B-cell lymphomas of the skin: causes, symptoms, diagnosis, treatment

B-cell skin lymphomas account for approximately 25% of all lymphoproliferative processes in this organ, and, very importantly, primary B-cell skin lymphomas are characterized by a relatively favorable course unlike nodal analogues. B-lymphomas develop from B-series lymphocytes and mostly reflect the cytological characteristics of plasma cells and cells of the germinal series - centrocytes and centroblasts. This is due to the fact that during development of B-lymphocyte from the stem cell there are two different antigen-dependent B-cell responses. In one, they are transformed into immunoblasts - lymphoplasmocytoid cells - plasma cells, determining the plasma-cell response. Another antigen-inducing reaction of the B-cell system, which is a common central one, in which centroblasts-centrocytes-memory cells (B2) are induced.

Clinical variants of B-lymphomas are diverse. The tumor growth rate and its propensity for metastasis directly depend on the morphological type of the tumor, in particular on the degree of differentiation of the proliferating clone of lymphocytes.

Causes and pathogenesis of B-cell lymphomas of the skin. As with T-cell skin lymphomas, the basis of B-cell lymphomas of the skin (BCC) is the proliferation of abnormal B lymphocytes.

With VKLK there is a rapidly progressive lesion of the skin, lymph nodes and internal organs. Infiltrate is represented by B-lymphocytes. Unlike T-lymphocytes, B-cells do not possess epidermotropism and therefore are found mainly in the mesh layer of the dermis.

Symptoms of B-cell lymphomas of the skin. By the nature and severity of the clinical course, three types of B-cell lymphomas are distinguished.

The first, low degree of malignancy, the type of B-cell lymphoma of the skin is characterized by a relatively benign course, occurs in all age groups, but is common in the elderly. The clinical picture is represented by plaque and knotty elements.

The nodular form of B-cell lymphoma of the skin is characterized by the appearance of one or more hemispherical nodes without the preceding formation of spots and plaques. Knots of a dense consistency, up to 3 cm or more in diameter, have a yellow or brownish color, a smooth surface, often covered with teleangiogas. Often such nodes are not decomposed, but regress, leaving behind atrophy and hyperpigmentation. As the process progresses, they sharply increase in size. With plaque form (primary skin reticulum), the process begins with the appearance of spots of brown or yellow-pink color, rounded outlines with a follicular pattern. The spot gradually infiltrates, turning into plaques with fine-lamellar ecdysis. With severe infiltration of facial skin, the development of facies leonine is possible. Subjective feelings with this type are often absent.

The second, medium degree of malignancy, the type of B-cell lymph of the skin proceeds as reticulosarcomatosis Gotgron. Clinically, the rashes are represented by several large dense knots 3-5 cm in diameter, dark red or crimson, with poorly expressed ecdysis. The disease reaches its apogee in 2-5 years from the onset of the first manifestations. Dissemination of nodes is noted. In parallel, penetration of malignant cells into the lymph nodes and internal organs is observed.

The third, high degree of malignancy, the type of B-cell skin lymphomas is more common in individuals over 40 years of age and is characterized by the formation of a node (tumor) located deep in the skin. The node is 3-5 cm in diameter and has a bluish-purple color, a dense consistency. In 3-6 months. There is a dissemination of the process in the form of numerous nodes and the most pronounced malignancy of B lymphocytes is noted. There is lymphadenopathy and the disintegration of tumor cells. The duration of the disease is 1-2 years. Subjective sensations are expressed in the form of a weak fickle itch, soreness in lesions is absent.

Lymphoma from the cells of the follicular center (blue follicular lymphoma) is the primary lymphoma of the skin.

Clinically, lymphoma from the cells of the follicular centers is manifested by single, often multiple nodes or plaques on the scalp, trunk. Over time, the elements may ulcerate.

