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Skin (histology)


Our instructor share this image with us. She didn't specify much. She only said it was a skin sample. Could you tell me what is the thing that was pointed at with the blue arrow?

I believe that I found a similar image in Ross' Histology (e6) Plate 44.

Thank you


It is difficult to say based on the limited informations about the sample, but I could assume that this is a Masson's Trichrome staining. Briefly: blue/green - collagen, red/pink - cytoplasm, dark pink/brown - nucleus.

Presence of the adipose tissue (white area on the right) and a lot of collagen (green) suggest that the sample highly likely comes from dermis. The large structure pointed by the arrow looks like an eccrine sweat gland. Here, you can see it in classical haematoxylin and eosin staining:

Alternatively, see: http://medcell.med.yale.edu/histology/skin_lab/eccrine_sweat_glands.php


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  • Introduction -- Orientation to histology.
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            Skin (histology) - Biology

            This is a picture of an H&E stained section of the epidermis of thick skin.

            Can you identify the five major layers of the epidermis?

            Dermis: Thick skin has a thinner dermis than thin skin, and does not contain hairs, sebaceous glands, or apocrine sweat glands.

            Thick skin is only found in areas where there is a lot of abrasion - fingertips, palms and the soles of your feet.

            This is a picture of an H&E stained section of the epidermis of thin skin.

            There are only four layers in the epidermis of thin skin. The stratum lucidum layer is absent. What do you notice about thicknesses of the different layers?

            How pronounced are the dermal papillae compared to thick skin?

            Dermis: Thin skin actually has a thicker dermis than thick skin, which makes thin skin easier to suture, if it gets damaged. Thin skin also has fewer eccrine/merocrine sweat glands.

            This is a picture of a diseased skin - a very common condition - can you tell what it is?

            (Hint, witches or wizards will charm them away for you!)

            Histology Guide © Faculty of Biological Sciences, University of Leeds | Credits


            Skin Histology

            Now in order to make optimal dermatopathology slides, we must understand skin histology. On this slide here we have a schematic representation of the three layers of skin that we talked about, and as we spoke about the dermal-epidermal junction is of the utmost importance in making an accurate diagnosis by the pathologist. This is schematically the epidermis so the outer layer, is hair coming out, is the epidermis sitting on a basement membrane. And then below the epidermis is the dermis. And then below still is the adipose layer.

            If we look at a schematic of a higher power, we can see that basal cells which are indicated here by the red circular cells, sitting on the basement membrane, those will grow and divide and differentiate and push up toward the surface of the skin. And they'll differentiate firstly into squamous cells, which will flatten out to form granular cells which make protein that is on the surface of the skin and helps to seal the skin, protect it against moisture loss, protect it against bacteria and viruses.

            Now the basal layers grow and differentiate so that if a basal cell grows and differentiate or grows out of control, does not differentiate, stays as a basal cell, it results in a basal cell carcinoma. Similarly, these blue cells which depict squamous cells, if those grow and divide out of control, it will be a squamous cell carcinoma. Now both squamous cell and basal cell generally speaking will stay in the location that they arise in. Very rarely do they metastasize in the patient and continue to grow and cause troubles. However, this cell depicted right here, the brown melanocyte right in the middle, the melanocytes are a wandering cell, their job is to move through the epidermis between epidermal cells and infuse them with melanin to protect against UV light, so by their nature they're a wandering cell. So if they begin to grow and divide out of control, they may first stay localize within the epidermis but if they're not removed, and they continue to grow, they can grow down into the dermis and then eventually into the adipose layer. And at each one of these junctions, if they encounter blood vessels or lymphatic vessels, they may penetrate the vessels, get into the bloodstream of a lymphatic stream and be transported to other parts of the body where they metastasize in other organ systems such as the brain, the lung, liver, and that's ultimately deadly for the patient. So one of our major jobs as histologists is to help not only diagnose if there's a melanoma, but to ensure that it's completely and properly removed.

            Continuing with the schematics, if we look at a hair follicle, each hair follicle has structures associated with it. Here is the hair shaft itself, accompanied by an arrector pili muscle which will pull that hair erect when necessary. We have a nerve associated with the hair follicle, sebaceous glands, eccrine glands, and then you can see that at the bulb of the hair follicle, there may be melanin containing cells in the base of that as well and that can also be a source for a melanoma.


            Histology Laboratory Drawings

            The Histology Laboratory Drawings resource contains 104 hand drawn sketches by Dr. Christensen for the laboratory sessions he conducted in the Medical Histology Course for first year medical students. The drawings were done with felt markers on a white board in the lab during the morning of the day a particular topic was being studied in the course. When the laboratory session began, the drawings were briefly discussed, and they could be seen by the students throughout the laboratory period.

            You can view the drawings individually on flickr, or you can download the full collection of drawings by navigating to the materials tab.

            About the Creators

            A. Kent Christensen, Ph.D. (Emeritus)

            Dr. A. Kent Christensen is a Professor Emeritus, for the Department of Cell and Developmental Biology, University of Michigan Medical School. Dr. Christensen teaches histology to first-year medical students at the University of Michigan Medical School. He also teaches dental histology lectures for the U-M Dental School, and a graduate histology course for biomedical graduate students. His current research interests include the cell biology of the testis and the shape of bound polysomes. more.


