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.

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 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.

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.

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.

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.

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.

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.

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

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

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.

Adenosquamous lung carcinoma (AdSqLC) is a biphasic malignant tumor arising from lung tissue that is composed of at least 10% by volume each of squamous cell carcinoma (SqCC) and adenocarcinoma (AdC) cells.

Squamous-cell carcinoma (SCC) of the lung is a type of non-small-cell lung carcinoma and 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.

This form of cancer is often seen in those who chew tobacco or use snuff orally, so much so that it is sometimes referred to as "Snuff dipper's cancer." Chewing betel nuts is an additional risk factor commonly seen in Taiwan.

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 cancer is a large and exceptionally heterogeneous family of malignancies. Over 50 different histological variants are explicitly recognized within the 2004 revision of the World Health Organization (WHO) typing system ("WHO-2004"), currently the most widely used lung cancer classification scheme. Many of these entities are rare, recently described, and poorly understood. However, since different forms of malignant tumors generally exhibit diverse genetic, biological, and clinical properties — including response to treatment — accurate classification of lung cancer cases are critical to assuring that patients with lung cancer receive optimum management.

Under WHO-2004, lung carcinomas are divided into 8 major taxa:

- Squamous cell carcinoma

- Small cell carcinoma

- Adenocarcinoma

- Large cell carcinoma

- Adenosquamous carcinoma

- Sarcomatoid carcinoma

- Carcinoid tumor

- Salivary gland-like carcinoma

Salivary gland–like carcinomas of the lung generally refers a class of rare cancers that arise from the uncontrolled cell division (mitosis) of mutated cancer stem cells in lung tissue. They take their name partly from the appearance of their abnormal cells, whose structure and features closely resemble those of cancers that form in the major salivary glands (parotid glands, submandibular glands and sublingual glands) of the head and neck. Carcinoma is a term for malignant neoplasms derived from cells of epithelial lineage, and/or that exhibit cytological or tissue architectural features characteristically found in epithelial cells.

This class of primary lung cancers contains several histological variants, including mucoepidermoid carcinoma of the lung, adenoid cystic carcinoma of the lung, epithelial-myoepithelial carcinoma of the lung, and other (even more rare) variants. .

LCLC-RP are considered to be especially aggressive tumors with a dismal prognosis. Many published cases have shown short survival times after diagnosis. Some studies suggest that, as the proportion of rhabdoid cells in the tumor increases, the prognosis tends to worsen, although this is most pronounced when the proportion of rhabdoid cells exceeds 5%. With regard to "parent" neoplasms other than LCLC, adenocarcinomas with rhabdoid features have been reported to have worse prognoses than adenocarcinomas without rhabdoid features, although an "adenocarcinoma with rhabdoid phenotype" tumor variant has not been specifically recognized as a distinct entity under the WHO-2004 classification system.

Interestingly, there are case reports of rhabdoid carcinomas recurring after unusually long periods, which is unusual for a fast-growing, aggressive tumor type. One report described a very early stage patient whose tumor recurred 6 years after initial treatment. Although rapidly progressive, fulminant courses seem to be the rule in this entity, long-term survival has also been noted, even post-metastectomy in late stage, distant metastatic disease.

This type of cancer occurs most often in Caucasians between 60 and 80 years of age, and its rate of incidence is about twice as high in males as in females. There are roughly 1,500 new cases of MCC diagnosed each year in the United States, as compared to around 60,000 new cases of melanoma and over 1 million new cases of nonmelanoma skin cancer. MCC is sometimes mistaken for other histological types of cancer, including basal cell carcinoma, squamous cell carcinoma, malignant melanoma, lymphoma, and small cell carcinoma, or as a benign cyst. Researchers believe that exposure to sunlight or ultraviolet light (such as in a tanning bed) may increase the risk of developing this disease. Similar to melanoma, the incidence of MCC in the US is increasing rapidly.

Immunosuppression can profoundly increase the odds of developing Merkel-cell carcinoma. Merkel-cell carcinoma occurs 30 times more often in people with chronic lymphocytic leukemia and 13.4 times more often in people with advanced HIV as compared to the general population; solid organ transplant recipients have a 10-fold increased risk compared to the general population.

Clear-cell adenocarcinoma is a type of adenocarcinoma that shows clear cells.

Types include:

- Clear-cell adenocarcinoma of the vagina

- Clear-cell ovarian carcinoma

- Uterine clear-cell carcinoma

- Clear-cell adenocarcinoma of the lung (which is a type of Clear-cell carcinoma of the lung)

See also:

- Clear-cell squamous cell carcinoma of the lung

It most often arises centrally in larger bronchi, and while it often metastasizes to locoregional lymph nodes (particularly the hilar nodes) early in its course, it generally disseminates outside the thorax somewhat later than other major types of lung cancer. Large tumors may undergo central necrosis, resulting in cavitation. A squamous-cell carcinoma is often preceded for years by squamous-cell metaplasia or dysplasia in the respiratory epithelium of the bronchi, which later transforms to carcinoma in situ.

In carcinoma in situ, atypical cells may be identified by cytologic smear test of sputum, bronchoalveolar lavage or samples from endobronchial brushings. However, squamous-cell carcinoma in situ is asymptomatic and undetectable on X-ray radiographs.

Eventually, it becomes symptomatic, usually when the tumor mass begins to obstruct the lumen of a major bronchus, often producing distal atelectasis and infection. Simultaneously, the lesion invades into the surrounding pulmonary substance. On histopathology, these tumors range from well differentiated, showing keratin pearls and cell junctions, to anaplastic, with only minimal residual squamous-cell features.

Prognosis and treatment is the same as for the most common type of ovarian cancer, which is epithelial ovarian cancer.

The median survival of primary peritoneal carcinomas is usually shorter by 2–6 months time when compared with serous ovarian cancer. Studies show median survival varies between 11.3–17.8 months. One study reported 19-40 month median survival (95% CI) with a 5-year survival of 26.5%.

Elevated albumin levels have been associated with a more favorable prognosis.

While cancer is generally considered a disease of old age, children can also develop cancer. In contrast to adults, carcinomas are exceptionally rare in children..

The two biggest risk factors for ovarian carcinoma are age and family history.

Human papillomavirus infection (HPV) has been associated with SCC of the oropharynx, lung, fingers and anogenital region.

Acinic cell carcinoma appears in all age groups, but presents at a younger median age (approx. 52 years) than most other salivary gland cancers. Occurrences in children are quite common.