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Pigmentation disorders. Pathology of the melanocytic system of the epidermis. Melanocytic tumors

Melanocytes are located in the basal layer of the epidermis. Their number varies in different parts of the skin. Melanocytes synthesize melanin in specialized organelles - melanosomes, tyrosinase is involved in this process. This enzyme catalyzes the conversion of tyrosine to dioxiphenylalanine (DOPA), which is converted into melanin during other biochemical reactions. Melanosomes spread along them, which secrete melanin into the extracellular space. There, melanin is captured by keratinocytes, where it is cleaved by lysosomal enzymes. Its main purpose is to protect the underlying tissues from ultraviolet radiation. Skin color (including the intensity of tanning in individuals of the European race) is associated not so much with the number of melanocytes as with their activity.

Vitiligo. This is a violation of skin pigmentation, manifested in the appearance of depigmented macula of various sizes and shapes, with a milky white color and a fringing in the form of a narrow zone of moderate hyperpigmentation. Vitiligo is found in representatives of all races, but most of all it is expressed in people with dark skin. In people of the European race, skin changes can be completely invisible until the surrounding normal skin is tanned. From a clinical point of view, vitiligo is usually an asymptomatic disease. The size of the macula ranges from a few to many centimeters; Usually the skin of the wrists and armpits, the skin around the mouth and eye sockets, as well as the integument of the genitals and around the anus, are usually affected.

The foci of vitiligo are characterized by the loss of melanocytes. This is convincingly proven using electron microscopy. Thus, vitiligo is radically different from another diffuse pigmentary disease - albinism, in which there are melanocytes, but due to the cessation or violation of tyrosine synthesis, melanin is not produced in them. Both diseases can be distinguished from other forms of hypopigmentation (not related to the absence of melanocytes or tyrosinase) by histochemical determination of tyrosinase activity of melanocytes. The progressive violation of the formation of melanin is explained by the influence of autoimmune and neurohumoral factors, toxic intermediate products of melanin synthesis, leading to self-destruction of melanocytes. The greatest amount of evidence has been collected in favor of the first mechanism. We are talking about the presence of circulating antibodies to melanocytes in patients and the connection of vitiligo with diseases that can stimulate autoimmune mechanisms: pernicious anemia (see chapter 12), Addison's disease and autoimmune thyroiditis (see chapter 23). In addition, anomalies of the Langerhans cells of the epidermis and peripheral blood T-lymphocytes have recently been discovered, which indicate the possibility of participation in the pathogenesis of vitiligo abnormalities in cell-mediated immunity.

Freckles. These are the most common pigmented skin changes in childhood in people of the European race with fair skin. Freckles are small (1-10 mm in diameter) red or light brown macules that first appear in early childhood after sun exposure. Once having appeared, freckles disappear in the winter and appear again in the spring in a peculiar cyclic mode. The hyperpigmentation that appears in the elements of freckles is due to the increased amount of melanin in the keratinocytes of the basal layer of the epidermis. At the same time, the number of melanocytes does not exceed the norm, although some of these cells can be increased in size. It remains unclear whether freckles reflect a focal anomaly of melanin synthesis or the delivery of an increased amount of this pigment to adjacent keratinocytes of the basal layer, or both.

Melasma (skin melanosis). Melanosis is an excessive deposition of melanin in the skin, but more pronounced than in the elements of freckles. Usually, melasma is a masked area of ​​hyperpigmentation on the face that often occurs during pregnancy. We are talking about barely visible macules appearing on the cheeks, temples and forehead on both sides. Sunlight can enhance this pigmentation, which often passes spontaneously (especially at the end of pregnancy).

Two histological types of melasma are distinguished: epidermal, in which an increased amount of melanin is formed in the cells of the basal layer of the epidermis, and dermal, characterized by the accumulation of macrophages in the papillary dermis, which phagocytosed melanin from the epidermis (this process is called melanin incontinence). Recognizing both types is very important, since skin with epidermal melasma can react to hydroquinone with a local bleaching effect (hydroquinone is an intermediate in the production of dyes, a polymerization inhibitor, and an antioxidant that exhibits a reagent in photography). The pathogenesis of melasma is associated with functional changes in melanocytes, which lead to increased pigment transfer to basal keratinocytes or dermal macrophages. Besides the fact that melasma is associated with pregnancy, it can occur when using oral contraceptives and may be of unknown origin.

Lentigo. This hyperplasia of melanocytes, which occurs at any age, but especially often in infancy and early childhood. No sexual or racial predisposition has been identified, and the cause and pathogenesis of lentigo are unclear. The disease can affect both the mucous membranes and the skin. It manifests itself in the form of small (5-10 mm in diameter) oval brown maculae. Unlike freckles, lentigo does not darken when exposed to sunlight. Its main histological characteristic is linear hyperplasia of melanocytes (occurring in the plane of the epidermis), as a result of which a basal layer containing an excess amount of pigment is formed. With lentigo, thinning of the reticular dermis is often noted.

