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Pathophysio of lung cancer:

Predisposing factors

 Cigarette smoking

 Second hand smoker


Lung carcinoma is a malignant lung tumor usually categorized as small cell or

non–small cell. Cigarette smoking is the major risk factor for most types. Symptoms
include cough, chest discomfort, and, less commonly, hemoptysis, but many
patients are asymptomatic and some present with metastatic disease. Diagnosis is
suspected by chest x-ray or CT scan and confirmed by biopsy. Treatment is with
surgery, chemotherapy, and/or radiation therapy. Despite advances in treatment,
the prognosis is poor, and attention is focused on early detection and prevention.

Epidemiology, Pathophysiology, and Classification

An estimated 171,900 new cases of lung carcinoma are diagnosed each year in
the US, and the disease causes 157,200 deaths annually. The incidence is rising in
women and appears to be leveling off in men. Black men are at especially high risk.

Cigarette smoking, including passive (secondhand) smoking, is the most

important cause. Risk differs by age and smoking intensity and duration; risk after
smoking cessation declines but probably never returns to baseline. Exposure to
radon, a breakdown product of naturally occurring radium and uranium, is the most
important environmental risk factor in nonsmokers. Occupational exposure to radon
(in uranium miners); asbestos (in construction and demolition workers, pipefitters,
shipbuilders, and automotive mechanics); silica (in miners and sandblasters);
arsenic (in workers in copper smelting, pesticide manufacturing, and wood-
treatment plants); chromates (in stainless steel and pigment manufacturing plants);
nickel (in battery and stainless steel manufacturing plants); chloromethyl ethers;
beryllium; and coke oven emissions (in steel workers) accounts for a small number
of cases per year (see Environmental Pulmonary Diseases). The risk of cancer is
greater with combined exposure to occupational toxins and cigarette smoking than
with either one alone. COPD and pulmonary fibrosis may increase susceptibility; β-
carotene supplementation may increase susceptibility in smokers. Air pollution and
cigar smoke contain carcinogens but have never been shown to cause lung

Respiratory epithelial cells require prolonged exposure to cancer-promoting

agents and accumulation of multiple genetic mutations before becoming neoplastic.
Mutations in genes that stimulate cell growth (K-RAS, MYC ), code for growth factor
receptors (EGFR, HER2/neu), and inhibit apoptosis (BCL-2) contribute to proliferation
of abnormal cells. So do mutations that inhibit tumor-suppressor genes ( p53, APC ).
When enough of these mutations accumulate, lung carcinoma results.
Lung carcinoma is generally classified as small cell (SCLC) and non–small cell
(NSCLC). SCLC is a highly aggressive cancer almost always occurring in smokers
and causing widespread metastatic disease in 60% of patients by the time of
diagnosis. Clinical behavior of NSCLC is more variable and depends on histologic

Symptoms and Signs

About 25% of lung carcinomas are asymptomatic and are detected incidentally
with chest imaging. Symptoms and signs develop from local tumor, regional spread,
and metastasis. Paraneoplastic syndromes and constitutional symptoms may occur
at any stage.

Local tumor causes cough and, less commonly, dyspnea because of airway
obstruction, postobstructive atelectasis, and lymphangitic spread. Fever may occur
with postobstructive pneumonia. Up to 1⁄2 of patients report vague or localized
chest pain. Hemoptysis is less common, and blood loss is minimal, except in rare
instances when tumor erodes a major artery, causing massive hemorrhage and
death by asphyxiation.

Regional spread may cause pleuritic chest pain or dyspnea from pleural
effusion, hoarseness due to tumor encroachment on the recurrent laryngeal nerve,
and dyspnea and hypoxia from diaphragmatic paralysis due to involvement of the
phrenic nerve.

Compression or invasion of the superior vena cava (SVC syndrome) can

produce headache or a sensation of head fullness, facial or upper extremity
swelling, and supine breathlessness and flushing (plethora). Signs of SVC syndrome
are facial and upper extremity edema, dilated neck and subcutaneous veins over
the face and upper trunk, and facial and truncal plethora. SVC syndrome is more
common in patients with SCLC.

Apical tumors, usually NSCLC, can invade the brachial plexus, pleura, or ribs,
causing shoulder and upper extremity pain and weakness or atrophy of the
ipsilateral hand (Pancoast's tumor). Horner's syndrome (ptosis, miosis,
enophthalmos, and anhidrosis) results when the paravertebral sympathetic chain or
cervical stellate ganglion is involved. Spread of tumor to pericardium may be
asymptomatic or lead to constrictive pericarditis or cardiac tamponade. Rarely,
esophageal compression causes dysphagia.
Metastases always eventually cause symptoms that vary by location. Metastases to
the liver cause GI symptoms and ultimately hepatic insufficiency. Metastases to the
brain cause behavioral changes, confusion, aphasia, seizures, paresis or paralysis,
nausea and vomiting, and, ultimately, coma and death. Bone metastases cause
severe pain and pathologic fractures. Lung carcinoma commonly metastasizes to
the adrenal glands but rarely leads to adrenal insufficiency.

Paraneoplastic syndromes are not caused by cancer directly. Common

paraneoplastic syndromes in patients with lung carcinoma include hypercalcemia
(caused by tumor production of parathyroid hormone-related protein), syndrome of
inappropriate antidiuretic hormone secretion (SIADH), finger clubbing with or
without hypertrophic osteoarthropathy, hypercoagulability with migratory
superficial thrombophlebitis (Trousseau's syndrome), myasthenia (Eaton-Lambert
syndrome), and a variety of neurologic syndromes, including neuropathies,
encephalopathies, encephalitides, myelopathies, and cerebellar disease.
Mechanisms for neuromuscular syndromes involve tumor expression of
autoantigens with production of autoantibodies, but the cause of most others is

Constitutional symptoms most commonly include weight loss and fatigue and
are sometimes the first indication of underlying malignancy.