Metaplasia

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Metaplasia
Pancreatic acinar metaplasia - high mag.jpg
Micrograph of a gastro-esophageal junction with pancreatic acinar metaplasia. The esophageal mucosa (stratified squamous epithelium) is seen on the right. The gastric mucosa (simple columnar epithelium) is seen on the left. The metaplastic epithelium is at the junction (center of image) and has an intensely eosinophilic (bright pink) cytoplasm. H&E stain.

Metaplasia (Greek : "change in form") is the transformation of a cell type to another cell type. [1] The change from one type of cell to another may be part of a normal maturation process, or caused by some sort of abnormal stimulus. In simplistic terms, it is as if the original cells are not robust enough to withstand their environment, so they transform into another cell type better suited to their environment. If the stimulus causing metaplasia is removed or ceases, tissues return to their normal pattern of differentiation. Metaplasia is not synonymous with dysplasia, and is not considered to be an actual cancer. [2] It is also contrasted with heteroplasia, which is the spontaneous abnormal growth of cytologic and histologic elements. Today, metaplastic changes are usually considered to be an early phase of carcinogenesis, specifically for those with a history of cancers or who are known to be susceptible to carcinogenic changes. Metaplastic change is thus often viewed as a premalignant condition that requires immediate intervention, either surgical or medical, lest it lead to cancer via malignant transformation.

Contents

Causes

When cells are faced with physiological or pathological stresses, they respond by adapting in any of several ways, one of which is metaplasia. It is a benign (i.e. non-cancerous) change that occurs as a response to change of milieu (physiological metaplasia) or chronic physical or chemical irritation. One example of pathological irritation is cigarette smoke, which causes the mucus-secreting ciliated pseudostratified columnar respiratory epithelial cells that line the airways to be replaced by stratified squamous epithelium, or a stone in the bile duct that causes the replacement of the secretory columnar epithelium with stratified squamous epithelium (squamous metaplasia). Metaplasia is an adaptation that replaces one type of epithelium with another that is more likely to be able to withstand the stresses it is faced with. It is also accompanied by a loss of endothelial function, and in some instances considered undesirable; this undesirability is underscored by the propensity for metaplastic regions to eventually turn cancerous if the irritant is not eliminated.

The cell of origin for many types of metaplasias are controversial or unknown. For example, there is evidence supporting several different hypotheses of origin in Barrett's esophagus. They include direct transdifferentiation of squamous cells to columnar cells, the stem cell changing from esophageal type to intestinal type, migration of gastric cardiac cells, and a population of resident embryonic cells present through adulthood.

Significance in disease

Normal physiological metaplasia, such as that of the endocervix, is highly desirable.

The medical significance of metaplasia is that in some sites where pathological irritation is present, cells may progress from metaplasia, to develop dysplasia, and then malignant neoplasia (cancer). Thus, at sites where abnormal metaplasia is detected, efforts are made to remove the causative irritant, thereby decreasing the risk of progression to malignancy. The metaplastic area must be carefully monitored to ensure that dysplastic change does not begin to occur. A progression to significant dysplasia indicates that the area could need removal to prevent the development of cancer.

Examples

A micrograph of intestinalized epithelium in Barrett's esophagus. Histopathology of Barrett's esophagus, annotated.jpg
A micrograph of intestinalized epithelium in Barrett's esophagus.
Micrograph showing apocrine metaplasia of the breast with typical features H&E stain. Histopathology of apocrine metaplasia of breast, annotated.png
Micrograph showing apocrine metaplasia of the breast with typical features H&E stain.

Barrett's esophagus is an abnormal change in the cells of the lower esophagus, thought to be caused by damage from chronic stomach acid exposure.

The following table lists some common tissues susceptible to metaplasia, and the stimuli that can cause the change:

TissueNormalMetaplasiaStimulus
Airways Pseudostratified columnar epitheliumSquamous epitheliumCigarette smoke
Urinary bladder Transitional epithelium Squamous epitheliumBladder stone
Esophagus Squamous epitheliumColumnar epithelium (Barrett's Esophagus)Gastro-esophageal reflux
Cervix Glandular epitheliumSquamous epitheliumLow pH of vagina
Breast Acinar cells Apocrine cells Fibrocystic breast changes

Intestinal metaplasia

Intestinal metaplasia is a premalignant condition that increases the risk for subsequent gastric cancer. [4] Intestinal metaplasia lesions with an active DNA damage response will likely undergo extended latency in the premalignant state until further damaging hits override the DNA damage response leading to clonal expansion and progression. [4] The DNA damage response includes expression of proteins that detect DNA damages and activate downstream responses like DNA repair, cell cycle checkpoints or apoptosis. [4]

See also

Notes

Related Research Articles

<span class="mw-page-title-main">Cervix</span> Lower part of the uterus in the female reproductive system

The cervix or cervix uteri is the lower part of the uterus (womb) in the female reproductive system of most mammals, including humans. The cervix is usually 2 to 3 cm long and roughly cylindrical in shape, which changes during pregnancy. The narrow, central cervical canal runs along its entire length, connecting the uterine cavity and the lumen of the vagina. The opening into the uterus is called the internal os, and the opening into the vagina is called the external os. The lower part of the cervix, known as the vaginal portion of the cervix, bulges into the top of the vagina. The human cervix has been documented anatomically since at least the time of Hippocrates, over 2,000 years ago.

