Skin nontumor
General
Histology

Editorial Board Member: Robert E. LeBlanc, M.D.
Editor-in-Chief: Debra Zynger, M.D.
Mariantonieta Tirado, M.D.

Topic Completed: 29 September 2020

Minor changes: 29 September 2020

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PubMed Search: Skin[TIAB] histology[TI] review[PT]

Mariantonieta Tirado, M.D.
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Cite this page: Tirado M. Histology. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/skinnontumorgeneral.html. Accessed October 21st, 2020.
Definition / general
  • Membrane covering the exterior of the body composed of epidermis and dermis
Essential features
  • Skin is the largest organ of the body with a weight of approximately 5 kg and an area close to 2 m²
  • General functions of the skin:
    • Protection (against UV light, dehydration, microbial invasion, mechanical injury, chemical and thermal stresses)
    • Retains water and excretes drugs and waste
    • Thermoregulation through blood vessels and eccrine glands
    • Metabolic: vitamin D production
    • Sensorial: contains peripheral endings of sensory nerves
Terminology
  • Also called integument
Physiology
  • Epidermis
    • Outer stratified squamous epithelium composed of epidermal and intraepidermal adnexal (acrotrichial and acrosyringeal) keratinocytes
    • Main purpose is cornification
    • Keratinocytes are connected by desmosomes, adherens junctions, tight junctions and gap junctions
    • Basal layer
      • 10% are stem cells
      • Produces keratin 5
    • Squamous layer
      • Desmosomes develop and composition of keratin intermediate filaments change (↑ intracellular calcium)
      • Produces keratins 1 and 10
      • Langerhans cells and Merkel cells present
    • Granular layer
      • Profilaggrin which forms filaggrin: facilitates filament aggregation
      • Loricrin and involucrin: contribute to the formation of the insoluble cell envelope
      • Cells begin to lose nuclei
      • Production of the cell envelope
        • Located beneath the cell membrane
        • Composed of crosslinked proteins dependent on transglutaminase
      • Odland bodies
        • Lipid rich lamellated granules (mainly ceramide) secreted into intercellular spaces
        • Contribute to permeability barrier
    • Cornified layer
      • Formed because of keratinocytic maturation (cells flatten as they ascend to the surface)
      • Synthesis of lamellar granules and proteins
      • Cells lose their nuclei, cytoplasmic organelles, metabolic activity and eventually desquamate
  • Dermal epidermal junction: components bind the epidermis to the dermis
    • 4 major structural regions proceeding from the epidermis to the dermis
      • Basal cell plasma membrane
      • Lamina lucida: low electron density region, contains laminins (major laminin 332)
      • Lamina densa: electron dense region; its major component is collagen IV
      • Sublamina densa: upper papillary dermis contains loops of type VII collagen (anchoring fibrils)
    • Attachment structures
      • Hemidesmosomes: plaque proteins extend from basal plasma membrane of the keratinocyte to the lamina lucida (associated to the anchoring filaments)
      • Anchoring filaments: thread-like structures that cross the lamina lucida
      • Anchoring fibrils: extend from the lower lamina densa to the upper reticular dermis
    • Total epidermal renewal time, approximately 2 months
      • Cells take 26 - 42 days to transit from the basal layer to the granular layer
      • 14 days for keratin layer to be shed
  • Melanocytes
    • Neural crest derived dendritic cells that synthesize melanin
    • Melanin absorbs ultraviolet (UV) and protects from damaging UV Induced mutations
    • Melanin (produced from tyrosine) is transferred in melanosomes (lysosome type organelle), through melanocytic dendritic processes into adjacent keratinocytes and hair shafts
    • 2 types of melanin are produced: pheomelanin (yellow-red) and eumelanin (black-brown)
    • Racial skin color is due to amount of melanin in keratinocytes, not number of melanocytes
  • Dermis
    • Mainly supports the epidermis and plays varied other roles due to the presence of vessels, nerves and adnexa
    • Blood vessels provide nutrients and help regulate temperature
    • Sucquet-Hoyer canals
