Malignant melanoma of the skin

Malignant melanoma of the skin (syn: melanoblastoma, melanocarcinoma, melanosarcoma) is a high-grade tumor, consists of atypical melanocytes.

Genetic predisposition to the development of melanoma is noted - at least 10% of all cases of melanoma are familial.

[1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13]

Causes of the melanoma skin

A genetic defect is not currently known, but many patients in these families have a division of 9p21. The risk of developing melanoma in people with multiple (more than 50) normal melanocytic nevi is increased; with congenital nevi, especially giant ones; with multiple dysplastic nevi. One of the most important provoking factors is the negative effect on the skin of solar radiation. Great importance is attached to the total dose of solar radiation received in the first 5 years of life, and the presence in the anamnesis of sunburns in childhood. The relative risk of developing melanoma is related to the skin phototype. The risk group is mainly white people with light or red hair, blue eyes and numerous freckles, which do not tan well and easily get sunburn.

Malignant melanoma of the skin mainly develops in adults, but cases of congenital melanoma and its occurrence in childhood are described; it can occur on any areas of the skin, including the nail bed.

[14], [15], [16], [17], [18], [19], [20]

Symptoms of the melanoma skin

The tumor is asymmetrical, initially flat, slightly elevated, less often domed, strongly and unevenly pigmented. With the exception of amelanotic forms. Sometimes it reaches a very large size, the surface becomes uneven, grows crusty as it grows, easily traumatizes, bleeds. Pigmentation is intensified, the color becomes almost black with a bluish tinge. With spontaneous focal regression of the tumor, areas of depigmentation are identified. Ulceration and disintegration of the tumor may occur. Around her appear small, pigmented children.

The most commonly encountered surface-spreading melanoma, it is characterized by fairly long-existing patches or plaques of brown with pinkish-gray and black impregnations, is localized on the skin of the back, especially in men, and in women - mainly on the lower extremities. A non-pigment variant is possible.

Lentigo melanoma is usually localized on the face, neck, hind limbs, develops in old age against the backdrop of a long-standing malignant lentigo (Dufreille precancerous melanosis). With the onset of invasive growth within the unevenly pigmented spot, towering patches or individual nodules appear. A non-pigment variant is possible. Lentiginous melanoma of the akral localization and melanoma of the mucous membranes have a similar histological pattern and are characterized by a characteristic localization - on the mucous membranes, on the skin of the palms, soles, in the region of the nail dog.

Nodal melanoma protrudes above the surface of the skin in the form of exophytic, often symmetrical, formation of dark brown or black color or in the form of a polyp on the stem. The surface at first smooth, shiny, can be verrucous. Quite quickly, the tumor increases in size, often ulcerated. It is localized mainly on the back, head, neck, but it can also be on other sites. A non-pigment variant is possible. When a nodal melanoma is detected, one should keep in mind the possibility of metastasis from another primary focus.

Desmoplastic neurotropic melanoma occurs mainly in the region of the head and neck, usually has a form of pigmentless. Compacted at the base of a plaque or a dense tumor-like formation, sometimes against a malignant lentigo. It is characterized by a high risk of recurrence.

Malignant blue nevus is a malignant cell blue nevus and is characterized by an aggressive course, although cases with late metastasis are described. Sometimes there is against the background of the nevus Ogs. It is observed mainly in middle-aged and elderly people, mainly on the face and scalp, chest, buttocks.

Stages

According to this histological study, no more than 35% of melanomas develop in the area of melanocytic nevi. The rest are de novo on unchanged skin.

The clinico-morphological classification of melanoma is based on the definition of the phases of horizontal and vertical growth, proposed by WH Clark et al. (1986). In the phase of horizontal growth, the lateral spread of the flat pigmented area is determined due to intraepidermal proliferation of atypical melanocytes. The intraepithelial component of the tumor (to a greater extent its architectonics and growth pattern, to a lesser extent - cytological features) are different in the surface-spreading, lentigo-melanoma and lentiginous melanoma of the acral localization. The horizontal phase of growth precedes the vertical phase, with the exception of nodal melanoma and some other rare types of melanoma.

When the tumor progresses, the membrane of the epidermis breaks down and the invasive stage begins. However, invasion of the dermal papillary layer by single melanocytes or groups of cells does not mean that the tumor has passed into the phase of vertical growth, i.e. Has acquired the ability to metastasize. The phase of vertical growth of the tumor reflects a tumor progression and is not synonymous with an anatomical level of invasion. It presupposes the presence of volumetric formation in the dermis (tumorigenic phase) and usually corresponds to no less than level III of the invasion of melanoma by Clark:

• I level - melanoma cells are found only in the epidermis (melanoma in situ);
• II level - Melanoma cells are defined in the papillary dermis layer, but do not fill it completely and do not stretch it with their own mass;
• III level - the tumor node is completely defined, completely filling the papillary layer of the dermis to its border with the mesh, increasing its volume;  
• IV level - the melanoma cells infiltrating the mesh layer of the dermis are defined;
• V level - subcutaneous tissue invasion.

DE Elder and GF Murphy (1994) classified all forms of malignant melanoma of the skin into those having a horizontal growth phase (surface-spreading melanoma, lentigo-melanoma, lentiginous melanoma of the acral localization and mucous membranes, unclassifiable species) and not having it melanoma, desmoplastic and neurotropic melanoma, melanoma with minimal malignancy, malignant blue nevus, unclassifiable phase of vertical growth).

