Lung cancer Flashcards

Pathogenesis of lung cancer: recall the pathogenesis of lung cancer and summarise risk factors Lung tumours: explain the local and systemic complications of lung tumours Histopathology of lung cancer: explain the common types of lung cancer, their biological behavior, prognosis and treatment Investigation of lung cancer: explain the modalities by which lung cancer can be diagnosed Staging of lung cancer: explain the macroscopic appearance of lung tumours and recall pathological parameters us

1
Q

What is the epidemiology of lung cancer: Numbers? Proportion of all cancers? Survival time? Gender? Trend?

A

40,000 deaths per year in the UK. 25% of all cancer deaths. 5-year survival = 5.5%. Men at lifetime risk of 1 in 13, and women are at 1 in 23. Increased incidence in the developing world. But declining in developed world – has been since 1960s.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are the major causes of lung cancer? (x4)

A

Smoking (including passive smoking – spouses of smokers have higher incidence too), asbestos, radiation (radon exposure, therapeutic radiation), genetic predisposition (although familial lung cancers are rare).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is mutational compensation in relation to smoking?

A

Smoking damages the p53 genes, preventing cells from undergoing apoptosis and arrest, to allow them to become cancerous.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is the effect of smoking cessation on lung cancer risk?

A

Quitting at any age with decrease risk.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are the clinical features of lung cancer? Problem with clinical features? (x2)

A

Haemoptysis (coughing blood). Unexplained or persistent: cough, chest/shoulder pain, chest signs, dyspnoea, hoarseness, finger clubbing. PROBLEMS: There are not many! Coughing, hoarseness and breathlessness are normal things for smokers and even non-smokers, so cancer is not obvious.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is clubbing defined as?

A

Angle at the nail is more than 180 degrees.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are the two lung cancer types? How are cancers further categorised? (x2) Significance of identifying exact cancer?

A

Non-small cell cancer, and small cell lung cancer. FURTHER CATEGORISATION – based on molecular finger print of tumour cells, mutations (sub-group) and cell type. SIGNIFICANCE: Some sub-groups have more effective treatments, so identifying mutations can help if it is very treatable. IMMUNOPATHOLOGY important!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is the difference in malignancy of small and non-small cell cancer?

A

Small cell cancer is highly malignant, with shorted doubling time and earlier metastases.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are non-small cell lung cancers divided into? (x3)

A

Adenocarcinomas, squamous cell cancer, large cell cancer.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

How are lung cancers staged?

A

TNM staging: Tumour (T1-4 based on size – 4 is the biggest), Nodes (N0-3), Metastasis (M0-1). Invasion of the chest wall or major vessels automatically upgrades cancer to at least T3.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What does cancer staging tell us?

A

Prognosis and operability.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is the significance of lymph node sampling for lung cancer?

A

Sampling lymph nodes near the lung cancer tumour allows for staging AND diagnosis. So can save time doing different tests to establish both.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

How are lymph nodes taken for sampling?

A

Ultrasound is used to see the nodes in real-time. A needle is used to take a sample of the lymph nodes.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is the diagnostic strategy for lung cancer?

A

Typical symptoms submitted for CXR (of which there is a low threshold for testing). If abnormal, refer to Respiratory for CT scan of thorax for diagnosis and staging. Then, investigations with Pulmonary Function Test (PFTS), exercise tests and MRI of brain used to check for metastasis.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is the FDG-PET-CT?

A

It is only imaging, and it not a tissue diagnosis. Additional specimen collection is required to confirm diagnosis. The test uses a radio-labelled glucose (FDG) actively taken up by rapidly dividing cancer cells. Lung and lymph node tissue should not take it up. So, if the glucose is taken up, it can be an indication of spread – actively seen on CT.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is a trans-thoracic CT biopsy? Advantages (x2) and disadvantages (x2)? When is it used?

