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Pathology of Lung Cancer Flashcards

1
Q

What is the leading cause of lung cancer?

A

Tobacco

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2
Q

What are other other causes of lung cancer?

A 
Asbestos 
Environmental radon 
Occupational exposure: chromate, hydrocarbons, nickel
Air pollution 
Other radiation 
Pulmonary fibrosis
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3
Q

What are two important compounds in tobacco that are through to cause lung cancers?

A

Polycyclic aromatic hydrocarbons

N-Nitrosamines

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4
Q

What type of lung cancer are the N-nitrosamines thought to cause?

A

Adenocarcinomas in the periphery of the lungs

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5
Q

What type of lung cancer are polycyclic aromatic hydrocarbons thought to cause?

A

Squamous cell carcinoma in the central bronchi

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6
Q

What are the 3 effects of tobacco smoke that can lead to lung cancer?

A

Epithelial effects
Multi-hit theory of carcinogens
Host activation of pro-carcinogens

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7
Q

What is the multi-hit theory?

A

3-12 key significant changes must occur in cells that survive, and must occur in a specific sequence for tumour to develop

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8
Q

How can inherited polymorphisms predispose a person to developing lung cancer?

A

Metabolism of pro-carcinogens

Nicotine addiction

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9
Q

What type of cells are targets for carcinogens?

A

Stem cells

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10
Q

Describe the pathway of carcinogenesis in the lung periphery

A

Bronchioalveolar epithelial stem cell transforms - adenocarcinoma

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11
Q

Describe the pathway of carcinogenesis in the central lung airways

A

Bronchial epithelium stem cells transform - squamous cell carcinoma

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12
Q

Describe basic formation on the invasive bronchogenic carcinoma

A
  1. Squamous dysplasia in the epithelium of the bronchial tree
  2. Carcinoma in situ
  3. Has invasive potential allowing it to develop into an invasive carcinoma

Process strongly associated with smoking

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13
Q

Describe stages in development of peripheral lung adenocarcinoma

A
  1. Atypical adenomatous hyperplasia
  2. Adenocarcinoma in situ
  3. Invasive carcinoma

Can occur in non-smokers

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14
Q

What type of cancer can occur in non smokers?

A

Peripheral lung adenocarcinoma

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15
Q

What is the most common driver mutation in lung cancer?

A

KRAS

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16
Q

Name a driver mutation which is smoking induced?

A

KRAS

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17
Q

Name driver mutations which are not smoking induced?

A

EGFR
BRAF
HER2
ALK rearrangements

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18
Q

What is an addictive oncogene?

A

An oncogene that when inactivated will stop the growth of the cancer

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19
Q

What is important about addictive oncogenes in terms of treatment?

A

May allow molecular target therapy to inactivate this gene and stop the cancer from spreading

20
Q

What are 4 addictive oncogene targets for adenocarcinomas?

A

EGFR mutation
ALK rearrangement
ROS1 rearrangement
BRAF mutation

21
Q

Why aren’t addictive oncogene used in squamous cell carcinomas and what is used instead?

A

Very few addictive oncogenes

Inactivate mutations in tumour suppressor genes

22
Q

Give some examples of some tumours in the lung which arent lung cancer

A 
Carcinoid tumour
Tumour of bronchial glands
Lymphoma
Sarcoma
Metastases
23
Q

What is an example of a benign mass lesion of the lung?

24
Q

What are the four main cell types of carcinoma of the lung?

A

Squamous cell
Adenocarcinoma
Small cell
Large cell

25
Q

What is another name for bronchioalveolar cell carcinoma?

A

Adenocarcinoma in situ

26
Q

What cell types are in the non-small cell carcinomas (NSCLC)?

A

Adenocarcinoma
Squamous cell
Large cell
Other

27
Q

Why is term NSCLC used?

A

Sometimes in diagnosis because we cannot distinguish between some types of NSCLC on small biopsy samples

28
Q

Clinical presentation of primary lung cancers

A

Grows clinically silent for many years and presents late
May be found incidentally, during investigation for something else
Symptomatic lung cancer fatal

29
Q

What are the local effects of lung cancer in terms of bronchial obstruction?

A

Collapse
Endogenous lipoid pneumonia
Infection/abscess
Bronchiectasis

30
Q

What is endogenous lipoid pneumonia?

A

Occurs from obstruction of the airway which results in the accumulation of cellular breakdown debris, including cholesterol from destroyed alveolar cell walls (LDL)

31
Q

What are the local effects of lung cancer in terms of pleura?

A

Inflammation

Malignant

32
Q

What are the local effects of lung cancer in terms of direct invasion?

A

Chest wall and into ribs
Into mediastinum and its organs
Nerves

33
Q

Potential effects of nerve invasion

A

Phrenic - diaphragmatic paralysis
L Recurrent laryngeal - hoarse, bovine cough
Brachial plexus - pancoast T1 damage
Cervical sympathetic - Horner’s syndrome

34
Q

What are the local effects of lung cancer in terms of lymph node metastases?

A 
Mass effect 
Lymphangitis carcinomatosa (term given to tumour spread through the lymphatics of the lung)
35
Q

What are the distant effects of the lung?

A

Distant metastases: liver, adrenals, bone, brain, skin
Neural and vascular effects
Non-metastatic effects

36
Q

Name two non-metastatic effects

A

Finger clubbing

Hypertrophic pulmonary osteoarthropathy (HPOA)

37
Q

Name investigations for lung cancer

A

CXR

Bronchoscopy - biopsy
Trans-thoracic fine needle aspiration 
Trans-thoracic core biopsy 
Pleural effusion
Sputum cytology (rare)

CT
MRI, PET

38
Q

What determines the prognosis of lung cancer?

A

Stage of disease
Classification: type of disease
Markers/oncogene/gene expression profiles - MIGHT be used to select patients for ADJUVANT therapy

39
Q

Why is pleural effusion an investigation for lung cancer?

A

Cancer cells can spread to the pleura. This can cause fluid to build up and press on the lungs, causing breathlessness.

40
Q

What is adjuvant therapy?

A

Refers to surgery followed by chemo or radiotherapy to help decrease the risk of the cancer recurring

41
Q

What are predictive factors in lung cancer used for?

A

To select patients for therapy

42
Q

What are the main predictive markers are used in adenocarcinomas?

A

EGFR (and KRAS, HER2, BRAF mutation)

ALK translocations

43
Q

What are the main predictive markers are used in sqaumous cell carcinoma?

A

Little effective targeted therapy

44
Q

How do tumour evade the immune response?

A

Inhibitory immune checkpoints

Immune checkpoints control immune reactions and are controlled by tumours to avoid immune destruction

45
Q

What are the proteins at the immune checkpoint?

A

PD1
PD-L1
CTLA4

46
Q

How do drugs act against the immune check points in lung cancer therapy?

A

When PD-1 binds to PD-L1, it blocks immune response Some cancer cells have large amounts of PD-L1, which helps them evade immune attack

Target either PD-1 or PD-L1 can block this binding and boost the immune response against cancer cells

Respiratory System (29 decks)

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