Lung Cancer Flashcards by Izzie Setford

Describe the incidence of lung cancer.

Second most common cancer in both men and women
Incidence is falling in men and rising in women
Most people are old when they get it (low survival rate)

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In which UK country is lung cancer the most prevalent cancer?

Scotland - reflects high smoking prevalence

Greater Glasgow and Clyde have higher levels of lung cancer than the Scottish average

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What are the death rates for lung cancer?

Most common cause of death from malignant disease
5% of annual deaths
25% of male cancer deaths
18% of female cancer deaths

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What is the survival rates for lung cancer?

4% 1 year survival

7. 8% 5 year survival

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Describe aetiology of lung cancer.

Smoking - the single greatest cause of preventable illness and early death
90% of lung cancer is attributable to smoking
Stopping smoking reduces risk but depends on number of years smoking and takes time

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Which types of lung cancer is smoking most closely related to?

Squamous carcinoma

Small cell carcinoma

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What are the risk factors for lung cancer?

Environmental pollution
Ionising radiation (radon, uranium)
Asbestos
Other
- fibrosing conditions of lung
- HPV
- hereditary 
Smoking

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Describe the pathogenesis of lung cancer.

Chronic irritation/stimulation of cells by carcinogens
Increased cell turnover - increased accumulation of genetic abnormalities
Progressive accumulation of genetic abnormalities in molecules involved in the cell cycle, signalling and angiogenesis pathways
- e.g ras or p53
Little known about rate of progression/regression
Phenotype changes potentially reversible (but genotypic alterations persist)

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Describe the histological changes from normal lung tissue to lung cancer?

Normal
Hyperplasia
Metaplasia
Dysplasia
Carcinoma in situ
Clinical cancer

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What are the 4 major histological types of lung cancer?

Small cell carcinoma
Non-small cell carcinoma 
- squamous
- adenocarcinoma
- large cell

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What other histological types of lung cancer are there apart from the 4 main types?

Tumours of the neuroendocrine cells 
- carcinoid
Tumours of the pleura
- mesothelioma 
Tumours of the lymphatic system
- lymphoma 
Miscellanoeous 
- chondroid hamartoma

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Why have rates of adenocarcinomas risen, while squamous carcinomas have fallen?

This is because filter tips, lower tar and nicotine mean that smoking associated lung cancers (squamous) are decreasing.
For this same reason people are inhaling the smoke deeper into the lungs, exposing the peripheral areas -> adenocarcinoma rise

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Where do adenocarcinomas, squamous and small cell carcinomas arise?

Adenocarcinoma - peripheral

Squamous and small cell carcinomas - central tumours arise in the hilus of the lung

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Why is the separation of small cell carcinoma from non-small cell carcinomas important?

Treatment purposes

small cell requires chemotherapy as the first line of treatment
non-small cell can be operated on first (if the patient is amenable to surgery), and may require no chemotheapy

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What do small cell carcinomas looks like in the lung?

Black, discoloured lymph nodes embedded in a large tumour

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Describe small cell carcinoma.

Most aggressive form of lung cancer
Metastasises early and widely (very advanced when found)
Good response to chemotherapy, but often relapses

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Describe what small cell lung cancer looks like on histology.

Oval to spindle shaped cells
Inconspicuous nucleoli
Scant cytoplasm
Nuclear moulding (more prominent in cytology)
Apoptotic bodies
Cells tend to be smaller than cells involved in other forms of lung cancer

Where do squamous cell carcinomas often arise, and what problems does this cause?

Arise centrally from the major bronchi and block the airways

- can lead to retention pneumonia or lung collapse

Which type of lung cancer can undergo cavitation?

Squamous cell cancer

- cavitation means the tumour has become necrotic

Describe the appearance of a squamous cell carcinoma.

A malignant epithelial tumour showing keratinisation and/or intercellular bridges
In situ squamous cell carcinomas may be seen in the adjacent airway mucosa
Often have a dysplastic epithelium following squamous metaplasia

What are squamous cell carcinomas a good candidate for surgery?

Slow growing and metastasise late - easily removed when still small and at an early stage

Describe the appearance of an adenocarcinoma.

