Upper Respiratory Tract

Acute Inflammation

Infections of the nose, nasal sinuses, pharynx and larynx are common. They are usually mild and self-limiting. Most cases are due to viral infection, but this is often followed by bacterial superinfection.

1. Viral infection

This phase is characterised by features of acute inflammation but without the exudation of neutrophils.

Viruses involved

A wide variety, of which the major types are:

2. Bacterial phase Many bacteria are commensal in the respiratory tract (e.g. Streptococcus mutans, Haemophilus influenzae) and can superinfect the damaged tissue, which then exhibits the typical features of acute inflammation including exudation of neutrophils.

The wide variety of different viruses involved prevents protective immunity.

Rhinitis

Common Cold (Acute Coryza)

This common respiratory inflammation usually involves the nose and adjacent structures.

The 2 phases, viral and bacterial, are typically seen in this disease.

The drainage from the sinuses, especially the maxillary, is often blocked by swelling of the mucosa — giving rise to sinusitis.

The infection is acquired by droplet spread of viruses by sneezing.

Allergic Rhinitis ‘Hay Fever’

An allergic (immediate type hyper-sensitivity) type of inflammation (2. p.101) is often seen. Patients develop immediate symptoms of sneezing, itching and watery rhinorrhoea.

The repeated attacks frequently lead to chronic changes in the mucosa with polyp formation.

Nasal Polyps

These form particularly on the middle turbinate bones and within the maxillary sinuses.

In the nasopharynx, the lymphoid tissue may be greatly enlarged (adenoids) and contribute to the nasal obstruction.

Allergies

Seasonal Allergy

This is due to pollens liberated from trees and grass.

Non-Seasonal Allergy

The main cause is the house dust mite, Dermatophagoides pteronyssinus. Allergy to pets is common, e.g. cats – the allergens are usually glycoproteins secreted by sebaceous glands and found in cat skin and saliva.

Vasomotor Rhinitis

This is a clinical diagnosis. The pathological changes are, to some extent, similar to those of allergic rhinitis, but the condition is more continuous, less spasmodic. Although the cause is unknown, viral infections in a polluted atmosphere (usually an urban setting) are thought to initiate the ‘sensitivity’ and non-specific stimuli such as bright light and smells precipitate an attack.

Acute Pharyngitis, Tracheitis and Laryngitis

Acute Pharyngitis and Tracheitis

Most sore throats are caused by viruses – including adenovirus and Epstein–Barr virus.

Bacteria include Streptococcus pyogenes, Haemophilus parainfluenzae and Corynbacterium diphtheriae.

Tonsillitis is a common acute inflammation, historically due to streptococcal infection but, with the introduction of antibiotics, viruses are the initiating infective agents in most cases.

Diphtheria, now uncommon in countries where vaccination is widespread, is a serious infection.

The formation of a pseudomembrane is striking.

This pseudomembrane may spread to block the larynx, causing respiratory obstruction.

The exotoxin of diphtheria is encoded by a bacteriophage (a virus which infects the bacterium). It can cause myocarditis (p.212) and neuropathy (p.569).

In Acute epiglottitis, typically due to Haemophilus influenzae, there is severe inflammation and oedema. In young children, the larynx becomes obstructed necessitating tracheostomy and administration of antibiotics.

Acute laryngitis is often due to parainfluenza viruses. Acute oedema of the glottis is seen in some cases of anaphylaxis (p.101) and angioneurotic oedema.

Other Disorders of the Larynx

Chronic Laryngitis

Cigarette smoking, repeated attacks of infection and atmospheric pollution may lead to chronic inflammation of the larynx.

Two main features are (a) changes in the lining epithelium and (b) increase in mucus secretion.

The following sequence of events tends to take place:

Tuberculosis – this can cause severe ulceration of the larynx and is usually secondary to pulmonary tuberculosis.

Vocal Cord Nodule (Singer’s Node)

They consist of squamous epithelium overlying fibrin-rich and myxoid stroma.

Tumours of the Upper Respiratory Tract

Benign Tumours

(a) Epithelial

Papillomas may be single but are often multiple and due to infection by papilloma virus. The epithelium may be one of two types:

(b) Connective tissue

Haemangiomas, especially of the nasal septum, can cause persistent nose bleeds. A special form, angiofibroma, affects male children and grows throughout childhood but typically regresses.