            Masticatory mucosa

            Figure 3.16: Attached gingiva. Image credit: "Gingiva of the human mouth ” by John Crawford is licensed CC BY 3.0 / arrows added

            Attached gingiva

            Attached gingiva is a type of masticatory mucosa, lined with a para-keratinized stratified squamous epithelium ← . The increased amount of keratin, compared to alveolar mucosa , obscures the underlying blood supply, creating a lighter appearance (which can be described as whitish in the absence of melanin). The attached gingiva is named for its firm attachment to the tooth or to alveolar bone by groups of gingival fibers .

            Figure 3.17: Illustration of a partially keratinized epithelium of the attached gingiva.

            Large dermal papillae and rete pegs create the stippled (rough surface) appearance of the attached gingiva. The rough surface may also be described as orange-peel, which indicates the relative health of the attached gingiva due to sizeable rete pegs and dermal papillae between the oral epithelium and lamina propria .

            Figure 3.18: Interdental gingiva. Image credit: "Gingiva of the human mouth ” by John Crawford is licensed CC BY 3.0 / cropped and brackets added

            Interdental gingiva

            Interdental gingiva (or the interdental papilla) is similar to the attached gingiva .

            Figure 3.19: Marginal gingiva. Image credit: Figure 3.19: Marginal gingiva. Image credit: “Gingiva of the human mouth” by John Crawford is licensed CC BY 3.0 / cropped and brackets added by John Crawford is licensed CC BY 3.0 / cropped and brackets added

            Marginal gingiva

            Marginal gingiva epithelium is histologically similar to the attached gingiva — it has pronounced rete pegs and is partially keratinized. The gingival margin may be grouped together with junctional epithelium and sulcular epithelium (described below) and referred to as free gingiva. Unlike the attached gingiva, the sub-mucosa of free gingiva is not connected to bone tissue.

            Figure 3.20: The hard palate. Image credit: “ Pleomorphic adenoma of the left palate ” by the NIH is in the Public Domain CC0

            Hard palate

            The hard palate is lined by an ortho-keratinized stratified squamous epithelium ← and mostly lacks a sub-mucosa , making for a rigid connection to underlying bone tissue ← .


            Introduction to Skin Histology

            Epidermis, the epithelial layer of skin, is primarily protective. This layer, consisting of keratinized stratified squamous epithelium, is tough, relatively impermeable, and self-replacing. These functional qualities are conferred by the epidermis' principal cell type, the keratinocyte.

            The quality of the epidermis differs from place to place in the body (see regional differences). The quality of the epidermis can also be altered by various disease states which influence the rate of cell division and the quality of cell differentiation.

            The epidermis displays several layers. These layers are not distinctly different tissues (unlike epidermis and dermis, for example) but rather reflect visible changes or stages along the continuous process of keratinocyte maturation, or keratinization.

            The epidermis consists primarily of keratinocytes. Scattered among the keratinocytes are a few other cell types -- melanocytes, Langerhans cells, and Merkel cells

            Keratinocytes, which comprise most of the epidermis, are characterized by numerous intercellular junctions (desmosomes), reinforced by intracytoplasmic tonofilaments.

            Each desmosome is one spot of attachment. At high magnification, the desmosomes are visible as fine "prickles" extending across the gap (intercellular space) between adjacent keratinocytes. In between these junctions lie intercellular channels which permit nutrients to diffuse from dermis into epidermis. (More.)

            Keratinocytes in the stratum basale of the epidermis can undergo mitosis. The formation of new cells in this basal layer gradually pushes previously formed cells upward through the stratum spinosum. As keratinocytes approach the surface of the epidermis, they accumulate intracellular keratin and secrete a waxy material into the intercellular space these changes are visible in the stratum granulosum, a distinctive layer which is diagnostic for a keratinized epithelium. As maturing keratinocytes seal off the intercellular spaces through which they receive nutrients, they eventually die and form the stratum corneum, a tough and relatively inpermeable layer of hardened, dead cells. Eventually, as cells reach the surface, they are sloughed off. The entire epidermis above the basal layer is replenished (replaced by new cells) within about two weeks. Replacement is accelerated by injury.

            The stages in keratinocyte maturation appear as layers in the epidermis, so that a section across the epidermis illustrates the entire process.

            Other epidermal cell types

            Scattered among the much more numerous keratinocytes are several other epidermal cell types -- melanocytes, Langerhans cells, and Merkel cells. Because these cells lack the tough reinforcement and desmosomal attachments that characterize keratinocytes, they commonly shrink during preparation and appear surrounded by a clear "halo". (Together these cell types are all quite distinct from keratincytes. But they are difficult to distinguish from one another without special techniques.)

            • Recent research: "The melanoma revolution: From UV carcinogenesis to a new era in therapeutics," Science 346: 945-949

            The dermis consists of dense, fibrous connective tissue whose predominant connective tissue component is collagen.

