Tobacco smoking is by far the main contributor to lung cancer. Cigarette smoke contains at least 73 known carcinogens, including benzo["a"]pyrene, NNK, 1,3-butadiene and a radioactive isotope of polonium, polonium-210. Across the developed world, 90% of lung cancer deaths in men during the year 2000 were attributed to smoking (70% for women). Smoking accounts for about 85% of lung cancer cases.

Passive smoking—the inhalation of smoke from another's smoking—is a cause of lung cancer in nonsmokers. A passive smoker can be defined as someone living or working with a smoker. Studies from the US, Europe and the UK have consistently shown a significantly increased risk among those exposed to passive smoke. Those who live with someone who smokes have a 20–30% increase in risk while those who work in an environment with secondhand smoke have a 16–19% increase in risk. Investigations of sidestream smoke suggest it is more dangerous than direct smoke. Passive smoking causes about 3,400 deaths from lung cancer each year in the USA.

Marijuana smoke contains many of the same carcinogens as those in tobacco smoke. However, the effect of smoking cannabis on lung cancer risk is not clear. A 2013 review did not find an increased risk from light to moderate use. A 2014 review found that smoking cannabis doubled the risk of lung cancer.

Outdoor air pollutants, especially chemicals released from the burning of fossil fuels, increase the risk of lung cancer. Fine particulates (PM) and sulfate aerosols, which may be released in traffic exhaust fumes, are associated with slightly increased risk. For nitrogen dioxide, an incremental increase of 10 parts per billion increases the risk of lung cancer by 14%. Outdoor air pollution is estimated to account for 1–2% of lung cancers.

Tentative evidence supports an increased risk of lung cancer from indoor air pollution related to the burning of wood, charcoal, dung or crop residue for cooking and heating. Women who are exposed to indoor coal smoke have about twice the risk and a number of the by-products of burning biomass are known or suspected carcinogens. This risk affects about 2.4 billion people globally, and is believed to account for 1.5% of lung cancer deaths.

Taken as a class, long-term survival rates in BAC tend to be higher than those of other forms of NSCLC. BAC generally carries a better prognosis than other forms of NSCLC, which can be partially attributed to localized presentation of the disease. Though other factors might play a role. Prognosis of BAC depends upon the histological subtype and extent at presentation but are generally same as other NSCLC.

Recent research has made it clear that nonmucinous and mucinous BACs are very different types of lung cancer. Mucinous BAC is much more likely to present with multiple unilateral tumors and/or in a unilateral or bilateral pneumonic form than nonmucinous BAC. The overall prognosis for patients with mucinous BAC is significantly worse than patients with nonmucinous BAC.

Although data are scarce, some studies suggest that survival rates are even lower in the mixed mucinous/non-mucinous variant than in the monophasic forms.

In non-mucinous BAC, neither Clara cell nor Type II pneumocyte differentiation appears to affect survival or prognosis.

The incidence of bronchiolo-alveolar carcinoma has been reported to vary from 4–24% of all lung cancer patients. An analysis of Surveillance epidemiology and End results registry ( SEER) by Read "et al." revealed that although the incidence of BAC has increased over the past two decade it still constitutes less than 4% of NSCLC in every time interval. This difference in the incidence has been attributed to complex histopathology of cancer. While pure BAC is rare, the increase in incidence as seen in various studies can be due to unclear histological classification till WHO came up with its classification in 1999 and then in 2004.

Another distinguishing feature about BAC is that it afflicts men and women in equal proportions, some recent studies even suggest slightly higher incidence among women.

15% of lung cancers in the US are of this type. Small cell lung cancer occurs almost exclusively in smokers; most commonly in heavy smokers and rarely in non-smokers.

The prognosis of patients with FA as a whole is considered to be better than that of most other forms of non-small cell carcinoma, including biphasic pulmonary blastoma.

