Pathology of upper GI tract tumors Flashcards Preview

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Flashcards in Pathology of upper GI tract tumors Deck (27):
1

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

2

Carcinoma of the oesophagus?

Squamous cell carcinoma
•Adenocarcinoma
•Other rarer malignant tumours

3

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

4

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.

5

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

6

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

7

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

8

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

9

other oesophageal malignancies?

Small cell neuroendocrine carcinoma
•Malignant melanoma
•Leiomyosarcoma
•Rhabdomyosarcoma
•Lymphoma
•Others

 

10

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

11

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

12

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

13

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

14

types of gastric cancer?

Macroscopic
•Localised
•Linitis plastica (leather bottle stomach)
•Polypoid
•Ulcerating (confusion with peptic ulcer)
•Stricturing

15

signs of gastric cancer?

Weight loss
•Anaemia
•Pyloric obstruction
•Haematemesis
•Dyspepsia
•Metastatic Disease
•Diagnosis at endoscopy with multiple biopsies

16

TNM stagin for gastric cancer?

T1 Tumour invades lamina propria or submucosa
T2a Tumour invades muscularis propria
T2b Tumour invades subserosa
T3 Tumour penetrates serosa
T4 Tumour invades adjacent structures
N0 No lymph node metastases
N1 Involvement of 1-6 nodes
N2 Involvement of 7-15 nodes
N3 Involvement of >15 nodes
NX Regional lymph nodes cannot be assessed

17

special sites of metastases?

Liver
•Common, via portal vein
•Ovaries (Krukenberg tumours)
•Transcoelomic (trans-serosal) spread
•Cervical Lymph Nodes
•Troisier‟s sign - left supraclavicular nodes
•Virchow‟s node

18

siewerts classification of OGJ tumours?

A image thumb
19

early pT1 gastric cancer?

5 year survival >90% following surgery
•Lymph node metastases
•Intramucosal 3%
•Submucosal 20%
•60% of all gastric cancers in Japan
•Increasing frequency elsewhere due to better recognition

20

screening services wales 2009 review?

Incidence of gastric cancer too low to be cost effective
•Early gastric cancer produces Sx, but vast majority of people with these Sx (eg heartburn) are due to other causes
•H pylori eradication policy – antibiotic resistance issue
•Very low PPV for pepsinogen test due to low incidence
•High false negative rate of endoscopies and mortality/morbidity risks and unpleasant investigations
Previous studies have shown only 20% endoscopy uptake
•NO CURRENT ROLE

21

tumours of the gastric wall?

•Leiomyomas and leiomyosarcomas (Smooth muscle)
•Neurilemmomas, neurofibromas and malignant Schwannomas (neural)
•Lipomas (fat)
•Angiomas and angiosarcomas (blood vessels)
•Other rarities
•Gastrointestinal stromal tumours

22

gastrointetinal stromal tumours

•Arise with the wall of the GI tract
•Commonest in the stomach
•Recently recognised as different from smooth muscle tumours
•Tumours of interstitial cells of Cajal (pacemaker cells)

 

Masses within wall of stomach that may ulcerate
•Can present throughout the GI tract
•Present with bleeding, obstruction
•Treated by resection in first instance
•Spectrum of malignancy
•Size and mitotic count relate to prognosis
•Malignant GISTs have poor prognosis (until recently)…

23

Gastrointestinal stromal tumours?

Activating mutation of KIT (tyrosine kinase growth factor receptor)
•Rare examples have mutation of other TK receptors
•Dramatic response to imatinib (inhibitor of TKR) with little toxicity
•CD117 and DOG-1 antibodies used for Dx

24

malignant lymphomas of the stomach?

Hodgkin‟s disease - virtually never
•Non-Hodgkin‟s lymphoma
•B-cell - common in stomach
•T-cell - rare in stomach

25

B cell lymphoma?

Mucosa-associated lymphoid tissue
•Lymphoid follicles with germinal centres
•Acquired in the stomach in chronic gastritis
•Helicobacter pylori
•B-cell lymphoma may arise in MALT
•Lymphoma may be high or low grade

 

•May be ulcer, tumour mass or subtle mucosal abnormality

 

 

26

antibiotic treatment of gastric lymphoma?

Removes H pylori specific growth stimulus
•Results in sustained endoscopic and histological regression of lymphoma
•Lymphoma cells may remain dormant
•Relapse of H pylori infection may cause re-growth of lymphoma

27

HP treatment?

HP eradication
•Single agent chemotherapy for low grade
•Chlorambucil, fludarabine
•Low dose radiotherapy
•Surgery for local complications
•CHOP (Cyclophosphamide, Adriamycin, Vincristine, Presdnisone) (now with rituximab) for DLBCL
•Targets CD20 antibody (seen on B cells)