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

B-cell lymphomas of the skin account for approximately 25% of all lymphoproliferative processes in this organ, and, what is very important, primary B-cell lymphomas of the skin are characterized by a relatively favorable course in contrast to nodal analogues. B-lymphomas develop from B-series lymphocytes and mostly reflect the cytological characteristics of plasma cells and germinal cells - centrocytes and centroblasts. This is due to the fact that during the development of a B-lymphocyte from a stem cell, two different antigen-dependent B-cell reactions take place. In one, they are transformed into immunoblasts - lymphoplasmacytoid cells - plasma cells, determining the plasma cell reaction. The other is an 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 tendency to metastasize directly depend on the morphological type of the tumor, in particular on the degree of differentiation of the proliferating lymphocyte clone.

Causes and pathogenesis of cutaneous B-cell lymphomas. As with cutaneous T-cell lymphomas, cutaneous B-cell lymphomas (CBCL) are caused by the proliferation of abnormal B-lymphocytes.

In VKL, there is a rapidly progressing lesion of the skin, lymph nodes and internal organs. The infiltrate is represented by B-lymphocytes. Unlike T-lymphocytes, B-cells do not have epidermotropism and therefore are located mainly in the reticular layer of the dermis.

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

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

The nodular form of B-cell lymphoma of the skin is characterized by the appearance of one or more hemispherical nodes without the previous formation of spots and plaques. The nodes are of a dense consistency, up to 3 cm or more in diameter, have a yellow or brownish color, a smooth surface, and are often covered with telangiectasia. Often, such nodes do not decay, but regress, leaving behind atrophy and hyperpigmentation. As the process progresses, they increase sharply in size. In the plaque form (primary reticulosis of the skin), the process begins with the appearance of brown or yellow-pink spots, rounded outlines with a follicular pattern. The spot gradually infiltrates, turning into plaques with fine-lamellar peeling. With pronounced infiltration of the skin of the face, facies leonine may develop. Subjective sensations with this type are often absent.

The second, moderately malignant type of B-cell skin lymphomas occurs as Gottgron's reticulosarcoma. Clinically, the rash is represented by several large dense nodes 3-5 cm in diameter, dark red or purple in color, with weakly expressed peeling. The disease reaches its apogee 2-5 years after 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-grade malignancy type of B-cell lymphoma of the skin is more common in people 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, has a bluish-purple color, and a dense consistency. After 3-6 months, the process disseminates in the form of numerous nodes and the most pronounced malignancy of B-lymphocytes is noted. Lymph node adenopathy and disintegration of tumor elements are observed. The duration of the disease is 1-2 years. Subjective sensations are expressed in the form of a weak, intermittent itching, there is no pain in the affected areas.

Follicular center cell lymphoma (syn. follicular lymphoma) is a primary lymphoma of the skin.

Clinically, follicular center cell lymphoma manifests itself as single, more often multiple nodes or plaques on the scalp, trunk. Over time, the elements may ulcerate.

Pathomorphology. In the skin, a dense proliferation is located in the lower parts of the dermis with spreading into the subcutaneous fat tissue. Follicular structures with a weakly expressed or absent mantle zone are visible among the proliferate cells. A clearly delineated marginal zone is usually absent. The follicles contain centrocytes and centroblasts in various proportions. In the interfollicular zones, there are clusters of reactive small lymphocytes, histiocytes with an admixture of a certain amount of eosinophils and plasma cells. Phenotype: tumor cells demonstrate pan-B antigens CD19, CD20, CD79a, in some variants CD10. Antibodies to the CD21 antigen reveal follicular dendritic cells, which allows differentiation from lymphocytoma. The absence of BCL-2 protein expression on primary B-lymphoma cells from follicular center cells allows it to be differentiated from systemic lymphoma of this type, the cells of which have a BCL-2+ phenotype as a result of the t(14;18) translocation.

Immunocytoma. The second most common follicular center cell lymphoma, immunocytomas are low-grade lymphomas.