      • Specialized acral arteriovenous anastomoses
      • Allow blood shunting from arterioles to venules, bypassing capillaries
      • Surrounded by modified smooth muscle glomus cells (latter function as sphincters)
      • Primary function is of thermoregulation
    • Lymphatics
      • Play a role in tumor spread and removal of debris (fluid, cells and macromolecules)
      • Represent the primary route for Langerhans cells to reach regional lymph nodes
    • Nerves
      • Somatic sensory nerves mediate pain, itch temperature and touch
      • Autonomic motor nerves mediate vascular tone, pilomotor response and sweating
      • Afferent nerves consist of myelinated and nonmyelinated free nerve endings
      • 2 types of sensory receptors are present
        • Specialized (encapsulated): Meissner corpuscles have tactile function and Pacinian corpuscles detect pressure
        • Unspecialized: sensory non-encapsulated nerves linked to Merkel cells
  • Subcutis
    • Plays a role in cushioning, insulation, endocrine function and energy stores
    • 2 types of fat:
      • White
      • Brown: mostly present in infants and children, rich in mitochondria and produces heat
  • Adnexa
    • Skin associated structures each with specific functions including hair follicles, sebaceous glands, eccrine sweat glands and apocrine glands
    • Folliculosebaceous apocrine units: functional complex of hair follicle, sebaceous gland, erector pili muscle and (depending on site) apocrine gland
  • Hair follicle
    • Functions include temperature regulation, protection of other structures and tactile sensory input
    • Types of hair
      • Lanugo: present during late gestation and first month of life
      • Vellus: fine hair (face, trunk and extremities)
      • Terminal: coarse (scalp, eyebrows, eyelashes)
    • Cycle of hair
      • Anagen: growing phase (lasts 2 - 7 years)
      • Catagen: involuting phase (lasts 2 - 3 weeks, 1 - 2% of total hair)
      • Telogen: resting phase (lasts 100 days, 10 - 20% of total hair)
  • Sebaceous glands
    • Main function is protection by production and release of sebum
    • Secretion (governed by androgens) plays a role in waterproofing, control of epidermal water loss and inhibition of fungal and bacterial growth
    • Glands are holocrine (secretion depends on degeneration of acini with release of cells and lipid)
    • Sebaceous secretions (sebum) carry to the surface a mixture of fat, corneocytes and normal flora (yeasts, bacteria and mites)
    • Flora includes Propionobacterium acnes, Staphylococcus epidermidis and Demodex brevis
  • Apocrine sweat glands
    • Concentrated in axilla, groin, perineum, face, periumbilical, external auditory meatus, eyelid and areola
    • Function in humans is unknown; in other mammals they produce scent and play a role in sexual attraction
    • Odorless secretion is initially released and then modified by superficial bacteria producing body odor
  • Eccrine sweat glands
    • Regulate body temperature
    • Present almost everywhere in the skin except oral lips, clitoris, labia minora and external auditory canal
    • Eccrine duct possesses a conduit and metabolic (modifies secretion and reabsorbs water) function
    • Possess merocrine secretion
  • Nail unit
    • Protects tissues of the distal fingertip from injuries and enhances delicate movements by counterpressure
  • Langerhans cells
    • Bone marrow derived dendritic cells, described in 1868 by Paul Langerhans, a German pathologist, physiologist and biologist (Am J Dermatopathol 1985;7:347)
    • Function as intraepidermal macrophages phagocytosing antigens and then migrate to regional lymph nodes where they present antigens to T cells
  • Merkel cells
    • Part of the affector limb mechanoreceptors related with touch sensation
    • Described by in 1875 by Friedrich Merkel a Germany anatomist and histopathologist (Am J Dermatopathol 1982;4:521)
    • Located in the basal epidermis and concentrated in tactile areas of hairy skin, glabrous skin, lips, eccrine sweat glands and anal canal
    • Their close relation with nerve fibers represents a Merkel cell neurite complex
    • Heavily granulated cells containing keratin filaments and neuropeptides (Anat Rec A Discov Mol Cell Evol Biol 2003;271:225)
Diagrams / tables