A

Needle inserted into lung tissue under CT guidance (so it’s REAL-TIME and HIGHLY SENSITIVE). Yet, risk of pneumothorax (25%-30%) and the sample size is small. Used when you cannot get a biopsy through bronchoscopy or lymph nodes i.e. when the tumour resides in peripheral bronchioles that bronchoscopy cannot access, and has not metastasised.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is the purpose of a Bronchoscopy?

A

Done with Endobronchial Ultrasound (EBUS). Camera is inserted into the airway which allows you to view the tumour. You can do a BIOPSY with this procedure.

18
Q

What is typical treatment for small and non-small cell cancer? Why?

A

SMALL CELL: more rapidly growing, so use chemotherapy. NON-SMALL CELL: usually surgically excised with post-surgery adjuvant chemo/radiotherapy.

19
Q

What treatment is usually done when lung cancer is advanced?

A

Radio/chemotherapy combination, and surgery in best performers. In very advanced, chemo and immunotherapy.

20
Q

What is the diagnosis time of lung cancers? What does this mean for the patient?

A

Often, tumour has been present for many years before diagnosis. Issue: lung cancers become detectable only YEARS after cancer is first present, because tumour is only detectable from around 1cm in size. Means poor prognosis at diagnosis – also because there is an increased chance of metastasis by diagnosis.

21
Q

How does cancer (in the lungs) actually develop?

A

Called CARCINOMA DEVELOPMENT. It is the multi-step accumulation of mutations that cause disordered growth and dysplasia, loss of cell adhesion, invasion of tissue and angiogenesis, occurring in EPITHELIAL and STEM CELLS (remember, carcinomas are epithelial tumours!!!). Different pathways for different tumours, and early stages may be reversible.

22
Q

What is a squamous cell carcinoma, and cause?

A

Carcinoma of tough EPITHELIUM that lines the lung. Normal ciliated epithelium becomes irritated by smoke and undergoes metaplasia to become squamous cell epithelia without cilia. This means that it is more resistant to damage, BUT it means that there are no cilia to waft mucous – chronic cough and mucus accumulation. They typically spread locally and metastasise LATE. Actually study and digest the photo.

23
Q

What is the epidemiology of squamous cell carcinoma?

A

25-40% of pulmonary carcinomas, closely associated with smoking. Traditionally they were centrally arising from bronchial epithelium, but recently, there has been an increase in peripheral SqCC – because of less tar in cigarettes (but means that diagnosis is less simple).

24
Q

What is an adenocarcinoma?

A

GLANDULAR EPITHELIUM tumours that develop in interstitium and PERIPHERAL airways. Tumours are often MULTICENTRIC (have more than one centre – appear to represent separate tumours). Adenocarcinoma development: Proliferation of atypical cells along alveolar walls which increase in size and eventually become invasive and cancerous. Adenocarcinoma in-situ acquire invasive phenotype before invading local tissue and stroma (supportive tissue). Metastasise is EARLY and COMMON.

25
Q

RECAP: What does metastasise mean?

A

Means that the cancer has spread to a tissue of cells it does not belong to. Doesn’t mean it’s moved to another area of lung – this is LOCAL INVASION.

26
Q

What are the genetic causes of adenocarcinomas in smokers and non-smokers?

A

IN SMOKERS, glandular lung cell acquires K-ras mutation, p53 mutation, or there is DNA methylation. IN NON-SMOKERS, glandular lung cell acquires EGFR mutation. These are mutually exclusive – if you have one, you will not have the others e.g. if you have K-ras mutation, you will not have p53, EGFR or DNA methylation.

27
Q

What is the epidemiology of adenocarcinomas?

A

25-40% of pulmonary carcinomas. Not strongly associated with smoking unlike squamous cell carcinoma. More common in far-east in females and non-smokers. On the rise!

28
Q

What are large cell carcinomas?

A

Non-small cell carcinoma. Poorly differentiated tumours composed of large cells with no histological evidence of glandular/squamous differentiation – they are probably very poorly differentiated SMALL-CELL adeno/squamous cell carcinomas i.e. a cancer from another cancer. They have a poorer prognosis.

29
Q

Epidemiology of large cell carcinomas?