Asbestos can cause lung cancer that is identical to lung cancer from other causes. Exposure to asbestos is associated with all major histological types of lung carcinoma (adenocarcinoma, squamous cell carcinoma, large-cell carcinoma and small-cell carcinoma). The latency period between exposure and development of lung cancer is 20 to 30 years. It is estimated that 3%-8% of all lung cancers are related to asbestos. The risk of developing lung cancer depends on the level, duration, and frequency of asbestos exposure (cumulative exposure). Smoking and individual susceptibility are other contributing factors towards lung cancer. Smokers who have been exposed to asbestos are at far greater risk of lung cancer. Smoking and asbestos exposure have a multiplicative (synergistic) effect on the risk of lung cancer. Symptoms include chronic cough, chest pain, breathlessness, haemoptysis (coughing up blood), wheezing or hoarseness of the voice, weight loss and fatigue. Treatment involves surgical removal of the cancer, chemotherapy, radiotherapy, or a combination of these (multimodality treatment). Prognosis is generally poor unless the cancer is detected in its early stages. Out of all patients diagnosed with lung cancer, only 15% survive for five years after diagnosis.

Giant-cell lung cancers have long been considered to be exceptionally aggressive malignancies that grow very rapidly and have a very poor prognosis.

Many small series have suggested that the prognosis of lung tumors with giant cells is worse than that of most other forms of non-small-cell lung cancer (NSCLC), including squamous cell carcinoma, and spindle cell carcinoma.

The overall five-year survival rate in GCCL varies between studies but is generally considered to be very low. The (US) Armed Forces Institute of Pathology has reported a figure of 10%, and in a study examining over 150,000 lung cancer cases, a figure of 11.8% was given. However, in the latter report the 11.8% figure was based on data that included spindle cell carcinoma, a variant which is generally considered to have a less dismal prognosis than GCCL. Therefore, the likely survival of "pure" GCCL is probably lower than the stated figure.

In the large 1995 database review by Travis and colleagues, giant-cell carcinoma has the third-worst prognosis among 18 histological forms of lung cancer. (Only small-cell carcinoma and large-cell carcinoma had shorter average survival.)

Most GCCL have already grown and invaded locally and/or regionally, and/or have already metastasized distantly, and are inoperable, at the time of diagnosis.

Genetic changes are very high in SCLC and LCNEC, but usually low for TC, intermediate for AC.

In most series, LCLC's comprise between 5% and 10% of all lung cancers.

According to the Nurses' Health Study, the risk of large cell lung carcinoma increases with a previous history of tobacco smoking, with a previous smoking duration of 30 to 40 years giving a relative risk of approximately 2.3 compared to never-smokers, and a duration of more than 40 years giving a relative risk of approximately 3.6.

Another study concluded that cigarette smoking is the predominant cause of large cell lung cancer. It estimated that the odds ratio associated with smoking two or more packs/day for current smokers is 37.0 in men and 72.9 in women.

The true incidence, prevalence, and mortality of GCCL is generally unknown due to a lack of accurate cancer data on a national level. It is known to be a very rare tumor variant in all populations examined, however. In an American study of a database of over 60,000 lung cancers, GCCL comprised between 0.3% and 0.4% of primary pulmonary malignancies, with an age-adjusted incidence rate of about 3 new cases per million persons per year. With approximately 220,000 total lung cancers diagnosed in the US each year, the proportion suggests that approximately 660 and 880 new cases are diagnosed in Americans annually.

However, in a more recent series of 4,212 consecutive lung cancer cases, only one (0.024%) lesion was determined to be a "pure" giant-cell carcinoma after complete sectioning of all available tumor tissue. While some evidence suggests GCCL may have been considerably more common several decades ago, with one series identifying 3.4% of all lung carcinomas as giant-cell malignancies, it is possible that this number reflect

Most published case series and reports on giant cell-containing lung cancers show that they are diagnosed much more frequently in men than they are in women, with some studies showing extremely high male-to-female ratios (12:1 or more). In a study of over 150,000 lung cancer victims in the US, however, the gender ratio was just over 2:1, with women actually having a higher relative proportion of giant-cell cancers (0.4%) than men (0.3%).

