Every cancer, including lung cancer, starts out as single cell that changes from a normal cell into a cancerous cell. This usually occurs because one or more sections of the cell’s DNA have suffered mutation(s). When a tumor forms, it is made up of a collection of abnormal cells all descendants of that same cancerous cell. Therefore when a physician makes a diagnosis of cancer, it is important to determine which cell type is responsible for the tumor. The type of cell determines the course of treatment, the course of the disease, and the prognosis.
There are two main groups of lung cancer, small-cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). About 85% of all lung cancers are non-small cell lung cancers. Non-small cell lung cancers are divided into three main types: large cell carcinoma, squamous cell carcinoma, and adenocarcinoma of the lung. The remainder are small-cell lung cancers.
Non-small cell lung cancer (NSCLC) is the most common form of lung cancer. NSCLC gets its name from the way that the cancer cells look under a microscope. Since there are several different types of non-small cell lung cancer histologically, NSCLC is first distinguished from small-cell lung cancer and then further differentiated into subtypes.
In the overwhelming majority of cases, NSCLC arises from four major causes: active smoking, passive smoking (secondhand smoke), asbestos, and radon exposure. HIV/AIDS also increases the risk of lung cancer. Certain other metals and toxins have a role in lung cancer as well; however, they are much less frequently the cause of lung cancer than smoking and the other top four.
Smoking is responsible for as many as 90% of all lung cancers. Tobacco smoke can lead to lung cancer in several ways. Most notably, cigarette smoke contains a number of carcinogens (cancer-causing molecules) that can directly interfere with the DNA of a cell. These toxins cause mutations in the DNA that lead to abnormal cell growth and development. The carcinogens in inhaled smoke also interfere with the cell’s ability to inhibit its own growth. Therefore the cell begins to multiply uncontrollably, which creates a tumor.
Of the 10% of lung cancers that are not caused by active smoking, as many as 25% of these tumors are caused by secondhand smoke. It has been shown that some carcinogens can be inhaled by people that are near active smokers. The negative effects of these toxic compounds on the lungs are similar to those who actively smoke.
Another major cause of lung cancer is asbestos exposure, specifically exposure to silicate asbestos. Asbestos has been linked to a variety of lethal and debilitating lung diseases. Asbestos exposure increases the risk of lung cancer 5-fold; for those exposed to smoke AND asbestos, the chance of developing lung cancer is 55 to 85 times the risk of someone who has not been exposed to these environmental factors.
Adenocarcinoma of the lung is the single most common type of lung cancer; it accounts for about 40% of all lung cancers. Fortunately in the case of adenocarcinoma of the lung, this type also has the best prognosis, in general.
When the prefix adeno- is used to denote a cell type, it means that the cell’s primary purpose is to excrete something. In other words, adeno- means gland. An adenocarcinoma is a cancer that is comprised of cells that excrete a biological substance, though the cancerous mutation may have inhibited or accentuated this excretion. When the term adenocarcinoma is applied to the lung, it means that one of the lung’s mucin-secreting cells has become cancerous. Mucin is a thick, carbohydrate-rich coating that helps to protect the lungs from injury.
Adenocarcinoma of the lung can be divided into four categories, as laid out by the World Health Organization (WHO):
Acinus cells partly make up the air sacs or alveoli in the lungs. They act as a glandular cell in their normal state. Bronchoalveolar tumors come from cells higher up in the lungs, specifically type II pneumocytes. While the WHO considers bronchoalveolar tumors to be an adenocarcinoma, type II pneumocytes are not known for their ability to secrete mucin or other substances. The function of mucus-secreting cells is self-explanatory though this function may no longer apply once this cell type has mutated. Finally, papillary cells resemble nipples or pimples at the microscopic level and are differentiated from other adenocarcinomas by their appearance.
Adenocarcinoma of the lung often occurs at the periphery of the lung (outer edges). Therefore when cells are taken for diagnosis (biopsy), it is sometimes possible to guide a needle from the outside of the body. A fluoroscope, which is a CT/X-ray hybrid that can take real-time images, is used to help direct the biopsy needle to the tumor. If fluoroscopy is not possible, ultrasound may be used instead.
Squamous cell carcinoma is the second most common type of lung cancer accounting for about one quarter of all lung cancers. Squamous cells are “scale-shaped” and occur along the “tubes” of the lungs, that is, the trachea and bronchi. Under a microscope, squamous cell carcinoma is characterized by “keratin pearls” that are recognized by a pathologist. In some ways squamous cells are like skin cells: they can tolerate contact with air (for the most part) and they tend to slough off (exfoliate) like skin cells.
Squamous cells are relatively hearty cells since they are exposed to the environment during breathing; however, they can only tolerate cigarette smoke and other toxic substances for a certain period of time. Squamous cell carcinoma shows a remarkable dose-dependence with cigarette smoking. This means that the risk of developing this type of lung cancer increases in direct proportion to the number of cigarettes smoked over time.
In contrast to lung adenocarcinoma, squamous cell carcinoma is usually found near the center of the lungs. While it is usually not possible to obtain a biopsy of squamous cell carcinoma from the outside of the body, it may be possible to collect cells for analysis from the inside. To perform a biopsy in this fashion, a bronchoscope (a thin tube with a light, a camera, and small surgical instruments in the tip) can be advanced down the throat, into the trachea, and to the bronchus that contains the tumor.
Since squamous cell carcinoma usually occurs near the bronchi, the tumor can cause cough (sometimes a cough that is tinged with blood), shortness of breath, wheezing, and pneumonia in the area between the tumor and the edge of the lung. The relative position of squamous cell carcinoma is actually beneficial since it causes symptoms early in the disease. These symptoms usually prompt patients to seek medical help and treatment. Therefore diagnosis of squamous cell carcinoma is usually slightly earlier than other lung cancers, overall. Also speeding diagnosis is the fact that squamous cell carcinoma is most likely to cause an abnormal elevation of calcium in the blood that can be detected on routine blood tests.
Large cell carcinoma is a subtype of non-small cell lung cancer. It is responsible for about one in ten lung cancers making it among the rarest (though still common in terms of numbers of all cancers). Large cell carcinoma is identified as being different from the other types of lung cancers histologically. These cells do not have the necessary equipment to secrete substances like adenocarcinoma. Nor do they look like scales with keratin pearls, which would indicate squamous cell carcinoma. Large cell carcinoma appears rather strange under a microscope in that it looks like sheets of abnormal cells with an area of dead cells in the middle.
Large cell lung cancers do not necessarily occur near the chest wall, though they often occur near the edge of the lung rather than near a bronchus (in the center). Therefore, a needle biopsy may or may not be possible, depending on location. If a needle biopsy is not possible, a tissue sample may need to be gathered using a surgical approach. When this is needed, the entire tumor may be removed both for purposes of diagnosis and treatment.