Respiratory - Lung cancer

Question 1

How common are benign lung tumours?

Answer 1

Genuinely benign lung tumours are rare. Most “bronchial adenomas” are in fact carcinoid tumours arising from lung neuroendocrine cells; these may be locally invasive and occasionally metastasise. They have a similar histological appearance as carcinoid tumours of the GIT.

Question 2

What are bronchogenic carcinomas?

Answer 2

The vast majority of primary malignant tumours of the lung are carcinomas which arise in the bronchi and are therefore called bronchogenic carcinomas.

Question 3

What aetiological factors predispose to lung carcinoma?

Answer 3

Cigarette smoking is the major aetiological agent. Other less important factors include exposure to radiation, asbestos (especially when combined with smoking) as well as other minerals such as nickel and chromium. Air pollution and other genetic predispositions are other possible factors.

Question 4

What are the four main types of bronchopulmonary carcinoma?

Answer 4

1) Differentiated squamous cell carcinoma
2) Differentiated adenocarcinoma
3) Undifferentiated squamous/ adenocarcinoma (large cell)
4) Malignant neuroendocrine carcinoma (small cell carcinoma)

The current classification system divides primary lung malignancies into small cell carcinomas (number 4) and to group all the other types together as non small cell carcinoma. This grouping is based on the likely response of the tumour to therapy.

Secondary metastases (usually blood born) are also common in the lung.

Question 5

What is mesothelioma?

Answer 5

This is a potentially fatal pleural tumours which occur almost exclusively in patients exposed to asbestos.

Question 6

Where are squamous cell carcinomas most commonly located?

Answer 6

Squamous cell carcinoma is the most common primary malignancy of the lung, and usually arises in the main bronchi or their larger branches close to the lung hilum and often in an area of epithelium that has previously undergone squamous metaplasia, for example from cigarette smoking.

These tumours invade the local parenchyma and tend to obstruct the involved airway as well as spreading via local lymphatics to regional lymph nodes.

Question 7

What are the histological features of squamous cell carcinomas?

Answer 7

These tumours have a varying degree of differentiation at presentation. At one end of the spectrum is the well differentiated keratinising type where the likeness to stratified squamous epithelium is clear and there is formation of keratin in some areas.

Towards the other end of the spectrum are poorly differentiated tumours in which squamous characteristics such as intracellular bridges are only visible at high magnification.

Large cell undifferentiated carcinoma is the name reserved for tumours that are so poorly differentiated that squamous features cannot be seen by light microscopy.

Question 8

Where do small cell carcinoma occur?

Answer 8

Alongside squamous cell carcinoma these tumours are located at the proximal bronchi. These are also known as “oat cell carcinoma”.

Question 9

What are the histological features of small cell carcinoma?

Answer 9

Seen at high magnification, the name derives from the small, tightly packed, darkly stained ovoid tumour cells which resemble oat grains. These tumours rapidly and extensively invade the bronchial wall and surrounding parenchyma and may compress and invade nearby pulmonary veins. Early lymphatic and blood-borne spread is a feature of these tumours.

Small cell carcinoma carries the worst prognosis of ALL bronchogenic carcinoma because, although they are most responsive to chemotherapy, they almost always relapse early.

Question 10

Adenocarcinoma of the lung is found…

Answer 10

More peripherally in small bronchi and bronchioles. They have a particular predilection for old areas of scar tissue, for example healed TB.

Question 11

Adenocarcinoma of the lung is less associated with…

Answer 11

Smoking, as compared to other primary lung malignancies such as small cell carcinoma.

Question 12

The main histological feature of adenocarcinoma is…

Answer 12

The formation of the tumours cells into a glandular acinar pattern, the acini often being filled with mucus. The tumour (in common with many others) excites a local inflammatory response in the alveoli in the adjacent lung parenchyma containing numerous alveolar macrophages.

Question 13

Bronchoalveolar lavage and sputum cytology may show what in adenocarcinoma?

Answer 13

Clusters of large adenocarcinoma cells with prominent nucleoli, which contrast with the occasional normal bronchial epithelial cells.

Question 14

What is bronchioloalveolar cell carcinoma?

Answer 14

This is an uncommon subtype of adenocarcinoma which may appear as a solitary well defined mass in the lung periphery on X ray or more commonly as a diffuse infiltrate. The characteristic feature of this tumour is that the malignant cells grow along the alveolar walls. The alveolar epithelium is replaced by crowded columnar cells with enlarged hyperchromatic nuclei. The alveolar walls are somewhat fibrotic and inflamed.

Question 15

What is large cell undifferentiated carcinoma?

Answer 15

Together with squamous cell carcinoma and adenocarcinoma, large cell carcinoma completes the non small cell group of primary lung cancers.

Large cell undifferentiated carcinomas include extremely poorly differentiated squamous cell carcinomas and adenocarcinomas with no discernable features of squamous or adenocarcinoma by light microscopy but such features may be visible on electron microscopy.

Question 16

What are the histological features of large cell undifferentiated carcinoma?

Answer 16

These tumours consist of large anaplastic epithelial cells growing in nests and sheets. There is no evidence of keratinisation, intercellular bridges or mucin. Invasion of adjacent alveolar spaces is common.

Question 17

What are the histological features of mesothelioma?

Answer 17

Mesothelioma is a primary malignant tumour of the pleura and is related to a history of asbestos exposure.

Pleural mesotheliomas form a dense sheet of tumour extending over the pleural surface often encasing the lung in a hard white shell. But the tumour extends only a little distance into the lung parenchyma and metastatic spread is uncommon.

