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Pathomorphology of the Skin

For medical students3 min readUpdated 2026-10-10

The skin is a complex organ that maintains homeostasis and protects the body against external aggression. Breakdown of its adaptive mechanisms leads to typical pathological processes, ranging from inflammation and dystrophies to neoplastic growth and genetic anomalies.

Keratinocyte layersBasal, spinous, granular, cornified. The stratum lucidum is present only on palms and soles.
RenewalThe differentiation life cycle of a keratinocyte takes about 30 days.
Birbeck granulesSpecific tennis racket-like structures in Langerhans cells.
Filaggrin geneMutations in this gene cause ichthyosis vulgaris and increase the risk of atopic dermatitis.

Histological Structure of the Epidermis and Dermis

The skin consists of two main compartments: the epidermis (of ectodermal origin) and the dermis (connective tissue of mesenchymal origin). The subcutaneous adipose tissue (hypodermis) lies deeper.

The epidermis is a stratified squamous keratinizing epithelium. Its main components are keratinocytes, which progressively differentiate and migrate from the basement membrane to the surface. In addition to keratinocytes, the epidermis contains clear cells identified by special staining methods:

The dermis is separated from the epithelium by a basement membrane and includes two layers: papillary and reticulocutaneous (reticular). It contains blood and lymphatic vessels, nerves, and skin appendages.

Morphology of Skin Appendages

Skin appendages play a key role in integumentary physiology and frequently serve as the source of tumors or targets for inflammatory reactions.

Sweat glands are divided into two types:

  1. Eccrine glands: distributed universally. Their secretory portion lies at the lower border of the dermis and consists of large clear cells (containing glycogen) and small basophilic cells (containing mucopolysaccharides). The excretory duct pursues a corkscrew course through the epidermis.
  2. Apocrine glands: localized in the axillary, perianal, and perigenital regions, and around the nipples. They exhibit a merocrine type of secretion. Unlike eccrine glands, their duct opens into the hair follicle.

Sebaceous glands are alveolar structures with a holocrine type of secretion (cells disintegrate to release their secretion). They are present everywhere except the palms and soles and open into the pilosebaceous canal (hair funnel).

Hair follicles have a complex structure (base with hair bulb and dermal papilla, isthmus, funnel). The hair is surrounded by an internal root sheath (contains trichohyalin, keratinizes) and an external root sheath (continuation of the epidermis). The hair cycle consists of three phases: anagen (growth), catagen (transition), and telogen (resting).

Principles of Classification of Skin Diseases

All skin pathologies are divided into two massive groups:

  1. Tumors and tumor-like lesions. They are classified according to histogenesis: derived from the epidermis, melanin-producing tissue, appendages, fibrous, adipose, muscular, and vascular tissues, as well as lymphoproliferative processes.
  2. Non-neoplastic diseases. This group features immense clinical and morphological diversity. It includes hereditary disorders (genodermatoses), inflammatory conditions (erythematosquamous, vesiculobullous, granulomatous), vasculitides, and toxic-allergic reactions. It also includes damage caused by physical factors (ultraviolet light, radiation, cold), pigmentation disorders, and infectious-parasitic processes.

Pathomorphology of Genodermatoses: Ichthyosis

Ichthyosis is a heterogeneous group of genetic disorders characterized by impaired keratinization. Clinically, it manifests as widespread hyperkeratosis.

Ichthyosis vulgaris is the most common form (1:3,000), inherited in an autosomal dominant manner. The primary cause is a mutation in the filaggrin gene. Patients exhibit dry skin with polygonal scales and accentuated palmar and plantar creases. The disease is frequently associated with atopic dermatitis. Histology: prominent hyperkeratosis (including follicular hyperkeratosis) accompanied by thinning or complete absence of the granular layer of the epidermis. Sebaceous glands are atrophic.

X-linked ichthyosis (ichthyosis nigricans) is less common (1:6,000) and manifests fully only in males. It is caused by a genetic defect (deletion in the Xp22.32 locus) leading to a deficiency of steroid sulfatase and arylsulfatase enzymes. It features a more severe clinical course with brown scales. Histology: hyperkeratosis is accompanied by a normal or even thickened granular layer, which is a key distinguishing feature from the vulgaris form. The dermis remains unchanged.

Mnemonic

How to remember the histology of ichthyosis: in the vulgaris form, the granular layer is "vulgarly erased" (absent), whereas in the X-linked form, it is preserved or thickened.

Frequently asked questions

How does the biochemical synthesis of melanin occur in melanocytes?

The biochemical synthesis of melanin occurs via the sequential oxidation of the amino acid tyrosine with the participation of enzymes. The key rate-limiting enzyme is tyrosinase (cofactor: copper ion), and DOPA oxidase is also involved in the process.

Stages of biosynthesis:

  • Tyrosine — oxidized to DOPA (dihydroxyphenylalanine / 3,4-dihydroxyphenylalanine).
  • DOPA — converted to dopachrome.
  • Dopachrome — transformed into 5,6-dihydroxyindole.
  • Melanins — formed at the final stage of polymerization of 5,6-dihydroxyindole.
What layers are distinguished in the dermis, and which specific receptors are located in each of them?

The dermis has two main layers: the papillary layer and the reticular layer. Specific nerve endings are located in each.

  • Papillary layer — contains encapsulated Meissner corpuscles (tactile) and unencapsulated (free) receptors responsible for sensing temperature and pain.
  • Reticular layer — includes deeply situated encapsulated receptors: Pacinian corpuscles (pressure and vibration sensing), Ruffini endings (stretch sensation), and Krause end bulbs (mechanoreceptors).
With which nerve fibers do Merkel cells contact?

Merkel cells contact the dendritic endings of sensory neurons. This contact forms a tactile receptor (Merkel disc) that detects very light touch. The dendrite of the sensory neuron emerging from the disc becomes myelinated just beyond the epidermal basement membrane. Meanwhile, the receptor itself is classified as a free nerve ending because it lacks a connective tissue capsule and modified glial cells.

What is the difference in the localization of sweat gland ducts?

Eccrine ducts pierce the epidermis and open directly onto the skin surface, whereas apocrine ducts empty into the hair follicle.

What are Langerhans cells?

They are intraepidermal macrophages of bone marrow origin. They participate in the immune response, express MHC class I and II molecules, and contain characteristic Birbeck granules.

Where are sebaceous glands and hair absent?

They are absent on the palms and soles. Hairs are also absent on the dorsum of the terminal phalanges, glans penis, nipples, and inner surfaces of the labia minora.

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