Kaposi's sarcoma

Kaposi's sarcoma (synonyms: idiopathic multiple hemorrhagic sarcoma, Kaposi's angiomatosis, Kaposi's hemangiosarcoma) is a multifocal malignant tumor of vascular origin affecting the skin and mucous organs.

Men are much more likely to get sick than women. The incidence is high in Africa: in Congo it is 9% of all malignant tumors.

Kaposi's sarcoma affects people between the ages of 40 and 70.

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Causes of Kaposi's sarcoma

The causes and pathogenesis of Kaposi's sarcoma have not been fully studied. There are reports of a presumably viral nature of the disease. There is a special, as yet unidentified virus that causes both an immunosuppressive and oncogenic effect. A.A. Kalamkaryan et al. (1986) observed the occurrence of Kaposi's sarcoma in patients receiving immunosuppressive therapy for other diseases. The clinical features of this form of Kaposi's sarcoma are expressed in the rapid progression of the process with damage to internal organs, which gave grounds for distinguishing an immunosuppressive (immune-dependent) form. This is also confirmed by the frequent occurrence of Kaposi's sarcoma in AIDS: from 10 to 25%, according to IL Ziegler et al. (1987). DNA of a new virus, human herpesvirus type 8, has been isolated from tumor tissue in patients with Kaposi's sarcoma. For example, the presence of cytomegalovirus (CMV) infection is confirmed by serological and virological studies, as well as by the tropism of CMV for endothelial cells and its oncogenic potential. On the other hand, some scientists believe that the "transformation" of endothelial cells may be mediated by the secretion of a specific tumor growth factor (TGF). Endogenous production of TGF may serve as a constant stimulus for continuous cell division, resulting in the formation of localized or widespread foci of endothelial proliferation.

An opinion is expressed about the important role of T-lymphotropic virus (HTLV-III), which was isolated from patients with Kaposi's sarcoma and AIDS. In this case, the key role belongs to the damage of T-lymphocytes.

Some scientists believe that Kaposi's sarcoma develops in the endothelium of blood and lymphatic capillaries and, apparently, it is not a true malignant neoplasm, but a pronounced proliferation of endothelial cells that occurs under the influence of humoral factors.

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Pathomorphology of Kaposi's sarcoma

The picture is polymorphic, depending on the duration of the element's existence and the predominance of one or another morphological component. In the initial stages of the disease (spotted elements, superficial plaques) in the reticular layer of the dermis there are perivascular proliferates of different sizes, consisting of rounded cells with large nuclei, among which lymphoid elements, histiocytes, and sometimes plasma cells can be seen. Vessels are often formed in the proliferates, which are clusters of concentrically located elongated cells. In places, foci of hemorrhage and hemosiderin deposits are detected, which is pathognomonic for the early stages of Kaposi's sarcoma. In more mature elements (nodules, infiltrated plaques, nodes), the histological picture has several variants depending on the predominance of one or another component of proliferating cells and newly formed spindle-shaped cells. In case of predominance of the vascular component (angiomatous variant), a large number of vessels are determined in the lesion - both pre-existing and newly formed, in different stages of differentiation. The latter can be of different types: capillaries, arterioles, venules and lymphatic clefts. Many thin-walled vessels are sharply dilated and filled with blood, forming lacunae of the "blood lake" type. Sometimes proliferation of lymphatic vessels predominates, as a result of which the picture can resemble that of lymphangioma, especially if some vessels are cystically dilated.

In the foci of proliferation, elongated cells (fibroblastic variant) form bundles intertwined in different directions. These cells have elongated nuclei, similar in structure to those of fibroblasts. Electron microscopic examination revealed that their cytoplasm contains a large number of ribosomes and polysomes, vacuoles, expanded cisterns of the enloplasmic reticulum, lysosomal structures. Nuclei with large nucleoli, elongated. Heterochromatin is distributed near the nuclear membrane.

Among the cells, there are a significant number of very active forms, characterized by the presence of a large number of lysosomal structures in the cytoplasm, sharply expanded cisterns of the endoplasmic reticulum. Quite a lot of mitoses. The proliferation of spindle-shaped cells can be diffuse, occupying the entire thickness of the dermis, or limited in the form of nodes surrounded by a connective tissue capsule. Freely lying erythrocytes, lumens of newly formed vessels and hemorrhages are visible between the spindle-shaped cells.

In the mixed variant, both angiomatous changes and proliferation of spindle cells are histologically detected. In these cases, there is a lot of hemosiderin in the tissue.

In regressing foci, fibroblastic changes gradually increase with desolation of vessels, homogenization, and sometimes hyalinosis of the collagen substance. However, even in such cases, perivascular proliferates of young undifferentiated cells of a round shape with an admixture of lymphoid elements and plasma cells, as well as new formation of vessels, which is a morphological expression of further progression of the process, can often be seen.

