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Adenocarcinoma, NOS
Classification and external resources

Micrograph of an adenocarcinoma showing mucin containing vacuoles. Pap test.
ICD-9 151.0, 182.0
ICD-O: M8140/3
MeSH D000230

Adenocarcinoma is a cancer originating in glandular tissue. This tissue is also part of a larger tissue category known as epithelial. Epithelial tissue includes, but is not limited to, skin, glands and a variety of other tissue that lines the cavities and organs of the body. Epithelium is derived embryologically from ectoderm, endoderm and mesoderm. To be classified as adenocarcinoma, the cells do not necessarily need to be part of a gland, as long as they have secretory properties. This form of carcinoma can occur in some higher mammals, including humans.[1] Well differentiated adenocarcinomas tend to resemble the glandular tissue that they are derived from, while poorly differentiated may not. By staining the cells from a biopsy, a pathologist will determine whether the tumor is an adenocarcinoma or some other type of cancer. Adenocarcinomas can arise in many tissues of the body due to the ubiquitous nature of glands within the body. While each gland may not be secreting the same substance, as long as there is an exocrine function to the cell, it is considered glandular and its malignant form is therefore named adenocarcinoma. Endocrine gland tumors, such as a VIPoma, an insulinoma, a pheochromocytoma, etc, are typically not referred to as adenocarcinomas, but rather, are often called neuroendocrine tumors. If the glandular tissue is abnormal, but benign, it is said to be an adenoma. Benign adenomas typically do not invade other tissue and rarely metastasize. Malignant adenocarcinomas invade other tissues and often metastasize given enough time to do so.

Contents

Diagnostic significance

A diagnosis of adenocarcinoma which is not further described, known as adenocarcinoma not otherwise specified or adenocarcinoma NOS, is significant because it indicates a cancerous process is present. However, it is not very useful for treatment decisions and prognosis, as these are determined by the tissue from which the tumour cells arose, i.e. the tissue of origin; an adenocarcinoma of the colon has a different prognosis and treatment than an adenocarcinoma of the ovary.

Adenocarcinoma not otherwise specified is often a preliminary diagnosis and can frequently be clarified by a pathologist with the use of immunohistochemistry.[2]

Cancer for which a primary site cannot be found is called cancer of unknown primary.

Histopathology

Examples of tissues where adenocarcinomas may arise:

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Colon

Gross appearance of a colectomy specimen containing two adenomatous polyps (the brownish oval tumors above the labels, attached to the normal beige lining by a stalk) and one invasive colorectal carcinoma (the crater-like, reddish, irregularly-shaped tumor located above the label).
Histopathologic image of colonic carcinoid stained by hematoxylin and eosin.

The vast majority of colorectal cancer is an adenocarcinoma. This is because the colon has numerous glands within the tissue. Normal colonic glands tend to be simple and tubular in appearance with a mixture of mucus secreting goblet cells and water absorbing cells. These glands are called glands because they secrete a substance into the lumen of the colon, this substance being mucus. The purpose of these glands are twofold. The first is to absorb water from the feces back into the blood. The second purpose is to secrete mucus into the colon lumen to lubricate the now dehydrated feces. This is crucial as a failure to lubricate the feces can result in colonic damage by the feces as it passes towards the rectum.[3]

When these glands undergo a number of changes at the genetic level, they proceed in a predictable manner as they move from benign to an invasive, malignant colon cancer. In their research paper "Lessons from Hereditary Colorectal Cancer", Vogelstein, et al., suggested that colon cells lose the APC tumor suppressor gene and become a small polyp. Next, they suggested that k-Ras becomes activated and the polyp becomes a small, benign, adenoma. The adenoma, lacking the "carcinoma" attached to the end of it, suggests that it is a benign version of the malignant adenocarcinoma. The gastroenterologist uses a colonoscopy to find and remove these adenomas and polyps to prevent them from continuing to acquire genetic changes that will lead to an invasive adenocarcinoma. Volgelstein et al. went on to suggest that loss of the DCC gene and of p53 result in a malignant adenocarcinoma.[4]

Grossly, one will see a mass that looks of a different color than the surrounding tissue. Bleeding from the tumor is often apparent as the tumor tends to grow blood vessels into it in a haphazard manner via secretion of a number of angiogenesis promoting factors such as VEGF. Histologically, a glandular structure, similar to the healthy normal surrounding glands may be seen. If they look very similar, this is a low grade, well differentiated tumor. Often these glands will be disorganized and they will be seen growing back to back. However, if the tumor does not look like a gland anymore, it is a high grade tumor with poor differentiation. Regardless of the grade, malignant tumors tend to have a large nucleus with prominent nucleoli. There will also be a noticeable increase in the incidence of mitoses, or cell divisions.