Malignant Tumours

These are mainly squamous carcinomas and are commonly seen in the larynx. Intraepithelial neoplasia (carcinoma-in-situ) is a frequent precursor.

Smoking and alcohol consumption are aetiologically important. The rate of growth and spread is influenced by the site within the larynx.

Nasopharyngeal carcinoma is common in Eastern countries and is associated with Epstein–Barr virus infection.

Adenocarcinoma of the nose is a rare tumour, sometimes seen in woodworkers.

Lungs – Anatomy

Acinus

This is the functional unit of the lung, where gas transfer takes place. It consists of the respiratory bronchiole and associated alveolar ducts and sacs supplied by one terminal bronchiole. There are approximately 25 000 acini in the normal adult male lung.

Lobule

This is served by one preterminal bronchiole and is the smallest anatomic compartment of lung that is grossly apparent. It contains 3 to 30 acini and is bound by connective tissue septa. These connective tissue septa may be accentuated in smokers.

The total area for air exchange is very large (equivalent to a tennis court) allowing considerable reserve capacity.

Histology of the Alveolus

Two types of cell (pneumocytes) line the alveoli:

Macrophages and mast cells are also present in the alveoli.

Pulmonary Vasculature

Respiration

The normal intake of air is around 7 litres per minute; of this, after allowing for nonfunctioning dead space (trachea, bronchi, etc.), approximately 5 litres per minute are available for alveolar ventilation. A definite flow of air is maintained as far as the terminal bronchiole. Beyond this point the actual flow ceases and gas exchange is effected by diffusion.

Three factors are involved in the maintenance of adequate respiration:

Interference with any of these factors will result in respiratory embarrassment (dyspnoea) and even respiratory failure.

Acute Bronchitis

This is an inflammation of the large and medium bronchi. The condition may be serious if associated with pre-existing respiratory disease. Mucous and serous glands in the walls of the bronchi provide abundant mucoid secretion during the inflammation. Ciliated epithelia lining the bronchi aid passage of the exudate upward and help prevent spread down to the bronchioles.

In most cases, the process is initiated by a viral or mycoplasmal infection. It is a common complication of influenza and measles. This initial phase is followed by bacterial invasion. Streptococcus pneumoniae and Haemophilus influenzae are commonest, but Staphylococcus aureus and Streptococcus pyogenes may be found, especially in infants.

The condition is usually mild, and spread to the bronchioles is unusual in healthy adults due to the effective ciliary action of the bronchial epithelium. Spread may occur however in debilitated people. Bronchiolitis and bronchopneumonia result and can prove fatal. Equally important is the serious effect of repeated attacks of acute infection in patients with chronic bronchitis (p.258).

In children:

1. Whooping cough (due to Bordetella pertussis) may cause permanent damage due to the severity of the infection and the stress on the airways during the coughing and whooping attacks.

2. Bronchiolitis in the very young (<2 years), in the majority of cases, is due to Respiratory Syncytial Virus and the risk of progression to bronchopneumonia is high.

Bronchial Asthma

In asthma, there are spasmodic attacks of reversible bronchial obstruction with wheezing and dyspnoea and often a dry cough. The prevalence has markedly increased in recent years, although has now plateaued. There are 2 main patterns:

1. Atopic asthma (p.102)

– typically starts in childhood.

– often a strong family history of asthma or atopic conditions (e.g. eczema).

– attacks provoked by predominantly IgE type I hypersensitivity reaction to inhaled allergens, e.g. pollen, cats, house mite dust.

2. Non-atopic asthma

– usually in middle age.

– usually no history of atopy: family history uncommon.

– no particular antigens incriminated.

Other varieties include occupational asthma and aspirin-induced asthma.

The basic mechanism is as follows:

ACUTE ASTHMA

Recurrent episodes of inflammation lead to irreversible damage

The histological changes are a combination of allergic reaction and muscular hypertrophy, the result of prolonged spasm.

