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Metaplasia

What Is It, Types, Causes, and More

Author:Lily Guo

Editors:Alyssa Haag,Józia McGowan, DO,Kelsey LaFayette, DNP, RN

Illustrator:Jessica Reynolds, MS

Copyeditor:David G. Walker


What is metaplasia?

Metaplasia refers to the replacement of a mature, differentiated cell type by another mature, differentiated cell type that does not typically occur in the tissue in which it is found. Metaplasia typically occurs as a response to chronic irritation of cells, which can be environmental (e.g., smoking and alcohol) or pathological (e.g., acid reflux). Metaplasia itself is a benign, non-cancerous condition; however, if left untreated, the cells undergoing metaplasia can become dysplastic (i.e., atypical in shape and size), which can eventually lead to cancer. 

Two different cell types battling to occupy one outlined space.

What is intestinal metaplasia?

Intestinal metaplasia refers to a transformation in cell type typically of the upper digestive tract, which includes the stomach and esophagus. The nonkeratinized squamous epithelium that typically covers the esophagus transforms into nonciliated columnar epithelial cells. This condition is also known as Barrett esophagus and is a consequence of gastroesophageal reflux disease (GERD), which occurs as a result of stomach acid flowing backwards into the esophagus. Barrett esophagus can be reversed by treating the underlying GERD; however, if the condition persists, esophageal cells can become dysplastic. On the other hand, intestinal metaplasia that occurs in the stomach is typically associated with a bacterial infection known as Helicobacter pylori (H. pylori). H. pylori can affect the protective mucus lining of the stomach, allowing the acidic contents to irritate the underlying stomach epithelial cells, ultimately leading to metaplasia

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What is squamous metaplasia?

Squamous metaplasia refers to the transformation of mature, non-squamous epithelium into stratified squamous epithelium (i.e., epithelium defined by large flattened cells with a small round central nucleus). This can be seen in various pathological processes, including in the respiratory tract. The bronchial airway is typically lined by pseudostratified columnar epithelium and can be replaced by squamous epithelial cells as a result of chronic tobacco smoke inhalation and inflammation. Additionally, squamous metaplasia can occur in the endometrium, which lines the uterus. The endometrium is typically composed of glandular cells lined by ciliated columnar epithelium and the supporting mesenchymal cells (i.e., stromal cells). The glandular cells supply the nutrients for fetal implantation and conception, while the columnar epithelium provides the attachment site for potential embryos. Chronic endometritis (i.e., inflammation of the endometrium), intrauterine devices, and trauma can result in transformation of the endometrial ciliated columnar epithelial cells into squamous cells. Adenocarcinoma, a form of uterine cancer, may also lead to squamous metaplasia. Lastly, the cervix, which is typically lined with columnar epithelial, can undergo squamous metaplasia. A common cause of cervical metaplasia includes long standing human papillomavirus (HPV) infection. 

What causes metaplasia?

Oftentimes, metaplasia is caused by stressors (e.g., cigarette smoke, stomach acid, excessive hormones) that initiate the transformation into a new type of cell that is better adapted to handle the increased stress. More specifically, intestinal metaplasia can be caused by H. pylori infection, high salt intake, alcohol consumption, and chronic acid reflux. Squamous cell metaplasia of the respiratory tract is typically induced by toxins from cigarette smoke. Risk factors for endometrial metaplasia include obesity; greater estrogen exposure (e.g., early menarche, late menopause); diet high in animal fat; and a family history of endometrial, ovarian, and/or colon cancers. Lastly, human papillomavirus is the leading cause of cervical metaplasia and is mainly transmitted through sexual contact. 

Is metaplasia reversible?

Metaplasia is reversible. The key factor for reversing metaplasia is removing the offending stimulus, such as smoking cessation in the case of respiratory squamous metaplasia or administering antibiotics (e.g., amoxicillin, clarithromycin) and acid-reducing proton pump inhibitors (e.g., omeprazole, esomeprazole) in the case of intestinal metaplasia due to H.pylori infection. Prevention of cervical metaplasia is highly recommended via the HPV vaccine and routine screening via pap smears. Lastly, endometrial metaplasia can be asymptomatic and may not need to be treated. In symptomatic cases where the individual is experiencing infertility or dysmenorrhea (i.e., painful menstruation), hormonal treatment including gonadotropin-releasing hormone agonists (GnRHa), such as leuprolide acetate, may be administered. While metaplasia is a risk factor for cancer, it is not cancer. If metaplasia undergoes another stage of transformation, the cells will become dysplastic. Dysplastic cells are considered a precancerous cell type and, if left untreated, will typically become cancerous.

What are the most important facts to know about metaplasia?

Metaplasia refers to the replacement of a mature cell type by another mature cell type. Types of metaplasia include intestinal metaplasia and squamous metaplasia. Intestinal metaplasia can occur in the esophagus and results in the transformation of non-keratinized squamous epithelium into nonciliated columnar epithelial cells. This is typically a consequence of longstanding GERD, characterized by the reflux of stomach acid into the esophagus. Intestinal metaplasia may also occur in the stomach as a result of H. pylori infection. Squamous metaplasia may occur in the bronchial airways, endometrium of the uterus, and the cervix. Various factors, including smoking, trauma, and viral infection, can result in squamous metaplasia. Metaplasia is reversible and can be treated. Treatment depends on the cause and can include removing the offending stimulus, administering medication, and focusing on prevention. 

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Related links

Metaplasia and dysplasia
Cervical cancer: Pathology review

Resources for research and reference

Amico, P., Caltabiano, R., Zizza, G., & Lanzafame, S. (2010). About a case of diffuse endometrial squamous metaplasia after resectoscopic myomectomy: a potential diagnostic pitfall for gynecologists and pathologists. Applied Immunohistochemistry & Molecular Morphology, 18(4): 392-395. DOI: 10.1097/PAI.0b013e3181d6bd31

Cervical Cancer. (2022, February 22). In World Health Organization. Retrieved from https://www.who.int/news-room/fact-sheets/detail/cervical-cancer 

Figueira, P. G. M., Abrão, M. S., Krikun, G., & Taylor, H. S. (2011). Stem cells in endometrium and their role in the pathogenesis of endometriosis. Annals of the New York Academy of Sciences, 1221(1): 10-17. DOI: 10.1111/j.1749-6632.2011.05969.x

Giroux, V., & Rustgi, A.K. (2017). Metaplasia: tissue injury adaptation and a precursor to the dysplasia-cancer sequence. Nature Reviews Cancer, 17: 594-604. DOI: 10.1038/nrc.2017.68

Intestinal metaplasia. In My Pathology Report. Retrieved March 21, 2022, from https://www.mypathologyreport.ca/intestinal-metaplasia/ 

Metaplasia. In National Cancer Institute. Retrieved March 21, 2022, from https://www.cancer.gov/publications/dictionaries/cancer-terms/def/metaplasia 

Squamous Cell Metaplasia. In ScienceDirect. Retrieved February 15, 2022, from https://www.sciencedirect.com/topics/nursing-and-health-professions/squamous-cell-metaplasia 

Squamous Metaplasia. In ScienceDirect Topics. Retrieved February 15, 2022, from https://www.sciencedirect.com/topics/medicine-and-dentistry/squamous-metaplasia 

Sun, Q., Tsutsumi, K., Kelleher, M. B., Pater, A., & Pater, M.M. (1992). Squamous metaplasia of normal and carcinoma in situ of HPV 16-immortalized human endocervical cells. Cancer Research, 52(15): 4254-4260. Retrieved from https://pubmed.ncbi.nlm.nih.gov/1379123/