It should be noted that in the histological picture of Kaposi's sarcoma, there is no parallelism with the clinical picture and course of the disease; there is only a predominance of one or another structural component (angiomatous, fibroblastic and mixed).

Histogenesis of Kaposi's sarcoma

Despite the large number of works on the histogenesis of Kaposi's sarcoma, the origin and convergence of its typical spindle-shaped cells has not been fully elucidated. Ultrastructural data show that the tumor consists mainly of cells with endothelial characteristics and fibroblast-like elements, among which there are predominantly atypical lymphocytes. Cells of endothelial origin are usually surrounded by a basal membrane, fibroblast-like cells with signs of high functional activity, and lymphocytes have a very narrow cytoplasm with high electron density, almost without organelles, and an electron-dense nucleus, which indicates their weak activity. The latter is also confirmed by the fact that lymphocytes are separated from tumor elements by light spaces and have no contact with them.

Recent studies based on the concept of the mononuclear phagocyte system indicate the possibility of involving endothelial cells and stromal fibroblasts in the processes of the immune response and tumor proliferation. E. R. Aschida et al. (1981) found that endothelial cells participate in immune reactions by activating T-lymphocytes. They have receptors for the Fc fragment of IgG and the C3 component of complement on their surface. They can interact with immunocompetent cells that secrete various mediators, including prostaglandin E1 and heparin, which have the ability to stimulate angiogenesis. Immunomorphological detection of the endothelial marker - factor VIII antigen (a protein specific for endothelial cells) in many Kaposi's sarcoma cells indicates their endothelial origin. I. A. Kazantseva et al. (1986) as a result of a comprehensive study of biopsies from the lesion using electron microscopic, immunomorphological, and radioautographic methods confirmed the origin of tumor elements from the endothelium and perivascular fibroblast-like cells with high functional activity. The authors also found, especially in nodular elements with a large number of spindle-shaped cells, a high content of type IV collagen, i.e., collagen of the basal membranes produced by both endotheliocytes and pericytes. Radioautographic research allowed the authors to establish the active incorporation of ³ H-thymidine both into the endotheliocytes of proliferating capillaries and into perivascular cells, which indicates active DNA synthesis and their ability to enter mitosis.

Analysis of the presented data gives grounds to believe that both endothelial cells and perivascular pluripotent undifferentiated cells participate in the histogenesis of Kaposi's sarcoma.

Histopathology

Histologically, two main features are distinguished: disordered formation of vessels and proliferation of spindle-shaped cells.

At an early stage (in spotted elements, superficial plaques) perivascular infiltrates are detected in the reticular layer of the dermis, which consist of rounded cells with large nuclei (lymphoid elements, histiocytes, rarely plasma cells). Vessels, small foci of hemorrhage and hemosiderin deposits are often found in proliferates, which is pathognomonic even for the early stages of Kaposi's sarcoma. More mature elements (nodules, infiltrative plaques, nodular-tumor formations) are characterized by vascular proliferation (angiomatous variant) and the formation of spindle-shaped cells (fibroblastic variant). In the foci of proliferation there are spindle-shaped cells, which are located in the form of strands intertwined in different directions. These cells have elongated nuclei similar in structure to those of fibroblasts. Focal hemorrhages with hemosiderin deposition, as well as angiomatous changes and proliferation of spindle cells are possible.

Symptoms of Kaposi's sarcoma

Clinical symptoms of Kaposi's sarcoma vary and depend on the duration of the disease. In the initial stages, reddish-bluish spots of various sizes and shapes, nodular elements of pink and then bluish color appear. Later, the rash takes the form of infiltrated nodular elements of various sizes, reddish-bluish color with a brownish tint. Nodules can merge, forming large bumpy foci, ulcerate with the formation of sharply painful ulcers. Often in the area of the lesion, the skin is dense, edematous, purple-bluish color. The foci are localized mainly on the skin of the distal parts of the extremities, tend to be located near the superficial veins. According to A.A. Kalamkaryan et al. (1986), IL Ziegler (1987), in 93.8% of cases they are located on the lower extremities, mainly on the feet and anterolateral surfaces of the shins. Symmetry of the lesion is characteristic. However, other areas of the skin and mucous membranes can also be affected.

The course of the disease can be acute, subacute and chronic. The acute course is characterized by rapidly progressing symptoms with fever and generalized skin lesions in the form of multiple nodular lesions on the limbs, face and trunk. This is accompanied by lesions of the lymph nodes and internal organs. The duration of the disease is from 2 months to 2 years. In the subacute course, generalization of skin rashes is less common. In the chronic course, there is a gradual progression of skin rashes in the form of spotted-nodular and plaque elements. The duration of the disease is 8-10 years or more.

Clinical forms of Kaposi's sarcoma

Currently, the following clinical forms of Kaposi's sarcoma are distinguished: classical (sporadic, European); endemic (African); epidemic; iatrogenic (immune-dependent, immunosuppressive). According to the course, acute, subacute and chronic forms of Kaposi's sarcoma are distinguished.

