Mastocytosis (Fat Cell Leukemia)

What is Mastocytosis (Mast Cell Leukemia)?

Mastocytosis (mast cell leukemia) is a systemic disease, the morphological substrate of which is massive infiltration of the skin, various organs and tissues with fat cells (mast cells, labrocytes, tissue basophils). The disease is rare, its frequency does not depend on gender. It usually develops during the first two years of a child’s life (75% of cases) and in half of cases is spontaneously resolved by puberty. Systemic mastocytosis is more common for adults.

Causes of Mastocytosis

The etiology and pathogenesis of mastocytosis are unknown. Sometimes it is transmitted by an autosomal dominant route, although in most cases patients do not have a family history.

Pathogenesis during Mastocytosis

The histological picture of all forms of mastocytosis is manifested by infiltrates, consisting mainly of mast cells. Mast cell granule metachromasia is detected using toluidine, methylene blue, and naphthol-AS-D-esterrase chloroacetate (Leder method), which stains mast cell cytoplasmic granules in red. In maculopapular and tele-angiectatic types of mastocytosis, mast cells are located mainly in the upper third of the dermis around the capillaries. Mast cell nuclei are more often spindle-shaped, less often round or oval. Due to the fact that mast cells may be present in a small amount and on sections stained with hematoxylin and eosin, their nuclei resemble the nuclei of fibroblasts or pericytes, special stains are required to establish the correct diagnosis. With multiple nodes or plaques, as well as with large solitary nodes, mast cells form large clusters according to the type of tumor, infiltrating the entire dermis and subcutaneous fatty tissue. When mast cells lie in dense clusters, their nuclei are more cubic than spindle-shaped, have eosinophilic cytoplasm and well-defined cell boundaries. This gives them a rather distinctive appearance, so the diagnosis can be made even without special staining. When diffuse (erythrodermic) type in the upper part of the dermis there are dense ribbon-like mast cell infiltrates with round or oval nuclei and clearly defined cytoplasm. In all types of mastocytosis (with the exception of teleangiectatic), eosinophils can be found among mast cells. An increase in the number of eosinophils and extracellular mast cell granules in the biopsy specimen taken after friction of the focus indicates the release of the granules from the mast cells. The nature of the bubbles in mastocytosis subepidermal; however, due to the regeneration of the epidermis at the base of the bubbles, the aging bubbles can be localized intraepidermally. The bladder often contains mast cells as well as eosinophils. The pigmentation of elements during mastocytosis is caused by an increase in the amount of melanin in the cells of the basal layer of the epidermis, less often by the presence of melanophages of the upper part of the dermis. In systemic mastocytosis, along with skin lesions, para-bacterial accumulations of mast cells in the bone marrow, diffuse infiltration of red spleen pulp by them, periportal infiltrates in the liver, and obstruction of the perifollicular and paracortical lymph nodes are found. Accumulations of mast cells are observed in the heart, kidneys, and mucous membrane of the gastrointestinal tract.

Symptoms of Mastocytosis

There are 4 forms of mastocytosis:

  • infant mastocytosis of infancy or early childhood, in which the skin lesions are resolved in puberty, systemic changes are usually absent, and progression with the development of the systemic form occurs extremely rarely;
  • cutaneous mastocytosis in adolescents and adults with frequent systemic lesions, which is often accompanied by systemic disorders, but they usually do not progress. Spontaneous regression in adults, unlike children, is not described. Sometimes this form progresses, goes into systemic mastocytosis with a progressive lesion of internal organs;
  • systemic mastocytosis;
  • malignant mastocytosis (mast cell leukemia) is a very rare form, characterized by the presence of cytologically malignant mast cells in many organs and tissues, especially in the bones and peripheral blood, with a rapid fatal outcome; usually not accompanied by skin manifestations.

More than half of patients with mastocytosis complaints are limited to skin lesions. About 1/3 of patients complain of itching, episodes of reddening of the skin, paroxysmal tachycardia, a drop in blood pressure, a periodic increase in body temperature, and so on. These symptoms are due to mast cell degranulation and are observed with common forms of mastocytosis of the skin or internal organs.