Pathomorphology. In the skin, a thick proliferate is located in the lower parts of the dermis with the spreading into the subcutaneous fatty tissue. Among proliferative cells, follicular structures with a mild or absent mantle zone are visible. A clearly delineated marginal zone, as a rule, is absent. Follicles contain centrocytes and centroblasts in various proportions. In the interfollicular zones there are accumulations of reactive small lymphocytes, histiocytes with an admixture of a certain number of eosinophils and plasmocytes. Phenotype: tumor cells exhibit pan-B antigens CD19, CD20, CD79a, in some cases CD10. Antibodies to the CD21 antigen reveal follicular dendritic cells, which allows differentiation with the lymphocytoma. The lack of expression of BCL-2 protein on primary B-lymphoma cells from follicular cells allows it to be differentiated from systemic lymphoma of this type, whose cells have a BCL-2 + phenotype as a result of translocation t (14; 18).

An immunocytoma. The second fastest lymphoma from the cells of the follicular center. Immunocytomas belong to low-grade lymphomas.

According to WHO classification - lymphoplasmocyte lymphoma / immunocytoma; according to EORTC classification - immunocytoma / lymphoma of the marginal zone.

Clinically, lesions on the skin with these diseases differ little from typical manifestations of B-lymph: solitary tumors appear, usually of large size, cyanotic red, spherical, localized more often in the lower extremities.

Pathomorphology. In the dermis, large-focal or diffuse proliferates with dissemination into the hypodermis, in which, along with lymphocytes, there is a certain number of plasmacytoid and plasma cells, a small number of immunoblasts, macrophages. Lymphoplasmocytoid cells with sparse, sharply basophilic cytoplasm, eccentrically located nucleus with large-dispersed chromatin. In the nuclei of plasmacytoid or plasma cells, PAC - + - inclusions in the form of globules (the so-called Dutcher's bodies) can often be. Immunocytochemically, they correspond to immunoglobulins, mainly IgM-k. Phenotype: CD19 +, CD02 +, CD22 +, CD79a-, CD5-, CD10-. Tumor cells demonstrate the monoclonal expression of IgM-k immunoglobulin light chains. Tumors in secondary skin lesions are more widespread and diffuse than in the primary immunocytoma, histologically, unlike the primary immunocytes, monotypic proliferating cells of lymphoplasmocytoid nature are distributed throughout the infiltrate, in the blood in systemic processes an increased content of immunoglobulins (IgM), paraproteins, and also leukemia (in 30-40% of cases), caused by the ingress of peripheral blood cells of lymphoplasmocytic series from the affected organs. These cells have phenotypic markers: CD20 +, CD45RO +. Patients with systemic lymphoplasmacytic lymphoma often have autoimmune diseases: Sjogren's disease, thrombocytopenia, bullous epidermolysis, which should also be taken into account in the differential diagnosis of primary and secondary processes.

Plasmacytoma develops from cells that resemble plasma cells of varying degrees of maturity. In the vast majority of cases, it is associated with myeloma. Extrammedullary myeloma of the skin (plasmacytoma), in contrast to myeloma, proceeds without a specific bone marrow injury, as well as other organs that are usually involved in the systemic process (spleen, lymph nodes). Skin lesion with extramedullary myeloma occurs in 4% of cases. Primary skin plasmacytoma refers to B-lymphomas with a relatively favorable clinical course. In the absence of metastasis involving bone marrow and hypercalcemia, life expectancy in 40% of patients reaches 10 years.

Clinically, single or multiple nodes of dark red color with a bluish tinge appear on the skin, which tend to ulcerate. The tumor consists mainly of monomorphous, densely attached complexes of mature plasma cells. In the cytoplasm, Schick-positive, diastasis-resistant inclusions are determined, which are particularly noticeable in electron microscopy. Immunoblasts, plasmablasts, lymphocytes, as a rule, are absent. Sometimes among the tumor cells or in the walls of the vessels there are deposits of amyloid. A number of observations have described the presence of pseudoangiomatous structures containing erythrocytes in lacunoid formations without endothelial lining. The method of direct immunofluorescence in the cytoplasm of cells of the plasmocyte series reveals immunoglobulins. Phenotypic characteristic of the plasmacytoma: CD20-; CD79a ±; CD38 +; LCA-; p63 +. Genetic studies have shown the presence of monoclonal rearrangement of genes encoding the light and heavy chains of immunoglobulins.

