Lung cancer
Lung cancer, also called lung carcinoma, is a malignant tumor that originates in the tissues of the lungs. Lung cancer is caused by genetic damage to the DNA of cells in the airways, often caused by cigarette smoking or inhaling damaging chemicals. Damaged airway cells gain the ability to multiply unchecked, causing the growth of a tumor. Without treatment, tumors spread throughout the lung, damaging lung function. Eventually lung tumors metastasize, spreading to other parts of the body.
Early lung cancer often has no symptoms and can only be detected by medical imaging. As the cancer progresses, most people experience nonspecific respiratory problems: coughing, shortness of breath, or chest pain. Other symptoms depend on the location and size of the tumor. Those suspected of having lung cancer typically undergo a series of imaging tests to determine the location and extent of any tumors. Definitive diagnosis of lung cancer requires a biopsy of the suspected tumor be examined by a pathologist under a microscope. In addition to recognizing cancerous cells, a pathologist can classify the tumor according to the type of cells it originates from. Around 15% of cases are small-cell lung cancer, and the remaining 85% are adenocarcinomas, squamous-cell carcinomas, and large-cell carcinomas. After diagnosis, further imaging and biopsies are done to determine the cancer's stage based on how far it has spread.
Treatment for early stage lung cancer includes surgery to remove the tumor, sometimes followed by radiation therapy and chemotherapy to kill any remaining cancer cells. Later stage cancer is treated with radiation therapy and chemotherapy alongside drug treatments that target specific cancer subtypes. Even with treatment, only around 20% of people survive five years on from their diagnosis. Survival rates are higher in those diagnosed at an earlier stage, diagnosed at a younger age, and in women compared to men.
Most lung cancer cases are caused by tobacco smoking. The remainder are caused by exposure to hazardous substances like asbestos and radon gas, or by genetic mutations that arise by chance. Consequently, lung cancer prevention efforts encourage people to avoid hazardous chemicals and quit smoking. Quitting smoking both reduces one's chance of developing lung cancer and improves treatment outcomes in those already diagnosed with lung cancer.
Lung cancer is the most diagnosed and deadliest cancer worldwide, with 2.2 million cases in 2020 resulting in 1.8 million deaths. Lung cancer is rare in those younger than 40; the average age at diagnosis is 70 years, and the average age at death 72. Incidence and outcomes vary widely across the world, depending on patterns of tobacco use. Prior to the advent of cigarette smoking in the 20th century, lung cancer was a rare disease. In the 1950s and 1960s, increasing evidence linked lung cancer and tobacco use, culminating in declarations by most large national health bodies discouraging tobacco use.
Signs and symptoms
Early lung cancer often has no symptoms. When symptoms do arise they are often nonspecific respiratory problems – coughing, shortness of breath, or chest pain – that can differ from person to person. Those who experience coughing tend to report either a new cough, or an increase in the frequency or strength of a pre-existing cough. Around one in four cough up blood, ranging from small streaks in the sputum to large amounts. Around half of those diagnosed with lung cancer experience shortness of breath, while 25–50% experience a dull, persistent chest pain that remains in the same location over time. In addition to respiratory symptoms, some experience systemic symptoms including loss of appetite, weight loss, general weakness, fever, and night sweats.Some less common symptoms suggest tumors in particular locations. Tumors in the thorax can cause breathing problems by obstructing the trachea or disrupting the nerve to the diaphragm; difficulty swallowing by compressing the esophagus; hoarseness by disrupting the nerves of the larynx; and Horner's syndrome by disrupting the sympathetic nervous system. Horner's syndrome is also common in tumors at the top of the lung, known as Pancoast tumors, which also cause shoulder pain that radiates down the little-finger side of the arm as well as destruction of the topmost ribs. Swollen lymph nodes above the collarbone can indicate a tumor that has spread within the chest. Tumors obstructing bloodflow to the heart can cause superior vena cava syndrome, while tumors infiltrating the area around the heart can cause fluid buildup around the heart, arrhythmia, and heart failure.
About one in three people diagnosed with lung cancer have symptoms caused by metastases in sites other than the lungs. Lung cancer can metastasize anywhere in the body, with different symptoms depending on the location. Brain metastases can cause headache, nausea, vomiting, seizures, and neurological deficits. Bone metastases can cause pain, bone fractures, and compression of the spinal cord. Metastasis into the bone marrow can deplete blood cells and cause leukoerythroblastosis. Liver metastases can cause liver enlargement, pain in the right upper quadrant of the abdomen, fever, and weight loss.
