T-cell lymphoma of the skin

Most often, T-cell lymphomas are recorded in the elderly, although there are isolated cases even in children. Men are sick twice as often as women. T-cell lymphomas are epidermotropic in nature.

Causes of the t-cell lymphomas of the skin

The causes and pathogenesis of T-cell lymphomas are not fully understood. Currently, most researchers consider human T-cell leukemia type 1 (HTLV-1) I virus as the main etiologic factor initiating the development of T-cell malignant lymphomas of the skin. Along with this, the role of other viruses in the development of T-cell lymphoma is discussed: Epstein Barr virus, herpes simplex type 6. In patients with T-cell lymphoma, viruses are found in the skin, peripheral blood, Langerhans cells. Antibodies to HTVL-I are detected in many patients with fungal mycosis.

An important place in the pathogenesis of T-cell lymphomas is played by immunopathological processes in the skin, the main of which is the uncontrolled proliferation of clonal lymphocytes.

Cytokines produced by lymphocytes, epithelial cells and cells of the macrophage system have a pro-inflammatory and proliferative effect (IL-1, responsible for differentiation of lymphocytes, IL-2 - T cell growth factor, IL-4 and IL-5, which increase inflow into the lesions of eosinophils and their activation, etc.). As a result of inflow into the lesion of T-lymphocytes, micro-abscesses are formed. Simultaneously with the increased proliferation of lymphocytes, the activity of antitumor protection cells is suppressed: natural killers, lymphocyte toxic lymphocytes, dendritic cells, in particular, Langerhans cells, as well as cytokines (IL-7, IL-15, etc.), tumor growth inhibitors. The role of hereditary factors is not excluded. The presence of family cases, the frequent detection of some histocompatibility antigens (HLA B-5 and HLA B-35 in lymphomas of high skin malignancy, HLA A-10 in less aggressive lymphomas, HLA B-8 in the erythrodermic form of fungal mycosis) confirm the hereditary nature of dermatosis.

Clinical observations indicate a possible transformation of long-term chronic dermatoses (neurodermatitis, atopic dermatitis, psoriasis, etc.) into mushroom mycosis. At the same time, a key factor is the long-lasting persistence of lymphocytes in the inflammatory focus, which disrupt immune surveillance and promote the appearance of a clone of malignant lymphocytes and, thus, the development of a malignant proliferative process.

Exposure of physical factors such as insolation, ionizing radiation, or chemicals to the body can lead to the appearance of a clone of "genotratic" lymphocytes, which have a mutagenic effect on lymphoid cells and the development of malignancy of lymphocytes.

Consequently, T-cell lymphomas can be considered as a multifactorial disease that begins with the activation of lymphocytes under the influence of various carcinogenic, "genotouring" factors and the emergence of a dominant T-cell clone. The severity of impaired immune surveillance, a clone of malignant lymphocytes, determines clinical manifestations (spotted, plaque or tumor elements) of T-cell lymphomas.

Pathogenesis

In the early stage of fungal mycosis, acanthosis with broad processes, hyperplasia and condensation of basal keratinocytes, vacuolar degeneration of basal cells, atypical mitoses in different layers of the epidermis, epidermogropism of the infiltrate with penetration of lymphocytes into the epidermis are noted. There are small infiltrates around the vessels in the dermis, consisting of single mononuclear cells with hyperchromic nuclei, the "mycotic" cells. In the second stage, there is an increase in the severity of the dermal infiltrate and epidermotropism of the infiltrate cells, as a result of which malignant lymphocytes penetrate the epidermis, forming clusters in the form of microabscesses. In the third, tumor stage, massive acanthosis and insignificant atrophy of the epidermis, an increase in the infiltration of the epidermis by tumor lymphocytes, which form multiple microabscesses, are formed. Massive infiltrate is located in the entire thickness of the dermis and capturing part of the hypodermis. Blast forms of lymphocytes are noted.

Large cell anaplastic T-cell lymphoma of the skin

Presented by a group of lymphoproliferative processes, which are characterized by the presence of proliferates from atypical clonal large anaplastic CD30 + T cells. As a rule, it develops secondarily in the tumor stage of fungal mycosis or with Sie-zary syndrome, however it can develop independently or during dissemination of systemic lymphomas of this type. Clinically, such lymphomas correspond to the so-called decapitated form of fungal mycosis in the form of single or multiple nodes, usually grouped.

Histologically, proliferates occupy almost the entire dermis with or without epidermotropism, when the epidermis is atrophy.

Cytologically tumor cells can vary in size and shape. On the basis of these properties, medium- and large-cell pleomorphic T-cell lymphoma with nuclei of various irregular configurations - convolute, multi-lobed, with dense chromatin, well expressed nucleolus and quite abundant cytoplasm, are isolated; immunoblastic - with large round or oval nuclei with an enlightened karyoplasm and one centrally located nucleolus; anaplastic - with ugly very large cells with nuclei of irregular configuration and abundant cytoplasm. Phenotypically the whole group belongs to T-helper lymphomas and can be CD30 + or CD30-.

R. Willemze et al. (1994) showed that the course of CD30 + -lymphoma is more favorable. The clonal reorganization of the T-lymphocyte receptor is genotypically revealed.