Lymphoma of the marginal zone. According to WHO classification - B-cell lymphoma of the marginal zone; according to EORTC classification - immunocytoma / lymphoma of the marginal zone.

Lymphoma of the marginal zone develops from lymphocytes with cytological, immunological and genetic characteristics of lymphocytes in the marginal zone of the lymph node. It is rare. According to their morphological properties, cells of the marginal zone are so similar to monocytic B cells that K. Lennart and A. Feller (1992) included lymphoma from marginal cells in lymphoma from monocytic B cells.

Clinically, skin manifestations are papular, plaque or knotty elements, usually on the limbs or trunk.

Pathomorphology. Cellular proliferates may be superficial or deep, diffuse or nodular. The epidermis, as a rule, is intact and is separated from the proliferates by a narrow strip of collagen fibers. Proliferates contain different amounts of centrocyte-like cells, lymphoplasmocytoid and plasma cells, and single immunoblasts. Characteristic features are the presence of reactive hermetic centers containing macrophages and the colonization of follicular structures by the neoplastic cells of the marginal zone. In the case of a high content of plasma cells, the process is very difficult to differentiate from the immunocytoma. The phenotypic characteristic of B-lymphoma from marginal cells is as follows: CD20 +; CD79a +; CD5-; KiMlp +; CDw32 +. In 40-65% of cases, monotypic expression of light chains of immunoglobulins is determined. Positive expression of bcl-2, except cells of reactive hermetic centers. In some patients, a HHV-8 or Borrelia burgdorferi gene was found in tumor cells.

Lymphoma of the mantle zone is about 4% of all B-lymphomas and about 1% of all cutaneous lymphomas. It is believed that the tumor consists not of centricity of the hermetic center, but of a subpopulation of CD5 + cells with signs of mantle lymphocytes. As a rule, the skin is affected again during the development of the system process. The likelihood of primary lymphoma remains in question.

Clinical manifestations in the form of plaques and nodes, more often on the face, upper limbs, trunk.

Pathomorphology. Monomorphic clusters of small or medium-sized cells with irregularly shaped nuclei, sometimes with constrictions, finely dispersed chromatin and a small nucleolus, are detected. The cytoplasm of cells is practically not determined. Basophilic cells such as centroblasts and immunoblasts are rare. Polytypic blast cells (centroblasts and immunoblasts) can occur as remnants of hermetic centers. Among the tumor cells there are macrophages, dendritic cells of the follicular center, forming a rare-cell network, and plasmablasts - precursors of reactive plasma cells.

Phenotypic characteristics of B-lymphoma from mantle cells: CD19 +, CD20 +; CD79a +; CD5 +. It is possible to differentiate with centroblast-centrocytic lymphoma from cells of the follicular center by means of genotyping. With lymphoma from mantle cells, a translocation takes place, which is accompanied by a rearrangement of the bct-1 locus. With lymphoma from the cells of the follicular center, a translocation t (l4; 18) occurs with a rearrangement of the bcl-2 locus.

Diffuse large cell B-cell lymphoma. According to WHO classification - diffuse large-cell B-cell lymphoma; by classification EORTC - a diffuse large-cell B-cell lymphoma of the lower extremities.

The disease can have a systemic nature or develop primarily in the skin. The EORTC group, especially mentioning the localization in the name, confirms the fact of more aggressive flow of this process on the lower extremities, although such a justification for isolation as an independent nosological form is controversial.

Clinically - rashes in the form of plaques or knots with a tendency to ulceration.

