Giant-cell carcinoma of the lung (GCCL) is a rare histological form of large-cell lung carcinoma, a subtype of undifferentiated lung cancer, traditionally classified within the non-small-cell lung carcinomas (NSCLC).

The characteristic feature of this highly lethal malignancy is the distinctive light microscopic appearance of its extremely large cells, which are bizarre and highly pleomorphic, and which often contain more than one huge, misshapen, pleomorphic nucleus ("syncytia"), which result from cell fusion.

Although it is common in the lung cancer literature to refer to histologically mixed tumors containing significant numbers of malignant giant cells as "giant-cell carcinomas", technically a diagnosis of "giant-cell carcinoma" should be limited strictly to neoplasms containing "only" malignant giant cells (i.e. "pure" giant-cell carcinoma).

Aside from the great heterogeneity seen in lung cancers (especially those occurring among tobacco smokers), the considerable variability in diagnostic and sampling techniques used in medical practice, the high relative proportion of individuals with suspected GCCL who do not undergo complete surgical resection, and the near-universal lack of complete sectioning and pathological examination of resected tumor specimens prevent high levels of quantitative accuracy.

Patients typically present with a non-productive cough and weight loss.

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.

Approximately 99% of lung cancers are carcinoma, a term that indicates that the malignant neoplasm is composed of, or descended from, cells of epithelial lineage (i.e. derived from embryonic endoderm, as is the case in lung carcinomas, or from ectoderm), and/or that the malignant cells exhibit tissue architectural, cytological, or molecular features characteristically found in epithelial cells. 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

SCLC is generally considered to be the most aggressive of these major forms of lung cancer, with the worst long term prognosis and survival rates. As a result, it is recommended that all multiphasic malignant lung tumors (i.e. those with more than one histological pattern) that are found to contain "any" proportion of SCLC cells should be classified as c-SCLC, and "not" as combined forms of any of the other histological variants present in the tumor. Currently, the only exception to this recommendation occurs in cases where anaplastic large cell lung carcinoma (LCLC) is the second histological component. In these instances, a minimum of 10% of the viable malignant cells present must be identified as LCLC before the tumor is considered to be a c-SCLC. Under the WHO-2004 classification scheme, c-SCLC is the only recognized variant of SCLC.

Combined small cell lung carcinoma (or c-SCLC, and rarely rendered as "small-cell lung carcinoma") is a form of multiphasic lung cancer that is diagnosed by a pathologist when a malignant tumor arising from transformed cells originating in lung tissue contains a component of small cell lung carcinoma (SCLC) admixed with one (or more) components of non-small cell lung carcinoma (NSCLC).

Large cell lung carcinoma with rhabdoid phenotype (LCLC-RP) is a rare histological form of lung cancer, currently classified as a variant of large cell lung carcinoma (LCLC). In order for a LCLC to be subclassified as the phenotype variant, at least 10% of the malignant tumor cells must contain distinctive structures composed of tangled intermediate filaments that displace the cell nucleus outward toward the cell membrane. The whorled eosinophilic inclusions in LCLC-RP cells give it a microscopic resemblance to malignant cells found in rhabdomyosarcoma (RMS), a rare neoplasm arising from transformed skeletal muscle. Despite their microscopic similarities, LCLC-RP is not associated with rhabdomyosarcoma.

Although rhabdoid variants of LCLC are sometimes referred to as "rhabdoid carcinomas", this particular term should be reserved for examples of "pure" rhabdoid neoplasms (i.e. those that do not contain cells containing other histological variants)

Lung cancer is an extremely heterogeneous family of malignant neoplasms, with well over 50 different histological variants recognized under the 4th revision of the World Health Organization (WHO) typing system ("WHO-2004"), currently the most widely used lung cancer classification scheme. Because these variants have differing genetic, biological, and clinical properties, including response to treatment, correct classification of lung cancer cases are necessary to assure that lung cancer patients receive optimum management.

The WHO-2004 scheme groups lung carcinomas into 8 major types:

- Squamous cell carcinoma

- Small cell carcinoma

- Adenocarcinoma

- Large cell carcinoma

- Adenosquamous carcinoma

- Sarcomatoid carcinoma

- Carcinoid tumor

- Salivary gland-like carcinoma

EMECL is considered a subtype of salivary gland-like carcinoma, tumors so named because their histological appearance and characteristics closely resemble malignant neoplasms arising in the major and minor salivary glands.

