Adenocarcinoma of the lung is a common histological form of lung cancer that contains certain distinct malignant tissue architectural, cytological, or molecular features, including gland and/or duct formation and/or production of significant amounts of mucus.[1]
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Lung cancer is an extremely heterogeneous family of malignant neoplasms,[3] with over 50 different histological variants recognized in the 4th revision of the World Health Organization (WHO) typing system, currently the most widely used lung cancer classification scheme.[1] 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.[4][5] Approximately 98% of lung cancers are carcinoma, with the remainder being mainly sarcoma or tumors of hematopoietic or germ cell origin.[6]
Approximately 98% of lung cancers are carcinoma, which are tumors composed of cells with epithelial characteristics.[6] Adenocarcinomas (AdC's) are one of 8 major groups of lung carcinomas recognized in WHO-2004:[1]
Adenocarcinoma is the most common type of lung cancer in lifelong non-smokers.[7] 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.[1] 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.[8]
Adenocarcinomas account for approximately 40% of lung cancers.[9]
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,[10][11] although it may also occur as central lesions.[10] By 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.[10] The adenocarcinoma has an increased incidence in smokers, and is the most common type of lung cancer seen in non-smokers and women.[10] The peripheral location of adenocarcinoma in the lungs is due to the use of filters in cigarettes which prevent the larger particles from entering the lung.[12] Generally, adenocarcinomas grow more slowly and form smaller masses than the other subtypes.[10] However, they tend to form metastases widely at an early stage.[10] 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.[10]
Adenocarcinomas are highly heterogeneous tumors, and several major histological subtypes are currently recognized:[1]
In as many as 80% of tumors that are extensively sampled, components of more than one of these subtypes will be recognized. In such cases, the tumors should be classified as a fifth "subtype", namely "adenocarcinoma, mixed subtypes".[1]
Adenocarcinoma of the lung tends to stain mucin positive as it is derived from the mucus producing glands of the lungs. Similar to other adenocarcinoma, if this tumor is well differentiated (low grade) it will resemble the normal glandular structure. Poorly differentiated adenocarcinoma will not resemble the normal glands (high grade) and will be detected by seeing that they stain positive for mucin (which the glands produce).[13][14]
To reveal the adenocarcinomatous lineage of the solid variant, demonstration of intracellular mucin production may be performed. Foci of squamous metaplasia and dysplasia may be present in the epithelium proximal to adenocarcinomas, but these are not the precursor lesions for this tumor. Rather, the precursor of peripheral adenocarcinomas has been termed atypical adenomatous hyperplasia (AAH).[10] Microscopically, AAH is a well-demarcated focus of epithelial proliferation, containing cuboidal to low-columnar cells resembling Clara cells or type II pneumocytes.[10] These demonstrate various degrees of cytologic atypia, including hyperchromasia, pleomorphism, prominent nucleoli.[10] However, the atypia is not to the extent as seen in frank adenocarcinomas.[10] Lesions of AAH are monoclonal, and they share many of the molecular aberrations (like KRAS mutations) that are associated with adenocarcinomas.[10]
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