Lung

Adenocarcinoma of the lung is currently the most common type of lung cancer in lifelong non-smokers.[5] Adenocarcinomas account for approximately 10% 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,[6][7] although it may also occur as central lesions.[6] 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.[6] The adenocarcinoma has an increased incidence in smokers, and is the most common type of lung cancer seen in non-smokers and women.[6] 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[8]. Generally, adenocarcinomas grow more slowly and form smaller masses than the other subtypes.[6] However, they tend to form metastases widely at an early stage.[6] 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 by surgically, for example by pneumonectomy or lobectomy.[6]

Histopathology

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).[9][10] They may appear in many forms, including acinar (gland forming), papillary, and solid types.[6] 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).[6] Microscopically, AAH is a well-demarcated focus of epithelial proliferation, containing cuboidal to low-columnar cells resembling Clara cells or type II pneumocytes.[6] These demonstrate various degrees of cytologic atypia, including hyperchromasia, pleomorphism, prominent nucleoli.[6] However, the atypia is not to the extent as seen in frank adenocarcinomas.[6] Lesions of AAH are monoclonal, and they share many of the molecular aberrations (like KRAS mutations) that are associated with adenocarcinomas.[6]

Urogenital

Other

Etymology

The term adenocarcinoma is derived from 'adeno' meaning 'pertaining to a gland' and 'carcinoma', which describes a cancer that has developed in the epithelial cells.

References

  1. ^ Fauquier D, Gulland F, Haulena M, Spraker T (Jul 2003). "Biliary adenocarcinoma in a stranded northern elephant seal (Mirounga angustirostris)". J Wildl Dis. 39 (3): 723–6. PMID 14567238. http://www.jwildlifedis.org/cgi/pmidlookup?view=long&pmid=14567238. 
  2. ^ Dabbs DJ, Silverman JF (Jul 2001). "Immunohistochemical Workup of Metastatic Carcinoma of Unknown Primary". Pathology Case Reviews 6 (4): 146–53. doi:10.1097/00132583-200107000-00003. http://www.pathologycasereviews.com/pt/re/pathcr/abstract.00132583-200107000-00003.htm. 
  3. ^ Heath JE, Young B, Wheater PR, Lowe JN, Stevens A (2006). Wheater's Functional histology: a text and colour atlas (5th ed.). Edinburgh: Churchill Livingstone Elsevier. pp. 283. ISBN 0-443-06850-X. 
  4. ^ Kinzler KW, Vogelstein B (October 1996). "Lessons from hereditary colorectal cancer". Cell 87 (2): 159–70. doi:10.1016/S0092-8674(00)81333-1. PMID 8861899. http://linkinghub.elsevier.com/retrieve/pii/S0092-8674(00)81333-1. 
  5. ^ Subramanian J, Govindan R (February 2007). "Lung cancer in never smokers: a review". Journal of Clinical Oncology 25 (5): 561–70. doi:10.1200/JCO.2006.06.8015. PMID 17290066. 
  6. ^ a b c d e f g h i j k l m Chapter 13, box on morphology of adenocarcinoma in: Mitchell, Richard Sheppard; Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson. Robbins Basic Pathology. Philadelphia: Saunders. ISBN 1-4160-2973-7.  8th edition.
  7. ^ Travis WD, Travis LB, Devesa SS (January 1995). "Lung cancer". Cancer 75 (1 Suppl): 191–202. doi:10.1002/1097-0142(19950101)75:1+<191::AID-CNCR2820751307>3.0.CO;2-Y. PMID 8000996. 
  8. ^ Goljan USMLE Audio Tapes, 2001
  9. ^ Diseases of Lung
  10. ^ Adenocarcinoma of Lung (Mucin Stain)
  11. ^ "Detailed Guide, Pancreatic Cancer, What is Cancer of the Pancreas?". http://www.cancer.org/docroot/CRI/content/CRI_2_4_1X_What_is_pancreatic_cancer_34.asp?sitearea=. Retrieved 2009-21-2. 

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