Giant-cell carcinomas have been reported to be diagnosed in a significantly younger population than all non-small-cell carcinomas considered as a group. Like nearly all lung carcinomas, however, GCCs are exceedingly rare in very young people: in the US SEER program, only 2 cases were recorded to occur in persons younger than 30 years of age between 1983 and 1987. The average age at diagnosis of these tumors has been estimated at 60 years.

The vast majority of individuals with GCCL are heavy smokers.

Although the definitions of "central" and "peripheral" can vary between studies, GCCL are consistently diagnosed much more frequently in the lung periphery. In a review of literature compiled by Kallenburg and co-workers, less than 30% of GCCLs arose in the hilum or other parts of the "central" pulmonary tree.

A significant predilection for genesis of GCCL in the upper lobes of victims has also been postulated.

A number of PPBs have shown trisomy 8 (17 out of 23 cases studied per the PPB registry). Trisomy 2 and p53 mutations/deletions have also been described.

An association with mutations in the DICER1 gene has been reported. Mutations in this gene are found in 2/3 cases.

EMECL is extremely rare, with only a handful of cases reported in the literature.

In the lung, two salivary gland-like carcinomas, mucoepidermoid carcinoma and adenoid cystic carcinoma, while extremely uncommon, occur far more often than does EMECL.

Although reliable and comprehensive incidence statistics are nonexistent, LCLC-RP is a rare tumor, with only a few hundred cases described in the scientific literature to date. LCLC's made up about 10% of lung cancers in most historical series, equating to approximately 22,000 cases per year in the U.S. Of these LCLC cases, it is estimated that about 1% will eventually develop the rhabdoid phenotype during tumor evolution and progression. In one large series of 902 surgically resected lung cancers, only 3 cases (0.3%) were diagnosed as LCLC-RP. In another highly selected series of large-cell lung carcinoma cases, only 4 of 45 tumors (9%) were diagnosed as the rhabdoid phenotype using the 10% criterion, but another 10 (22%) had at least some rhabdoid cell formation. It appears likely, therefore, that LCLC-RP probably comprises between 0.1% and 1.0% of all lung malignancies.

Similar to nearly all variants of lung carcinoma, large cell lung carcinoma with rhabdoid phenotype appears to be highly related to tobacco smoking. It also appears to be significantly more common in males than in females.

All in all, small-cell carcinoma is very responsive to chemotherapy and radiotherapy, and in particular, regimens based on platinum-containing agents. However, most people with the disease relapse, and median survival remains low.

In "limited-stage" disease, median survival with treatment is 14–20 months, and about 20% of patients with limited-stage small-cell lung carcinoma live 5 years or longer. Because of its predisposition for early metastasis, the prognosis of SCLC is poor, with only 10% to 15% of patients surviving 3 years.

The prognosis is far more grim in "extensive-stage" small-cell lung carcinoma; with treatment, median survival is 8–13 months; only 1–5% of patients with extensive-stage small-cell lung carcinoma treated with chemotherapy live 5 years or longer.

Smoking is the most important risk factor for laryngeal cancer. Death from laryngeal cancer is 20 times more likely for heaviest smokers than for nonsmokers. Heavy chronic consumption of alcohol, particularly alcoholic spirits, is also significant. When combined, these two factors appear to have a synergistic effect.

Some other quoted risk factors are likely, in part, to be related to prolonged alcohol and tobacco consumption. These include low socioeconomic status, male sex, and age greater than 55 years.

People with a history of head and neck cancer are known to be at higher risk (about 25%) of developing a second cancer of the head, neck, or lung. This is mainly because in a significant proportion of these patients, the aerodigestive tract and lung epithelium have been exposed chronically to the carcinogenic effects of alcohol and tobacco. In this situation, a field change effect may occur, where the epithelial tissues start to become diffusely dysplastic with a reduced threshold for malignant change. This risk may be reduced by quitting alcohol and tobacco.