Lung tumors often cause the release of body-altering hormones, which cause unusual symptoms, called paraneoplastic syndromes. Inappropriate hormone release can cause dramatic shifts in concentrations of blood minerals. Most common is hypercalcemia caused by over-production of parathyroid hormone-related protein or parathyroid hormone. Hypercalcemia can manifest as nausea, vomiting, abdominal pain, constipation, increased thirst, frequent urination, and altered mental status. Those with lung cancer also commonly experience hypokalemia due to inappropriate secretion of adrenocorticotropic hormone, as well as hyponatremia due to overproduction of antidiuretic hormone or atrial natriuretic peptide. About one of three people with lung cancer develop nail clubbing, while up to one in ten experience hypertrophic pulmonary osteoarthropathy. A variety of autoimmune disorders can arise as paraneoplastic syndromes in those with lung cancer, including Lambert–Eaton myasthenic syndrome, sensory neuropathies, muscle inflammation, brain swelling, and autoimmune deterioration of cerebellum, limbic system, or brainstem. Up to one in twelve people with lung cancer have paraneoplastic blood clotting, including migratory venous thrombophlebitis, clots in the heart, and disseminated intravascular coagulation. Paraneoplastic syndromes involving the skin and kidneys are rare, each occurring in up to 1% of those with lung cancer.
Diagnosis
A person suspected of having lung cancer will have imaging tests done to evaluate the presence, extent, and location of tumors. First, many primary care providers perform a chest X-ray to look for a mass inside the lung. The X-ray may reveal an obvious mass, the widening of the mediastinum, atelectasis, consolidation, or pleural effusion; however, some lung tumors are not visible by X-ray. Next, many undergo computed tomography scanning, which can reveal the sizes and locations of tumors.A definitive diagnosis of lung cancer requires a biopsy of the suspected tissue be histologically examined for cancer cells. Given the location of lung cancer tumors, biopsies can often be obtained by minimally invasive techniques: a fiberoptic bronchoscope that can retrieve tissue, fine needle aspiration, or other imaging-guided biopsy through the skin. Those who cannot undergo a typical biopsy procedure may instead have a liquid biopsy taken which may contain circulating tumor DNA that can be detected.
Imaging is also used to assess the extent of cancer spread. Positron emission tomography scanning or combined PET-CT scanning is often used to locate metastases in the body. Since PET scanning is less sensitive in the brain, the National Comprehensive Cancer Network recommends magnetic resonance imaging – or CT where MRI is unavailable – to scan the brain for metastases in those with NSCLC and large tumors, or tumors that have spread to the nearby lymph nodes. When imaging suggests the tumor has spread, the suspected metastasis is often biopsied to confirm that it is cancerous. Lung cancer most commonly metastasizes to the brain, bones, liver, and adrenal glands.
Lung cancer can often appear as a solitary pulmonary nodule on a chest radiograph or CT scan. In lung cancer screening studies as many as 30% of those screened have a lung nodule, the majority of which turn out to be benign. Besides lung cancer many other diseases can also give this appearance, including hamartomas, and infectious granulomas caused by tuberculosis, histoplasmosis, or coccidioidomycosis.
Classification
At diagnosis, lung cancer is classified based on the type of cells the tumor is derived from; tumors derived from different cells progress and respond to treatment differently. There are two main types of lung cancer, categorized by the size and appearance of the malignant cells seen by a histopathologist under a microscope: small cell lung cancer and non-small-cell lung cancer.SCLC tumors are often found near the center of the lungs, in the major airways. Their cells appear small with ill-defined boundaries, not much cytoplasm, many mitochondria, and have distinctive nuclei with granular-looking chromatin and no visible nucleoli.
NSCLCs comprise a group of three cancer types: adenocarcinoma, squamous-cell carcinoma, and large-cell carcinoma.
- Nearly 40% of lung cancers are adenocarcinomas. Their cells grow in three-dimensional clumps, resemble glandular cells, and may produce mucin.
- About 30% of lung cancers are squamous-cell carcinomas. They typically occur close to large airways. The tumors consist of sheets of cells, with layers of keratin. A hollow cavity and associated cell death are commonly found at the center of the tumor.
- Less than 10% of lung cancers are large-cell carcinomas, so named because the cells are large, with excess cytoplasm, large nuclei, and conspicuous nucleoli.
Several lung cancer types are subclassified based on the growth characteristics of the cancer cells. Adenocarcinomas are classified as lepidic, acinar and papillary, or micropapillary and solid pattern. Lepidic adenocarcinomas tend to be least aggressive, while micropapillary and solid pattern adenocarcinomas are most aggressive.
In addition to examining cell morphology, biopsies are often stained by immunohistochemistry to confirm lung cancer classification. SCLCs bear the markers of neuroendocrine cells, such as chromogranin, synaptophysin, and CD56. Adenocarcinomas tend to express and ; squamous cell carcinomas lack and, but express p63 and its cancer-specific isoform p40. CK7 and CK20 are also commonly used to differentiate lung cancers. CK20 is found in several cancers, but typically absent from lung cancer. CK7 is present in many lung cancers, but absent from squamous cell carcinomas.