At low magnification the tumour can be seen to have both a glandular epithelial component and a fibrous stromal component. At higher magnification, both epithelial and stromal components exhibit pleomorphism characteristic of malignancy.

Question 18

Name some other primary malignant tumours of the lung?

Answer 18

1) Bronchial carcinoid tumours: low grade malignant tumours arising in the central airways. They are highly vascular and commonly present with haemoptysis or result in bronchial obstruction. Resection is usually curative. Ectopic ACTH release can be a rare cause of Cushings syndrome
2) Malignant mesenchymal tumours (sarcoma): are extremely rare but the commonest primary type is synovial sarcoma
3) Primary pulmonary lymphomas: rare tumours presenting as pulmonary disease with or without hilar lymph node involvement but without clinical evidence of disease elsewhere. HIV/ AIDS patients have increased risk of pulmonary lymphoma

Question 19

What are the clinical features of lung cancer?

Answer 19

Patients with lung cancer can present with a variety of symptoms that can either relate to the primary lesion in the lung and the local effect this has or to distant metastases.

Central tumours arising in the more proximal airways can ulcerate and bleed causing haemoptysis. As it grows the tumour may obstruct the bronchus with either collapse or distal consolidation causing breathlessness or features suggesting a pneumonia.

Local spread can involve adjacent structures:

• Pleura: blood stained effusion, empyema, chest wall invasion
• SVC: compression or invasion causes superior vena caval syndrome
• Pericardium: pericarditis with haemorrhagic effusion
• Bone involvement: direct spread into ribs, sternum and spine result in pain, hypercalcaemia and pathological fracture
• Oesophagus: dysphagia or broncho-oesophageal fistula
• Nerves: spread to axilla - Pancoast tumour - with invasion of the brachial plexus or cervical sympathetic chain - Horner’s syndrome - recurrent laryngeal nerve palsy - hoarseness

Question 20

Other than local spread, how else can lung cancer metastasise?

Answer 20

1) Lymphatic spread: occurs early with invasion of regional intrapulmonary, hilar and extrapulmonary tracheobronchial and other mediastinal nodes. Further spread can involve cervical or supraclavicular nodes. Nodal involvement can be massive and can be the presenting feature with caval obstruction or tracheal compression
2) Blood: widespread systemic invasion is common and metastases not uncommonly present as the first clinical manifestation. Adrenals, liver, brain and bone are common
3) Transcoelomic

Question 21

What ectopic hormones are produced by lung carcinomas?

Answer 21

1) ADH: causing syndrome of inappropriate ADH secretion, hyponatraemia and cerebral dysfunction. Most commonly associated with small cell cancer
2) ACTH: producing metabolic and occasionally clinical Cushing’s syndrome. Most commonly associated with small cell carcinoma
3) Parathyroid like substances: causing hypercalcaemia and most commonly associated with squamous cell carcinoma

Question 22

How is lung carcinoma staged?

Answer 22

Staging assesses the extent of tumour spread and uses the TNM classification (non small cell lung cancer). Lung cancer is divided into 5 stages:

i) Occult
ii) Stage I - TIS-T2/N0/M0
iii) Stage II - local nodal involvement
iv) Stage IIIa - high grade tumour with single local node involvement
v) Stage IIIb - high grade tumour with multiple local node involvement
vi) Stage IV - distant metastases

Question 23

What determines the prognosis of lung cancer?

Answer 23

The main prognostic factors are the stage and cell type.

The overall 5 year survival for carcinoma of lung is between 5-15%.

Non small cell tumours i.e. tumours other than small cell carcinomas are treated surgically for anticipation of cure, but 75% are inoperable at presentation and have a poor prognosis. Of the 25% that are operable, 20% of these have early stage disease with a 30-50% 5 year survival. The remaining 80% have a 10-15% survival at 5 years.

Small cell carcinoma. Overall less than 2% of patients are alive at 5 years. These tumours are usually treated non surgically by chemotherapy or radiotherapy.

Question 24

What is a coin lesion?

Answer 24

The term coin lesion refers to the radiological finding of a solitary peripheral parenchymal nodule that has a circular outline with no other specific radiological features.

Causes include:
- Common: bronchial carcinoma, metastatic tumour, granulomatous inflammation, histoplasmosis, lung abscess, hamartoma, bronchial carcinoid

-Uncommon: other primary tumours, AVMs, foreign bodies, intrapulmonary lymph node, Wegener’s

Question 25

How are non small cell tumours treated?

Answer 25

Surgery is the treatment of choice for peripheral tumours with no metastatic spread, stage I/II (25%). Currative radiotherapy is an alternative therapy if respiratory reserve is poor. Chemotherapy +/- radiotherapy for ore advanced disease. Regimens may be platinum based - e.g. with monocloncal antibodies targetting the epidermal growth factor receptor (cetuximab).

Question 26

How are small cell tumours treated?

Answer 26

These are nearly always disseminated at presentation. They MAY respond to chemotherapy but invariably relapse (cyclophosphamide + doxorubicin + vincristine + etoposide OR cisplatin + radiotherapy if limited disease.

Question 27

What palliative options are available for patients with lung cancer?

Answer 27

Radiotherapy is used for bronchial obstruction, SVC obstruction, haemoptysis, bone pain and cerebral metastases.

SVC stent + radiotherapy and dexamethasone are used for SVC obstruction.

Drugs: analgesia, steroids, antiemetics, cough linctus (codeine), bronchodilators and antidepressants are also used.