1.1.1.1 Keratinocytes
Keratinocytes originated from the ectoderm，are the main cells of the epidermis，and they can produce keratin which is one of the main structural proteins of keratinocytes.It serves as a cytoskeleton to maintain cell structure and participate in physiological and pathological processes such as epidermal differentiation and keratinization.According to the differentiation stage and characteristics of keratinocytes，the epidermis can be divided into 5 parts from deep to shallow，i.e.，stratum basale，stratum spinosum，stratum granulosum，stratum lucidum，and stratum corneum，respectively（Figure 1-1）.
（1）Stratum basale：It is located at the bottom of the epidermis.Stratum basale consists of a layer of cylindrical basal cells，usually arranged neatly，like a fence.Its long axis is perpendicular to the boundary line between the epidermis and the dermis.The cytoplasm is deeply basophilic，the nucleus is oval，the nucleolus is obvious，and the mitosis is common.The melanin granules can be seen on the top of the nucleus to gather or arrange in a cap.The basal cells and the spinous cells above it are connected by intercellular bridges.The bottom of the basal cells are attached to the basement membrane zone under the epidermis by hemidesmosomes.This zone is not easy to be identified during HE staining and can only be revealed by special staining，e.g.，periodic acid schiff（PAS）staining.Basal cells express keratin K5/K14.
It is a precisely regulated process for the basal cells to divide，differentiate，mature into stratum corneum，and finally fall off from the skin surface.Under normal circumstances，about 30％of the basal cells are in the mitotic phase.The new keratinocytes move up in an orderly manner.It takes about 14 days to migrate from the basal layer to the granular layer，and another 14 days to migrate to the surface of the stratum corneum and fall off.The whole 28 days are termed as the cuticle transit time or replacement time.
（2）Stratum spinosum：It is located above the basal layer.Stratum spinosum is usually composed of 4-8 layers of polygonal cells.The closer to the surface，the flatter the cells shape.Each cell has many cytoplasmic processes，called spinous processes，so this layer of cells is also called spinous cells.The spinous processes of normal skin are not clearly visible under high magnification but are visible when there is intercellular edema.Under the electron microscope，it can be seen that there are many tension filaments in the cytoplasm gathered in bundles and attached to the desmosomes.In the cytoplasm of the upper spinous layer，there are scattered coated particles with a diameter of 100-300 nm，called keratinocytes or Odland bodies.Spinous cells express keratin K1/K10.(https://www.daowen.com)
（3）Stratum granulosum：It is located above the spinous layer.Stratum granulosum is usually composed of 1-3 layers of flat or diamond-shaped cells，with the long axis paralleling to the skin surface.The cytoplasm is filled with large，deeply basophilic transparent keratinous granules.The thickness of the stratum granulosum of normal skin is directly proportional to the thickness of the stratum corneum.Where the stratum corneum is thin，there are only 1-3 layers of stratum granulosum.While where the stratum corneum is thick（e.g.，palm and plantar），the stratum granulosum can be up to 10 layers.The nucleus and organelles are dissolved，and a large number of transparent keratinous particles with irregular shapes can be seen in the cytoplasm deposited between the tension filaments.
（4）Stratum lucidum：It is located between the granular layer and the stratum corneum.Stratum lucidum is only seen in areas with thicker epidermis（e.g.，palm and plantar），especially in the skin tissue sections of the heel area，where this layer is the most obvious.This layer is composed of 2-3 layers of relative flat cells.The cell boundaries are unclear and easily stained by eosin.The cytoplasm is homogeneous and highly refractive under light microscope.
（5）Stratum corneum：It is located at the uppermost layer of the epidermis.Stratum corneum is composed of 5-20 layers of dead flat cells（40-50 layers at the palm and plantar area）.In the stratum corneum，the normal structure of the cell disappears，the staining is eosinophilic，and the cytoplasm is full of keratin formed by the combination of tension filaments and homogeneous substances.The desmosomes between cells in the upper stratum corneum disappear or form residues，thus they are easy to fall off.Since the outer layer of the stratum corneum is constantly falling off，it is difficult to determine its thickness.In formalin-fixed specimens，the stratum corneum has large intracellular and extracellular spaces，so it is often reticulated.