            • The texture of collagen fibers serves as the basis for recognizing two layers of dermis.
              • The papillary layer of the dermis lies adjacent to the epidermis and consists of relative small, finely textured collagen fibers. This layer is named after dermal papillae, the protrusions of dermal connective tissue which indent the base of the epidermis.
              • The reticular layer of the dermis lies beneath the papillary layer and consists of larger, more coarsely textured collagen fibers. ("Reticular" means "like a network" and describes the texture of collagen fibers in this layer.)

              Like ordinary connective tissue throughout the body, connective tissue of the dermis serves several distinct functions.

              Within the dermis are embedded several other structures, including epidermal appendages (sweat glands and hair follicles) as well as blood vessels and nerve endings.

              The connective tissue of the dermis grades into hypodermis, without a sharp transition or distinct boundary.

              Over most of the body, hypodermis is characterized by adipocytes and may comprise a thick layer of adipose tissue. In some sites (e.g., "dimples"), hypodermis is fibrous and binds the dermis to underlying structures.

              Blood vessels are generally larger in the deeper layers of skin, with only capillaries in the papillary layer of the dermis.

              The appearance of the skin can have considerable clinical significance. The skin is readily accessible for examination (no invasive procedures needed), and its color and texture can reveal much about underlying physiology.

              Color: Skin is moderately transparent. Light which penetrates the skin is reflected back from varying depths by epidermal cells, by collagen, and by blood. Recent research: "Shedding light on skin color," Science 346: 934-936

              Melanin produced by melanocytes and stored in basal keratinocytes contributes a yellow/brown color to the epidermis. If the epidermis is not heavily pigmented, light readily penetrates into the dermis.

              Collagen scatters light from the dermis without altering its color. Hence, the whiteness of "white" skin is primarily a reflection of collagen.

              Hemoglobin in red blood cells scatters red light and is responsible for the pinkness of unpigmented skin. The relative amount of pink in any given patch of skin reflects how closely blood approaches the base of the epidermis (i.e., how much collagen intervenes to scatter white light before red blood cells can absorb the non-red colors).

              Each of these elements contributes to the apparent color of skin. Variations in skin color in different parts of the body (see regional differences) are based on variations in these elements, most especially the amount of pigment, the thickness of dermis, and the degree of perfusion in dermal capillaries.

              Perhaps most significantly, blood flow through the dermis is highly variable and is regulated in response to many conditions (heat, pain, fluid balance, inflammation, emotional reaction). Resulting variations in pinkness can provide indicators of underlying physiology, both locally and systemically. Obvious examples include inflammation, overheating, dehydration, shock, and even embarrassment (i.e., blushing) .

              Texture: Skin texture is affected the thickness and smoothness of the epidermis, by the quality of fibers in the dermis, and by the amount of fluid in dermal connective tissue.

              Because the epidermis is continually being replenished by cell divisions among basal keratinocytes and because this tissue is exposed to a variety of insults, the epidermis is especially prone to disturbances of growth. See any pathology book for examples.

              The connective tissue fibers of the skin are permanent, enduring without replacement (except by repair after injury) throughout life. Although collagen is quite durable, elastin commonly deteriorates with age and loses its elasticity. This is easily demonstrated by a "pinch test". In youthful skin, loose skin that has been pinched into a ridge quickly returns to its normal position when released. Elderly skin commonly remains in its deformed position, returning more slowly if at all.

              Both edema (accumulation of excess fluid in connective tissue) and dehydration can dramatically alter the appearance of skin.

              Sweat glands are simple tubular glands. The secretory portion of the gland lies deep in the dermis, where the tubule is twisted into a fairly compact tangle. A duct communicates outward through the overlying dermis and the epidermis.

              The secretory portion is comprised of larger cells than the duct. These cells form a simple cuboidal epithelium, along with interspersed myoepithelial cells (which can expel sweat by contraction).

              Cells comprising the duct, or conducting portion of the tubule, usually form a two-layered stratified cuboidal epithelium. These cells are usually stained more intensely than those comprising the secretory portion of the tubule. As fluid flows through the duct, its composition is modified by reabsorption of certain elements from the fluid. (This is primarily a means of conserving salt.)

              Sweat glands are vital for thermoregulation. They also influence water and ion balance.

              The primary function for sweating is evaporative cooling of the body. Thus, the amount of sweat is regulated as a function of body temperature.

              However, sweat also contains salt. Normally, sweat which comes out on the surface of the skin has a lower salt concentration than the precursor fluid produced by the secretory cells of the sweat gland. Salt is reabsorbed by the duct of the sweat gland. The effectiveness of this salt reabsorption is regulated by aldosterone (the hormone responsible for maintaining electrolyte homeostasis) in response to bodily salt balance.

              There are two types of sweat glands, ordinary eccrine sweat glands found over most of the body, and large apocrine sweat glands of axillary, pubic, and perianal regions.

              Both types of sweat glands have the same basic shape, but apocrine glands have taller cells and much larger diameter.

              Hair follicles are tubular invaginations lined by stratified squamous epithelium similar to epidermis.

              Toward the bottom of each follicle, processes of cell division, growth, and maturation similar to those in the epidermis yield a cylindrical column of dead, keratinized cells (the hair shaft) which gradually extrudes from the follicle. (For details, consult your histology textbook.)

