Carcinoma of the Lung

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Carcinoma of the lung is the most common cause of death from neoplasia in industrialized nations.
Once mainly a disease of males it is now increasingly common in females.
The peak incidence is between the ages of 40 and 70 years, reflecting cumulative exposure to several
potential causative carcinogens.

There are four main histological types of lung cancer.
The four main histological types of carcinoma of the lung are squamous cell carcinoma (50%),
small-cell anaplastic carcinoma (oat-cell carcinoma) (20%), adenocarcinoma (including bronchioloalveolar carcinoma) (20%), and large-cell anaplastic carcinoma (10%).
Because of differences in natural history and response to treatment, many clinicians group tumours into either small-cell lung carcinoma (SCLC) or non-small-cell lung cancers (NSCLC).

A small proportion of tumours may show a mixed pattern of differentiation, particularly mixed adenocarcinoma/squamous carcinoma.
70% of all tumours arise in relation to the main bronchi (central or hilar tumours).
30% of lung cancers arise from peripheral airways or alveoli (peripheral tumours).
Central carcinomas of the lung appear as friable white masses of tissue, which extend into the lumen of bronchi and invade into adjacent lung.
Peripheral carcinoma of the lung appear as ill-defined masses, often occurring in relation to scars, and frequently extend to the pleural surface.

Squamous cell carcinoma is the most common type of cancer of the bronchus.

Squamous cell carcinomas are believed to be derived from metaplastic squamous epithelium,
which develops to line the main bronchi as the result of exposure to agents such as cigarette smoke.
Tumours, which are most common in males, are usually central and close to the carina, frequently
presenting with features related to bronchial obstruction. Compared with other types, they
are relatively slow growing and may be resectable.
Squamous cell carcinoma of the lung shows a range of differentiation from well-differentiated
lesions producing lots of keratin, through to lesions with only a few keratin-producing cells.
Adenocarcinoma of the lung is usually a peripheral tumour
Adenocarcinomas have an equal sex incidence and are not as closely linked with cigarette
smoking as other types. They characteristically develop as a peripheral tumour, although they
may also occur as a central lesion arising from a main bronchus. A proportion of adenocarcinomas
are thought to originate in areas of pre-existing lung scarring (scar cancers).
There are four main histological patterns: acinar (gland-like spaces),
papillary (fronds of tumour on thin septa), solid carcinoma with mucin production}
(poorly differentiated lesions), and bronchioloalveolar.
Most tumours do not produce signs of airways obstruction because of their peripheral location.
It is not unusual for extremely extensive systemic metastatic tumour to have originated from a very
small peripheral adenocarcinoma of the lung.

Bronchioloalveolar carcinoma is a special type of adenocarcinoma

Bronchioloalveolar carcinoma of the lung is a special type of adenocarcinoma, accounting
for about 5% of all cases and derived from alveolar or bronchial epithelial cells (Clara
cells and Type II pneumocytes). A distinct histological feature is spread through lung
along alveolar septa.
Half of all cases are multifocal diffuse infiltrative tumours, which replace areas of
lung in a manner resembling pneumonic consolidation.
Cells are tall, columnar and relatively uniform, have few mitoses and secrete mucin.
The remaining half are single, grey masses of tumour, up to 10 cm in diameter. Cells are cuboidal,
with hyperchromatic nuclei and mitoses, and form papillary structures. There is often no mucin
secretion. In the absence of metastasis, this sub-type has a better prognosis than other
forms of lung cancer.
Small-cell anaplastic carcinoma is the most highly malignant of lung cancers
Small-cell anaplastic lung cancer (also called oat-cell carcinoma
because the cell nuclei histologically resemble oat grains) is a highly malignant
condition. Tumours arise from bronchial epithelium, but exhibit differentiation into
neuroendocrine cells containing neurosecretory granules.
Tumours are usually centrally located and are associated with a rapid rate of growth,
relative to other forms of lung cancer. It is usual for metastases to be present at
the time of diagnosis. Because of the neuroendocrine type, this form of cancer is often associated
with ectopic hormone production.

