Bronchial carcinoma accounts for 95% of all primary tumours of the lung. Alveolar cell carcinoma accounts for 2% of lung tumours and other less malignant or benign tumours account for the remaining 3%.
This is the most common benign tumour of the lung and is usually seen as a very well-defined round lesion 1-2 em in diameter in the periphery of the lung. Growth is extremely slow, but the tumour may reach several centimetres in diameter. Rarely it arises from a major bronchus and causes obstruction.
This rare tumour resembles intestinal carcinoid tumour and is locally invasive, eventually spreading to mediastinal lymph nodes and finally to distant organs. It is a highly vascular tumour that projects into the lumen of a major bronchus causing recurrent haemoptysis. It grows slowly and eventually blocks the bronchus, leading to lobar collapse. Rarely, it gives rise to the carcinoid syndrome.
Cylindroma, chondroma and lipoma
These are extremely rare tumours that may grow in the bronchus or trachea, causing obstruction.
Primary tumours of the trachea are very rare-the relative incidence compared to laryngeal and bronchial tumours is 1 : 75 and 1 : 180 respectively. The majority are malignant. Benign tumours are extremely rare but include squamous papilloma, leiomyoma, haemangiomas and tumours of neurogenic origin.
DIAGNOSIS AND TREATMENT
These tumours are diagnosed in the same way as bronchial carcinoma. Tracheal tumours cause severe and rapidly progressive dyspnoea and stridor. Flow-volume curves show typical and dramatic reductions in inspiratory flow (extrathoracic tracheal tumours).
Laser treatment provides rapid and effective destruction of tumour with temporary relief of symptoms. Radiotherapy is often given and occasionally surgery may be possible. The prognosis is very poor.
This is the most common malignant tumoUl: in the Western World and is now the third most common cause of death in the UK after heart disease and pneumonia. Mortality rates worldwide are highest in Scotland, closely followed by England and Wales. In the UK, 35000 people die each year from bronchial carcinoma, with a male-tofemale ratio of 3.5 : 1. Although the rising mortality from this disease has levelled off in men, it continues to rise in women, accounting for 1 in 8 of all deaths from malignant disease in women, second only to carcinoma of the breast.
The strength of the association between cigarette smoking and bronchial carcinoma overshadows any other aetiological factors but there is a higher incidence of bronchial carcinoma in urban compared with rural areas, even when allowance is made for cigarette smoking. Passive smoking (the inhalation of other people’s smoke by non-smokers) increases the risk of bronchial carcinoma by a factor of 1.5. Occupational factors include exposure to asbestos, and an association is also claimed for workers in contact with arsenic, chromium, iron oxide, petroleum products and oils, coal tar,
products of coal combustion, and radiation. Tumours associated with occupational factors are mostly adenocarcinomas and appear to be less related to cigarette smoking.
Bronchial carcinoma is divided into small-cell carcinoma and non-small-cell carcinoma, a division based on the characteristics of the disease and its response to treatment. Studies of mean doubling times of carcinomas indicate that development from the initial malignant change to presentation takes many years; for adenocarcinoma it takes approximately 15 years, for squamous carcinoma 8 years and for small-cell carcinoma 3 years.
QUAMOUS OR EPIDERMOID CARCINOMA is the commonest carcinoma in this group, accounting for approximately 40% of all carcinomas. It occasionally cavitates, and widespread metastases occur relatively late.
LARGE-CELL CARCINOMA represents a less welldifferentiated tumour that metastasizes early. It accounts for 25% of all tumours.
ADENOCARCINOMA arises peripherally from mucous glands in the small bronchi and often produces a subpleural mass. Invasion of the pleura and the mediastinal lymph nodes is common, as are metastases to the brain and bones. Adenocarcinoma accounts for approximately 10% of all bronchial carcinomas and frequently arises in or around scar tissue. It is the commonest bronchial carcinoma associated with asbestos and is proportionally more common in non-smokers, in women, in the elderly, and in the Far East.