Sputum

In some cases the following may be seen:

1. Curschmann’s spirals – appear as small white granules in sputum.

2. Charcot–Leyden crystals – in association with eosinophils.

Chronic Obstructive Pulmonary Disease (COPD)

This term describes three entities that show considerable clinical overlap:

1. Chronic bronchitis

2. Emphysema

3. Small airways disease

COPD is common and is the fourth leading cause of death worldwide.

Aetiology The main factors are:

1. SMOKING – by far the major risk factor and dose related.

2. α₁-antitrypsin deficiency. Reduced levels of this protease inhibitor correlate with lung damage, especially in smokers.

3. OCCUPATION, especially exposure to dusts, e.g. coal mining.

Chronic Bronchitis

The clinical definition is based on the presence of a productive cough lasting at least 3 months and occurring annually for at least 2 years.

Pathologically the following changes are seen:

The increase in thickness of the mucous gland layer is striking: at post-mortem the Reid index is measured – i.e. the ratio of the submucous layer (X) to the whole thickness (Y): a value greater than 1:2 is significant.

The effect of these changes is:

Emphysema

This is defined as a permanent dilatation of air spaces distal to the terminal bronchiole due to destruction of their walls without fibrosis. It is an important component of COPD (p.258) and has the same aetiological factors.

Changes Seen On Clinical Examination

Normal

Anatomical changes due to increased use of accessory muscles of respiration and increased lung volume.

Pathological changes At post-mortem the lungs are over-inflated When removed the lung tends to collapse unless it is inflated with fixative and cut later.

On the sectioned lung 2 main patterns are seen.

1. Panacinar emphysema and

2. Centriacinar (centrilobular) emphysema.

Panacinar Emphysema

The enlarged air spaces are distributed across the entire acinus.

Special stains show loss of elastic tissue. The capillaries are stretched and thinned. The reduction in blood supply is probably a factor in leading to rupture of alveoli.

There is little evidence of bronchiolitis. The voluminous lungs produce characteristic radiological changes. The distension eventually spreads to involve the respiratory bronchiole, i.e. the whole acinus is affected – panacinar emphysema.

Centrilobular Emphysema

In this form the dilated air spaces immediately surround and involve the respiratory bronchioles.

Chronic inflammation of the respiratory bronchioles is an important feature: eventually, in many cases, the distension extends to produce panacinar emphysema.

Bronchiectasis

Bronchiectasis means a permanent dilatation of one or more bronchi. There are 2 main subdivisions

1. Obstructive due to tumour, foreign body or enlarged lymph nodes

2. Post-infective due to repeated respiratory infection, e.g. Cystic Fibrosis or immunodeficiency syndromes.

Pathogenesis

Effects

Pneumonia – Bronchopneumonia

Pneumonia is an inflammatory process involving the alveolar tissue of the lungs. It is discussed under 3 main headings:

1. Bronchopneumonia

2. Lobar pneumonia

3. Miscellaneous pneumonias

1. BRONCHOPNEUMONIA

Bronchopneumonia caused by a variety of bacteria is the commonest form. It may affect all ages, but it is particularly frequent in 4 circumstances:

(a) as a terminal event in a chronic debilitating disease

(b) in infancy

(c) in old age

(d) as a manifestation of secondary infection in viral conditions, e.g. influenza, measles.

Bronchopneumonia is primarily an inflammation spreading from terminal bronchioles to their related alveoli.

The lesions are initially focal, involving one or more lobules.

First red, then grey, they show a central bronchiole containing pus.

Possible Sequels

1. Resolution – complete or partial (antibiotic and physiotherapy are important).

2. Patchy scarring.

3. Rarely, continuing sepsis with lung abscess formation.

Lobar Pneumonia

2. LOBAR PNEUMONIA

As the name suggests, a complete lobe or even two lobes of a lung are affected, the most striking changes occurring in the alveoli. The disease is now rare in Western countries. It is seen typically in adults aged 20–50 years with males predominating and is caused by Streptococcus pneumoniae. Occasionally Klebsiella pneumoniae is the agent in the debilitated elderly, diabetics and alcoholics.

The whole affected lobe progresses uniformly through 4 distinct phases illustrating the classic progression of an acute inflammation: this has been so radically altered by antibiotic treatment that the following description is to some extent historical.

