Adenocarcinoma of the lung
Encyclopedia
Adenocarcinoma of the lung
Lung
The lung is the essential respiration organ in many air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located near the backbone on either side of the heart...

is a common histological form of lung cancer
Lung cancer
Lung cancer is a disease characterized by uncontrolled cell growth in tissues of the lung. If left untreated, this growth can spread beyond the lung in a process called metastasis into nearby tissue and, eventually, into other parts of the body. Most cancers that start in lung, known as primary...

 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.

Classification

Lung cancer is an extremely heterogeneous family of malignant neoplasms, with over 50 different histological variants recognized in the 4th revision of the World Health Organization
World Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...

 (WHO) typing system, 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. Approximately 98% of lung cancers are carcinoma
Carcinoma
Carcinoma is the medical term for the most common type of cancer occurring in humans. Put simply, a carcinoma is a cancer that begins in a tissue that lines the inner or outer surfaces of the body, and that generally arises from cells originating in the endodermal or ectodermal germ layer during...

, with the remainder being mainly sarcoma
Sarcoma
A sarcoma is a cancer that arises from transformed cells in one of a number of tissues that develop from embryonic mesoderm. Thus, sarcomas include tumors of bone, cartilage, fat, muscle, vascular, and hematopoietic tissues...

 or tumors of hematopoietic or germ cell
Germ cell
A germ cell is any biological cell that gives rise to the gametes of an organism that reproduces sexually. In many animals, the germ cells originate near the gut of an embryo and migrate to the developing gonads. There, they undergo cell division of two types, mitosis and meiosis, followed by...

 origin.

Approximately 98% of lung cancers are carcinoma
Carcinoma
Carcinoma is the medical term for the most common type of cancer occurring in humans. Put simply, a carcinoma is a cancer that begins in a tissue that lines the inner or outer surfaces of the body, and that generally arises from cells originating in the endodermal or ectodermal germ layer during...

, which are tumors composed of cells with epithelial characteristics. Adenocarcinomas (AdC'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

Epidemiology

Adenocarcinoma is the most common type of lung cancer
Lung cancer
Lung cancer is a disease characterized by uncontrolled cell growth in tissues of the lung. If left untreated, this growth can spread beyond the lung in a process called metastasis into nearby tissue and, eventually, into other parts of the body. Most cancers that start in lung, known as primary...

 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
Nurses' Health Study
The Nurses Health Study, established in 1976 by Dr. Frank Speizer, and the Nurses' Health Study II, established in 1989 by Dr. Walter Willett, are the most definitive long-term epidemiological studies conducted to date on older women's health. The study has followed 121,700 female registered...

, the risk of adenocarcinoma of the lung increases substantially after a long duration of previous tobacco smoking
Tobacco smoking
Tobacco smoking is the practice where tobacco is burned and the resulting smoke is inhaled. The practice may have begun as early as 5000–3000 BCE. Tobacco was introduced to Eurasia in the late 16th century where it followed common trade routes...

, with a previous smoking duration of 30 to 40 years giving a relative risk
Relative risk
In statistics and mathematical epidemiology, relative risk is the risk of an event relative to exposure. Relative risk is a ratio of the probability of the event occurring in the exposed group versus a non-exposed group....

 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. 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. 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. 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
Radiation therapy
Radiation therapy , radiation oncology, or radiotherapy , sometimes abbreviated to XRT or DXT, is the medical use of ionizing radiation, generally as part of cancer treatment to control malignant cells.Radiation therapy is commonly applied to the cancerous tumor because of its ability to control...

 as is small cell lung carcinoma, but is rather treated surgically, for example by pneumonectomy
Pneumonectomy
A pneumonectomy is a surgical procedure to remove a lung. Removal of just one lobe of the lung is specifically referred to as a lobectomy, and that of a segment of the lung as a wedge resection .-Indications:...

 or lobectomy
Lobectomy
Lobectomy means surgical excision of a lobe. This may refer to a lobe of the lung, a lobe of the thyroid , or a lobe of the brain ....

.

Histopathology

Adenocarcinomas are highly heterogeneous tumors, and several major histological subtypes are currently recognized:
  • Acinar adenocarcinoma
    Acinar adenocarcinoma
    Acinar adenocarcinoma is a histological subtype of gland-forming cancer that is diagnosed when cuboidal and/or columnar shaped malignant cells in the neoplastic tissue form acini and tubules...

  • Papillary adenocarcinoma
    Papillary adenocarcinoma
    Papillary adenocarcinoma is a histological form of lung cancer that is diagnosed when the malignant cells of the tumor form complex papillary structures and exhibit compressive, destructive growth that replaces the normal lung tissue.- External links :...

  • Bronchioloalveolar adenocarcinoma
  • Solid adenocarcinoma with mucin production


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".

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 pneumocyte
Type II pneumocyte
Type II pneumocytes also called great alveolar cells or septal cells are granular and roughly cuboidal in shape. Type II pneumocytes are typically found at the alveolar-septal junction...

s. These demonstrate various degrees of cytologic atypia, including hyperchromasia
Hyperchromasia
In pathology, hyperchromasia is a descriptive term referring to the hyperchromatic state of the nucleus , where there is an abundance of DNA that stains darkly when stained for histological viewing. The hyperchromatic state of the nucleus suggests malignancy....

, pleomorphism
Pleomorphism (cytology)
Pleomorphism is a term used in histology and cytopathology to describe variability in the size and shape of cells and/or their nuclei. It is a feature characteristic of malignant neoplasms....

, 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
KRAS
GTPase KRas also known as V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog and KRAS, is a protein that in humans is encoded by the KRAS gene. Like other members of the Ras family, the KRAS protein is a GTPase and is an early player in many signal transduction pathways...

mutations) that are associated with adenocarcinomas.
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