With mastopitosis, five types of skin lesions are distinguished (the first two of them occur in both infants and adults).

The maculopapular type of mastocytosis, represented by dozens or even hundreds of small red-brown hyperpigmented spots and papules, which after friction (Darya-Unna’s test) acquire urticaria-like character, is the most frequent.

The multiple knotty type of mastocytosis is represented by multiple dense hemispherical nodes of pink, red or yellow color, 0.5-1 cm in diameter with a smooth surface, sometimes the nodes merge into plaques, the Dare-Unna phenomenon is mild, especially in adults.

The type of large solitary knot, or mastocytoma, is manifested by a node with a diameter of 2-5 cm. It has a smooth or shriveled, orange-peel surface and a rubber consistency. Occasionally found up to 3-4 knots. Nodes occur only in babies, in the neck, trunk, forearms. Darya’s test — Unny positive. Trauma leads to the formation of bubbles on the surface of the node, pustules or bubbles, as well as a tingling sensation. Mastocytomas usually regress spontaneously, while they sink and flatten. In some cases, the nodes are associated with rashes characteristic of maculopapular mastocytosis.

Diffuse (erythrodermic) type of mastocytosis always begins in early childhood. It is characterized by large pruritic foci of yellow-brown infiltration, usually in the armpits and interdigital folds. The centers have an irregular shape, clear boundaries, a dense (up to woody) consistency, ulcerations, cracks, and excoriation easily arise on their surface. The progression of the pathological process can lead to erythroderma. At the same time, the integuments acquire a testovatuyu or dense texture, their color varies from pink-red with a yellow-brown shade to dark brown. The test of Darya-Unna is positive, and even a slight trauma to the lesion leads to the appearance of blisters, often accompanied by intense itching. With the prevalence of blisters in the clinical picture, they speak about bullous mastocytosis. The course of the disease is gradually improving, progression to systemic mastocytosis is rare, death occurs only in infants as a result of histamine shock.

The teleangiectic type of mastocytosis (a type of persistent spotted teleangiectasia) is a rare form of mastocytosis, occurs predominantly in adults, mainly in women. Manifested common brownish-red spots of various outlines, consisting of bright telangiectasia. located on the pigmented background. There is a slight tendency to blister in areas of friction or spontaneously. The skin of the chest and the extremities is affected. Itchy. In some cases, there is a lesion of bones and peptic ulcer.

Systemic mastocytosis is characterized by damage to the internal organs in combination with skin mastocytosis or without it, occurs equally often in men and women. Observed in 10% of patients with cutaneous manifestations of mastocytosis. In most cases, skin lesions precede the signs of a systemic process. Changes in the skin during systemic mastocytosis are represented by maculopapular, multiple nodular or diffuse (erythrodermic) types.

The process of mastocytosis can involve any organs and systems. Most often – bones, liver, spleen, lymph nodes, gastrointestinal tract, central nervous system. 20-30% of patients with mastocytosis have bone lesions that appear on x-ray examination with osteoporosis and osteosclerosis. Osteolytic changes are accompanied by pain. About 1/4 of bone lesions are mastocytomas, but they are infrequent in children. Liver lesions are manifested by asymptomatic fat-cell infiltrates and fibrosis with hepatomegaly and diffuse mastocytosis.

Systemic mastocytosis with the flow can be benign and malignant. Malignant mastocytosis includes mast cell leukemia, mast cell sarcoma, systemic mastocytosis variants associated with lymphomas, solid neoplasms or malignant blood diseases.

Diagnosis of Mastocytosis

Maximus leukemia is manifested by basophilia, neutrophilia with a significant shift of the nucleus to the left, hepato and splenomegaly, slight lymphatic hyperplasia. In the bone marrow punctate, foci of blast mast cells are found.

The diagnosis of mastocytosis of the skin is established on the basis of the clinical picture, the positive test of Darya-Unna, the increase in mast cells in the lesions. However, it should be noted that it may be absent during mastocytoma and if the lesion has been injured 2-3 days before the study (the time taken for the restoration of mast cell granules – 2-3 days).