Clinically, the onset is acute with fever and often rigors. There is a dry cough and rusty sputum; dyspnoea and often chest pain due to pleurisy.

The Pathology is described in 4 phases merging sequentially: all the alveoli in the lobe are uniformly affected.

Phase 1 CONGESTION

Phase 2 RED HEPATISATION

Phase 3 GREY HEPATISATION

Phase 4 – RESOLUTION begins dramatically on day 8–10 and restoration to normal is rapid.

Legionnaire’s Disease

Previously confused with pneumococcal pneumonia, Legionnaire’s disease occurs in small epidemics, is more common in males and is due to a tiny Gram-negative bacillus – Legionella pneumophila. The death rate can be high – up to 20%. Infection is associated with inhalation of aerosol from contaminated water storage systems.

Clinical Features

Two phases are recognised:

Prodromal phase – vague flu-like illness lasting about 5 days.

Active phase

A dry cough develops. There is pyrexia and the patient may become seriously unwell with confusion.

Signs of consolidation appear. Severe vomiting and diarrhoea may develop.

Laboratory Findings

Hyponatraemia. Lymphopenia. Neutrophils normal.

Signs of disseminated intravascular coagulation may develop. The most useful diagnostic tests are to detect the bacteria in sputum or Legionella antigens in urine. Serology may show an increase in antibody titre after 10–15 days.

Pathology

Both lungs are consolidated, dark red, heavy and oedematous. Fibrinous pleurisy or pleural effusion may be found.

Histology

Two stages are evident:

The exudate may organise, causing an increasing interstitial fibrosis with permanent loss of lung function.

Viral Pneumonias

Influenza

In most cases, influenzal infection is confined to the upper respiratory tract, but in debilitated persons and during epidemics, the whole respiratory tract is affected.

Trachea and Bronchi

Intense inflammation with haemorrhage develops.

Pneumonia Changes

The lungs are bulky, purple red and exude blood-stained froth when cut. The microscopic changes vary from one part to another.

Infective Agents

Of the three main types A, B and C, type A is the most virulent, and mutants of this type are responsible for most epidemics and the fatalities which occur. The 2009 pandemic was due to a swine influenza of type A known as H1N1. Severe disease and death was more common in children and pregnant women.

Secondary infection is common, the bacteria most frequently involved being Staphylococcus aureus, Haemophilus influenzae and Streptococcus pneumoniae.

Sars

Severe acute respiratory syndrome is a recently recognised infectious atypical pneumonia caused by a novel corona virus, the SARS-associated corona virus. The disease was first recognised in Asia in February 2003 and caused a pandemic over the ensuing months.

Atypical Pneumonias

There are a number of pneumonic conditions due to viruses and bacteria in which a common pattern of pathological change is observed.

1. Necrotising bronchiolitis

2. Interstitial pneumonia

3. Reactive changes

The lining epithelial cells of bronchioles and alveoli are stimulated by the presence of the virus.

Variations in the basic pattern occur in different infections. Confluent consolidation is often found in psittacosis and ornithosis (excreted by infected birds) and in measles giant cell pneumonia. Interstitial pneumonia is produced by cytomegalovirus and in rickettsial infections such as Q fever and ‘scrub typhus’. In mycoplasma pneumonia, inflammation spreads from the bronchioles into the lung parenchyma and may become chronic with fibrosis.

Pneumonia – Special Types

Aspiration Pneumonia

This is due to inhalation of food or infected material from the mouth or pharynx. It may occur during anaesthesia or coma or may complicate conditions associated with frequent regurgitation, e.g. oesophageal obstruction, pyloric stenosis or poor swallowing due to stroke or motor neurone disease.

In adult cases the inhalation of acid gastric contents may cause an initial shock reaction: in other cases the onset is insidious.

Possible progression is as follows:

Lipid Pneumonia

– The exogenous form is due to long-continued inhalation of small quantities of oily material usually derived from nasal medicaments: it is often clinically silent. Oily vacuoles are seen in the lung tissue.

– The endogenous form is derived from tissue lipid debris distal to local bronchial obstruction. Foamy macrophages accumulate and the lung tissue is golden yellow in colour.

