What Is Squamous Metaplasia?

Overview

Human cells are specifically designed to perform certain functions: as highly specialised units, these cells have characteristics that differentiate them from others. Epithelial cells are different from cartilage cells and from muscle cells, for example. But what happens when cells of a tissue or organ start mutating and looking less like themselves?

This process is known as metaplasia. It’s the transformation of a certain somatic cell type into another cell type within the same tissue.¹ When it comes to squamous metaplasia, it means that other types of epithelial cells (cells that line our organs and make up our skin, for example) like cuboidal or columnar cells are changing into squamous cells.¹ And as the identity of the cells starts to change, so do their functions.¹ But what causes squamous metaplasia? And what consequences can this change mean? 

Types of epithelial cells

Epithelial cells cover the skin, body cavities and blood vessels.² They are named and organised according to their shape and number of layers:

• Simple epithelium contains one layer of cells, while stratified epithelium contains multiple layers. Pseudostratified epithelium might look like multiple layers, as the nuclei (where the DNA is located) of the cells are at different heights, but it is in fact a single layer.²
• As for the shape, there are cuboidal, columnar, and squamous shapes: cuboidal cells are square, having equal width, height, and depth, while columnar cells are taller and rectangular, and squamous cells are flat and sheet-like.²
• Some cells have special apparatus like microvilli, cilia, and stereocilia.²
  • Microvilli are finger-like projections commonly found in the intestines.²
  • Cilia are motile projections that can aid in transportation, commonly found in the airways.²
  • Stereocilia are a combination of finger-like projections supported by actin filaments that aid in hearing and balance.²
• Transitional epithelium is a separate category of epithelial cells that are irregular in shape and can be found in areas that need to stretch. They can look like cuboidal cells when the tissue is relaxed and change into squamous cells as the tissue distends.²

Combining these two characteristics (number of layers and shape) results in a combination which represents the epithelial tissue of a certain organ:

• Simple squamous epithelium lines blood vessels (endothelium) and body cavities (mesothelium)².
• Simple cuboidal cells make up ducts of glands.²
• Simple columnar cells can be found in the intestines.²
• Stratified cuboidal and columnar epithelium make up exocrine gland ducts.²
• Stratified squamous epithelium is often a protective lining present in the oral mucosa and skin.²
• Transitional epithelium can be found in the urogenital tract, and sometimes, it is called urothelium because of it.²

Causes of metaplasia

Metaplasia occurs in tissue that is constantly exposed to injury or damaging environmental agents¹. When the normal cells that should compose a tissue are not strong enough to withstand the constant aggression, these cells mutate into a tougher, more resilient type. In the case of squamous metaplasia, they mutate into squamous cells¹.

Common stimuli agents that can induce metaplasia are:

• Cigarette smoke
• Low vaginal pH
• Infection by virus like the human papillomavirus (HPV) or by bacteria like Helicobacter pylori
• Inflammation
• Acid or bile¹

Although metaplasia in itself is not a disease nor a malignant condition, it is known that metaplasia can progress to dysplasia and to cancer.¹ Intestinal metaplasia can lead to adenocarcinoma, while squamous metaplasia can lead to squamous cell carcinoma.¹

There is a clear difference between metaplasia, dysplasia and cancer: Metaplasia is the mutation of cells into another cell type; dysplasia is the growth of abnormal cells and altered tissue architecture (organisation); and cancer is the proliferation of abnormal, malignant cells that can overtake the tissue and the body through metastasis.³ Metaplastic cells are normal cells found somewhere where they weren’t supposed to exist. Even though dysplastic cells can also be found where they are supposed to be (like finding stratified squamous cells in the oral mucosa, something this tissue is normally made out of), they are abnormal cells in form and function.³ Dysplastic cells can have atypical shapes and sizes, enlarged nuclei and nucleoli, and an unusual number of cells undergoing division.³ Both metaplasia and dysplasia are localised and restricted changes to tissue, and neither is malignant.³ Cancerous cells, as well as dysplastic alterations, can completely lose the defining characteristics of normal tissue and infiltrate surrounding tissues and even distant organs through metastasis.³

Common sites of squamous metaplasia

Sites of squamous metaplasia often include:

• Bladder, urethra and pelvis: transformation of the transitional urothelium into squamous epithelium⁴.
  • This type is associated with chronic inflammation, catheters, kidney stones and urinary tract infections by Escherichia coli, Proteus and Streptococcus faecalis⁴. Other risk factors include schistosomiasis, tumours, neurogenic bladder, previous bladder surgery, and vitamin A deficiency.⁴
  • The non-keratinizing type of metaplasia found in the bladder in assigned female at birth (AFAB) patients is considered a normal variation in anatomy, while the keratinizing type is more common in assigned male at birth (AMAB) patients and presents a risk of squamous cell carcinoma.⁴

• Uterine cervix: the transformation of the simple columnar epithelium into stratified squamous epithelium.⁵
  • Commonly found in the external cervix canal, this type of metaplasia is associated with excess oestrogen and an acidic vaginal environment⁵.
  • This metaplasia makes patients vulnerable to HPV infection, which further increases the risk of developing dysplasia and cancer.⁵

• Mammary glands: keratinizing squamous metaplasia of lactiferous ducts (SMOLD) is a form of metaplasia affecting the lactiferous ducts of the breasts.⁶
  • It is associated with chronic inflammation, smoking and vitamin A deficiency.⁶
  • It can be found in older patients of both sexes, and common signs and symptoms include swelling, redness, pain and purulent discharge of the affected nipple; inverted nipple, and abscess or fistula formation can also happen.⁶

• Lung airways: transformation of the bronchial cells into squamous cells⁷.
  • This type of metaplasia is strongly associated with smoking, and those AMAB are more affected.⁷
  • Although asymptomatic, these lesions can precede cancerous tumours by many years.⁷

• Sebaceous glands and skin: lesions of these tissues can arise from chronic inflammation¹. Skin metaplasia can often lead to dysplasia (such as angular cheilitis of the lips and oral leukoplakia) and consequently to squamous cell carcinoma. 

Diagnosis

The method of diagnosing metaplasia can vary, depending on the affected site. Clinical evaluation and a thorough medical history are essential to help your doctor in diagnosing, and, assessing your risk of developing metaplasia, as well as other alterations like dysplasia. Risk factors should also be discussed when consulting a healthcare professional.¹

Skin lesions may undergo a biopsy and subsequent examination under a microscope (histopathology) to test for metaplasia². Likewise, a pap smear is recommended to test for metaplasia, as well as uterine cancer, and all AFAB people between the ages of 25 to 64 are recommended by the NHS to do a cervical screening for an evaluation of their cells and screening for HPV (which is a cancer risk factor).

A cystoscopy can be performed when there is suspicion of metaplasia of the bladder.⁴ Airway lesions in the lungs and trachea can undergo an endoscopy, ultrasound or CT scan in order to locate a lesion before biopsy.⁷

Management and treatment

Management and treatment depends on the site and extension of the metaplastic lesions. Generally, prognosis is good and continuous follow-up throughout months and years is necessary to detect any dysplasia and/or malignant transformation.⁴ Prophylactic removal of the affected organ or tissue to prevent complications isn’t a common procedure, and only reserved for extensive cases of metaplasia.⁴

In some cases, there might be a spontaneous resolution (especially when any risk factors have been removed).⁴

Prevention

Removing risk factors is a first-order priority in preventing metaplasia.

• Reducing or completely stopping smoking⁶
• Vitamin A supplementation (especially if there is a previous history of tobacco use, as smoking depletes vitamin A levels)⁶
• Prevention of urinary tract infections and kidney stones through adequate hydration⁴
• Prevention of HPV infection: practising safe sex is essential not only to avoid HPV infection and metaplasia but also to prevent cervical cancer and many other sexually transmitted infections (STIs)⁵ Being vaccinated against HPV is also important.

Summary

Squamous metaplasia is a type of transformation of tissue in which other types of epithelial cells transform into squamous cells (a type of flat, sheet-like epithelium). This mutation is caused by continuous injury to the tissue, caused by inflammation or external environmental agents that constantly damage the cells. This forces cells to mutate to a more resilient type of epithelial cell to withstand damage. Common sites for squamous metaplasia include the skin, sebaceous glands, bladder and urinary tract, uterine cervix, lungs and mammary glands. Diagnosis is made through a combination of clinical evaluation of the lesion, medical history, complementary exams like ultrasound and CT scans, and a biopsy. Management and treatment includes medical follow-up, elimination of risk factors, and in extreme cases, surgical removal of the affected tissue or organ. Elimination of risk factors like smoking, infection, inflammation and vitamin A deficiency are important in preventing and treating metaplasia.