              Hair follicles are associated with sebaceous glands as well as nerve endings and smooth muscle to form the pilosebaceous apparatus.

              • A network of nerve endings detects deflection of the hair shaft and also controls piloerection (hair "standing on end", or "goose bumps").
              • Piloerection is effected by smooth muscle, with a small bundle of smooth muscle cells called the arrector pili attached to the connective tissue sheath around each hair follicle.
              • Sebaceous glands secrete oil into the hair follicle.

              Hair growth is moderately complex, resulting in considerable variation in appearance of hair follicles related to growth phase (i.e., anagen, catagen, and telogen, or growing, regressing, and resting) and to body region, age, and gender.

              Sebaceous glands are associated with hair follicles. The complex of hair follicle, hair shaft, and sebaceous gland is sometimes called the pilosebaceous apparatus.

              Histologically, sebaceous glands quite different from all other glands. They are holocrine glands, which means that the whole cell is secreted. The process of holocrine secretion is more similar to maturation of keratinocytes than to ordinary glandular function. Cells formed by mitosis at the base of the gland are pushed toward the surface as new cells form below. Along the way, the cells become packed with lipid and then die. The secretion consists of breakdown-products of the cells themselves, which extrude into the lumen of the associated hair follicle. So, basically, sebaceous glands are small masses of epidermal cells in which sebum (a mixture of lipids) accumulates rather than keratin.

              The dying cells in sebaceous glands provide a good opportunity to learn the appearance of pyknotic nuclei, one of the more conspicuous signs of cell death.

              Please consult an in-depth text (e.g., Chapter 3, Histology for Pathologists, Sternberg, 1998 newer edition: Mills, Histology for Pathologists, 3rd ed., 2007) if you desire histological details on fingernails and toenails.

              The skin is richly innervated, served by a variety of sensory nerve endings which respond to a variety of modalities (e.g., pressure, vibration, heat, cold, itch, pain) and by motor nerve endings which control blood flow, sweat secretion, and piloerection.

              For richer information on the following, see Neuroscience Online, Somatosensory systems.

              • Free nerve endings (no conspicuous, specialized structures) terminate within the epidermis, penetrating almost to the stratum corneum.
              • Merkel's touch corpuscles are nerve endings associated with Merkel cells at the base of the epidermis in thick (glabrous) skin of palms and soles.
              • Meissner's corpuscles (images at right) are encapsulated endings in dermal papillae, most common in palmar and plantar skin, especially in fingertips.
              • Pacinian corpuscles, located deeper in dermis (image at right), are simple nerve endings but are each encapsulated by multilamellar, ovoid structures resembling small onions. Pacinian corpuscles respond to deep pressure.
              • Ruffini endings have numerous fine branches from a single axon within the fluid-filled space of a single thin capsule.
              • Hair follicle receptors are unencapsulated nerve endings wrapped around hair follicles.

              The distribution of sensory nerve endings varies from place to place in the body (see regional differences).

              Except for the characteristic capsules of Meissner's and Pacinian corpuscles, nerve endings are inconspicuous in ordinary histology preparations of skin.

              Special stains are generally used to observe nerve endings. And except for these same, fairly conspicuous encapsulated endings, the functional details of most sensory endings remain obscure. For more information on tactile sensation, see Principles of Neural Science by Kandel, Schwartz and Jessel.

              Peripheral nerves (i.e., bundles of axons, within a connective tissue sheath or epineurium) can often be found in dermis, with smaller branches toward the surface (i.e., often near sweat glands or hair follicles) and larger branches in deeper layers (often running parallel to blood vessels). The following examples show nerves in dermis.

              The papillary layer of the dermis is richly supplied with capillaries, while larger blood vessels may be found in deeper levels of the dermis.

              Since the skin does not have a very high metabolic demand for nutrients and oxygen, this rich vascular network serves mainly for regulation of body temperature. Essentially, regulation of the amount of blood flowing through superficial capillaries allows for either conservation or dissipation of body heat.

              Arteriovenous shunts, controlled by associated sphincters, allow blood to bypass capillaries and flow directly from arteries into veins. These shunts occur in both deep and superficial dermis.