FA is a rare tumor, with a relative incidence estimated to be no more than 0.5% of all lung cancers.

FA is exceptionally rare in children, with only a handful of cases reported to date, However, several case reports have involved FA's in pregnant women or the early postnatal period.

Squamous cell carcinoma (SCC) of the lung is more common in men than in women. It is closely correlated with a history of tobacco smoking, more so than most other types of lung cancer. According to the Nurses' Health Study, the relative risk of SCC is approximately 5.5, both among those with a previous duration of smoking of 1 to 20 years, and those with 20 to 30 years, compared to never-smokers. The relative risk increases to approximately 16 with a previous smoking duration of 30 to 40 years, and approximately 22 with more than 40 years.

The prognosis of EMECL is relatively good, and considerably better than most other forms of NSCLC. The skull and dura are possible sites for metastasis from pulmonary EMC. The MIB-1 index is a predictive marker of malignant potential.

Current consensus is that the long-term prognosis of c-SCLC patients is determined by the SCLC component of their tumor, given that "pure" SCLC seems to have the worst long-term prognosis of all forms of lung cancer. Although data on c-SCLC is very sparse, some studies suggest that survival rates in c-SCLC may be even worse than that of pure SCLC, likely due to the lower rate of complete response to chemoradiation in c-SCLC, although not all studies have shown a significant difference in survival.

Untreated "pure" SCLC patients have a median survival time of between 4 weeks and 4 months, depending on stage and performance status at the time of diagnosis.

Given proper multimodality treatment, SCLC patients with limited disease have median survival rates of between 16 and 24 months, and about 20% will be cured. In patients with extensive disease SCLC, although 60% to 70% will have good-to-complete responses to treatment, very few will be cured, with a median survival of only 6 to 10 months.

Some evidence suggests that c-SCLC patients who continue to smoke may have much worse outcomes after treatment than those who quit.

Nearly 40% of lung cancers in the US are adenocarcinoma, which usually originates in peripheral lung tissue. Most cases of adenocarcinoma are associated with smoking; however, among people who have smoked fewer than 100 cigarettes in their lifetimes ("never-smokers"), adenocarcinoma is the most common form of lung cancer. Its incidence has been increasing in many developed Western nations in the past few decades, where it has become the most common major type of lung cancer in smokers (replacing squamous cell lung carcinoma) and in lifelong nonsmokers. According to the Nurses' Health Study, the risk of adenocarcinoma of the lung increases substantially after a long duration of previous tobacco smoking, with a previous smoking duration of 30 to 40 years giving a relative risk of approximately 2.4 compared to never-smokers, and a duration of more than 40 years giving a relative risk of approximately 5.

This cancer usually is seen peripherally in the lungs, as opposed to small cell lung cancer and squamous cell lung cancer, which both tend to be more centrally located, although it may also occur as central lesions. For unknown reasons, it often arises in relation to peripheral lung scars. The current theory is that the scar probably occurred secondary to the tumor, rather than causing the tumor. The adenocarcinoma has an increased incidence in smokers, and is the most common type of lung cancer seen in non-smokers and women. The peripheral location of adenocarcinoma in the lungs may be due to the use of filters in cigarettes which prevent the larger particles from entering the lung. Deeper inhalation of cigarette smoke results in peripheral lesions that are often the case in adenocarcinomas of the lung. Generally, adenocarcinomas grow more slowly and form smaller masses than the other subtypes. However, they tend to form metastases widely at an early stage. Adenocarcinoma is a non-small cell lung carcinoma, and as such, it is not as responsive to radiation therapy as is small cell lung carcinoma, but is rather treated surgically, for example by pneumonectomy or lobectomy.

LCC is, in effect, a "diagnosis of exclusion", in that the tumor cells lack light microscopic characteristics that would classify the neoplasm as a small-cell carcinoma, squamous-cell carcinoma, adenocarcinoma, or other more specific histologic type of lung cancer.

