Adenocarcinoma of the lung (pulmonary adenocarcinoma) 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.
Pie chart showing incidence of adenocarcinoma of the lung (shown in yellow) as compared to other lung cancer types, with fractions of non-smokers versus smokers shown for each type.
Adenocarcinoma is the most common type of lung cancer in lifelong non-smokers. 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.
Adenocarcinomas account for approximately 40% of lung cancers.
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 is due to the use of filters in cigarettes which prevent the larger particles from entering the lung.[clarification needed] 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.
Adenocarcinomas are highly heterogeneous tumors. Several major histological subtypes are currently recognized by the WHO  and IASLC/ATS/ERS
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".
Signet ring and clear cell adenocarcinoma are no longer histological subtypes, but rather cytological features that can occur in tumour cells of multiple histological subtypes, most often solid adenocarcinoma.
Some variants are not clearly recognized by the WHO and IASLC/ATS/ERS classification:
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).
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). Microscopically, AAH is a well-demarcated focus of epithelial proliferation, containing cuboidal to low-columnar cells resembling Clara cells or type II pneumocytes. These demonstrate various degrees of cytologic atypia, including hyperchromasia, pleomorphism, prominent nucleoli. However, the atypia is not to the extent as seen in frank adenocarcinomas. Lesions of AAH are monoclonal, and they share many of the molecular aberrations (like KRAS mutations) that are associated with adenocarcinomas.
^British Journal of Cancer (2004) 90, 646 – 651 T Marugame et al, Filter cigarette smoking and lung cancer risk; a hospital-based case–control study in Japan
^ abVan Schil, P. E.; Asamura, H; Rusch, V. W.; Mitsudomi, T; Tsuboi, M; Brambilla, E; Travis, W. D. (2012). "Surgical implications of the new IASLC/ATS/ERS adenocarcinoma classification". European Respiratory Journal39 (2): 478–86. doi:10.1183/09031936.00027511. PMID21828029. edit
^Travis, W. D.; Brambilla, E; Van Schil, P; Scagliotti, G. V.; Huber, R. M.; Sculier, J. P.; Vansteenkiste, J; Nicholson, A. G. (2011). "Paradigm shifts in lung cancer as defined in the new IASLC/ATS/ERS lung adenocarcinoma classification". European Respiratory Journal38 (2): 239–43. doi:10.1183/09031936.00026711. PMID21804158. edit
^Yousem, S. A. (2005). "Pulmonary intestinal-type adenocarcinoma does not show enteric differentiation by immunohistochemical study". Modern Pathology18 (6): 816–21. doi:10.1038/modpathol.3800358. PMID15605076. edit