              • Thickness of epidermis.
                • Skin on palms of hands and soles of feet has much thicker epidermis than other regions of skin (up to a millimeter or more, with many cell layers). This so-called thick skin also lacks hair follicles and sebaceous glands. Thick skin has an especially well-developed, abrasion-resistant stratum corneum.
                • Elsewhere epidermis is substantially thinner than palms and soles, typically with only a few cell layers. Nonetheless, its thickness varies from region to region -- e.g., commonly about a half-millimeter over most of the body, but as thin as a tenth of a millimeter over eyelids.
                • Dermis is commonly one to two millimeters in thickness.
                • Dermis is quite thin in the eyelid (about half a millimeter) and quite thick (several millimeters) over the back.
                • Rather obviously, hairs are thicker and longer on the scalp, axilla, and pubis than on most other regions.
                • Less obviously, tiny hair (vellus hair) occurs even on seemingly hairless regions like eyelids.
                • Hair is absent from "thick skin" of palmar and plantar skin.
                • Certain regions of the body (e.g., nose, forehead) are notorious for large and active sebaceous glands.
                • Sebaceous glands are absent from "thick skin" of palmar and plantar skin.
                • The distribution of sweat glands varies over the body, with high concentrations in palmar and plantar skin. (Incidently, sweat glands of palms and soles respond more to mental and emotional stress than to heat stress.)
                • Large apocrine sweat glands are concentrated in axillary, pubic and perianal areas. These sweat glands are responsible for "body odor", by including organic substances (and, consequently, bacteria) in their secretions.
                • Different sensory modalities are concentrated in different regions.
                • Skin of fingertips has the highest concentrations of Meissner's and Pacinian corpuscles.
                • Tactile resolution varies tremendously from region to region, as can be readily demonstrated by a two-point discrimination test. (Unbend a paperclip so that the two ends can pressed simultaneously against the skin. Then, with randomly varying touches from one or both ends, see how far apart the ends need to be before the two-end touch is felt as two distinct touches. The greatest difference is likely to be found between fingertip and the back of the trunk.)
                • Bundles of smooth muscle may be found in the dermis of nipple, areola, scrotum, penis, and perianal region.
                • In non-human mammals, skeletal-type muscle may be found in dermis (allowing, for example, horses to "twitch" a patch of skin to discourage biting flies).
                • Although the stratum spinosum is permeable to water, the epidermis becomes relatively impermeable in the stratum granulosum and stratum corneum.
                • Damage to extensive areas of epidermis, e.g. by burns, renders the skin highly permeable and constitutes a medical emergency.
                • Epidermis serves as a simple mechanical barrier. This is probably the most obvious function for skin.
                • Keratinocytes are crucial for the barrier function, both in their tonofilaments and desmosomes which establish the mechanical integrity of the epidermis and in their formation of hardened squames in the stratum corneum.
                • Melanocytes produce melanin pigment, which shields underlying cells from ultraviolet light.
                  Recent research: "The melanoma revolution: From UV carcinogenesis to a new era in therapeutics," Science 346: 945-949 "Shedding light on skin color," Science 346: 934-936
                • Collagen of the dermis provides main strength to resist tearing. The thickness of the dermis is correlated with vulnerability to injury.
                Immunological surveillance and defense -- Immune cells of skin stand ready to defend against invasion by microorganisms.
                • Langerhans cells detect foreign antigens in the epidermis.
                • Mast cells stand ready to trigger an inflammatory response if the skin is injured or the epidermal barrier is breached.
                • Recent research: "Dialogue between skin microbiota and immunity," Science 346: 954-959.
                • Cells in the basal layer of the epidermis respond quickly to damage, proliferating and migrating to cover the site of injury (moving in under the scab).
                • Epithelial replacement can spread from deep hair follicles and sweat glands if the surface epidermis has been damaged over an extensive area.
                • Fibroblasts also become activated by injury, to proliferate and to manufacture new collagen. The resulting scar may be eventually remodelled into a nearly-normal configuration of fibers. Also see WebPath example of scar formation in skin.
                • Epidermal appendages play an especially important role in recovery from superficial scrapes and burns. Even when the epidermis has been removed over a fairly large area, it can grow back quickly from the epithelial cells which remain in deeper hair follicles and/or sweat glands. Third-degree burns are so serious precisely because tissue damage extends deep enough into the dermis to destroy these sources of replacement cells.
                • Recent research: "Advances in skin grafting and treatment of cutaneous wounds," Science 346: 941-945.

                III. Scalp and Hair

                Slide 107 Scalp hair H&E View Virtual Slide

                Underneath the thin epidermis, there are numerous circular to oblong structures with a hollow or yellow-brown center and surrounding cellular layers. These structures are hair follicles slide 107 View Image sectioned transversely or tangentially at different levels. The keratinized component of the hair occupies the central cavity of the follicle, and appears yellow-brown when present. However, the hair often falls out during tissue processing, in which case the central cavity will appear to be occupied by just empty space. The surrounding layers of clear cells form the external root sheath of the hair, which is a downgrowth of the epidermis. In fact, in cases where most of the epidermis is removed (such as severe abrasions or when taking skin graft), it is cells of the external root sheath that will divide and spread over the exposed surface to re-establish the epidermis. In some sections, you may also see an internal root sheath of darker staining cells right up against the hair follicle - this is the layer of cells that actually produce the keratinized hair shaft. Note also the presence of sebaceous glands slide 107 View Image and the arrector pili muscle slide 107 View Image near the hair follicle. In most instances, you will not find complete pilosebaceous units in a single section, so a bit of mental reconstruction will be required.


                Skin (histology) - Biology

                The skin appendages are epidermal and dermal-derived components of the skin that include hair, nails, sweat glands, and sebaceous glands. Each component has a unique structure, function, and histology. This article describes the unique characteristics of each of these components and provides insight into tissue preparation for microscopic evaluation and the clinical significance of these structures.[1][2][3]

                Structure

                The skin appendages include sweat glands, nails, and the pilosebaceous unit of the skin, comprised of the hair shaft, hair follicle, sebaceous gland, and arrector pili muscle &mdash these appendages derive from a down growth of the epidermis beginning in the third month of fetal life. 

