Histologic Diagnosis of Inflammatory Skin Diseases
Chapter 1. Embryologic, Histologic, and Anatomic Aspects
Topography and Regional Variation
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What is this feature?
Melanocytes synthesize melanin. From precursors in the neural crest, melanocytes migrate normally to the epidermis, the bulb of hair follicles, epithelia of various mucous membranes, leptomeninges, inner ear, and a few other tissues (
). Primitive melanocytes first appear in the skin during the eighth week of fetal life, but at that time they produce little melanin. Only in postnatal life do normal melanocytes begin to function fully, except in certain cutaneous loci, such as nipples and genitalia, and in the bulb of follicles, where in the fetus they make melanin copiously.
Melanocytes (black dots) are derived from primordial neural crest and migrate especially to skin, mucous membranes, ocular structures, and leptomeninges.
When scrutinized through a conventional microscope, melanocytes appear as "clear cells" in and immediately beneath the row of epidermal basal cells, that is, the dermoepidermal junction (
). The space characteristic of melanocytes, and for which they were named "clear cells" by Masson, actually is an artifact of fixation during which cytoplasm shrinks and becomes concentrated around the nucleus, thereby creating a lacuna. In fact, melanocytes are not clear cells; they possess abundant translucent cytoplasm. The nucleus of a melanocyte is smaller and more deeply basophilic than that of a basal keratocyte, and the cytoplasm of it is dendritic, unlike that of a keratocyte (
). Dendrites of melanocytes are revealed more effectively with silver salts that stain melanin black; they then are seen to arborize in all directions among neighboring keratocytes and even extend into the uppermost part of the dermis (
). It has been estimated that in this manner a single melanocyte is connected to about 36 keratocytes, a relationship that has been termed, imprecisely, "the epidermal melanin unit." The unit really consists of a melanocyte and keratocytes that are supplied by it. In sections stained by hematoxylin and eosin, the average ratio of melanocytes to basal keratocytes is about 1 to 10, but the concentration of melanocytes varies according to the region of the body, being more numerous in the skin of the face (up to 2,900 melanocytes per mm
) than on the trunk (up to 1,250 melanocytes per mm
Epidermal melanocytes, when viewed through a conventional microscope, appear as "clear cells" in and immediately beneath the basal layer. Vacuity of melanocytes is an artifact of fixation caused by the collapse of cytoplasm around the nucleus. A tad of stellate-shaped cytoplasm still can be seen attached to the nucleus. Note that nuclei of melanocytes are smaller and darker than those of contiguous keratocytes. (
Dendrites of melanocytes are exaggerated in a split-skin preparation from a rhesus monkey that was irradiated for 28 days prior to biopsy. (Dopa stain.) (Courtesy of William Montagna, Ph.D.)
Dendrites of a melanocyte extend in all directions, especially along the basal layer and between keratocytes in the spinous zone. Once melanin has been formed, it is transferred from melanocytes to keratocytes by a process called apocopation.
Melanosomes within the cytoplasm of melanocytes are factories for manufacture of melanin and warehouses for storage of it (
). They are spherical or ellipsoid membrane-bound particles with a highly organized internal structure composed of longitudinally oriented concentric lamellae that possess a characteristic periodicity (
). Once melanosomes are formed, melanized, and transported to the tip of dendrites, they are transferred to keratocytes by apocopation, i.e., a process in which the tip of dendrites is snipped off and engulfed by keratocytes. That phenomenon enables collections of melanosomes to be housed in epidermal and follicular keratocytes, and there to serve their purpose. In the epidermis, melanosomes become concentrated in umbrella-like array above the nucleus of keratocytes, on the side of a nucleus closest to the surface of the skin. After transfer to keratocytes, fully melanized melanosomes are conveyed outward as those keratocytes mature, eventually becoming degraded by lysosomal enzymes and shed along with desquamated corneocytes.
A melanocyte contains melanosomes but no tonofibrils. (
17,000) (Courtesy of Ken Hashimoto, M.D.)
In a melanocyte, spherical and elliptical membrane-bound melanosomes are present at various stages of development. (Courtesy of Alvin Zelickson, M.D.)
Melanosomes in a melanocyte have a distinctive structure formed of concentric lamellae with characteristic periodicity. (
929,000) (Courtesy of Alvin Zelickson, M.D.)
Because the absolute number of melanocytes in human skin is approximately the same for both sexes and all races, the amount of melanin in keratocytes and the distribution of it determines the degree of pigmentation of skin. Differences in color among the races result from differences in the number, size, degree of melanization, distribution, and rate of degradation of melanosomes within keratocytes. In dark-skinned peoples, melanosomes within keratocytes are numerous, large, melanized markedly, distributed as solitary units, and degraded slowly. In addition, the epidermis of dark-skinned peoples contains melanocytes whose dendrites are larger and more elongated. In contrast, melanosomes within epidermal keratocytes of light-skinned peoples are fewer, smaller, less abundantly melanized, and distributed as aggregates within phagosomes where they are degraded more rapidly; dendrites are shorter. When pale skin is exposed to ultraviolet light, however, melanocytes increase in number and size, and become more strikingly dendritic. Radiation by ultraviolet light accelerates synthesis, melanization, and transfer of melanosomes to keratocytes. As melanosomes become larger and melanized more copiously, melanin is synthesized actively. This series of events results in tanning. Melanocytes situated in the bulb of anagen follicles impart to hair various colors, those who bear them being known, colloquially, as blonds, brunettes, and redheads.
Aging is accompanied by a decrease in number and decline in activity of melanocytes positioned in follicular bulbs, the result being progressive graying of hair. Although epidermal melanocytes also decline in number with age, skin that has been exposed extensively and repeatedly to ultraviolet light is marked by greater density of melanocytes than regions that have been spared such exposure. Unlike the situation in an incipient stage of melanoma, however, the melanocytes stationed at the dermoepidermal junction of skin damaged severely by the effects of ultraviolet light, that being evidenced by an extraordinary amount of solar elastosis (elastotic material), are equidistant from one another and monomorphous.
The principal function of melanin is to protect the skin from harmful effects of sunlight, a task accomplished by its capability to scatter and absorb ultraviolet light.
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