Contributed by Mariantonieta Tirado, M.D.
Normal nail anatomy

Normal nail anatomy

Microscopic (histologic) description
  • Epidermis
    • Composed of 4 layers
      • Basal cell layer (stratum basale)
      • Prickle cell layer (stratum spinosum or Malpighian layer)
      • Granular cell layer (stratum granulosum)
      • Corneocyte layer (stratum corneum, horny layer)
    • Basal layer
      • Proliferating cell population with cuboidal shape, larger nuclei, conspicuous nucleoli and basophilic cytoplasm
      • Few mitotic figures may be present
      • Melanocytes surrounded by clear halo are present
      • Toker cells are clear cells present in the basal and suprabasal layers of the nipple epidermis of both males and females
    • Squamous layer
      • Several layers of larger eosinophilic polygonal cells with oval nuclei and conspicuous nucleoli
      • Cells attached to each other by spine-like processes (intercellular bridges)
    • Granular layer: 3 layers of flattened, diamond shaped cells with keratohyaline granules
    • Cornified layer: composed of flat, eosinophilic corneocytes without nuclei
    • Stratum lucidum
      • Homogenous eosinophilic zone
      • Present only in soles and palms, between granular and cornified layer
  • Melanocytes
    • Appear as clear cells (truly an artifact of fixation, secondary to shrinkage of the cytoplasm), with dendritic cytoplasm and a smaller and more basophilic nucleus than that of a basal keratinocyte
    • Ratio of melanocytes to basal cells ranges from approximately 1:4 on the cheek to 1:10 on the limbs
  • Dermis and subcutis
    • Divided into superficial papillary dermis and deeper reticular dermis
      • Papillary dermis: thin collagen fibers, located beneath the epidermis and around adnexa
      • Reticular dermis: thicker, extends from the base of the papillary dermis to the surface of the subcutis
    • Varies in thickness depending on anatomic location (eyelid: 0.5 mm; back: 5 mm)
    • Consists of connective tissue composed of collagen, elastic fibers and ground substance of mucopolysaccharides and mucoproteins
    • Harbors:
      • Scattered cells (fibrocytes, dendrocytes, histiocytes, mast cells, Langerhans cells and rare lymphocytes)
      • Adnexa
      • Smooth muscle
      • Nerves
      • Vessels: small arteries, arterioles and lymphatics
    • Small arteries, arterioles, venules, lymphatics and nerves conform a network of 2 connected plexuses parallel to the surface
      • Superficial plexus: located in the upper reticular dermis, supplies the papillary dermis with a capillary loop system
      • Deep plexus: located in the lower reticular dermis
      • Sensory receptors
        • Meissner corpuscles: ellipsoid lamellated structures, localized in the papillary dermis of lips, palms and soles
        • Pacinian corpuscles: ovoid structure with concentric lamellae, localized in the deep dermis and subcutis of genitalia, lips, palms and soles
    • Subcutis
      • Contains lobules of mature adipose tissue divided by thin connective tissue septa
      • Composed of adipocytes with a single globule of lipid that compresses the nucleus to the periphery
  • Hair follicles
    • Segments of the hair follicle in longitudinal sections
      • Upper segment: stationary
        • Infundibulum: from ostium of the follicle to the opening of the sebaceous duct; shape of a funnel with similar layers as the epidermis, with granular layer
        • Isthmus: from the opening of the sebaceous duct to the attachment of the arrector pili muscle at the hair bulge; contains a basal layer, spinous layer, absence of granular layer and an eosinophilic cornified layer
      • Lower segment: transient
        • Stem: from base of the isthmus to Adamson fringe (latter area between anucleated cells of the stem and nucleated cells of the bulb)
        • Bulb: contains matrix cells with large pale nucleus and prominent nucleoli and melanocytes that surround the dermal papillae
    • Layers of a terminal anagen hair follicle of the suprabulbar area in horizontal sections, from the center to the periphery
      • Hair shaft (medulla, cortex and cuticle)
      • Inner root sheath
        • Cuticular layer of the inner root sheath: 1 cell thick
        • Huxley layer: 2 cells thick with abundant eosinophilic trichohyalin granules
        • Henle layer: 1 cell thick, bright eosinophilic trichohyalin granules
      • Outer root sheath: composed of clear keratinocytes and keratohyaline granules
      • Vitreous and external fibrous layer (perifollicular connective tissue sheath)
    • Hair often contains Demodex folliculorum mites, clumps of Staphylococcus epidermidis or Pityrosporum yeasts
  • Sebaceous glands
    • Lobulated structures mostly connected to hair follicles
    • Distributed all over the skin with exception of palms, soles and dorsum of the feet
    • Have outer cuboidal or flattened, basophilic germinative cells that differentiate, move inward and accumulate intracytoplasmic lipid droplets, causing multivacuolation and indentations of nuclei
    • Excretory ducts are lined by keratinizing squamous epithelium
  • Apocrine sweat glands
    • Empty into the follicle above the sebaceous duct
    • Includes 2 components
      • Secretory
        • Located in the deep dermis or subcutis
        • Possesses an outer layer of myoepithelial cells and an inner layer of cuboidal to columnar eosinophilic cells
        • Shows luminal "decapitation" secretion
      • Ductal
        • Connects with the pilosebaceous follicle
        • Composed by a double layer of cuboidal cells
        • Histologically indistinguishable from eccrine ducts
  • Eccrine sweat glands
    • Includes 2 components
      • Secretory
        • Located deep in the dermis or subcutis
        • Has an outer layer of myoepithelial cells
        • Also possesses an inner layer of large clear pyramidal cells (secrete water) and smaller darker cells (secrete glycoproteins, mostly line the luminal surface)
      • Ductal
        • Opens directly into the epidermis
        • Composed of a double layer of basophilic cuboidal cells
        • Luminal surface is lined by an eosinophilic cuticle
        • Divided in 4 subunits: coiled secretory unit, coiled dermal duct, straight dermal duct, coiled intraepidermal duct (acrosyringium)
  • Nail unit
    • Comprised of the nail plate and surrounding tissues
    • Located in the dorsal aspect of the distal phalanx of fingers and toes
    • Anatomic structures include
      • Proximal nail fold: layer that extends superficially with the skin and deeply with the nail matrix
      • Eponychium (cuticle): cornified layer of the nail fold located between the nail plate and matrix
      • Nail matrix: produces the superficial and ventral portions of the nail plate
      • Lunula: white crescent shaped area representing the junction between the matrix and the bed
      • Nail plate: consists of corneocytes and is attached to the nail bed
      • Nail bed: epithelium lying over a vascularized dermis that provides support to the nail plate
      • Hyponychium: intermediate epithelium between the junction of the distal ventral edge of the free nail and the fingertip skin
      • Lateral nail folds: lateral overhanging skin folds that guide the growth of the nail plate
  • Langerhans cells
    • Dendritic cells with reniform nucleus scattered in the superficial epidermal spinous layer into the granular layer and in the dermis, difficult to see on H&E
  • Merkel cells
    • More common in outer root sheath of hair follicles and tactile hair discs
    • Not identified with H&E but with immunohistochemistry and electron microscopy
Microscopic (histologic) images

