Lung cancer overview

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Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Lung cancer from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Staging

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Laboratory Findings

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Dildar Hussain, MBBS [2];Kim-Son H. Nguyen M.D.;Saarah T. Alkhairy M.D;Cafer Zorkun, M.D., Ph.D. [3]

Overview

Today, lung cancer is one of the leading causes of death worldwide, killing over 1 million people per year but it was not always that way. Primary lung cancer can be classified into two main categories: small cell lung cancer (~15%) and non small cell lung cancer (~85%). The pathophysiology consists of genetics, smoking, radon gas, asbestos, viruses, infection, and inflammation. The main causes of any cancer include carcinogens (such as those in tobacco smoke), ionizing radiation, and viral infection. Lung cancer may be differentiated from other diseases that cause hemoptysis, cough, dyspnea, wheeze, chest pain, dysphonia, dysphagia, unexplained weight loss, unexplained loss of appetite, and fatigue such as pneumonia, bronchitis, metastatic cancer from a non-thoracic primary site, infectious granuloma, pulmonary tuberculosis, tracheal tumors, and a thyroid mass. Worldwide, lung cancer is the most common cancer in terms of both incidence and mortality with 1.35 million new cases per year and 1.18 million deaths. Lung cancer is the deadliest type of cancer for both men and women. Each year, more people die of lung cancer than breast, colon, and prostate cancers combined. Lung cancer screening is a strategy used to identify early lung cancer in people, before they develop symptoms. Screening refers to the use of medical tests to detect disease in asymptomatic people. Screening studies for lung cancer have only been done in high risk populations, such as smokers and workers with occupational exposure to certain substances. The majority of lung cancers present with advanced disease because the symptoms tend to occur later in the course of the disease. Lung cancer staging is an assessment of the degree of spread of the cancer from its original source. It is an important factor affecting the prognosis and potential treatment of lung cancer. Many of the symptoms of lung cancer (bone pain, fever, weight loss) are nonspecific; in the elderly, these may be attributed to comorbid illness. Generally, the most common signs of lung cancer are decreased/absent breath sounds, wheeze, chest pain, emaciation, lethargy, and pallor. The laboratory findings associated with lung cancer are the following: neutropenia, hyponatremia, hypokalemia, hypercalcemia, respiratory acidosis, hypercarbia, hypoxia, and tumor cells in sputum and pleural effusion cytology. Performing a chest x-ray is the first step if a patient reports symptoms that may be suggestive of lung cancer. CT scans help stage the lung cancer. MRI is useful for the evaluation of a patient with spinal cord compression, superior sulcus tumors, and brachial plexus tumors. A transthoracic needle biopsy and a bronchoscopy are conducted to diagnose lung cancer. Other diagnostic tests include bone scintigraphy, PET scan, and molecular tests. The medical therapy for lung cancer consists of surgery, radiation therapy, chemotherapy, and targeted therapy. Lung cancer surgery involves the surgical excision of cancer tissue from the lung. Smoking cessation and avoidance of second hand smoking are the most important measures for the prevention of lung cancer. Secondary prevention for lung cancer consists of smoking cessation and screening.

Historical Perspective

Prior to the introduction of cigarette smoking and industrial carcinogens, lung cancer was thought to be a rare disease. Of all tumors detected upon autopsy, lung cancer accounted for only 1% of cancers in the 1800s. The majority of cases of lung cancer were associated with occupational hazards due to radon exposure. The association between lung cancer and smoking was not defined until the mid-20th century. Today, lung cancer is one of the leading causes of death worldwide, killing over 1 million people per year but it was not always that way. Approximately 150 years ago, lung cancer was actually a very rare disease. At the Institute of Pathology of the University of Dresden in Germany, lung cancer represented only 1% of all cancers seen at autopsy. Lung cancer steadily rose from this point on and in 1918 the percentage had risen to nearly 10% and by 1927, it represented more than 14% of all cancers. Around this time period, the disease had a life expectancy from about 6 months to 2 years and in most cases, the afflicted individual had long term chronic bronchitis.

Classification

Primary lung cancers may be classified into two main categories: small cell lung cancer (~15%) and non small cell lung cancer (~85%). Non small cell lung cancer are a heterogenous group of lung cancers that are often grouped together because they share similar clinical features (e.g. prognosis and management). The 2004 WHO histological classification of tumors of the lung categorized lung tumors into malignant epithelial tumors, benign epithelial tumors, lymphoproliferative tumors, miscellaneous tumors, and metastatic tumors.

Pathophysiology

The pathophysiology of lung cancer includes both genetic and environmental factors. Genetic mutations, namely mutations in K-ras oncogene and TP53 tumor-suppressor gene, are associated with the development of lung cancers. Environmental factors often include smoking (most important carcinogen), radon, asbestos, viral infections, and states of chronic lung inflammation, all of which may predispose to cellular damage and DNA mutations that predispose to the development of lung cancers.

Causes

The direct cause of lung cancers is DNA mutations that often result in either activation of proto-oncogenes (e.g. K-RAS) or the inactivation of tumor suppressor genes (e.g. TP53) or both. The risk of these genetic mutations may be increased following exposure to environmental components.

Differential Diagnosis

Lung cancer must be differentiated from other diseases that cause hemoptysis, cough, dyspnea, wheeze, chest pain, dysphonia, dysphagia, unexplained weight loss, unexplained loss of appetite, and fatigue such as pneumonia, bronchitis, metastatic cancer from a non-thoracic primary site, infectious granuloma, pulmonary tuberculosis, tracheal tumors, and a thyroid mass.