                The pilosebaceous unit is found in nearly all regions of the skin except for the lips, palmar and plantar surfaces, and is most dense on the scalp.

                Hair Structure

                The hair structure divides into the hair shaft and hair follicle.

                The hair shaft is the portion of the hair that is visible on the outside of the skin. It is made up of cuticle cells that surround the cortex, with a central medulla present in thicker hair. The cortical layer provides the bulk of the hair shaft structure and is comprised of keratin.

                The hair follicle is the primary structure for hair growth and divided into three segments:

                1. Infundibulum
                2. Isthmus
                3. Inferior segment

                The infundibulum comprises the portion from the epidermal invagination to the level of the ductal opening of the sebaceous gland. The isthmus is the portion from the opening of the sebaceous gland to the insertion of the arrector pili muscle. The bulge area, where stem cells are thought to reside, is located between the ductal opening of the sebaceous gland and the insertion of the arrector pili muscle. The inferior segment is the growing portion of the follicle and, at its base, expands to form the bulb, which is invaginated by a tuft of vascularized loose connective tissue called the dermal papilla, which actively produces hair. The hair bulb contains matrix cells that function to promote the growth of the hair follicle, allowing hair to grow longer. The dermal papilla is surrounded by a dermal sheath that contains progenitor cells that function to regenerate the dermal papilla and participate in wound healing. These regenerative and proliferating regions define the hair cycle, which comes in phases known as anagen, catagen, and telogen (growth, regression, rest).

                The hair follicle is further divided histologically into the inner root sheath and outer root sheath.

                The Outer Root Sheath encloses the inner root sheath and is continuous with the epidermis. This layer contains multipotent stem cells, melanocytes, and keratinocytes. The melanocytes are pigment (melanin) producing cells that originate from the neural crest and contribute to the color of hair, and keratinocytes are keratin producing cells.

                The Inner Root Sheath further divides into the Henle layer, Huxley layer, and the cuticle. This layer only extends up to the level of where the sebaceous gland meets the hair follicle.

                • Henley's layer: outermost layer made of cuboidal cells in direct contact with the outer root sheath
                • Huxley's layer: the second and middle layer made of two rows of flattened cells that contain granular protoplasm
                • Cuticle: the third, innermost layer made of flat overlapping squamous cells that is continuous with the outermost layer of the hair fiber

                Nail Structure

                The nail unit includes the nail plate, eponychium, hyponychium, nail folds, lunula, and nail matrix. The prefix onycho- pertains to the nails.

                The nail matrix lacks a granular layer, has a thick stratified squamous epithelium, long rete ridges, and contains melanocytes, epithelial cells, Merkel cells, stem cells, and Langerhans's cells. It is also known as the germinative zone where stem cells divide, migrate, differentiate, and produce keratin for the formation of the nail. At the edge of the lunula, as the epithelium transitions to the nail bed, the epithelium thins.

                The nail plate is the visible portion of the nail that is rigid and composed of compact keratinocytes called onychocytes, which are flatter than the corneocytes found in the skin, and do not desquamate. The nail plate is curved and fits tightly into the proximal and lateral nail folds. Histologically, the nail plate is comprised of anucleate keratinocytes and contributes to the translucency of the nail plate. Though the nail plate resembles the stratum corneum of the skin, it has a lower percentage of fat and water and a higher percentage of the amino acid cysteine resulting in strong disulfide bond formation, contributing to its strength.

                The hyponychium (nail bed) is the portion of the skin beneath the nail plate and spans from the lunula to the hyponychium. Histologically, its epithelium lacks a stratum granulosum but contains a spinous layer and a monocellular basal layer. It consists of epithelial cells that are continuous with the stratum spinosum and basal, with the nail plate serving as the stratum corneum. The deeper portion of the nail bed is made up of a uniform compartment of collagen bundles and elastic fibers with a rich vascular network. Arteriovenous anastomoses involved in thermoregulation, known as glomus bodies, are found in the dermal portion. The thickened portion at the interface between the hyponychium and the nail plate termed the onychodermal band, which serves as a barrier to pathogens.

                The eponychium (cuticle) is the tissue overlapping the nail plate at the most proximal edge made of hard keratin that does not desquamate. Histologically, the epidermis is thin and resembles normal skin. The cuticle is also an important barrier to pathogens.

                The lunula is a crescent-shaped white area near the nail root. The color arises from the thick, opaque layer of partially keratinized matrix cells. 

                Sebaceous Glands

                Sebaceous glands are part of the pilosebaceous unit, and there are typically multiple sebaceous glands per hair follicle. Sebaceous glands are made up of lobules and ducts and true exocrine glands found in all areas of the skin except for the palms, soles, lip, and tops of the feet. The lobules are made up of sebocytes that produce sebum, a fatty material that lubricates hair and has bactericidal and fungicidal properties. These "oil glands" are also categorized as holocrine exocrine glands, which means that the entire sebocyte loses its cytoplasm and dies in the process of discharging its contents during the excretory process toward the middle of the gland into its lumen.

