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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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