ALVEOLAR CELL CARCINOMA (BRONCHIOLAR CARCINOMA)accounts for only 1-2% of lung tumours and occurs either as a peripheral solitary nodule or as diffuse nodular lesions of multicentric origin. Occasionally this tumour is associated with expectoration of very large volumes of mucoid sputum.
This tumour, often called oat-cell carcinoma, accounts for 20-30% of all lung cancers. It arises from endocrine cells (Kulchitsky cells). These cells are members of the APUD system, which explains why many polypeptide hormones are secreted by these tumours. Some of these polypeptides act in an autocrine fashion, i.e. they feed back on the cells and cause cell growth. Small-cell carcinoma is now considered to be a systemic disease. Although the tumour is rapidly growing and highly malignant, it is the only one of the bronchial carcinomas that responds to chemotherapy.
The frequencies of the common symptoms of lung cancer on presentation. Chest pain and discomfort are often described as fullness and pressure in the chest. Sometimes the pain may be pleuritic owing to invasion of the pleura or ribs.
Commonly there are no abnormal physical signs. Enlarged supraclavicular lymph nodes are frequently found with small-cell carcinoma. There may be signs of a pleural effusion or of lobar collapse. Signs of an unresolved pneumonia or of associated underlying disease (e.g, diffuse pulmonary fibrosis in asbestosis) may be present.
The tumour may directly involve the pleura and ribs. Carcinoma in the apex of the lung can erode the ribs and involve the lower part of the brachial plexus (C8, Tl and T2), causing severe pain in the shoulder and down the inner surface of the arm (Pancoast’s tumour). The sympathetic ganglion may also be involved, producing Horner’s syndrome. Further extension may involve the recurrent laryngeal nerve as it passes down the aortic arch, causing unilateral vocal cord paresis with hoarseness and a bovine cough, and rarely the tumour may cause spinal cord compression.
Bronchial carcinoma can also directly invade the phrenic nerve, causing paralysis of the diaphragm. It can involve the oesophagus, producing progressive dysphagia, and the pericardium, producing pericardial effusion and malignant dysrhythmias. It can also involve the superior vena cava, producing superior vena caval obstruction . leading to early morning headache, facial congestion and oedema involving the upper limbs; the jugular veins are distended, as are the veins on the chest that form a collateral circulation with veins arising from the abdomen.
Bony metastases are common, giving rise to severe pain and pathological fractures. There is frequent involvement of the liver. Secondary deposits in the brain present as a change in personality, epilepsy or a focal neurological lesion. Carcinoma of the bronchus is a cause of secondary deposits in the adrenal gland.
Non-metastatic extrapulrnonary manifestations Although approximately 10% of small-cell tumours are thought to produce ectopic hormones at some stage, clinically important extra pulmonary manifestations are relatively rare apart from finger clubbing. Hypertrophic pulmonary osteoarthropathy (HPOA) occurs in approximately 3% of all bronchial carcinomas, particularly squamous-cell carcinomas and adenocarcinomas. Symptoms include joint stiffness and severe pain in the wrists and ankles, sometimes associated with gynaecomastia. X-rays show the characteristic proliferative periostitis at the distal ends of long bones, which have an onion-skin appearance. HPOA is invariably associated with clubbing of the fingers. It may regress after resection of the lung tumour or as a result of vagotomy at thoracotomy.
This is the most valuable screening test for bronchial carcinoma. It is a relatively insensitive test, however, since the tumour mass needs to be between 1 and 2 em in size to be recognized reliably. CT scanning can identify small tumour masses (see Fig. 12.12), but is at present too timeconsuming and expensive to replace the chest X-ray. About 70% of all bronchial carcinomas arise centrally, the rest peripherally (particularly adenocarcinomas). At the time of clinical presentation the chest X-ray will demonstrate over 90% of carcinomas. A small proportion arise within the main bronchus or trachea or else present with metastatic or non-metastatic complications but with no detectable mass on the chest X-ray.
Bronchial carcinoma can appear as round shadows on a chest X-ray (see p. 644). Characteristically the edge of the tumour has a fluffy or spiked appearance, though sometimes it may be entirely smooth with cavitation, particularly when the tumour is epidermoid in type. Carcinoma can also cause collapse of the lung.