For several decades, primary lung cancers were consistently dichotomously classified for treatment and research purposes into small-cell lung carcinomas (SCLCs) and non-small-cell lung carcinomas (NSCLCs), based on an oversimplified approach that is now clearly outmoded. The new paradigm recognizes that lung cancers are a large and extremely heterogeneous family of malignant neoplasms, with over 50 different histological variants included in the 4th (2004) revision of the World Health Organization typing system, the most widely used lung cancer classification scheme ("WHO-2004"). These variants are increasingly appreciated as having different genetic, biological, and clinical properties, including prognoses and responses to treatment regimens, and therefore, that correct and consistent histological classification of lung cancers are necessary to validate and implement optimum management strategies.

About 1% of lung cancers are sarcomas, germ cell tumors, and hematopoietic tumors, while 99% of lung cancers are carcinoma. Carcinomas are tumors composed of transformed, abnormal cells with epithelial tissue architecture and/or molecular characteristics, and which derive from embryonic endoderm. Eight major taxa of lung carcinomas are recognized within the WHO-2004 classification:

1. Small-cell carcinoma

2. Squamous cell carcinoma

3. Adenocarcinoma

4. Large-cell carcinoma

5. Adenosquamous carcinoma

6. Sarcomatoid carcinoma

7. Carcinoid

8. Salivary gland-like carcinoma

The subclassification of GCCL among these major taxa has undergone significant changes in recent decades. Under the 2nd revision (1981) of the WHO classification, it was considered a subtype of large-cell carcinoma. In the 3rd (1999) revision, it was placed within a taxon called "Carcinomas with Pleomorphic, Sarcomatoid, or Sarcomatous Elements", along with pleomorphic carcinoma, spindle cell carcinoma, carcinosarcoma, and pulmonary blastoma, which are (arguably) related variants. While the 4th revision ("WHO-2004") retained the same grouping of lesions as the 3rd revision, the name of the major taxon was shortened to "sarcomatoid carcinomas".

The current rules for classifying lung cancers under WHO-2004, while useful and improved, remain to some extent fairly complex, ambiguous, arbitrary, and incomplete. Although it is fairly common for mixed tumors that are seen to contain malignant giant cells to be called "giant-cell carcinomas", "accurate" classification of a pulmonary tumor as a GCCL requires that the "entire tumor" consists "only" of malignant giant cells. Therefore, complete sampling of the entire tumor — obtained via a surgical resection — is absolutely necessary for a definitive diagnosis of GCCL to be made.

The differential diagnosis of LCLC-RP includes secondary metastatic lesions, melignant melanoma of the lung with rhabdoid phenotype, mucinous adenocarcinomas (particularly those featuring signet-ring cells), rhabdomyosarcoma, epitheloid angiosarcoma, pleural mesothelioma, and plasmacytoma.

The newest revisions of the World Health Organization (WHO) "Histological Typing of Lung Cancer schema" include several variants of LCC, including:

- Giant-cell carcinoma of the lung

- Basaloid large cell carcinoma of the lung

- Clear cell carcinoma of the lung

- Lymphoepithelioma-like carcinoma of the lung

- Large-cell lung carcinoma with rhabdoid phenotype

- Large cell neuroendocrine carcinoma of the lung

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

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. .

The epithelial component in EMECL's typically strongly express cytokeratins, but are negative for actin and S-100 protein, while the myoepithelial component is stains strongly for actin and S-100 protein, and only focally weakly for cytokeratins.

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.

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.

Very rarely, the primary site for small-cell carcinoma is outside of the lungs and pleural space, it is referred to as extrapulmonary small-cell carcinoma (EPSCC). Outside of the respiratory tract, small-cell carcinoma can appear in the cervix, prostate, liver, pancreas, gastrointestinal tract, or bladder. It is estimated to account for 1,000 new cases a year in the U.S. Histologically similar to small-cell lung cancer, therapies for small-cell lung cancer are usually used to treat EPSCC. First line treatment is usually with cisplatin and etoposide. In Japan, the first line treatment is shifting to irinotecan and cisplatin.

When the primary site is in the skin, it is referred to as a cutaneous metastasis.

Small-cell lung carcinoma can occur in combination with a wide variety of other histological variants of lung cancer, including extremely complex malignant tissue admixtures.

When it is found with one or more differentiated forms of lung cancer, such as squamous cell carcinoma or adenocarcinoma, the malignant tumor is then diagnosed and classified as a combined small cell lung carcinoma (c-SCLC). C-SCLC is the only currently recognized subtype of SCLC.

