Histology, Skin Appendages

Article Author:
Hani Yousef
Article Author (Archived):
Julia Miao
Article Editor:
Talel Badri
12/1/2019 2:55:06 PM
PubMed Link:
Histology, Skin Appendages


The epidermis is derived from ectoderm during embryonic development. Cells of ectoderm (forming epidermis) grow downward into the dermis and give rise to hair follicles, fingernail, toenails, sweat glands, and sebaceous glands. Hence, they are named, epidermal or skin appendages.[1][2][3]


 Hair Follicles[4][5]


  • Develop in the third month of fetal life; epidermis sends down growth into the dermis
  • Downgrowth becomes follicle
  • Invading epidermis to form a cap over the connective tissue papilla
  • As development proceeds, a mature adult follicle is formed.


Hair is formed from 3 segments:

  1. Infundibulum from the surface opening of the follicle to the level of opening of its sebaceous gland
  2. Isthmus from infundibulum to level of insertion of the arrector pili muscle
  3. Inferior segment growing follicle portion; at base expands to the bulb which is invaginated by a tuft of vascularized loose connective tissue called (dermal papilla)
  • Deepest down growth becomes germinal matrix, a cluster of cells which can germinate hair
  • Includes melanocytes and keratinocytes
  • Gives rise to the hair shaft and internal root sheath

Internal root sheath is soft keratin and is broken down at the isthmus level, where sebaceous secretions enter follicle.

Dividing matrix cells in germinative layer differentiate into keratin producing cells of internal root sheath, which has three layers:

  • Henley’s layer: cuboidal cells in direct contact with outermost part of the hair follicle, the external root sheath
  • Cuticle: squamous cells.
  • Huxley's layer: flattened cells



  • Nails develop about the third month of embryonic life, the epidermis of fingers and toes “invade” underlying dermis along a curved line to form the nail
  • Nail plate rest on the nail bed
  • Nail bed consists of epithelial cells continuous with spinosum of epidermis and stratum basale; there is no stratum granulosum, and the nail itself serves as the stratum corneum
  • The proximal part of the nail, the nail root, is buried in the fold of epidermis covering cells of the germinative zone, the matrix
  • The matrix of nails has melanocytes, epithelial cells, Merkel’s, stem cells and Langerhans’ cells
  • The stem cells divide, migrate toward the root and differentiate and produce keratin of the nail.


The nail is formed from the following:

  • Lunula: Crescent-shaped white area near nail root. Color is from thick, opaque layer of partially keratinized matrix cells.
  • Eponychium (cuticle): Edge of skin fold covering nail root, also hard keratin, does not desquamate.
  • Hyponychium: Epidermis underlying distal tip of the nail where stratum corneum of distal free edge contacts the nail; a thickened epidermal layer which secures the free edge of the nail plate at the fingertip

 Sebaceous Glands[7]

  • Cells of external root sheath in approximately the upper third of follicle grow out into the adjacent dermis and differentiate into the sebaceous gland.
  • Ducts open into follicle at the site of outgrowth; hence, empty into the upper third of follicle called a neck.
  • Usually several sebaceous glands per follicle
  • Secret sebum, which is a fatty material that oils and lubricates hair. Also, may possess bactericidal and fungicidal properties
  • Sebaceous glands are holocrine glands (the whole cell dies in the excretory process)

Sweat Glands

Eccrine are the most common glands, distributed all over the body except lips and part of the external genitalia; no loss of cytoplasm (merocrine secretion). Apocrine glands limited to the axilla, areola, nipple, skin around anus and external genitalia. Ceruminous glands of external meatus of the ear and glands of eyelashes were originally thought to be apocrine secretion (membrane budding) but are merocrine.

Eccrine Sweat Glands

  • Simple tubular gland with a secretory part and an excretory duct; secretory part below dermis in subcutaneous tissue, independent from hair follicle; excretory duct to the surface of the skin.
  • Secretory part produces secretion similar in composition to an ultrafiltrate of blood; resorption of some sodium and water in duct results in the release of hypotonic sweat low in protein with different amounts of sodium chloride (NaCl), urea, uric acid, and ammonia
  • Secretory segment cells: Comprised of clear cells (abundant glycogen, pale cytoplasm, cuboidal to simple columnar; secrete water, NaCl, can urea. Canaliculi conduct sweat to the lumen of ducts) or dark cells (secretory granules, secrete glycoprotein [proteoglycans]). Also, myoepithelial cells (basal aspect, oriented obliquely and longitudinally around secretory portions of tubules, spindle-shaped; contractions aid in expelling sweat; the excretory duct does not have myoepithelial cells)