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

Symptoms of the t-cell lymphomas of the skin

The most common disease in the group of T-cell lymphomas of the skin is mushroom mycosis, which accounts for about 70% of cases. There are three clinical forms of the disease: classical, erythrodermic and decapitated. T-cell lymphomas are characterized by polymorphism of rashes in the form of spots, plaques, tumors.

The erythrodermal form of fungal mycosis usually begins with an uncontrollable itching, swelling, universal hyperemia, the appearance of erythematous-squamous foci on the skin of the trunk and extremities, which tend to merge and develop erythroderma within 1-2 months. Virtually all patients have palmar-plantar hyperkeratosis and diffuse hair thinning throughout the skin. All groups of lymph nodes are sharply enlarged. The enlarged inguinal, femoral, axillary, cubital lymph nodes are palpated in the form of "packets" of a dense elastic consistency, not soldered to surrounding tissues, painless. The general condition sharply worsens: there is a fever with a body temperature up to 38-39 ° C, night sweats, weakness and weight loss. Currently, Cesary syndrome by many dermatologists is considered as the most rare leukemia variant of the erythrodermic form of fungal mycosis,

There is a pronounced leukocytosis in lymphocytograms - Cesari cells. Cesari cells are malignant T-helpers, whose nuclei have a folded cerebral surface with deep invaginations of the nuclear membrane. The lethal outcome is observed after 2-5 years, the frequent cause of which is cardiovascular pathology and intoxication.

The headless form of fungal mycosis is characterized by the rapid development of tumor-like foci on apparently healthy skin without previous long-lasting plaques. This form is characterized by a high degree of malignancy, which is regarded as a manifestation of lymphosarcoma. The lethal outcome is noted throughout the year.

Stages

The classical form of fungal mycosis is characterized by three stages of development: erythematous-squamous, plaque and tumor.

The first stage resembles the clinical picture of some benign inflammatory dermatoses - eczema, seborrheic dermatitis, plaque parapsoriasis. In this stage of the disease there are spots of different size, intense pink, pink-red with a violet hue, rounded or oval outlines, with relatively clear boundaries, superficial otrepid or small-plate scaling. Elements are often located on different parts of the skin, more often on the trunk and face. Gradually the number of them increases. Over time, the process can take the nature of erythroderma (erythrodermic stage). Rashes can exist for years or spontaneously disappear. In contrast to benign inflammatory dermatoses, rash and itching elements at this stage are resistant to ongoing therapy.

Infiltrative-bpley stage develops within several years. In place of pre-existing macular eruptions, plaques of rounded or irregular contours appear, intensely violet, clearly delineated from healthy skin, dense, with a peeling surface. Their consistency resembles "thick cardboard". Some of them are spontaneously resolved, leaving areas of dark brown hyperpigmentation and / or atrophy (poikilodermia). Itching at this stage is even more intense and painful, fever is noted, weight loss is noted. In this stage, lymphadenopathy can be observed.

In the third, tumor stage, there is the appearance of painless tumors of tight-elastic consistency of yellow-red color, developing from plaques or appearing on apparently healthy skin. The shape of the tumors is spherical or flattened, often resembling a mushroom cap. Tumors can appear all over the place. The number of them varies widely from single to dozens, with sizes ranging from 1 to 20 cm in diameter. With the disintegration of long-term tumors, ulcers with uneven edges and a deep bottom are formed, reaching the fascia or bones. The most commonly affected lymph nodes, spleen, liver and lungs. The general condition worsens, appear and grow into the phenomenon of intoxication, develops weakness. The average life expectancy of patients with a classical form of fungal mycosis from the time of diagnosis is 5 to 10 years. Mortality is usually noted from chronic diseases: pneumonia, cardiovascular insufficiency, amyloidosis. Itching is felt subjectively, and with the disintegration of tumors - the pain in the lesions.

[13], [14], [15], [16], [17]

Treatment of the t-cell lymphomas of the skin

In the erythematous-squamous stage, patients do not need antitumor therapy, they are prescribed external corticosteroids (derivatives of prednisolone, betamethasone, dexamethasone), interferon alfa (3 million IU daily, then 3 times a week for 3-6 months depending on the clinical manifestations or the effectiveness of treatment), interferon-gamma (100,000 IU per day for 10 days, the cycle is repeated 12-3 times with a break of 10 days), PUVA therapy or Re-PUVA therapy. The effectiveness of the PUVA therapy is based on the selective formation of covalent cross-linking of psoralens with DNA in proliferating T-helper cells, which inhibits their division. In the second stage, in addition to the above, systemic corticosteroids (30-40 mg per day for prednisolone for 1.5-2 months), cytostatics (proppedin 100 mg daily, 4-5 injections daily) are used. Combination of interferons with other methods of therapy has a more pronounced therapeutic effect (interferons + PUVA, interferons + cytostatics, interferons + aromatic retinoids).

In the tumor stage, the main method is polychemotherapy. Use a combination of vincristine (0.5-1 mg iv once a day, 4-5 injections in total) with prednisolone (40-60 mg per day for the period of chemotherapy), prospidin (100 mg per day, total 3 g), interferons. Recommended photodynamic, electron beam therapy, phototherapy (extracorporeal photochemotherapy).