                These glands are pear-shaped, and their duct, the pilosebaceous canal, opens into the neck (upper third) of the hair follicle. On microscopy, these glands have a foamy appearance because the lipid content is poorly staining.

                Sweat Glands (Sudoriferous)

                The sweat glands categorize as either eccrine and apocrine glands. Eccrine is the most common of the sweat glands, distributed all over the body except the lips and part of the external genitalia.  Apocrine glands are limited to the axilla, areola, nipple, skin around the anus, and external genitalia and have an odor. These glands differ in their mode of secretion. Eccrine glands exhibit merocrine secretion meaning there is no loss of cellular cytoplasm during secretion, and apocrine glands lose a portion of the top of the cell cytoplasm with each apocrine secretion.

                Histologically, the eccrine sweat glands are present in the dermis and upper portion of the hypodermis. There is a secretory portion and a duct portion.

                The secretory portion appears coiled, with epithelial cells that stain both light (contain watery/electrolyte material) and dark (contain glycoprotein material) on hematoxylin & eosin stain and are either cuboidal or pyramidal in shape. The secretory tubule is surrounded by myoepithelial cells (smooth muscle-like) that contract to help with the secretory process. The myoepithelial cells are oriented obliquely and longitudinally around secretory portions of tubules. The secretory coil divides into the coiled segment, the straight segment that extends into the epidermis, and the intraepidermal segment, which appears between epithelial cells.

                The excretory duct portion does not have myoepithelial cells and is lined by a double layer of cuboidal cells, containing microvilli. The basal cells are connected by the microvilli and contain opaque granules.

                Histologically, the apocrine glands are not as coiled and found in the dermis and subcutaneous fat. Like the eccrine glands, the apocrine glands have a secretory and excretory duct portion. These glands are hormonally controlled and become active at puberty.

                The secretory portion has a lining of simple cuboidal epithelial cells, and the lumen is much larger than that of the eccrine gland lumen. The cells of the secretory portion vary in size depending on the stage of secretion, and the contents are odorous oily, yellow, viscous secretions.

                The excretory portion contains a body and an excretory duct that opens into the hair follicle. The body (tubulo-alveoli) is lined by cuboidal and columnar epithelial cells and surrounded by myoepithelial cells in a sac-shaped out pocket. The excretory duct lining is simple cuboidal epithelium. [4][5][6][7][8][9][10][11][12][13]

                Function

                Hair Function

                Hair serves many functions, including protection, body temperature regulation, facilitation of perspiration, sensation, aesthetics, and psychosocial health. Hair protects our skin from UV radiation in areas that are more hair dense. Hair can retain heat when we are cold and stand on end with the contraction of arrector pili muscles, promoting heat loss through sweat production when we are hot. Hair can also contribute to tactile sensation by transmission through the hair follicles. Socially, hair can be a symbol of beauty and health, contributing to confidence in an individual's psychosocial well-being.

                Nail Function

                The functions of the finger and toenails include protection from injury and infection, help with grasping and manipulating objects, aesthetic and cosmetic purposes, augmentation of sensation. The sheer strength of the nail mediates protection as a direct result of keratinization and the preservation of the cuticle, onychodermal band, and lateral nail folds to prevent infection.

                Sebaceous Gland Function

                Sebaceous glands are essential for the secretion of sebum that serves to lubricate the skin and protect the skin against friction, but also contribute to the modulation of bacterial and fungal growth by the presence of triglycerides and proteolytic enzymes.

                Sebum Secretion

                The process of sebum secretion begins with the proliferation of cells at the basal layer (the secretory portion of the gland).

                1. Cells become pushed to the center of the gland towards the excretory duct.
                2. Fatty material is then formed and accumulates in the cytoplasm.
                3. Cells burst and die as they accumulate sebum and are pushed further from the basal layer.
                4. Sebum empties onto the hair.
                5. Contraction of arrector pili muscle can speed up secretion.

                Sweat Gland Function

                Eccrine (cholinergic sympathetic stimulation)

                            There are three main functions of the eccrine glands:

                1. Protection: by preserving the skin's acidic composition and protect from microbial overgrowth.
                2. Thermoregulation: the production of sweat that cools the skin surface and reduces body temperature.
                3. Excretion: by the excretion of water and electrolytes

                Apocrine (adrenergic sympathetic stimulation)

                The main functions of the apocrine glands are not fully known, but there is pheromone secretion through sweat, which may influence sexual attraction, secretion of lubricating material assisting with increased frictional resistance, and androgenic activity shown by the activity of 5&alpha-reductase, and stimulation of function at puberty.[4][5][6][7][8][9][10][11][12][13]

                Tissue Preparation

                Skin Biopsy

                Skin biopsy can be completed in multiple ways, including excisional biopsy, incisional biopsy, shave biopsy, punch biopsy, curetting, fine needle aspiration.

                • An excisional biopsy: the entire lesion of interest is cut out.
                • An incisional biopsy: a segment of a lesion is removed.
                • A shave biopsy: a horizontal section is removed.
                • A punch biopsy: a round specimen (2 to 6 mm in diameter) is removed, curetting fragments of tissue.