<span class="mw-page-title-main">Esophagus</span> Vertebrate organ through which food passes to the stomach

The esophagus or oesophagus, colloquially known also as the food pipe, food tube, or gullet, is an organ in vertebrates through which food passes, aided by peristaltic contractions, from the pharynx to the stomach. The esophagus is a fibromuscular tube, about 25 cm (10 in) long in adults, that travels behind the trachea and heart, passes through the diaphragm, and empties into the uppermost region of the stomach. During swallowing, the epiglottis tilts backwards to prevent food from going down the larynx and lungs. The word oesophagus is from Ancient Greek οἰσοφάγος (oisophágos), from οἴσω (oísō), future form of φέρω + ἔφαγον.

<span class="mw-page-title-main">Barrett's esophagus</span> Medical condition

Barrett's esophagus is a condition in which there is an abnormal (metaplastic) change in the mucosal cells lining the lower portion of the esophagus, from stratified squamous epithelium to simple columnar epithelium with interspersed goblet cells that are normally present only in the small intestine and large intestine. This change is considered to be a premalignant condition because of its potential to further transition to esophageal adenocarcinoma, an often-deadly cancer.

<span class="mw-page-title-main">Epithelium</span> Tissue lining the surfaces of organs in animals

Epithelium or epithelial tissue is a thin, continuous, protective layer of compactly packed cells with a little intercellular matrix. Epithelial tissues line the outer surfaces of organs and blood vessels throughout the body, as well as the inner surfaces of cavities in many internal organs. An example is the epidermis, the outermost layer of the skin. Epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. These tissues also lack blood or lymph supply. The tissue is supplied by nerves.

<span class="mw-page-title-main">Leukoplakia</span> Medical condition

Oral leukoplakia is a potentially malignant disorder affecting the oral mucosa. It is defined as "essentially an oral mucosal white lesion that cannot be considered as any other definable lesion." Oral leukoplakia is a white patch or plaque that develops in the oral cavity and is strongly associated with smoking. Leukoplakia is a firmly attached white patch on a mucous membrane which is associated with increased risk of cancer. The edges of the lesion are typically abrupt and the lesion changes with time. Advanced forms may develop red patches. There are generally no other symptoms. It usually occurs within the mouth, although sometimes mucosa in other parts of the gastrointestinal tract, urinary tract, or genitals may be affected.

<span class="mw-page-title-main">Neoplasm</span> Tumor or other abnormal growth of tissue

A neoplasm is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists in growing abnormally, even if the original trigger is removed. This abnormal growth usually forms a mass, which may be called a tumour or tumor.

<span class="mw-page-title-main">Squamous metaplasia</span>

Squamous metaplasia is a benign non-cancerous change (metaplasia) of surfacing lining cells (epithelium) to a squamous morphology.

<span class="mw-page-title-main">Atrophic gastritis</span> Medical condition

Atrophic gastritis is a process of chronic inflammation of the gastric mucosa of the stomach, leading to a loss of gastric glandular cells and their eventual replacement by intestinal and fibrous tissues. As a result, the stomach's secretion of essential substances such as hydrochloric acid, pepsin, and intrinsic factor is impaired, leading to digestive problems. The most common are vitamin B12 deficiency possibly leading to pernicious anemia; and malabsorption of iron, leading to iron deficiency anaemia. It can be caused by persistent infection with Helicobacter pylori, or can be autoimmune in origin. Those with autoimmune atrophic gastritis (Type A gastritis) are statistically more likely to develop gastric carcinoma, Hashimoto's thyroiditis, and achlorhydria.

<span class="mw-page-title-main">Precancerous condition</span> Medical condition

A precancerous condition is a condition, tumor or lesion involving abnormal cells which are associated with an increased risk of developing into cancer. Clinically, precancerous conditions encompass a variety of abnormal tissues with an increased risk of developing into cancer. Some of the most common precancerous conditions include certain colon polyps, which can progress into colon cancer, monoclonal gammopathy of undetermined significance, which can progress into multiple myeloma or myelodysplastic syndrome. and cervical dysplasia, which can progress into cervical cancer. Bronchial premalignant lesions can progress to squamous cell carcinoma of the lung.

Gastrointestinal cancer refers to malignant conditions of the gastrointestinal tract and accessory organs of digestion, including the esophagus, stomach, biliary system, pancreas, small intestine, large intestine, rectum and anus. The symptoms relate to the organ affected and can include obstruction, abnormal bleeding or other associated problems. The diagnosis often requires endoscopy, followed by biopsy of suspicious tissue. The treatment depends on the location of the tumor, as well as the type of cancer cell and whether it has invaded other tissues or spread elsewhere. These factors also determine the prognosis.