Non-cellular nevus (pigmented nevus, mole). A mole is one of the most diverse, dynamic, and biologically significant skin tumors. The name "non-cellular extravascular nevus" is used in relation to any congenital or acquired tumor consisting of melanocytes. The most common (acquired) non-extracellular nevus is a small reddish-brown, uniformly pigmented, dense papule, which, as a rule, is less than 6 mm in diameter and has well-defined rounded borders. There are a large number of clinical and histological types of non-cellular nevus, the most important of which are given in table. 25.1. Non-cellular nevus is formed from melanocytes, which turn from single process cells scattered among basal keratinocytes into round or oval cells growing in groups or nests along the junction of the epidermis and dermis. The nuclei of the nevus cells have a rounded shape, are relatively monomorphic and contain not very noticeable nucleoli. Their mitotic activity is negligible.

The surface form of the tumor reflects the early stage of its development and is called borderline nevus. Gradually, the majority of borderline nevi grows into the underlying dermis in the form of cell nests and cords (complex nevus) (Fig. 25.2, A). In more mature neoplasms, these nests may already be completely isolated from the epidermis. This is the dermal (intradermal) nevus (Fig. 25.2, B). Complex and dermal nevi, as a rule, rise above the surface of the skin, in contrast to their borderline analogues. The progressive growth of nevus cells from the area of ​​the dermatoepidermal junction into the underlying dermis is accompanied by a process called maturation. Despite the complete maturation, those nevus cells that are closer to the skin surface have larger sizes, a tendency to melanin production and the formation of nests. More: Really nevus cells, located deeper, are smaller. They grow in strands and synthesize a small amount of melanin or

Table 25.1.

Characterization of morphological forms of noncellular nevi

they don’t produce it at all. The most mature nevus cells can be found in the very core of the tumor, where they often acquire a fusiform shape and grow in bundles resembling nerve tissue. In such non-pigment synthesizing, deeply located nevus cells similar to nerve structures, changes in enzyme activity (progressive loss of tyrosinase activity and the appearance of cholinesterase activity) are noted.

More rare variants of non-extracellular nevus compared with those described are blue nevus (Fig. 25.3, A, B) and halo nevus (Fig. 25.3, C).

Dysplastic nevus. The relationship of non-cellular nevus with the development of malignant melanoma was discovered more than 160 years ago.
However, the true precursor of malignant melanoma was studied in detail only about 20 years ago. In 1978, WHClark et al. described in detail the lesions that they called VK moles (based on the initial letters of the names of the first two families studied). Birthmarks VK (dysplastic

Fig. 25.2.

Nevi of various types


A - complex nevus, B - dsrmal (ntradsrmal) nevus (negatives of TA, Novitskaya and I.N. Chuprova).

Rice, 25.3,

Nevi of various structures


A -

blue nevus

, general view, in the deep sections of the dermis are masses of melanin; B - light cells lacking pigment in the so-called proliferative part of the blue nevus.

Fig. 25.3. To be continued.

IN -

halonevus, foci of nevus cells in the papillary dermis

protruding into the epidermis (negatives of T. A. Novinka and I. N. Chuprova).

nevi) are larger than other acquired moles: often their diameter exceeds 5 mm. These are flat macules, or plaques, protruding slightly above the surface of the skin and have an uneven surface. As a rule, the degree of pigmentation varies, and the edges have irregular contours.

Unlike freckles, dysplastic nevi appear on the surface of the skin, both exposed to sunlight and covered clothing. These neoplasms are found in many family members who have a tendency to develop malignant melanomas (suffering from hereditary melanoma syndrome). Genetic analyzes performed in such individuals revealed an autosomal dominant type of inheritance of dysplastic nevi. It was suggested that a sensitive gene that is localized on the short arm of chromosome 1 near the Rh locus is involved in hereditary transmission [according to Cotran RS, Kumar V., Collins T., 1998]. Dysplastic nevi can also occur as independent neoplasms that are not associated with hereditary melanoma syndrome, in which case the risk of malignancy is low. Using a serial study of biopsy samples clinically and histologically in some lines, the transformation of dysplastic nevus into an early form of melanoma was traced. It turned out that it occurs within a few weeks. However, most of these nevi are nevertheless stable (benign) neoplasms.