In the diagnosis of mastocytosis, the determination of histamine in the urine (histaminuria) is used, but its level also increases in inflammatory, allergic diseases, as well as in healthy individuals (for example, in athletes). To exclude systemic mastocytosis, the main metabolite of histamine, 1-methyl-4-imidazole acetic acid, is determined, the content of which correlates with the activity of mast cell proliferation and increases dramatically during systemic mastocytosis, whereas in skin forms its level is close to normal.

The differential diagnosis of mastocytosis is carried out with pigmented nevi, freckles, lenti-gynosis, from which mastocytosis is characterized by the presence of a positive Darya-Unna phenomenon. Papular and knotty elements of mastocytosis are distinguished from xanthomas, dematofibroma, histiocytosis X, and neuroxantoendothelioma based on histological examination. Unlike drug toksidermii, with mastocytosis there is no connection of the disease with the medication. With insect bites, epidermal pemphigus of newborns, erythema multiforme exudative, differential diagnosis is carried out on the basis of clinical data and results of urine for histamine. Mastocytosis is difficult to distinguish from an inborn poikiloderma of Rotmund-Thomson an autosomal recessive disease, clinically manifested in the first years of life and characterized by erythematous spots, alternating with reticular hyperpigmentation, atrophy and tele-angiectasia on the skin of the face, neck, less often – on the limbs. In contrast to mastocytosis, there is a low growth, microcephaly, degeneration of teeth, hair and nails, cataracts, mental retardation. The teleangiectatic form of mastocytosis differs from atrophic vascular poikiloderma of Jacobi, characterized by focal hyper- and hypopigmentation, telangiectasias and atrophy of the skin, by the generalized nature of the process, by the presence of maculopapular rashes, prone to fusion, with the formation of large foci of appendages, and by the presence of large papular lesions that are prone to fusion, with the formation of large foci of lesions, and the presence of large papular eruptions that are prone to fusion, with the formation of large foci of lesions, and the presence of large papular eruptions that are prone to fusion, with the formation of large foci of lesions, and the presence of large podular eruptions that are prone to fusion, with the formation of large foci of lesions, and the presence of large podular eruptions that are prone to fusion, with the formation of large foci of lesions, and the presence of large podular eruptions that are prone to fusion, with the formation of large lesions, there are also survivors. “, Increased itching, tachycardia, etc.) or lesions of internal organs. The pigment purpurase and lichenoid angiodermatitis of Guzhero-Blum, unlike mastocytosis, affects predominantly middle-aged men and is characterized by shiny lichenoid papules, hemorrhagically pigmented spots in the lower extremities, as well as a negative Darier-Unna phenomenon.

The differential diagnosis of mastocytosis is also carried out with diseases accompanied by an increase in the number of mast cells in histological specimens. The fat-cell proliferates take place in reactive mastocytoplasia, in hemangioma, dermatofibroma, lymphoma, lymphogranulomatosis, etc. An important feature of the histological diagnosis of mastocytosis is that in the “old” center of mastocytosis, mast cells can be in small numbers. In this regard, the diagnosis of mastocytoma having a nevoid structure can be established most reliably from the histological picture. In other cases, the diagnosis is established on the basis of histological data, taking into account clinical data.

Treatment of Mastocytosis

Treatment of mastocytosis is not effective enough. Isolated mastocytomas are surgically removed. For the treatment of mastocytosis, cyproheptadine hydrochloride (periactin) is used at a dose of 16 mg / day, H2-histamine blockers, and serotonin inhibitors. drugs that inhibit mast cell degranulation (zadyden etc.), cytotoxic drugs (prospidin, spirobromin), PUVA therapy. When itching and “tides” antihistamines are used. For bullous forms, corticosteroid hormones are prescribed.

Prevention of Mastocytosis

Prevention of mastocytosis is the prevention of effects on the body of mast cell degranulation activators, such as colds, exposure to cold, heat, trauma, insolation, drugs (especially the morphine-opium group of alkaloids and acetylsalicylic cyst).