This type of carcinoma shows neuroendocrine differentiation. Cells are round to oval
and have little cytoplasm; in certain situations there can be diagnostic confusion with a tumour
of lymphoid cells. Other types have elongated nuclei and more cytoplasm (intermediate cell variant).
Tissue diagnosis of lung cancer.
The natural history of lung cancer allows no opportunity for screening

Lung cancer spreads by four main routes
Lung cancer frequently causes non-metastatic extrapulmonary syndromes
Systemic syndromes associated with non-metastatic effects are common in lung cancer and may be
a presenting feature of disease.
Endocrine disturbances, seen in 12% of patients with lung cancer, are nearly all associated with
small-cell lung cancer because it has a neuroendocrine phenotype with neurosecretory
granules. Common syndromes include inappropriate ADH (low sodium and plasma osmolality with high
urine osmolality) and ectopic ACTH secretion associated with a Cushing's syndrome, Hypercalcaemia,
in contrast to other endocrinopathies, is most common with squamous cell carcinomas, and is due
to secretion of parathormone-related peptide.
Several neurological syndromes can be caused by lung cancer including peripheral sensory/motor
neuropathy, cerebellar degeneration causing ataxia, proximal myopathy, dermatomyositis, and Lambert-Eaton
myasthenic syndrome, which is associated with small-cell tumours and may precede clinical detection of tumour.
Hypertrophic pulmonary osteoarthropathy (finger clubbing, swelling of wrists and ankles with
periosteal new bone formation) is seen in 2-3% of squamous cell carcinomas and adenocarcinomas.
Large-cell anaplastic carcinomas are insufficiently differentiated to permit further classification
by light microscopy. However, if electron microscopy is used, features that favour
either squamous or adenocarcinomatous origin can be often seen. This is therefore a diagnostic
grouping of convenience, as further histogenetic subdivision is of no clinical or biological importance.
Lesions may be either central or peripheral, and are composed of large cells with nuclear pleomorphism
and frequent giant cell forms. They have a poor prognosis and are frequently widely disseminated
at the time of diagnosis.

Lung cancer frequently causes non-metastatic extrapulmonary syndromes
Systemic syndromes associated with non-metastatic effects are common in lung cancer and may be
a presenting feature.
Most lung cancers have verypoor 5-year survival with treatment
Staging and histological type determine outcome in lung cancer
The factors that determine the outcome of lung cancer, and its likely response to treatment, are
histological type and stage. For example, squamous cell carcinomas grow slowly and carry
a good prognosis if detected at an early stage and are operable, some forms of bronchioalveolar cell
carcinoma have a better prognosis than other forms of lung cancer, and small-cell
tumours metastasize widely and have the poorest prognosis.
Survival is better for early stage disease, except for small-cell carcinoma.
TNM staging of carcinoma of the lung.

The staging of lung cancer has an important bearing on prognosis. In addition, once tumours are past
a certain stage they are regarded as inoperable.
Careful staging is a pre-requisite to surgical intervention in lung cancer. The key elements that
offer a reasonable prospect of success with surgery are:
Tumour must be within a lobar bronchus or at least 2 cm distal to the carina.
No direct extension to chest wall, diaphragm, pericardium.
No involvement of heart, great vessels, trachea, oesophagus or vertebrae.
No malignant pleural effusion.
No contralateral nodal involvement.
No distant metastases.

Metastases and hamartomas are common pulmonary mass lesions
After primary cancers, the two most common mass lesions in the lung are metastases and hamartomas.
Metastatic tumours are common by blood-borne spread, particulary from kidney, breast, testis,
and gastrointestinal tract.
Metastatic tumour, whether from lung or extrapulmonary sites, may diffusely infiltrate pulmonary lymphatic
vessels, producing the syndrome oflymphangitis carcinomatosa.
This presents as severe breathlessness, as blockage of lymphatics causes failure of removal of interstitial fluid, which accumulates in lung parenchyma in much the same way as in early cardiogenic pulmonary oedema.
The chest radiograph shows diffuse shadowing, and dilated intrapulmonary lymphatic vessels may be
visible as linear streaks.

This is a dire condition, which is rapidly fatal.
Carcinoid tumours of the lung are neuroendocrine tumours, representing about 5% of all pulmonary
neoplasms. They grow either as bronchial lesions that protrude into the lumen, presenting early with
airway obstruction, or as locally infiltrative lesions extending from the bronchus into adjacent lung.
Histological examination shows some lesions that have no atypical cytological features, and these
behave in a benign fashion. Others lesions, particularly the infiltrative group, show mitoses
and nuclear atypia. This group has the potential for local recurrence or metastasis in a small
proportion of cases, being termed atypical pulmonary neuroendocrine tumours. The term 'pulmonary
carcinoid' is perhaps inappropriate for such lesions,as a clinical carcinoid syndrome is unusual in most
cases, and most lesions do not secrete 5-hydroxytryptamine.
There is about 80% ten-year survival for resected cases showing no atypical features, whereas atypical
forms have about 50% five-year survival.
Bronchial hamartomas are common benign lesions composed of tissue normally encountered in the lung.
Most are 1-3 cm in diameter and largely consist of cartilage, being firm and glistening white in appearance.
Other elements are bronchial epithelium, fat, and muscle. They are asymptomatic and are mainly
discovered at post mortem examination.
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