Miscellaneous Pneumonias

Opportunistic infections are seen in therapeutically immunosuppressed patients and in AIDS cases.

The causative agents include:

Viruses – e.g. Cytomegalovirus

Bacteria – e.g. Mycobacterium avium intracellulare

Fungi – e.g. Pneumocystis jiroveci, Cryptococcus neoformans, Aspergillus fumigatus, Candida albicans.

Lung Abscess

This is now an uncommon condition due to prompt treatment of preceding infection. The usual causes are:

1. Inhalation of infected material from the larynx or pharynx.

2. Obstruction of a bronchus by tumour growth or foreign body. Site depends on size of bronchus affected.

3. Infection of pre-existing cavities, e.g. in tuberculosis or bronchiectasis.

4. Pneumonia. Abscess is most likely to occur in debilitated persons with bronchopneumonia.

Rarer causes of abscess are: pyaemia, trauma to lung, extension from suppuration in mediastinum, spinal column or subphrenic region, and infection with Entamoeba histolytica.

Sequelae of Lung Abscess

1. Small abscesses may heal.

2. Subpleural abscesses may extend to cause empyema.

3. Bronchopleural fistula resulting in pyopneumothorax is a further complication following on (2).

4. If a large pulmonary vessel is eroded, fatal haemorrhage can occur.

5. Rarely, blood spread leads to meningitis or cerebral abscess.

Tuberculosis (TB)

The lungs are more commonly affected by TB than any other organ. The incidence of TB in developed countries is rising, partly due to AIDS. Drug resistant strains of Mycobacteria are an increasing problem.

There are 2 patterns of pulmonary tuberculosis — primary and secondary.

Primary Infection

This occurs in patients, usually children, who have not been previously exposed to TB or vaccinated against it.

Infection is by inhalation.

The COMBINATION of Ghon focus + hilar nodes is termed the primary complex.

In most patients, the lesions undergo fibrosis or calcification and heal. Spread can, however, occur.

Secondary Infection

This is a recurrence of TB in later life — either reactivation or reinfection. The patients have immunity to TB and develop a cellular response leading to caseation.

Spread of Tuberculosis

Pneumoconioses (Dust Diseases)

The reaction to inhaled dust varies very considerably. Some dusts, e.g. pure carbon, are inert: others, e.g. silicates, cause severe lung disease.

Anthracosis

Pure carbon is biologically inert and is deposited as in (a) above with no ill effects. Damage to the lung seen in coal-miners and in populations exposed to carbon polluted atmosphere is potentiated by the content of silicates and other pollutants.

Coal-Miner’s Pneumoconiosis

1. Simple aggregation of coal dust particles may progress with the formation of small dust nodules and mild centrilobular emphysema (p.260) with minimal function loss.

2. In a few cases, Progressive Massive Fibrosis supervenes with severe disability.

The cause is unknown, theories include tuberculous infection as an initiator dust dose and composition, genetic factors and deviant immune responses.

The severe diseases caused by inorganic dust inhalation, usually occupationally, are described.

1. Silicosis – stone workers, sandblasters, miners.

2. Asbestosis – shipbuilding, insulation, electrical work.

The damage caused depends on:

(a) The type of dust e.g. soluble/insoluble.

(b) The shape of the particle, e.g.

(c) The size of the particle — particles longer than 5μm are likely to be trapped in the nose and large airways.

(d) The amount of exposure — large amounts overwhelm the defence mechanisms (especially lung macrophages).

Silicosis

The lung lesions are slowly progressive over many years. Silicates are particularly damaging to lung macrophages (see p. 272).

Patients develop increasing breathlessness and may die of respiratory failure and cor pulmonale.

The silicotic lung is particularly susceptible to tuberculosis (which may be due to the effects of silica on pulmonary macrophages). Historically, this was an important cause of death.

Asbestosis

Asbestos is the generic name for a group of fibrous silicates widely used in heavy industry for insulation (particularly in shipbuilding).

There are two distinct forms of asbestos – serpentine (curly and flexible) and amphibole (straight and stiff). Amphibole fibres (crocidolite and amosite) are more pathogenic than serpentine fibres (principally chrysotile).