Glandular, solid, papillary or lepidic

- gland formation - produces mucin

How is a large cell carcinoma diagnosed?

A diagnosis of exclusion - when you realise it is not any of the other forms of lung cancer

Where do large cell carcinomas arise within the lungs?

Usually centrally

Describe the histological appearance of a large cell lung cancer.

An undifferentiated malignant epithelial tumour that lacks the cytological features of small cell lung cancer, AND glandular or squamous differentiation

Why is differentiation of the three different types of non-small cell carcinoma important?

Treatment may differ Some adenocarcinomas and large cell cancers may have mutations in EGFR or ALK genes which means they cant receive targeted chemotherapy - e.g. gefitinib, erlotinib and crizotinib

Describe ECGR mutations in non-small cell lung cancer cases.

EGFR is a tyrosine kinase involved in intracellular signalling In many NSCLC cases, EGFR is mutated so it becomes constantly active and can leads to excessive cell proliferation and various other processes.

Briefly describe the mechanism of action of Gefitinib.

This is a tyrosine kinase inhibitor - so it binds to the EGFR tyrosine kinase domain with high specificity and affinty This results in potent inhibition of the signlling pathways

Where do most mutations of the EGFR occur?

``` In the kinase domain of EGFR - specifically in exons 18-21 Most mutations (90%) occur from deletions in exon 19 and a point mutation in exon 21 ```

What are the signs and symptoms of lung cancer?

``` Cough Haemoptysis Chest pain Metastases Peripheral - may have a few of these symptoms Central - may cause bronchial obstruction with collapse of consolidation of the lung distal to the tumour (retention pneumonia) ```

Where can lung cancer spread to locally?

Pleura - hemorrhagic effusion Hilar lymph nodes - initially, and then to other groups in the chest Adjacent lung tissue - may involve large blood vessels (haemoptysis) Pericardium Mediastinum Pancoast tumour

Describe what happens when lung cancer spread to the pericardium.

Pericardial effusion with subsequent involvement of the pericardium

Describe what happens when lung cancer spreads to the mediastinum.

The SVC, phrenic nerve and recurrent laryngeal nerve can be obstructed - recurrent laryngeal nerve obstruction can cause a hoarse voice - phrenic nerve obstruction can cause palsy - SVC obstruction causes increased venous pressure in the upper part of the body (oedema, cyanosis, respiratory distress)

What is a Pancoast tumour, and what does it cause?

A tumour in the apices of the lung that compresses the brachial plexus - impairment of the sensory and motor fibres Causes Horner's syndrome/occulosympathetic palsy - cervical sympathetic chain - ptosis - enophthalmos - miosis - anhydrosis

What are the two ways in which lung cancer can spread to distant places?

Haematogenous - common due to invasion of the pulmonary veins - spreads to liver, bone, brain, adrenal Lymphatic - spreads to cervical lymph nodes

What are the possible non-metastatic effects of lung cancer?

ACTH secretion - adrenal hyperplasia causes raised blood cortisol (Cushing's syndrome) ADH secretion - causes water retention (dilutional hyponatraemia - SIADH) Parathyroid hormone related peptide (PTHrP) secretion - increased osteoclastic activity causing hypercalcaemia

What are common secondary tumours in the lungs?

Carcinoma of the breast, colon, kidneys, stomach, oesophagus and the thyroid. Sarcoma Teratomas

What are the symptoms of secondary lung cancer?

``` Similar to primary lung cancer No symptoms Increased breathlessness Persistent cough Weight loss Occasionally hemoptysis ```

What is the treatment for secondary lung cancer?

Chemotherapy Radiotherapy Surgery - metastatectomy (only if isolated disease)

Describe a mesothelioma.

Primary pleural tumour (also occurs in the peritoneum, pericardium and tunica vaginalis of the testes) Due to asbestos exposure - long lag period before disease develops Tumour has either an epithelial or a sarcomatoid appearance (or a mixture of both - biphasic)

How is a mesothelioma diagnosed?

Asbestos body can be seen on cytology | CT scan - encircles the chest cavity