Pathomorphology. In the dermis, diffuse proliferates with proliferation in the tissue of the subcutaneous fat base, consisting of large-sized lymphocytes such as immunoblasts and centroblasts. Among them there are large cells with many-bladed, usurized nuclei, anaplastic cells. Mitotic activity is high. Phenotype: the expression of tumor cells by antigens CD20, CD79a and light chains of immunoglobulins is characteristic. When aggressive forms of the disease with localization on the lower extremities, the expression of BCL-2 protein occurs. Genetically determined reordering of JH-genes. In some patients a translocation t (8; l4) was detected.

Intravascular B-cell lymphoma. The obsolete name is "malignant angioendotheliomatosis". In this type of lymphoma, clonal lymphocytes proliferate inside the vessels. Primary skin lesions are extremely rare and, as a rule, are combined with tumoral formations of internal organs and the central nervous system. Clinically, the changes resemble those of panniculitis. On the skin of the trunk and extremities, plaque and knotty elements may appear.

Pathomorphology. In the dermis there is an increased number of vessels, inside of which there is proliferation of atypical lymphoid cells, in places with phenomena of complete occlusion of lumens and recanalization. Phenotype: tumor cells express CD20, CD79a, and common cell carcinogen (LCA). Markers of endothelial cells - factor VIII and CD31 - clearly delineate the endothelial lining and intravascular tumor proliferates. Genetically, in most cases, monoclonal rearrangement of Jh-genes is recorded.

B-cell lymphoblastic lymphoma develops from the precursors of B lymphocytes (lymphoblasts) and is characterized by an extremely aggressive course. Primary skin lesions practically do not occur.

Clinically, the appearance of multiple plaque-nodular elements on the skin of the head and neck, mainly in young people.

Pathomorphology. In the dermis, diffuse proliferates are determined from lymphocytes of medium size with round or bean-shaped nuclei, finely dispersed chromatin, and scant cytoplasm. Mitotic activity is high. In addition to the pool of lymphocyte cells, there is a large number of macrophages. Phenotype: CD19 +, CD79a +, TdT +, dgM +, CD10 +, CD34 +. Genetically identified monoclonal rearrangement of JH-genes and chromosomal abnormalities: t (l; 19), t (9; 22), l lql3.

B-cell lymphoma, rich in T cells. For this type of lymphomas, there is a large amount of reactive T-lymphocytes in the proliferation, in addition to clonal B-cells, which distort the true nature of the process. Most often the disease has a systemic nature, primary skin lesions are an exception, although the latter is more favorable.

Clinically on the skin of the face and trunk appear papular-plaque and nodular elements, sometimes imitating erythema nodosum.

Pathomorphology. Diffuse proliferates in the dermis mainly consists of small lymphocytes, among which there are large blast forms. It is impossible to recognize the B-cell character of the process when using routine stains. Phenotype: tumor cells show expression of CD20 and CD79a antigens. The reactive lymphocytes by their characteristics are T-helper CD3 +, CD4 +, CD43 +, CD45RO +, CD8-.

Genetically revealed monoclonal rearrangement of JH-genes, confirming the presence of a tumor clone of B-lymphocytes.

Histopathology. Histologically, B-cell lymphomas of the skin of the skin in infiltrates reveal mainly B-lymphocytes of varying degrees of malignancy. In the plaque form of B-cell skin lymphomas in the infiltrate, in addition to lymphocytes, many histiocytes and fibroblasts and a small number of lymphoblasts are found, whereas in B-cell lymphomas of skin with a high degree of malignancy, the prolifras is essentially made up of immunoblasts.

Treatment of B-cell lymphomas of the skin. Treatment depends on the degree of malignancy. With the plaque form of B-cell skin lymphomas, electron-beam therapy with total focal doses of 30-40 g is most effective. At medium and high degrees of malignancy, polychemotherapy is used - CAVP-cyclophosphamide, adriomycin, vincristine and prednisolone or CVP-cyclophosphamide, vincristine and prednisolone.

[1], [2], [3], [4]