Although combined small-cell lung carcinoma is currently staged and treated similarly to "pure" small-cell carcinoma of the lung, recent research suggests surgery might improve outcomes in very early stages of this tumor type.

Smoking is a significant risk factor.

Symptoms and signs are as for other lung cancers. In addition, because of their neuroendocrine cell origin, small-cell carcinomas will often secrete substances that result in paraneoplastic syndromes such as Lambert-Eaton myasthenic syndrome.

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.

Pulmonary neuroendocrine tumor are classified according to tumoral grade:

- Low grade pulmonary neuroendocrine tumor: Typical pulmonary carcinoid tumour (TC; low-grade);

- Intermediate-grade pulmonary neuroendocrine tumor: Atypical pulmonary carcinoid tumour (AC; intermediate-grade)

- High-grade pulmonary neuroendocrine tumor

- Small cell lung cancer (SCLC)

- Large cell neuroendocrine carcinoma (LCNEC of the lung)

Low-grade nodular neuroendocrine proliferations ≥ 0.5 cm are classified as carcinoid tumors and smaller ones are called pulmonary tumorlets.

When neuroendocrine cell hyperplasia and tumorlets are extensive, they represent the rare preinvasive lesion for carcinoids known as "diffuse idiopathic pulmonary neuroendocrine cell hyperplasia".

Both LCNEC and SCLC can demonstrate histologic heterogeneity with other major histologic types of lung carcinoma, such as pulmonary adenocarcinoma or pulmonary squamous cell carcinoma, but is not characteristic of TC or AC.

Histological variants of lung cancer classified as sarcomatoid carcinoma include pleomorphic carcinoma, giant cell carcinoma, spindle cell carcinoma, carcinosarcoma, and pulmonary blastoma.

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.

Currently, four variants (papillary, small-cell, clear-cell, and basaloid) of squamous-cell carcinoma of the lung are recognized. Of these variants, there is some evidence that the basaloid and poorly differentiated small-cell variants may have worse prognoses than "conventional" squamous-cell carcinomas. The papillary variant occurs more frequently as a primarily superficial, endobronchial lesion, with a modestly better prognosis Very little data is currently available on the clear-cell variant of squamous-cell carcinoma, and no consensus has been reached on the prognostic implications of clear-cell changes in lung cancer.

Basophilic, bland cells similar to acinar cells. Growth pattern: solid - acinar cells, microcytic - small systic spaces mucinous or eosinophilic, papillary-cystic - large cystic lined by epithelium, follicular - similar to thyroid tissue.

These tumors which resemble serous acinar cells vary in their behavior from locally aggressive to blatantly malignant.

It can also appear in the breast. The pancreatic form of acinic cell carcinoma is a rare subtype of exocrine pancreatic cancer. Exocrine pancreatic cancers are the most common form of pancreatic cancer when compared to endocrine pancreatic cancer.

Acinic cell carcinomas arise most frequently in the parotid gland. Other sites of primary tumors have included the submandibular gland and other major and minor salivary glands. There have been rare cases of primary tumors involving the parapharyngeal space and the sublingual gland.

MCC usually presents as a firm, painless, nodule (up to 2 cm diameter) or mass (>2 cm diameter). These flesh-colored, red, or blue tumors typically vary in size from 0.5 cm (less than one-quarter of an inch) to more than 5 cm (2 inches) in diameter, and usually enlarge rapidly. Although MCC's may arise almost anywhere on the body, about half originate on sun-exposed areas of the head and neck, one-third on the legs, and about one-sixth on the arms. In about 12% of cases, no obvious anatomical site of origin ("primary site") can be identified.

Merkel-cell cancers tend to invade locally, infiltrating the underlying subcutaneous fat, fascia, and muscle, and typically metastasize early in their natural history, most often to the regional lymph nodes. MCCs also spread aggressively through the blood vessels, particularly to liver, lung, brain, and bone.

Carcinoma is a type of cancer that develops from epithelial cells. Specifically, a carcinoma is a cancer that begins in a tissue that lines the inner or outer surfaces of the body, and that arises from cells originating in the endodermal, mesodermal and ectodermal germ layer during embryogenesis.

Carcinomas occur when the DNA of a cell is damaged or altered and the cell begins to grow uncontrollably and become malignant. It is from the Greek καρκίνωμα 'karkinoma' meaning sore, ulcer, or cancer, itself derived from "karkinos" 'crab'.