Contributed by Mariantonieta Tirado, M.D.
Layers of the epidermis

Layers of the epidermis

Melanocytes

Melanocytes

MelanA+ melanocytes

MelanA+ melanocytes

HMB45+ melanocytes

HMB45+ melanocytes

Stratum lucidum

Stratum lucidum

Superficial and deep neurovascular plexuses

Superficial and deep neurovascular plexuses


Pacinian corpuscle

Pacinian corpuscle

Meissner corpuscles

Meissner corpuscles

Brown fat

Brown fat

Segments of hair follicle

Segments of hair follicle

Layers of terminal anagen hair follicle

Layers of terminal anagen hair follicle

Demodex folliculorum mites

Demodex folliculorum mites


Sebaceous gland

Sebaceous gland

Adipophilin+ sebaceous gland

Adipophilin+ sebaceous gland

Eccrine gland, myoepithelial cell

Eccrine gland, myoepithelial cell

Eccrine duct

Eccrine duct

Intraepidermal portion of eccrine duct (acrosyringium)

Intraepidermal portion of eccrine duct (acrosyringium)

Apocrine gland

Apocrine gland


Apocrine gland with decapitation secretion

Apocrine gland with decapitation secretion

CD1a+ Langerhans cells

CD1a+ Langerhans cells

CK20+ Merkel cell

CK20+ Merkel cell

Positive stains
Negative stains
Electron microscopy description
  • Melanosomes: spherical membrane bound particle with periodic longitudinal concentric lamellae
  • Birbeck granules (rod shaped structure with zipper-like striations, often with bulbous end)
Electron microscopy images

Images hosted on other servers:

Birbeck granules

Board review style question #1

What is this structure and what does it make?

  1. Apocrine gland produces odorless secretion
  2. Eccrine gland produces merocrine secretion
  3. Hair follicle produces hair shafts
  4. Sebaceous gland produces sebum
Board review answer #1
A. Apocrine gland produces odorless secretion

Comment Here

Reference: Basic skin histology
Board review style question #2

Which skin cell type is CK20+?

  1. Keratinocyte
  2. Langerhans cell
  3. Melanocyte
  4. Merkel cell
Board review answer #2
D. Merkel cell

Comment Here

Reference: Basic skin histology
Board review style question #3

Which immunostain is expected to be expressed by this cell?

  1. CD1a
  2. CK5/6
  3. CK20
  4. MelanA
Board review answer #3
D. MelanA

Comment Here

Reference: Basic skin histology
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