<span class="mw-page-title-main">Cervical intraepithelial neoplasia</span> Medical condition

Cervical intraepithelial neoplasia (CIN), also known as cervical dysplasia, is the abnormal growth of cells on the surface of the cervix that could potentially lead to cervical cancer. More specifically, CIN refers to the potentially precancerous transformation of cells of the cervix.

<span class="mw-page-title-main">Koilocyte</span>

A koilocyte is a squamous epithelial cell that has undergone a number of structural changes, which occur as a result of infection of the cell by human papillomavirus (HPV). Identification of these cells by pathologists can be useful in diagnosing various HPV-associated lesions.

<span class="mw-page-title-main">Keratin 8</span>

Keratin, type II cytoskeletal 8 also known as cytokeratin-8 (CK-8) or keratin-8 (K8) is a keratin protein that is encoded in humans by the KRT8 gene. It is often paired with keratin 18.

In cell biology and pathophysiology, cellular adaptation refers to changes made by a cell in response to adverse or varying environmental changes. The adaptation may be physiologic (normal) or pathologic (abnormal).

<span class="mw-page-title-main">Intestinal metaplasia</span> Medical condition

Intestinal metaplasia is the transformation (metaplasia) of epithelium into a type of epithelium resembling that found in the intestine. In the esophagus, this is called Barrett's esophagus. Chronic inflammation caused by H. pylori infection in the stomach and GERD in the esophagus are seen as the primary instigators of metaplasia and subsequent adenocarcinoma formation. Initially, the transformed epithelium resembles the small intestine lining; in the later stages it resembles the lining of the colon. It is characterized by the appearance of goblet cells and expression of intestinal cell markers such as the transcription factor, CDX2.

Epithelial dysplasia, a term becoming increasingly referred to as intraepithelial neoplasia, is the sum of various disturbances of epithelial proliferation and differentiation as seen microscopically. Individual cellular features of dysplasia are called epithelial atypia.

<span class="mw-page-title-main">Cystitis glandularis</span>

Cystitis glandularis is the transformation of mucosal cells lining the urinary bladder. They undergo glandular metaplasia, a process in which irritated tissues take on a different form, in this case that of a gland. The main importance is in the findings of test results, in this case histopathology. They must distinguish a benign metaplastic change from the cancerous condition urothelial cell carcinoma. It is a very common finding in bladder biopsies and cystectomies, and most often found in the trigone area. Cystitis glandularis lesions are usually present as small microscopic foci; however, occasionally it can form raised intramucosal or polypoid lesions. The cystitis glandularis lesions are within the submucosa.

<span class="mw-page-title-main">Chromoendoscopy</span>

Chromoendoscopy is a medical procedure wherein dyes are instilled into the gastrointestinal tract at the time of visualization with fibre-optic endoscopy. The purposes of chromoendoscopy is chiefly enhance the characterization of tissues, although dyes may be used for other functional purposes. The detail achieved with chromoendoscopy can often allow for identification of the tissue type or pathology based upon the pattern uncovered.

<span class="mw-page-title-main">Field cancerization</span> Biological process

Field cancerization or field effect is a biological process in which large areas of cells at a tissue surface or within an organ are affected by carcinogenic alterations. The process arises from exposure to an injurious environment, often over a lengthy period.

Gastrointestinal intraepithelial neoplasia is also known as gastrointestinal dysplasia. Gastrointestinal dysplasia refers to abnormal growth of the epithelial tissue lining the gastrointestinal tract including the esophagus, stomach, and colon. Pancreatic, biliary, and rectal Intraepithelial Neoplasia are discussed separately. The regions of abnormal growth are confined by the basement membrane adjacent to the epithelial tissue and are thought to represent pre-cancerous lesions. 

References

  1. Slack, Jonathan M. W. (2007-03-21). "Metaplasia and transdifferentiation: from pure biology to the clinic". Nature Reviews Molecular Cell Biology. 8 (5): 369–378. doi:10.1038/nrm2146. ISSN   1471-0072.
  2. Abrams, Gerald. "Neoplasia I" . Retrieved 23 January 2012.
  3. Image by Mikael Häggström, MD. Reference for findings: Carlos C. Diez Freire, M.D., Shahla Masood, M.D. "Apocrine metaplasia". Pathology Outlines.{{cite web}}: CS1 maint: multiple names: authors list (link) Last author update: 28 May 2020.
  4. 1 2 3 Krishnan, V; Lim, DXE; Hoang, PM; et al. (October 2020). "DNA damage signalling as an anti-cancer barrier in gastric intestinal metaplasia". Gut. 69 (10): 1738–1749. doi:10.1136/gutjnl-2019-319002. PMC   7497583 . PMID   31937549.