node metastasis
NX Regional lymph nodes cannot be assessed
M0 No distant metastasis
M1 Distant metastasis
MX Distant metastasis cannot be assessed
gastric adenocarcinoma?
Rare inherited tumours (germline E-cadherin mutation)
95% of all stomach cancers are adenocarcinomas
•Strong link with social deprivation
Diet
•Salt, dried or pickled foods, alcohol - BAD
•Fresh fruit and vegetables, carotenoids, green tea - GOOD
•Helicobacter pylori
•Chronic gastritis with atrophy and incomplete (Type III) intestinal metaplasia
•Microsatellite instability – HNPCC syndrome
H.pylori?
Gram negative spiral shaped bacteria
•Discovered about 30 years ago
•Lives stomach and duodenum
•Survives in microenvironment in stomach away from gastric acid (under mucus production)
•Can then battle against gastric acid with urease
•Urea from stomach concerted to ammonia & CO2
•Most people acquire infection at some point
•>50 years age = >50% infection rates; 2-3 billion
Related to social deprivation
•Nearly all with duodenal ulcers have HP infection
•Majority of gastric ulcers have HP infection
NSAIDs and other drugs also have role in stomach
•Most gastric cancers occur in people infected
•Breath test, blood test and endoscopy
•Risk of non-cardia gastric cancers 6x higher in people with helicobacter infection
gastric adenocarcinoma?
Microsatellite instability
•epigenetic (methylation of MLH1)
•mutation of mismatch repair gene
•Somatic mutation/amplification
•K-ras, K-sam, APC, c-met, EGFR, HER2, p53, TGFalpha TGFbeta CD44, bcl-2, cyclin E, E-cadherin, nm23, SMAD4
•Allele loss
•1p, 1q, 3p, 5q, 7q, 13q, 17p, 18q
•Telomerase expression
types of gastric cancer?
Macroscopic
•Localised
•Linitis plastica (leather bottle stomach)
•Polypoid
•Ulcerating (confusion with peptic ulcer)
•Stricturing
signs of gastric cancer?
Weight loss
•Anaemia
•Pyloric obstruction
•Haematemesis
•Dyspepsia
•Metastatic Disease
•Diagnosis at endoscopy with multiple biopsies
siewerts classification of OGJ tumours?
