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respiratory system year 1 > pathology of pulmonary neoplasia > Flashcards

pathology of pulmonary neoplasia Flashcards

1
Q

aetiology of lung cancer

A 
TOBACCO
asbestos
environmental radon 
occupational exposure - chromates, hydrocarbons, nickel
air pollution and urban environment 
other radiation 
pulmonary fibrosis
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2
Q

what is the predominant cause of 1y lung cancer

A

tobacco smoke

tobacco smoke and asbestos combined have a multiplicative effect in causing lung cancer

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3
Q

what % of lung cancers are attributable to tobacco

A

85

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4
Q

what % of smokers get lung cancer

A

10

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5
Q

increases in risk of lung cancer in smokers

A

22x in males
12x in females
females may be more susceptible to carcinogenic effects of tobacco smoke
risk related to consumption (inhalation and pack years)
NO safe smoking threshold

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6
Q

passive smoking

A

50-1005 increased risk

causes at least 25% of “non-smoking” lung cancers

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7
Q

how does risk reduce with abstinence from smoking

A

risk reduces but slowly due to persisting genomic damage

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8
Q

in what areas of the lung do adenocarcinoma and squamous/SCLC occur

A

adenocarcinoma - peripheal

squamous/SCLC - central parts arising from large airways

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9
Q

how does tobacco smoke result in lung cancer

A

epithelial effects
multi-hit theory
host activation of pro-carcinogens

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10
Q

host activation of pro-carcinogens

A

inherited polymorphisms predispose metabolism of pro-carcinogens and nicotine addiction

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11
Q

pathway of carcinogenesis in the lung periphery

A

bronchioalveolar epithelial stem cells transform
adenocarcinoma
less strongly but still associated with smoking, does occur in non-smokers

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12
Q

pathway of carcinogenesis in the central lung airways

A

bronchial epithelial stem cells transform
squamous cell carcinoma
strongly associated with smoking

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13
Q

molecular biology of adenocarcinogenesis

A

oncogene addiction - key driver mutations
KRAS ~ 35% - smoking induces
EGFR ~15%, BRAF/HER2 ~1-2% each, ROS1 gene rearrangements ~1%, ALK rearrangements ~2% - not related to tobacco carcinogenesis

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14
Q

what molecular aspects can be targeted with therapy

A

EGFR mutation
BRAF mutation
ALK rearrangement
ROS1 rearrangement

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15
Q

squamous cell targets and therapy

A

very few suitable targets - very few addictive oncogenes

the most common alterations are inactivating mutations in tumour suppressor genes

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16
Q

types of tumours of the lung

A 
benign causes of mass lesion
carcinoid tumour
tumours of bronchial glands 
lymphoma 
sarcoma 
mets to the lung - common
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17
Q

carcinoid tumour

A

<5% of lung neoplasms

low grade malignancy

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18
Q

bronchial gland tumours

A

very rare
adenoid cystic carcinoma
mucoepidermoid carcinoma
benign adenomas

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19
Q

cell types in lung carcinoma

A

squamous cell 40%
adenocarcinoma 41%
small cell carcinoma ( heavy tobacco consumption) 15%
large cell carcinoma 5%

20
Q

primary lung cancer

A

clinically silent for yrs
presents late in natural hx
few if any signs or symptoms until advanced disease
may be found incidentally
symptomatic lung cancer is generally fatal

21
Q

local effects of lung cancer

A 
bronchial obstruction
pleural 
direct invasion
mediastinum - SVC, pericardium 
lymph node mets
22
Q

bronchial obstruction

A

collapse
endogenous lipoid pneumonia - not infection but retention of things that would normally be cleared
infection/abscess
bronchiectasis

23
Q

pleural involvement

A

inflammatory or malignant

can result in effusion

24
Q

direct invasion

A

chest wall

nerves - phrenic, L recurrent laryngeal, brachial plexus, cervical sympathetic

25
Q

what would phrenic nerve involvement result in

A

diaphragmatic paralysis

26
Q

what would L recurrent laryngeal nerve involvement result in

A

Hoarse, bovine cough

L vocal cord paralysis

27
Q

what would brachial plexus involvement result from

A

T1 damage by pancoast tumour

28
Q

what would cervical sympathetic involvement result in

A

Horner’s syndrome

29
Q

lymph node metastases (local)

A

mass effect

lymphangitis carcinomatosa

30
Q

lung cancer distant effects

A

distant mets
2y to local effects - neural, vascular
non-metastatic paraneoplastic effects

31
Q

where does lung cancer commonly metastasise to

A 
liver
adrenals
bone 
brain 
skin
32
Q

non-metastatic paraneoplastic effects of lung cancer

A 
skeletal 
endocrine 
neurological 
cutaneous 
haematologic 
cardiovascular
renal
33
Q

skeletal non-metastatic paraneoplastic effects of lung cancer

A

finger clubbing

hypertrophic pulmonary oesteoarthropathy (HPOA) - pain in wrists, knees, ankles

34
Q

investigations for lung cancer

A 
CXR 
bronchoscopy 
trans-thoracic FNA
trans-thoracic core biopsy 
pleural effusion cytology and biopsy 
advanced imagint techniques - CT, MRI, PET
35
Q

endocrine non-metastatic paraneoplastic effects of lung cancer

A

ACTH, SIADH - SCLC
PTH - squamous
carcinoid syndrome
gynecomastia

36
Q

neurological non-metastatic paraneoplastic effects of lung cancer

A

polyneuropathy
encephalopathy
cerebellar degeneration
Myasthenia (Eaton-Lambert)

37
Q

cutaneous non-metastatic paraneoplastic effects of lung cancer

A

acanthosis nigricans

dermatomyositis

38
Q

haematologic non-metastatic paraneoplastic effects of lung cancer

A

granulocytosis
eosinophilia
DIC

39
Q

cardiovascular non-metastatic paraneoplastic effects of lung cancer

A

thrombophlebitis migrans

40
Q

renal non-metastatic paraneoplastic effects of lung cancer

A

nephrotic syndrome

41
Q

prognostic factors in lung cancer

A

stage of disease
classification of disease

ALSO: markers/oncogenes/gene expression profile
growth rate 
cell proliferation
DNA aneuploidy 
immune cell infiltration
42
Q

what is the prognosis for lung cancer

A

Generally very bad
<9.8% 5YS in scotland

operable lung cancer: (10-12% of pts in Scotland)
stage I >60% 5YS
stage II 35% 5YS
overal correlation w/ stage

43
Q

5YS for non-small cell carcinomas

A

10-25%

44
Q

small cell carcinoma 5YS

A

4%

median survival 9mths

45
Q

what are predictive biomarkers used for in lung cancer

A

selection fo patients for therapy
adenocarcinoma - EGFR, ALK and ROS1 translocations can be targeted

squamous cell - little or no effective molecular targeted therapy

immunotherapy in NSCLC has transformed practice

46
Q

therapeutic targets in NSCLC immunotherapy

A

PD/PD-L1 axis immune checkpoint
persuades the immune system to switch back on
can be curative

47
Q

immune checkpoints

A

control immune reactions
adopted by tumours to avoid immune destruction
PD1, PD-L1, CTLA4

respiratory system year 1 (25 decks)

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