Asbestosis results from chronic exposure.

Other important complications are:

1. Lung cancer

Asbestos workers have an increased risk of lung cancer, especially if they also smoke. Risk of cancer = risk due to smoking × risk due to asbestos.

2. Pleural pathology

(a) Pleural plaques – these are the most common manifestation of asbestos exposure.

(b) Mesothelioma (Malignant tumour of the pleura.)

This can occur up to 40 years after a brief exposure to asbestos (particularly crocidolite).

Note: There are usually significantly fewer asbestos fibres/bodies in mesothelioma than in asbestosis.

Note: Mesothelioma may also affect the pericardium and peritoneum.

Diffuse Parenchymal Lung Disease

This encompasses a group of conditions in which the lung is altered by a combination of interstitial inflammation and fibrosis. Several histological patterns are recognised but it is thought that regardless of the type the earliest manifestation is alveolitis and that this accumulation of leucocytes results in release of mediators that can injure parenchymal cells and stimulate fibrosis.

1. Usual Interstitial Pneumonia (UIP) (idiopathic pulmonary fibrosis)

UIP is considered to be the caused by repeated cycles of alveolitis. Healing after each cycle gives rise to fibroblastic proliferation known as fibroblastic foci such that as the disease progresses the fibrosis is a different stages (temporal heterogeneity).

Infection is a common terminal event, and there is an increased risk of lung cancer.

2. Non-Specific Interstitial Pneumonia (NSIP)

This form of fibrosis has a much better prognosis than UIP and is usually steroid responsive. The lung is uniformly affected by interstitial fibrosis and inflammation of variable severity. Fibroblastic foci are abscent and progression to honeycombing is rare. This pattern is commonly seen in association with connective tissue diseases.

3. Desquamative Interstitial Pneumonia (DIP) and Respiratory Bronchiolitis Interstitial Lung Disease (RBILD)

These patterns are both seen almost exclusively in cigarette smokers. In RBILD macrophages accumulate in a patchy distribution around respiratory bronchioles. In DIP there is diffuse distribution of macrophages.

4. Cryptogenic Organising Pneumonia

(Bronchiolitis obliterans organising pneumonia). This characterised by a patchy distribution of polypoid plugs of fibroblastic tissue in alveoli, alveolar ducts and sometime bronchioles. A similar pattern may be seen with certain infections, drugs or connective tissue diseases.

Diffuse Alveolar Damage

This is the pathological correlate of Adult Respiratory Distress Syndrome. It may be caused by sepsis, gastric aspiration, trauma and inhaled toxins. It may also be idiopathic – Acute Interstitial Pneumonia (AIP; synonymous with Hamman–Rich Syndrome).

Lung Cancer

Lung cancer (carcinoma of the bronchus) is the commonest form of cancer and one which is largely preventable. Approximately 35000 patients die of lung cancer in the United Kingdom each year.

Non-Metastatic Effects

These include:

1. ACTH secretion → Adrenal hyperplasia → Raised blood cortisol → Cushing’s syndrome.

2. ADH secretion → Retention of water → Dilutional hyponatraemia

3. Parathyroid hormone related peptide (PTHrP) secretion → Hypercalcaemia (p.25).

Other syndromes include: encephalopathy, cerebellar degeneration, neuropathy, myopathy, Eaton Lambert myasthenia-like syndrome, etc.

Histological Types

Four main types are recognised

1. Small cell … … … … … … … … … …	20%.	The proportions vary between series.
2. Squamous carcinoma … … … … … … …	30%.
3. Adenocarcinoma … … … … … … … …	40%.
4. Large cell carcinoma … … … … … … …	10%.

The separation of small cell carcinoma from non-small cell variants is extremely important as the former tumour is treated by chemotherapy. Sub-classification of non-small cell variants is now important for certain targetted chemotherapies.

Small Cell Lung Carcinoma

This is the most aggressive form of lung cancer and metastasises early and widely. It does respond well, at least initially, to cisplatin based chemotherapy – some patients survive for up to 2 years.

The tumour arises from neuro-endocrine cells and expresses markers such as NCAM-1. It is the form which most commonly has endocrine and other non-metastatic humoral effects.