LCC is differentiated from small-cell lung carcinoma (SCLC) primarily by the larger size of the anaplastic cells, a higher cytoplasmic-to-nuclear size ratio, and a lack of "salt-and-pepper" chromatin.

Reliable comprehensive incidence statistics for c-SCLC are unavailable. In the literature, the frequency with which the c-SCLC variant is diagnosed largely depends on the size of tumor samples, tending to be higher in series where large surgical resection specimens are examined, and lower when diagnoses are based on small cytology and/or biopsy samples. Tatematsu "et al." reported 15 cases of c-SCLC (12%) in their series of 122 consecutive SCLC patients, but only 20 resection specimens were examined. In contrast, Nicholson "et al." found 28 c-SCLC (28%) in a series of 100 consecutive resected SCLC cases. It appears likely, then, that the c-SCLC variant comprises 25% to 30% of all SCLC cases.

As the incidence of SCLC has declined somewhat in the U.S. in recent decades, it is likely that c-SCLC has also decreased in incidence. Nevertheless, small cell carcinomas (including the c-SCLC variant) still comprise 15–20% of all lung cancers, with c-SCLC probably accounting for 4–6%. With 220,000 cases of newly diagnosed lung cancer in the U.S. each year, it can be estimated that between 8,800 and 13,200 of these are c-SCLC.

In a study of 408 consecutive patients with SCLC, Quoix and colleagues found that presentation as a solitary pulmonary nodule (SPN) is particularly indicative of a c-SCLC — about 2/3 of their SPN's were pathologically confirmed to be c-SCLC's containing a large cell carcinoma component.

Pulmonary neuroendocrine tumors are neuroendocrine tumors localized to the lung: bronchus or pulmonary parenchyma.

Pulmonary neuroendocrine tumors include a spectrum of tumors from the low-grade typical pulmonary carcinoid tumor and intermediate-grade atypical pulmonary carcinoid tumor to the high-grade pulmonary large cell neuroendocrine carcinoma (LCNEC) and pulmonary small cell carcinoma (SCLC), with significant clinical, epidemiologic and genetic differences.

Lung cancers have been historically classified using two major paradigms. Histological classification systems group lung cancers according to the appearance of the cells and surrounding tissues when they are viewed under a microscope. Clinical classification systems divide lung cancers into groups based on medical criteria, particularly their response to different treatment regimens.

Before the mid-1900s, lung cancer was considered to be a single disease entity, with all forms treated similarly. In the 1960s, small cell lung carcinoma (SCLC) was recognized as a unique form of lung cancer, based both on its appearance (histology) and its clinical properties, including much greater susceptibility to chemotherapy and radiation, more rapid growth rate, and its propensity to metastasize widely early on in its course. Since then, most oncologists have based patient treatment decisions on a dichotomous division of lung cancers into SCLC and non-small cell lung carcinomas (NSCLC), with the former being treated primarily with chemoradiation, and the latter with surgery.

An explosion of new knowledge, accumulated mainly over the last 20 years, has proved that lung cancers should be considered an extremely heterogeneous family of neoplasms with widely varying genetic, biological, and clinical characteristics, particularly their responsiveness to the large number of newer treatment protocols. Well over 50 different histological variants are now recognized under the 2004 revision of the World Health Organization ("WHO-2004") typing system, currently the most widely used lung cancer classification scheme. Recent studies have shown beyond doubt that the old clinical classification paradigm of "SCLC vs. NSCLC" is now obsolete, and that correct "subclassification" of lung cancer cases is necessary to assure that lung cancer patients receive optimum management.

Approximately 98% of lung cancers are carcinoma, which are tumors composed of cells with epithelial characteristics. LCLC's are one of 8 major groups of lung carcinomas recognized in WHO-2004:

- Squamous cell carcinoma

- Small cell carcinoma

- Adenocarcinoma

- Large cell carcinoma

- Adenosquamous carcinoma

- Sarcomatoid carcinoma

- Carcinoid tumor

- Salivary gland-like carcinoma