[21], [22], [23], [24]

Forms

Surface spreading melanoma is characterized by the proliferation of a large number of individual melanocytes or their "nests" throughout the thickness of the epidermis. Melanocytes with a light abundant cytoplasm containing finely dispersed (pulverized) melanin, and dark, atypical nuclei, resemble Paget cells. In the future, the epithelium of the appendages of the skin may be involved. The invasive component is characterized by the presence of rather large polymorphic cells of a cubic or polygonal shape, reminiscent of epithelial cells, sometimes elongated, spindle-shaped. There are also balloon-like, cricoid-shaped, nevusoloblobnye cells - small, round or oval, with hyperchromic nuclei, a narrow rim of the cytoplasm, in which the pigment is not visible. In all cases marked polymorphism of cellular elements is noted, mitoses are characteristic, including pathological ones.

With lentigo-melanoma, the intra-epidermal component is characterized by lentiginous proliferation of atypical melanocytes of polygonal contours, often with very large nuclei, usually located within the basal layer, sometimes in the form of "nests". Migration to the overlying layers of the epidermis is poorly expressed; Melanocytes resembling Paget cells are practically not found. Characteristic of early epithelial lesions of superficial areas of the appendages of the skin, especially the hair follicles. Often, this form shows atrophy of the epidermis. The invasive component is often represented by spindle-shaped cells, there are giant multinucleated cells. In the upper parts of the surrounding dermis, solar elastosis is usually expressed.

Nodular (nodal) melanoma is a special form of melanoma, which is said to be found in the histological preparation only of the vertical phase of growth with intact epidermis and papillary dermis. It is assumed that in this way nodal melanoma arises in the de novo derma, and at present there is no data for the pre-existence of a fast horizontal phase with subsequent regression of the intraepidermal component, although this theory is considered by some authors. The most common tumor is formed by rounded or polygonal epithelioid cells. It is necessary to differentiate from a metastatic melanoma.

Lentiginous proliferation of atypical melanocytes is noted in the case of the acantular lentigineous melanoma. Migration to the overlying layers of the epidermis is poorly expressed, melanocytes resembling Paget cells are practically not found.

The epidermis is distinguished by pronounced acanthosis, which has a characteristic rarely loopy structure. There is a significant depth of invasion with an apparent minor lesion of the epidermis.

Desmoplastic melanoma, as a rule, is pigmentless, formed by bundles of elongated cells resembling fibroblasts, separated by interlayers of connective tissue. Pleomorphism of cellular elements is usually poorly expressed, mitoses are few. Areas with pronounced differentiation are determined in the direction of Schwann cells and indistinguishable from Schwannoma. Focal clusters of lymphocytes and plasma cells are noted, neurotropism is possible. The tumor is characterized by a significant depth of infestation.

Malignant blue nevus is characterized by the presence in the neoplasm, which has the structure of the cellular blue nevus, of a poorly delineated high-grade region with signs of malignancy, such as pronounced nuclei polymorphism, atypical mitoses, necrosis foci and deep infiltrative growth. Unlike other forms of melanoma, there are pigmented cells within the tumor, elongated cells with long processes and there is no borderline activity of melanocytes. To confirm the diagnosis, an immunohistochemical reaction with the antiserum to the PCNA antigen, a marker of proliferative activity, is sometimes used.

In addition to the above features of various forms of melanoma, the large size of the tumor, the presence of multiple, including atypical, mitoses, the presence of sites of spontaneous necrosis with ulceration, pronounced atypism and polymorphism of cellular elements testify to the malignant process.

Melanoma is more characteristic of the invasion of the stroma by layers and nests of cells. Which, as it were, are advancing on the surrounding tissues, squeezing and destroying the adjacent structures of the dermis with its growth.

Considerable difficulties for differential diagnosis are the so-called melanoma with minimal signs of malignancy, a rare histological variation of melanoma with a more favorable clinical course and a prognosis (minimal deviation melanoma). In this group, melanomas resembling the Spitz nevus, small-cell nevoid melanomas, and some halonews can be found.

Melanoma with minimal signs of malignancy is characterized by the presence of a tumor in the dermis formed by a more or less monomorphic population of melanocytes with a poorly expressed atypism and low mitotic activity. Cells can be both epithelioid and spindle-shaped. Sometimes, lentiginous proliferation of atypical melanocytes is observed in the epidermis, but there is no phase of horizontal growth.

In cases of pigmentless melanoma melanin coloration by Massou-Fontan method, identification in cells by premelanosomes by electron microscopy, staining of S-100, MMB-45 and NKI / C-3 antigens using munomorphological methods helps to reveal the melanocytic nature of the tumor. Desmoplastic neurotropic melanoma is characterized by a negative reaction to the detection of the antimene HMB-45.

The results of immunomorphological studies with markers of p53 antigen, PCNA, Ki-67 (MIB-1) for melanocyte skin tumors are not the same under different conditions, generally poorly reproducible and variable.

[25], [26], [27], [28], [29]

Forecast

The prognosis of skin melanoma is based on the level of invasion of skin layers, the thickness of invasion in millimeters according to Breslow, the mitotic index, and also the features of the histological structure and the degree of mononuclear infiltration of tumor elements.

[30], [31], [32]