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

Clinically, the lesions on the skin in these diseases differ little from the typical manifestations of B-lymphomas: solitary tumors appear, usually large in size, bluish-red in color, spherical, localized most often in the lower extremities.

Pathomorphology. In the dermis, large-focal or diffuse proliferates spreading into the hypodermis, which, along with lymphocytes, contain a certain number of plasmacytoid and plasma cells, a small number of immunoblasts and macrophages. Lymphoplasmocytoid cells with scanty, sharply basophilic cytoplasm, an eccentrically located nucleus with coarsely dispersed chromatin. In the nuclei of plasmacytoid or plasma cells, there may often be PAS-+ inclusions in the form of globules (the so-called Dutcher's bodies). Immunocytochemically, they correspond to immunoglobulins, mainly IgM-k. Phenotype: CD19+, CD02+, CD22+, CD79a-, CD5-, CD10-. Tumor cells demonstrate monoclonal expression of the light chains of immunoglobulin IgM-k. Tumor foci in secondary skin lesions are more widespread and scattered than in primary immunocytoma; histologically, unlike primary immunocytomas, monotypic proliferating cells of lymphoplasmacytoid nature are distributed throughout the infiltrate; in the blood of systemic processes, increased levels of immunoglobulins (usually IgM), paraproteins, and leukemia (in 30-40% of cases) are determined, caused by the entry of lymphoplasmacytoid cells from affected organs into the peripheral blood. These cells have phenotypic markers: CD20+, CD45RO+. Patients with systemic lymphoplasmacytoid 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 resembling plasma cells of varying maturity. In the vast majority of cases, it is associated with myeloma. Extramedullary myeloma of the skin (plasmocytoma), unlike myeloma, occurs without specific bone marrow damage, as well as other organs that are usually involved in the systemic process (spleen, lymph nodes). Skin damage in extramedullary myelomas occurs in 4% of cases. Primary plasmacytoma of the skin is a B-lymphoma with a relatively favorable clinical course. In the absence of metastasis involving the bone marrow and hypercalcemia, life expectancy in 40% of patients reaches 10 years.

Clinically, single or multiple dark red nodes with a bluish tint appear on the skin, which have a tendency to ulcerate. The tumor consists mainly of monomorphic, tightly adjacent to each other complexes of mature plasma cells. In the cytoplasm, PAS-positive, diastase-resistant inclusions are determined, which are especially noticeable under electron microscopy. Immunoblasts, plasmablasts, lymphocytes, as a rule, are absent. Sometimes, amyloid deposits are noted among tumor cells or in the walls of blood vessels. In a number of observations, the presence of pseudoangiomatous structures containing erythrocytes in lacunae-like formations without an endothelial lining has been described. Immunoglobulins are detected in the cytoplasm of plasmacytic cells using the direct immunofluorescence method. Phenotypic characteristics of plasmacytoma: CD20-; CD79a±; CD38+; LCA-; p63+. Genetic studies have shown the presence of a monoclonal rearrangement of the genes encoding the light and heavy chains of immunoglobulins.

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

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

Clinically, cutaneous manifestations are represented by papular, plaque or nodular elements, usually on the extremities or trunk.

Pathomorphology. The cell proliferation may be superficial or deep, diffuse or nodular. The epidermis is usually intact and separated from the proliferation by a narrow strip of collagen fibers. The proliferation contains varying amounts of centrocyte-like cells, lymphoplasmacytoid and plasma cells, and single immunoblasts. Characteristic features include the presence of reactive germinal centers containing macrophages and colonization of follicular structures by neoplastic cells of the marginal zone. In the case of a high content of plasma cells, the process is very difficult to differentiate from immunocytoma. The phenotypic characteristics of marginal cell B-lymphoma are as follows: CD20+; CD79a+; CD5-; KiMlp+; CDw32+. Monotypic expression of immunoglobulin light chains is determined in 40-65% of cases. Positive expression of bcl-2, except in reactive germinal center cells. In some patients, the HHV-8 or Borrelia burgdorferi genome was detected in tumor cells.