                A fine-needle aspiration: drawn from the lesion for direct examination.

                The biopsy type is chosen based on the type of lesion.

                Following the skin biopsy, the sample must be placed in a fixative solution of neutral buffered formalin to preserve the tissue structure. In the laboratory, the sample is placed in formol saline for at least 24 hours before being processed.

                The specimen is then placed in a small cassette initially in fixative, but later in paraffin blocks. The cassette is a support for the paraffin block and helps cut the tissue into thin sections. Alcohol dehydration to eliminate water from the preparation takes place by the use of an automated processor followed by clearance of the alcohol by using dimethyl benzene and allows the tissue to become incorporated in paraffin wax.

                The tissue is removed from the cassette, put in a mold, and covered with hot liquid paraffin wax. When the wax cools, it becomes solid and forms the block for sectioning. Finally, the block is sectioned before being stained, typically with hematoxylin & eosin (H&E) with special stains later used if needed. Hematoxylin has bluish hues staining nucleic acids, and eosin will stain cytoplasmic components pink.

                Hair and Nail Examination

                Hair and nails may be studied in microscopy without performing a biopsy. Usually, a hair sample is collected by either clipping or plucking for microscopy, and clipping for nails. Clipping of hair is recommended when hair shaft disorders are suspected, while plucking is recommended when examination of the root is needed, as in alopecia areata and nails when infectious or immune-mediated conditions are suspected.

                There are mainly two types of tissue preparation clinicians use.

                • A dry mount: hair samples are put on a glass slide and covered with a coverslip.
                • Wet mount: uses KOH for suspected fungal infection (hair and nails).[14]

                Microscopy Light

                Light microscope examination serves to light and magnifies a specimen in the investigation of a variety of pathology. The examiner studies the specimen under light microscopy on a glass slide that was prepared, as stated above, in the tissue preparation section of this article.

                Skin biopsy with histopathological examination may be indicated in suspected skin cancers, inflammatory conditions, and other potential pathological conditions of the skin appendages.

                Nail plate biopsy followed by Periodic Acid Schiff stain may be useful in the diagnosis of onychomycosis (fungal nail infection) with a negative mycological examination. Nail biopsy may also be an option in inflammatory (like lichen planus) or tumoral changes.

                Polarized light microscopy is done if anomalies of the hair shaft are suspected. Clinicians typically use dermoscopy (trichoscopy) in the clinical setting.[14][15]

                Pathophysiology

                There are many inflammatory, immune-mediated, autoimmune, infectious, neoplastic, and traumatic causes of alterations to the normal function of the skin appendages, some of which include the following:

                Inflammatory and immune-mediated illnesses may result in damage to the hair follicle and can lead to permanent hair loss if the follicle scars. The follicles can become infected by various pathogens that lead to inflammation and pustule formation seen on the surface of the skin at the opening of the hair follicle. Endocrine-mediated illnesses like congenital adrenal hyperplasia, hypothyroidism, hyperthyroidism, and tumoral processes can affect hair growth and hair cycle.

                Trauma to the nail matrix can result in altered growth or even permanent failure of growth. Infections in the nail matrix can also alter nail growth patterns and the appearance of the nail plate. Many nail changes can present, such as pitting, koilonychia, onycholysis, ridging, among others from vitamin and nutrient deficiencies, trauma to the nail unit, psoriasis, alopecia, and many more. 

                Sebaceous gland overactivity in conjunction with cutibacterium acnes overgrowth can cause acne or seborrheic dermatitis if there is an overgrowth of Malassezia furfur. Sebaceous glands can also become hyperplastic, form cysts, and undergo neoplastic changes. 

                Sweat glands can become overactive, as seen in hyperhidrosis, and can contribute to excessive malodor, as seen in bromhidrosis. Many chronic conditions can result if the sweat ducts are blocked, like miliaria rubra and Fox-Fordyce disease. They, too, can undergo neoplastic changes and form tumors.[13][16]

                Clinical Significance

                Skin appendages have multiple areas of clinical significance.

                Pathology of the hair follicles can result in the following:

                • Alopecia: loss of hair
                • Folliculitis: infection of the hair follicle
                • Pediculosis: a lice infestation
                • Hirsutism: increased hair production, typically due to endocrine abnormalities
                • Hypertrichosis: increased hair production.

                Pathology of the nails may result in the following:

                • Onychomycosis: fungal infection of the nail
                • Psoriasis: irregular pitting, splitting, or &ldquooil drop&rdquo
                • Lichen planus: longitudinal ridging and splitting of the nails
                • Alopecia areata: geometric pitting of the nails
                • Melanonychia: pigmentation of the nails

                Pathology of the sebaceous glands may include the following:

                • Acne
                • Seborrheic dermatitis
                • Sebaceous cyst
                • Sebaceous hyperplasia
                • Sebaceous adenoma
                • Sebaceous carcinoma, among others

                Pathology of the sudoriferous (sweat) glands may result in the following[13][16]:


                Watch the video: Normal Skin Histology - Explained by a Dermatopathologist (January 2022).