Dysplastic nevi are built from the elements of a complex nevus that has architectural and cytological signs of abnormal growth. Intraepidermal nests from nevus cells are larger and often merge with each other. Part of this process is that individual nevus cells begin to replace keratinocytes of the basal layer, spreading along the dermatoepidermal compound. At the same time, atypia of nevus cells is observed, which manifests itself in the form of uneven, often angular contours and hyperchromasia of nuclei. Changes affect the surface of the dermis. Rare lymphoid infiltrates, loss of melanin from degrading nevus cells and its phagocytosis by dermal macrophages (melanin incontinence), as well as a characteristic linear fibrosis of the reticular layer are found here. The likelihood of developing melanoma in people aged 60 years with dysplastic nevus syndrome is currently estimated at 56%.

Malignant melanoma. This is a relatively widespread disease, which not so long ago was considered almost exclusively as fatal. In the vast majority of patients, melanoma occurs in the skin. With other localizations of this tumor, the mucous membranes are affected: the oral cavity, genitals, anus and esophagus. Especially often, this tumor develops in the choroid of the eye (see below). Occasionally, it is found in the membranes of the brain and mucous membranes of the urinary and biliary tract.

An important role in the occurrence of malignant melanoma of the skin is sunlight. For example, in men, it often develops on the upper back, and in women, on the back and legs. People with lighter skin are more at risk of developing melanoma than people with dark skin. Melanogenic factors include not only sunlight. The presence of a pre-existing nevus (especially dysplastic), hereditary factors, or even exposure to certain carcinogens - all this is important in the origin of the neoplasms. The earliest clinical manifestation of malignant melanoma of the skin is pruritus, and the most important symptom is a discoloration of the pigmented lesion. In contrast to the coloring of a benign (non-dysplastic) nevus, pigmentation with melan varies significantly and is manifested in all kinds of shades of black, brown, red and gray. Sometimes there are hypopigmentation zones of white or flesh-colored. The borders of melanoma are fuzzy, and the shape is not round, as with non-cellular extravascular nevus. They have the appearance of an irregular, crimped and not always clearly defined line.

Fig. 25.4.

Malignant lentigomelanoma


A -

superficial tumor spread

containing black pigment (melanin); B is a structural detail illustrating the malignant nature of growth (preparations by A.S. Gordeladze),

Fig. 25.5.

Malignant melanoma


A is the superficial type of tumor spread; B - structural detail of the surface distribution zone (appositional growth)

Fig. 25.5. To be continued.

IN -

stage of tumor node formation

(preparations by A.S. Gordeladz).

The interpretation of the structure of malignant melanoma is based on the concept of radial and vertical growth. Radial growth indicates a tendency of tumor cells to horizontal distribution (growth) in the epidermal and superficial dermal layers. Such growth often takes a long period of time. During its course, melanoma cells still do not exhibit metastatic ability. There are three types of radial growth of melanoma: malignant lentigo (Fig. 25.4, A, B), superficial distribution (Fig. 25.5, A, B), lentiginous lesions of the mucous membranes and limbs. They are determined by the general composition of the growth and structure of tumor elements in the epidermal layer, as well as by the biological behavior of melanoma. For example, malignant lentigo in the phase of radial growth usually occurs on the sun-damaged skin of the face of the elderly; it can exist several decades before it suddenly gives metastases. Over time, the radial growth changes to vertical. In the form of an expansively increasing mass, melanoma tissue rushes into the deeper layers of the dermis. In this mass, the cells remain at the stage of low differentiation and, as they spread into the reticular layer of the dermis, become increasingly smaller. Moreover, on the basis of the previous phase of planar and radial growth, the formation of a tumor node is visually (clinically) noted (Fig. 25.5, B). It is during this period that clones of tumor cells with metastatic potential are formed. The probability of metastasis can be predicted by a simple measurement (in millimeters) of the depth of invasion, which is determined by the thickness of the vertical growth zone, starting immediately below the granular layer of the epidermis.

As a rule, melanoma cells are much larger than the elements of the nevus. They have large nuclei with uneven contours and a marginally (under the nuclear membrane) located chromatin, as well as clearly defined eosinophilic nucleoli. These cells either form solid nests, or grow in small groups or singly. All this happens in all layers of the epidermis or in the dermis. As with other malignant tumors, it is important to note not only the degree of histological differentiation of tumor nests and complexes, but also the presence of melanin and the depth of invasion. The important prognostic indicators are considered to be the number of mitosis figures determined among tumor cells, the level of lymphocytic infiltration of the stroma and parenchymal complexes of the neoplasm.

As for eye melanoma, the incidence of this tumor is V5o from the same indicator for skin melanoma (for this tumor, see chapter 26).

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Pigmentation disorders. Pathology of the melanocytic system of the epidermis. Melanocytic tumors

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