Carcinoma causing partial obstruction of a bronchus interrupts the mucociliary escalator, and bacteria are retained within the affected lobe. This gives rise to the so-called secondary pneumonia that is commonly seen on a chest X-ray of a patient presenting with bronchial carcinoma.
The hilar lymph nodes on the side of the tumour are frequently involved in carcinoma of the lung. A large pleural effusion may also be present. Carcinoma can spread through the lymphatic channels of the lung to give rise to lymphangitis carcinomatosa ; this is usually unilateral and associated with striking dyspnoea. The chest X-ray shows streaky shadowing throughout the lung. This appearance may be seen in both lungs, particularly when it is due to metastatic spread, usually from turn ours below the diaphragm (the stomach and colon) and from the breast Computed tomography CT is particularly useful for identifying pathological changes in the mediastinum (e.g. enlarged lymph nodes, local spread of the tumour) and for identifying secondary spread of carcinoma to the opposite lung by detecting masses too small to be seen on the chest X-ray. Lymph nodes larger than 1.5 cm are considered pathological, although whether they are due to metastatictumour, reactive hyperplasia or previous lung disease (e.g. tuberculosis) can only be determined by biopsy. A normal CT scan prior to surgery excludes the need for mediastinoscopy and node biopsy. CT scanning should be extended to include the liver, adrenal glands and the brain to identify distant metastases if present.
Magnetic resonance imaging
This may have some advantages over CT in mediastinal lesions when they are near to major vessels . Fibreoptic bronchoscopy. This technique is used to obtain cytological specimens from peripheral lesions as well as to obtain biopsy evidence of any tumours seen. If the carcinoma involves the first 2 cm of either main bronchus, the tumour is inoperable. Widening and loss of the sharp angle of the carina indicates the presence of enlarged mediastinal lymph nodes, either malignant or reactive. They can be biopsied by passage of a needle through the bronchial wall. Vocal cord paresis on the left indicates involvement of the recurrent laryngeal nerve and inoperability. Transthoracic fine-needle aspiration biopsy This involves the direct aspiration through the chest wall of peripheral lung lesions under appropriate X-ray or CT screening. Specimens can be obtained from 75% of peripheral lesions that could not be biopsied transbronchially. Pneumothorax occurs in 25% of patients,
occasionally requiring drainage. Mild haemoptysis occurs in 5%. Implantation metastases do not occur.
Unlike some other cancers, there has been no improvement in survival from carcinoma of the bronchus apart from small cell cancer (see below). Only 20% of patients are alive 1 year after diagnosis and only 6-8% after 5 years (cf. 50% for breast or cervix).
Surgery The only treatment of any value for non-small-cell cancer of the lung is surgery. Only 20% of all cases are suitable for resection and only 25-30% survive for 5 years. The mortality of thoracotomy in patients over 65 years with metastatic disease exceeds the expected 5-year survival rate and should therefore be avoided.
PREOPERATIVE ASSESSMENT. Radionuclide scanning for detection of metastatic disease in liver and bone is rarely positive in the absence of symptoms or abnormal enzyme tests (serum alkaline phosphatase) and is therefore unnecessary. A normal chest CT scan indicates no mediastinal spread of the tumour and favours curative resection.
Because of their common aetiology, chronic bronchitis and emphysema are frequently present. An FEV I of less than 1.5 litres is not compatible with an active life following pneumonectomy, although the surgery itself can be successfully accomplished. This also applies when the gastransfer test is reduced by 50%.
Radiation therapy for cure
High-dose radiotherapy (6500 rad; 65 Gy) can produce results that are as good as those of surgery in patients who are fit and who have slowly growing squamous carcinoma. It is the treatment of choice if the tumour is inoperable for reasons such as poor lung function. Radiation pneumonitis (defined as an acute infiltrate precisely confined to the radiation area and occurring within 3 months of radiotherapy) develops in 10-15%. Radiation fibrosis, a fibrotic change occurring within 1 year or so of radiotherapy and not precisely confined to the radiation area, occurs to some degree in all cases. These complications are usually of little importance. Symptomatic radiation treatment Bone pain, haemoptysis and the superior vena cava syndrome respond favourably to irradiation in the short term.