Squamous Carcinoma

These tend to arise centrally from major bronchi, within dysplastic squamous epithelium following squamous metaplasia.

Although squamous carcinoma is often slow growing, there is often extensive destruction of local tissues. The affected bronchi are often blocked, leading to retention pneumonia or collapse.

Adenocarcinoma

This tumour is a common tumour in women and is seen in non-smokers, but is also associated with smoking. At least two-thirds arise in the periphery of the lung, sometimes in relation to scarring. In non-smoking women, particularly of East Asian origin, there is a high incidence of epidermal growth factor receptor mutations that confer responsiveness to certain chemotherapeutic agents.

Two main patterns are seen:

(a) A well defined mass of malignant cells arranged in acini with a fibrous stroma.

(b) Growth of tumour cells along the alveolar walls (so-called ‘bronchioalveolar carcinoma’).

Large Cell Carcinoma

As the name suggests, this tumour consists of large malignant cells without any specific differentiation. This is therefore a diagnosis of exclusion. The tumour usually arises centrally.

Aetiology of Lung Cancer

The main factors are:

1. Cigarette smoking – This is by far the major cause, established by epidemiological and animal studies. Cigarette smoke contains carcinogens such as 3,4 benzpyrene and nitrosamines. Passive smoking is also significant.

2. Industrial and atmospheric pollution — There is a large number of pollutant industrial processes e.g. asbestos workers, miners exposed to irradiation (e.g. radon, uranium) and metal smelters (e.g. chromium and nickel).

Lung cancer is more common in urban than in rural areas.

Secondary Lung Tumours

It must always be remembered that many other cancers spread to the lungs both by blood and lymphatic routes.

Other Tumours of the Bronchi and Lungs

Benign tumours of the bronchi and lung are unusual. There are 2 main types.

1. SQUAMOUS PAPILLOMA

Papillomas are similar to the papillary tumours of the larynx. They occur in young people and on occasion may cause stridor due to partial bronchial obstruction. They are due to papilloma virus infection (types 6 and 11). Malignant change is exceptional.

2. CHONDROID HAMARTOMA

These are uncommon lesions of the lung which consist of lobules of cartilage and cleft-like spaces lined by bronchial epithelium. Their importance is that they appear as ‘coin lesions’ on chest X-ray and may simulate primary or secondary tumours. Current evidence suggests they are benign neoplasms rather than hamartomas.

Carcinoid Tumours

These tumours account for 1–2% of primary lung neoplasms. They often appear around the age of 50 years. Usually the tumour is situated in a primary bronchus or at the lung periphery. The tumour is a smooth surfaced yellow nodule.

Histologically these resemble carcinoid tumours of the appendix (see p.334). A small proportion of these tumours metastasise to regional lymph nodes – all are potentially malignant.

Central tumours tend to block the bronchus in which they arise.

Atypical carcinoid tumours: This sub-group of tumours shows nuclear pleomorphism, mitotic activity and necrosis. Over half eventually metastasise.

Tumours of Bronchial Glands

Both benign and low grade malignant tumours of the bronchial glands are occasionally seen and show histological similarity to salivary gland tumours. These may present as obstructing lesions.

Diseases of the Pleura

Inflammation (Pleurisy)

There are several causes.

(a) Infection – usually due to spread from pneumonia or tuberculosis. – following penetrating injury, e.g. stab wound.

(b) Autoimmunity – e.g. rheumatoid arthritis, systemic lupus erythematosus.

(c) Overlying a pulmonary infarct (p.162).

Fibrinous Pleurisy

If fluid accumulates in excess, there is a pleural effusion – pain and friction rub disappear as the inflamed layers are separated.

If infection of the pleura proceeds, an empyema (a collection of pus in the pleura) may form. This is now unusual.

Pleural Effusion

The accumulation of fluid within the pleura can be explained as a form of local oedema.

The composition of the fluid is related to the underlying cause.

TRANSUDATE	EXUDATE
e.g. in heart failure – low protein content; – few inflammatory cells.	e.g. in fibrinous pleurisy – high protein content; – numerous inflammatory cells.