Histology, Epithelial Cell

Issues of Concern

Epithelial cells are among the most abundant cells covering the skin, body cavities, and blood vessels. They contribute significantly to several aspects of the human life cycle from embryogenesis to adulthood. Their highly specialized histologic feature is critical for their physiological functions in different organs. Disorders of epithelial cells morphology and function have been confirmed in multiple clinical conditions, including cancer, organ fibrosis, celiac disease, and bullous pemphigoid.[4][5] 

Structure

Epithelial cells have a structural polarity that causes three distinct regions or domains (apical, basal, and lateral). The apical domain faces the lumen of an organ or the external environment. This region often contains a structure that affects the cells' function, like microvilli, cilia, and stereocilia. Microvilli are finger-like projections with a core of cross-linked actin filaments attached to the terminal web parallel to the apical surface. Cilia are motile projections of the cell surface comprised of two central microtubules encompassed by nine microtubule doublets. Lastly, stereocilia are finger-like projections supported by actin filaments.[6][7] 

The basal domain is connected to the basal lamina by hemidesmosomes, which combine with intermediate filaments. The basal lamina separates connective tissue from the epithelium. The lateral domain connects neighboring cells and allows for communication between cells. There are a variety of junctional complexes that connect adjacent cells. Desmosomes anchor/adhere junctions that tightly join cells by integrating with the cytoskeletal structures. Tight junctions are occluding junctions that regulate the movement of fluid and solutes. Gap junctions are communicating junctions found throughout the lateral domain, creating channels that allow small molecules and ions to pass between adjacent cells.[8]

Epithelial cells are organized according to their shape and number of layers. Simple epithelial cells contain one layer, whereas stratified cells contain two or more layers. Pseudostratified epithelial cells contain only one layer of cells, but the cells are of different sizes, so cells appear to be stratified or layered. Regarding the shape of epithelial cells, there are three main shapes, squamous, cuboidal, and columnar. Squamous cells are flat sheet-like cells, cuboidal cells are cube-like with an equal width, height, and depth, and columnar cells are taller than they are wide, making them rectangular.[9][10]

Function

Epithelial cells are located throughout the body and have many functions based on morphology and location. Structures of the apical domain significantly affect function. Microvilli are involved in fluid transport and absorption. The number of microvilli correlates to the absorptive properties of the cells. Also, cilia transport substances across the surface of epithelial cells. Stereocilia are essential in hearing and balance.[7]

Simple squamous epithelium lines blood vessels (endothelium) or body cavities (mesothelium) and allows for diffusion of molecules like in gas exchange. Simple cuboidal cells have a secretory function and tend to form the lining of ducts. Simple columnar cells are found throughout the intestines and can have either an absorptive or secretory function.[11][3]

Some stratified forms of these cells have similar functions. For example, stratified cuboidal cells are found in exocrine ducts and still have a secretory function. Stratified columnar cells are present in large exocrine glands. Stratified squamous epithelium does not allow for as much diffusion of nutrients as simple squamous because the nutrients would have to traverse through many layers, but the layers provide protection. There are also two other categories of the epithelium, pseudostratified columnar and transitional (uroepithelium) epithelial cells. The pseudostratified epithelium is often ciliated to aid in transporting luminal contents. Transitional epithelial cells are present within distensible organs.[12][13] 

Tissue Preparation

Epithelial cell examination is possible via biopsy. Generally, after a sample is collected, it is fixed in formalin, embedded in an embedding medium such as paraffin, sectioned, and stained.[14]

Histochemistry and Cytochemistry

Epithelial cells have specialized cytoskeletons comprised of microtubules, actin filaments, and intermediate filaments. Intermediate filaments provide structural resilience to the cytoskeleton and show tissue-specific expression, unlike microtubules and actin filaments. These intermediate filaments are a valuable target for histochemical staining techniques. There are five main groups of intermediate filaments. Glial filaments are in astrocytes, neurofilaments are found in nerves, desmin filaments are found in muscles, vimentin filaments are seen in the mesenchyme, and keratin, which occur in epithelial cells. Keratin can not only define the tissue as epithelial cells but also differentiate between the types of epithelial cells. For example, keratin three is found in the corneal epithelium, whereas keratin 20 is present in Merkle cells and umbrella cells of the urothelium. These keratins are crucial to epithelial cells, and mutations in keratin or loss of keratin can cause or predispose a person to many diseases.[15][16]

Microscopy, Light

Understanding the appearance of normal, healthy epithelial cells is essential to identify when there is pathology present in a tissue specimen. Light microscopy (LM) is typically used to visualize stained epithelial cells. LM can be used to determine the morphology of the epithelium present in the tissue specimen. Columnar epithelial cells tend to be rectangular, cuboidal cells appear square, and squamous cells are long and flat.[17][18]

Microscopy, Electron

Electron microscopy (EM) is a form of microscopy that allows a higher magnification than light microscopy (LM). EM allows visualization of many ultrastructural features, such as tight junctions, adherens junctions, desmosomes, hemidesmosomes, gap junctions, and the basal lamina, which separates the epithelial cells from connective tissue.[19][20]

Clinical Significance

One of the biggest concerns with epithelial cells is the potential for malignancy development as adenocarcinoma or papillary carcinoma. Some of the common adenocarcinomas that have high morbidity and mortality rates are lung, prostate, colon, and breast cancer.[21]

Another clinical concern that relates to epithelial cells is metaplasia. Metaplasia is when one type of cell converts to another due to environmental stressors or changes. This process can occur in physiological or pathological conditions. For instance, a study on the cervical epithelium from postpartum women has shown the replacement of columnar epithelial tissue with squamous epithelial cells in the physiologic healing process of the postpartum period. [22] Pathologic metaplasia is more likely to be dysplastic, which can become malignant. One relatively common example of pathologic metaplasia is Barrett's esophagus. The esophagus is typically lined by squamous epithelium. When patients have uncontrolled gastroesophageal reflux disease (GERD), the constant stress induced by acid from the stomach causes the squamous cells of the esophagus to become mucin-producing columnar cells. The mucin-producing columnar cells are better equipped to handle the stress of the stomach acid, preventing erosion of the esophagus. If the GERD receives proper treatment, the columnar cells may revert to squamous cells; however, if the stressor goes untreated, metaplasia may progress to dysplasia, which can become malignant. Several studies have demonstrated that Barrett's esophagus increases predisposition to esophageal adenocarcinoma.[23][24]

In addition to cancer and metaplasia, another important aspect of epithelial cell biology is the epithelial-mesenchymal transition (EMT), a functional transition of fully differentiated polarized epithelial cells to mobile mesenchymal cells. Like metaplasia, EMT occurs in physiological and pathological circumstances, including embryonic gastrulation, tissue regeneration, inflammation, fibrosis, and cancer metastasis.[5][25]

Furthermore, other forms of epithelial cell disorder apply to various human diseases, particularly immune-related conditions. Celiac disease and certain bacterial infections in the intestines can damage the microvilli of epithelial cells lining the intestines. In the lungs of premature infants, the cuboidal cells in the alveoli (type II pneumocytes) have not fully developed, and the surfactant production is impaired, causing respiratory distress syndrome in premature babies. In the skin, bullous pemphigoid, an autoimmune subepidermal skin blistering disease, essentially renders hemidesmosomes ineffective. Human papillomavirus strains 1-4 can cause warts on the squamous cells of the epidermis. This virus causes an overgrowth of epithelial tissue on a connective tissue papilla. This vast array of diseases makes understanding epithelial cells clinically significant.[4]