This is not effective for the treatment of non-small-cell cancer of the lung. In small-cell cancer, single or combination chemotherapy has resulted in a fivefold increase in median survival from 2 to 10 months. A small number of patients enjoy several years of remission. Good results have been achieved with the combination of mitomycin, ifosfamide and cisplatin. The unwanted effects are greater than with single-agent chemotherapy with etoposide alone, which should be reserved for elderly patients and those with additional medical or physical disabilities.
Laser therapy, endobronchial irradiation and tracheobronchial stents This is used in the palliation of inoperable lung cancer. The techniques are complementary and considerable skill is required both in deciding which single or combination of therapies is required and in their execution. Tracheobronchial narrowing from intraluminal tumour or extrinsic compression causes disabling breathlessness, intractable cough and complications which may lead to death including infection, haemoptysis and respiratory failure. A neodymium-Yag (Nd-Yag) laser passed through a fibreoptic brochoscope can be used to vaporize inoperable fungating intraluminal carcinoma involving short segments of trachea or main bronchus. Benign tumours, strictures and vascular lesions can also be effectively treated with immediate relief of symptoms. Endobronchial irradiation (brachytherapy) is useful for the treatment of both intraluminal tumour and malignant extrinsic compression. A radioactive source is afterloaded into a catheter placed adjacent to the carcinoma under fibreoptic bronchoscope control. Radiation dose falls rapidly with distance from the source minimizing damage to adjacent normal tissue. Reduction in endoscopically assessed tumour size occurs in 70-95% of cases. Tracheobronchial stents made of silicone or as expandable metal springs are now available for insertion into strictures caused by tumour or from external compression or when there is weakening and collapse of the tracheobronchial wall.
Patients dying of cancer of the lung need attention to their overall well-being. They must not be ignored simply because they cannot be cured. A lot can be done to make the patient’s remaining life symptom-free and as active as possible.
Daily treatment with prednisolone (up to 15 mg daily) may improve appetite. Morphine or diamorphine must be given regularly for pain, either in the form of a sustained- release morphine sulphate tablet twice daily or else as regular elixirs or injections. Many patients benefit from a continuous subcutaneous injection of opiates given by a pump. Candidiasis and other infections in the mouth are common and must be looked for and treated. Patients taking opiates are frequently constipated, so regular laxatives should be prescribed. Short courses of palliative radiotherapy for bone pain, severe cough or haemoptysis are helpful.
Both the patient and the relatives require counselling, a task that should be shared between nurses, social workers, hospital chaplains and doctors.
SCREENING FOR LUNG CANCER
Screening programmes (yearly chest X-ray, 4-monthly sputum cytology) have been tried in high-risk groups but the success rate is minimal, underlining the need for prevention.
Secondary tumours Metastases in the lung are very common and usually present as round shadows 1.5-3 cm in diameter. They may
be detected on chest X-ray in patients already diagnosed as having carcinoma. The primary is usually in the
• Gastrointestinal tract
• Cervix or ovary
They nearly always develop in the parenchyma and are often relatively asymptomatic even when the chest X-ray shows extensive pulmonary metastases. It is rare for metastases to develop in the bronchi, when they may present with haemoptysis.
Carcinoma, particularly of the stomach, pancreas and breast, can involve mediastinal glands and spread along the lymphatics of both lungs (lymphangitis carcinornatosa), which can lead to progressive and severe breathlessness. On the chest X-ray, bilaterallymphadenopathy is seen together with streaky basal shadowing fanning out over both lung fields.
Occasionally a pulmonary metastasis may be detected as a solitary round shadow on chest X-ray in an asymptomatic patient. The commonest primary tumour to do this is a renal carcinoma. The differential diagnosis includes:
• Primary bronchial carcinoma
• Benign tumour of the lung
• Hydatid cyst
Single pulmonary metastases can be removed surgically but, as CT scans usually show the presence of small metastases undetected on chest X-ray, surgery is seldom performed.