A

Uncommon.

30
Q

What is a small cell carcinoma?

A

A PARANEOPLASTIC SYNDROME! Very chemo-sensitive as turnover is rapid (remember, they divide very quickly). 80% present with advanced disease: although very chemo-sensitive, they have an abysmal prognosis! Often present with brain/liver/bone metastasises. Often central near bronchi.

31
Q

What is the epidemiology of small cell carcinoma?

A

20-25% of lung cancer tumours. Closely associated with smoking.

32
Q

What is the significance of differentiating between small and non-small cell carcinomas in a clinical context?

A

SMALL: survival is shorter at 2-4 months if untreated. Chemoradiotherapy is the best treatment – surgery never attempted because most have spread by the time of diagnosis. NON-SMALL: less chemo-sensitive and can be suitable for surgery.

33
Q

What is immunomodulatory therapy?

A

Immunomodulatory therapy is used to activate (or suppress) the immune system. PROBLEM: Tumour cells express new antigens that can be targeted. However, they evolve ways to avoid the immune system using PDL1 to inhibit cytotoxic T cells, preventing them being targeted. IMMUNOMODULATORY THERAPY: PDL1 inhibitors stop this occurring to allow recognition and destruction of tumour cells. Histochemistry can be used to identify those expressing PDL1.

34
Q

What is cytology? How can cytology be used in diagnosing lung cancers? (x4)

A

CYTOLOGY = looking at cells. SO, analysing sputum, bronchial washings and brushings, sampling pleural fluid, endoscopic fine needle aspiration of tumour/enlarged lymph nodes.

35
Q

What is histology? How can histology be used to diagnose lung cancers? (x2 and x2)

A

BIOPSY: bronchoscopy (for central tumours), CT guided biopsy through skin – trans-thoracic (for peripheral tumours). SURGICAL BIOPSY: mediastinal lymph node biopsy, open biopsy at time of surgery.

36
Q

What are the local effects of lung cancer? (x3 – x2, x5, x1 consequences). BII

A

BRONCHIAL OBSTRUCTION: leading to (1) collapse of distal lung (the part of the lung that’s downstream from the tumour), leading to shortness of breath OR (2) impaired drainage of bronchus (mucus cannot be wafted past the tumour), leading to infections (pneumonia, abscesses). INVASION OF LOCAL STRUCTURES: invasion of local airways and vessels = cough and haemoptysis; invasion around large vessels = superior vena cava syndrome (causing venous construction in the head and arms); invasion of oesophagus = dysphagia (difficulty swallowing); invasion of chest wall = pain; invasion of nerves = Horner’s syndrome. INFLAMMATION/INVASION OF PLEURA/PERICARDIUM: leads to pleuritis/pericarditis (inflammation) with breathlessness and cardiac compromise.

37
Q

What are the systemic effects of lung cancer?

A

Caused by physical effects of distant spread: brain (fits), skin (lumps), liver (pain and deranged liver function tests (LFTs)), bones (pain and fracture).

38
Q

What are paraneoplastic syndromes?

A

System effect of tumour due to abnormal expression by tumour cells of factors (e.g. hormones and other factors) not normally expressed by the tissue from which the tumour arose

39
Q

What are the two types of neoplastic syndrome? Example for endocrine and non-endocrine?

A

ENDOCRINE: e.g. ‘Syndrome of inappropriate antidiuretic hormone’ causes hyponatremia (decrease in sodium concentration) and is found especially in SMALL CELL CARCINOMAS. NON-ENDOCRINE: e.g. haematologic/coagulation defects.

40
Q

What does differentiation mean in terms of cancer?

A

Describes how much or little tumour tissue looks like the normal tissue it came from.

41
Q

What is a mesothelioma?

A

Mesothelium is a layer of cuboidal epithelial cells lining the pleural cavity, and deposition of asbestos fibres in the lung parenchyma can cause penetration of the visceral pleura and development of plaques and tumour development.

42
Q

What is the main risk factor for mesothelioma?

A

Asbestos exposure.