Apocrine sweat glands

  • Develop from same down growths of the epidermis which give rise to hair follicles; connection to follicle remains
  • Also coiled, as eccrine, with secretory portion deep in the dermis or upper hypodermis
  • Lumens of the secretory portion is much wider than those of eccrine glands
  • Apocrine glands store secretory products in their lumens, eccrine glands do not
  • Only one secretory cell type, eosinophilic with bleb-like apical protrusions; myoepithelial cells are also present in duct portion (same as eccrine)
  • Duct epithelium stratified cuboidal (same as eccrine)
  • Unlike eccrine gland, reabsorption does not take place in the duct; the secretory product is not changed in its passage through the duct
  • Connected to hair follicle
  • A sympathetic portion of the autonomic nervous system (in general, eccrine/cholinergic and apocrine/adrenergic) innervates both eccrine and apocrine glands


Sebaceous Gland Function

Sebum Secretion

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

  1. Cells are pushed to the center of gland towards excretory duct
  2. After that, fatty material is formed and accumulates in the cytoplasm of these cells
  3. Cells then burst and die as they accumulate sebum and are pushed further from basal layer
  4. Sebum empties onto hair
  5. Contraction of arrector pili muscle can speed up secretion (sebum equals lipids)

Apocrine Sweat Gland Function

  • Produce secretion with protein, carbohydrate, ammonia, lipid, and some organic compounds that may give milky color; via bacterial action on the skin, secretion develops an odor
  • Become functional at puberty and may be linked to pheromones

Eccrine Sweat Gland Functions

  • Major role in temperature regulation by evaporation of water from sweat on the body surface

Apocrine Sweat Gland Function

  • The human apocrine sweat contains pheromone-like substances that may influence sexual response.  

Tissue Preparation

Skin Biopsy

When a skin biopsy is performed, the sample is put in a fixative solution of neutral buffered formalin to preserve the tissue structure by forming cross-links between lysine residues. In the laboratory, the sample is rapidly placed in formol saline for at least 24 hours before being processed.

The specimen is then put in a small cassette which plays the role of the support for the paraffin block.

Then, paraffin blocks are made to help cut the tissue into thin sections. Alcohol dehydration eliminates the water. Dimethylbenzene helps to remove alcohol allowing the tissue to be 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 to be sectioned. Finally, the block is cut into thin slices before being stained.

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. Clipping is done when hair shaft disorders are suspected while plucking is done when examination of the root is needed as in alopecia areata.

There are mainly 2 types of tissue preparation clinicians use.

  • Dry mount where hair samples are put on a glass slide and covered with a coverslip
  • Wet mount using KOH for suspected fungal infection (hair and nails)

Microscopy Light

Skin biopsy with histopathological examination may be indicated in inflammatory and tumoral diseases of the sebaceous or sweat glands, as well as in some hair follicle anomalies.

Nail plate biopsy followed by periodic acid Schiff stain may be useful in onychomycosis with a negative mycological examination. Nail biopsy may also be done in inflammatory or tumoral changes.

Polarized light microscopy is done if anomalies of the hair shaft are suspected. Dermoscopy (trichoscopy) may also be used in this indication.

Clinical Significance

Anomalies of Hair Follicles

  • Alopecia
  • Folliculitis
  • Pediculosis
  • Hirsutism, among others 

Anomalies of Nails

  • Onychomycosis
  • Psoriasis
  • Lichen planus
  • Alopecia areata
  • Melanonychia, among others

Anomalies of Sebaceous Glands

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

Anomalies of Sudoral Glands

  • Hyperhidrosis
  • Bromhidrosis
  • Miliaria rubra
  • Fox-Fordyce disease
  • Hidradenitis suppurativa
  • Tumors: hidrocystoma, syringoma, cylindroma, among others


[1] Brahs AB,Bolla SR, Histology, Nail 2019 Jan;     [PubMed PMID: 30969555]
[2] Agarwal S,Krishnamurthy K, Histology, Skin 2019 Jan;     [PubMed PMID: 30726010]
[3] Freeman SC,Sonthalia S, Histology, Keratohyalin Granules 2019 Jan;     [PubMed PMID: 30725734]
[4] Brown TM,Krishnamurthy K, Histology, Hair and Follicle 2019 Jan;     [PubMed PMID: 30422524]
[5] Polak-Witka K,Rudnicka L,Blume-Peytavi U,Vogt A, The role of the microbiome in scalp hair follicle biology and disease. Experimental dermatology. 2019 Apr 11;     [PubMed PMID: 30974503]
[6] Starace M,Alessandrini A,Piraccini BM, Nail Disorders in Children. Skin appendage disorders. 2018 Oct;     [PubMed PMID: 30410888]
[7] Fulton EH,Kaley JR,Gardner JM, Skin Adnexal Tumors in Plain Language: A Practical Approach for the General Surgical Pathologist. Archives of pathology     [PubMed PMID: 30638401]