Epidemiology and Demographics

Lung cancer is the deadliest cancer and the second most common cancer among both genders. Older individuals > 50 years of age who have a history of smoking are at increased risk. Historically, the incidence of lung cancer is significantly higher among males compared to females. This increased ratio is thought to be attributed to the increased rates of smoking among men. However, more women are being diagnosed with lung cancer due to the increased rate of smoking among women. In 2014, the incidence of lung cancer in the United States for 2014 was approximately 70 cases per 100,000.

Risk Factors

The most potent risk factor in the development of lung cancer is smoking. Other risk factors include secondhand smoke, air pollution, family history of lung cancer, radiation therapy to the chest, radon exposure, asbestos exposure and exposure to other chemical carcinogens.

Screening

Lung cancer screening is a strategy used to identify early lung cancer in people, before they develop symptoms. Screening refers to the use of medical tests to detect disease in asymptomatic people. Screening studies for lung cancer have only been done in high risk populations, such as smokers and workers with occupational exposure to certain substances. This is because radiation exposure from screening could actually induce carcinogenesis formation in a small percentage of screened subjects, so this risk should be mitigated by a (relatively) high prevalence of lung cancer in the population being screened. A pulmonary nodule larger than 5 to 6 mm is considered a positive result for screening with x-ray or computed tomography.

Natural History, Complications, and Prognosis

The majority of lung cancers present with advanced disease because the symptoms tend to occur later in the course of the disease. The patient experiences non-specific symptoms such as cough, hemoptysis, dyspnea, chest pain, dysphonia, dysphagia, fatigue, lack of appetite, weight loss, and fatigue from 3 weeks to 3 months before seeking medical attention. There are a variety of complications associated with lung cancer such as pleural effusion, leg weakness paresthesias, bladder/bladder dysfunction, seizures, hemiplegia, cranial nerve palsies, confusion, personality changes, skeletal pain, and/or pleuritic pain, atelectasis, and/or bronchopleural fistula. The prognosis of lung cancer is poor if diagnosed during the advanced stages.

Staging

The staging of lung cancer is based on the TNM classification of lung cancer. Lung cancer staging is an assessment of the degree of spread of the cancer from its original source. It is an important factor affecting the prognosis and potential treatment of lung cancer. Non-small cell lung carcinoma is staged from IA ("one A", best prognosis) to IV ("four", worst prognosis). Small cell lung carcinoma is classified as limited stage and extensive stage

History and Symptoms

Many of the symptoms of lung cancer (bone pain, fever, weight loss) are nonspecific; in the elderly, these may be attributed to comorbid illness. In many patients, the cancer has already spread beyond the original site by the time they have symptoms and seek medical attention. Common sites of metastasis include the bone, such as the spine (causing back pain and occasionally spinal cord compression), the liver and the brain. About 10% of people with lung cancer do not have symptoms at diagnosis; these cancers are incidentally found on routine chest x-rays.

Physical Examination

Generally, the most common signs of lung cancer are decreased/absent breath sounds, wheeze, chest pain, emaciation, lethargy, and pallor. Other signs include metastases to the liver, brain, and adrenal glands (Cushing's syndrome).

Diagnostic Studies

Diagnostic study of choice

Chest CT scan is the modality of choice in the diagnosis of lung cancer. Findings on CT scan suggestive of lung cancer include, a solitary pulmonary nodule, centrally located masses, mediastinal invasion. A CT scan of the abdomen and brain can help visualize the common sites of metastases: adrenal glands, liver, and brain. CT scans diagnose lung cancer by providing anatomical detail to locate the tumor, demonstrating proximity to nearby structures, and deciphering whether lymph nodes are enlarged in the mediastinum.

Laboratory Findings

The laboratory findings associated with lung cancer are the following: neutropenia, hyponatremia, hypokalemia, hypercalcemia, respiratory acidosis, hypercarbia, hypoxia, and tumor cells in sputum and pleural effusion cytology.

X-Ray

Performing a chest x-ray is the first step if a patient reports symptoms that may be suggestive of lung cancer. Often lung cancers are picked up on a routine chest X-ray in a person experiencing no symptoms.

CT

Chest CT scan is the modality of choice in the diagnosis of lung cancer. Findings on CT scan suggestive of lung cancer include, a solitary pulmonary nodule, centrally located masses, mediastinal invasion. CT scans help stage the lung cancer. A CT scan of the abdomen and brain can help visualize the common sites of metastases: adrenal glands, liver, and brain. CT scans diagnose lung cancer by providing anatomical detail to locate the tumor, demonstrating proximity to nearby structures, and deciphering whether lymph nodes are enlarged in the mediastinum.

MRI

The indication of MRI in lung cancer is when there is a suspicion of spinal cord canal invasion, Pancoast tumors i.e superior sulcus tumors, and brachial plexus tumors.

Biopsy

A transthoracic needle biopsy and a bronchoscopy are conducted to diagnose lung cancer.

Other Diagnostic Studies

Other diagnostic studies include bone scintigraphy, PET scan, and molecular tests.

Medical Therapy

The therapy for lung cancer consists of surgery, radiation therapy, chemotherapy, and targeted therapy.

Surgery

Lung cancer surgery involves the surgical excision of cancer tissue from the lung. It is used mainly in non-small cell lung cancer with the intention of curing the patient.

Primary Prevention

Effective measures for the primary prevention of lung cancer include smoking cessation and avoidance of second hand smoking. Lifestyle changes, such as healthy diet rich with fruits and vegetables and regular exercise, might decrease the risk of developing cancer in general.

Secondary Prevention

Secondary prevention for lung cancer consists of smoking cessation and screening. Secondary chemoprevention focuses on blocking the development of lung cancer in individuals in whom a precancerous lesion has been detected.

References


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