Mantle zone lymphoma accounts for about 4% of all B-lymphomas and approximately 1% of all cutaneous lymphomas. It is believed that the tumor does not consist of germinal center centrocytes, but of a subpopulation of CD5+ cells with features of mantle lymphocytes. As a rule, the skin is affected secondarily during the development of a systemic process. The probability of primary lymphoma remains questionable.

Clinical manifestations in the form of plaques and nodules, most often on the face, upper limbs, and 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 revealed. The cytoplasm of the cells is practically not determined. Basophilic cells of the centroblast and immunoblast type are rare. Polytypic blast cells (centroblasts and immunoblasts) can be found as remnants of germinal centers. Among the tumor cells there are macrophages, dendritic cells of the follicular center, forming a sparsely cellular network, and plasmablasts - precursors of reactive plasma cells.

Phenotypic characteristics of mantle cell B-lymphoma: CD19+, CD20+; CD79a+; CD5+. Differentiation with centroblast-centrocytic lymphoma from follicular center cells is possible using genotyping. In mantle cell lymphoma, there is a translocation, which is accompanied by rearrangement of the bct-1 locus. In follicular center cell lymphoma, there is a translocation t(l4;18) with rearrangement of the bcl-2 locus.

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

The disease may be systemic or develop primarily in the skin. The EORTC group, specifically stipulating the localization in the name, confirms the fact of a more aggressive course of this process on the lower extremities, although such a justification for isolating it as an independent nosological form is controversial.

Clinically - rashes in the form of plaques or nodules with a tendency to ulcerate.

Pathomorphology. In the dermis, there is a diffuse proliferation with spread into the subcutaneous fat tissue, consisting of large lymphocytes of the immunoblast and centroblast type. Among them, there are large cells with multilobed, eroded nuclei, anaplastic cells. Mitotic activity is high. Phenotype: tumor cells typically express CD20, CD79a antigens and immunoglobulin light chains. In aggressive forms of the disease localized on the lower extremities, there is expression of the BCL-2 protein. Genetically, rearrangement of the JH genes is determined. Translocation t(8;l4) was detected in some patients.

Intravascular B-cell lymphoma. An obsolete name is "malignant angioendotheliomatosis." In this type of lymphoma, clonal lymphocytes proliferate inside the vessels. Primary skin lesions are extremely rare and are usually combined with tumors of the internal organs and central nervous system. Clinically, the changes resemble those in panniculitis. Plaque and nodular elements may appear on the skin of the trunk and extremities.

Pathomorphology. The dermis shows an increased number of vessels with proliferation of atypical lymphoid cells, sometimes with complete occlusion of the lumen and recanalization. Phenotype: tumor cells express CD20, CD79a and common leukocyte antigen (LCA). Endothelial cell markers - factor VIII and CD31 - clearly differentiate the endothelial lining and intravascular tumor proliferation. Genetically, monoclonal rearrangement of Jh genes is registered in most cases.

B-cell lymphoblastic lymphoma develops from B-lymphocyte precursors (lymphoblasts) and is characterized by an extremely aggressive course. Primary skin lesions are almost never encountered.

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

Pathomorphology. In the dermis, a diffuse proliferation of medium-sized lymphocytes with round or bean-shaped nuclei, finely dispersed chromatin and scanty cytoplasm is determined. 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, monoclonal rearrangement of JH genes and chromosomal abnormalities are detected: t(l;19), t(9;22), l lql3.

B-cell lymphoma, rich in T-cells. This type of lymphoma is characterized by the presence in the proliferation, in addition to clonal B-cells, of a large number of reactive T-lymphocytes, which distort the true nature of the process. Most often, the disease is systemic in nature, primary skin lesions are an exception, although the course of the latter is more favorable.

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

Pathomorphology. Diffuse proliferation in the dermis mainly consists of small lymphocytes, among which there are large blast forms. It is impossible to recognize the B-cell nature of the process using routine stains. Phenotype: tumor cells demonstrate expression of CD20 and CD79a antigens. Reactive lymphocytes are T-helpers CD3+, CD4+, CD43+, CD45RO+, CD8-.

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

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

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

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