The most common form of the disease is the classic form, characterized by the presence of spots, nodules, infiltrative plaques, nodes and tumors.

In most patients, the rash begins with the appearance of spotted elements, in 1/3 - with the appearance of nodules, and in a small number - edema.

Primary lesions are most often located on the skin of the extremities, especially the lower ones, on the dorsal surfaces of the legs and the anterior surface of the shins. However, rash elements can also be located on other areas of the skin (auricles, eyelids, cheeks, hard palate, penis). During the period of full development of the disease, in almost all patients (95%) the process is widespread and symmetrical. Therefore, the characteristic features of Kaposi's sarcoma are: multifocality, prevalence and symmetry of rashes.

Kaposi's sarcoma begins with the appearance of reddish-bluish or reddish-brownish clearly demarcated spots the size of a lentil to 1 cm or more. Over time, they slowly increase in size and reach up to 5 cm in diameter, their color, as a rule, changes: the reddish-bluish color turns into dark brown. The surface of the spots is smooth, only in some cases they are covered with grayish scales. Later, infiltrated plaques, nodules, and knots appear against the background of the spots.

The resulting nodules are the size of a small pea and are spherical or flat in shape, initially pink, and eventually turning brown. The nodules can be isolated or in groups and merge into large plaques or nodes.

Infiltrative plaques from 1 cm to the size of a child's palm and more often have a round, rarely - oval shape. The surface of the plaques at the beginning of the disease is uneven, over time it becomes covered with papillomatous growths. Hemispherical tumors from a large pea to a hazelnut in size clearly rise above the level of normal skin. Their color at the beginning of the disease is reddish-bluish, later acquiring a bluish-brownish tint. As a result of the decay of tumors, rarely - infiltrative plaques, deep ulcers of irregular outlines with slightly everted edges of a bluish-purple color and a lumpy bloody-gangrenous bottom appear. Characteristic signs are swelling of the affected limb and the development of lymphostasis, elephantiasis.

Sometimes swelling can be the first symptoms of the disease. Subjectively, patients are bothered by itching and burning, and in case of ulceration of the elements - sharp excruciating pain. The mucous membranes of the oral cavity are often involved in the pathological process. In this case, the rash is located on the soft and hard palate, cheeks, lips, tongue, in the pharynx, larynx. Nodular-tumor-like and infiltrative formations differ sharply in color from the surrounding mucous membrane and have a cherry-red color. Lesions of internal organs, lymph nodes, and the musculoskeletal system can also be observed.

With a long course of the disease, individual foci regress. Complete spontaneous remission is observed very rarely (in 2% of patients).

Endemic Kaposi's sarcoma is observed mainly in young people, more often in men. This form is manifested by nodular, infiltrative and tumor formations, located mainly on the extremities; lymph nodes are rarely affected. The lymphadenopathic variant of endemic Kaposi's sarcoma occurs mainly in African children aged 10 years and younger. Malignant course with pronounced polyadenopathy and rapid involvement of internal organs in the pathological process is noted. The rash is highly sensitive to radiation and chemotherapy. Relapses occur faster than in the classical form. The prognosis is unfavorable: patients die within 5 months to 2 years.

Epidemic Kaposi's sarcoma is a kind of AIDS marker. The epidemic form of Kaposi's sarcoma differs from the classic one by its more aggressive course and is manifested by multiple skin lesions involving the lymph nodes and rapid spread of the process to the internal organs.

The iatrogenic (immunosuppressive) form of Kaposi's sarcoma occurs in cancer patients who have received cytostatics and in individuals who have received immunosuppressants after kidney transplantation.

Rare and distinctive forms of Kaposi's sarcoma are also described: hypertrophic, callus-like, pyogenic granuloma, etc.

The acute form of Kaposi's sarcoma is characterized by a rapid progression with generalization of the process and involvement of internal organs. A pronounced impairment of the patient's general condition is noted, and a fatal outcome may occur several months after the onset of the disease.

In the subacute form, in contrast to the acute form, a slow generalization of the rash is observed. A fatal outcome occurs in 3-5 years.

The chronic form of Kaposi's sarcoma proceeds benignly for up to 10 years or more.

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Differential diagnosis of Kaposi's sarcoma

Kaposi's sarcoma should be differentiated from pseudo-Kaposi's sarcoma, pyogenic granuloma, melanoma, leiomyoma, and angioleiomyosarcoma.

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Treatment of Kaposi's sarcoma

Currently, depending on the clinical picture of the disease, mono- or polychemotherapy is used (cyclophosphamide, vincristine, vinblastine, prospidin). The effectiveness of treatment increases with the use of interferon a 2 (viferon), interferon inducers.

For local treatment, radiation therapy is used, which is carried out in the presence of tumor formations of a large affected area. A single dose is 8 g, the total dose is up to 30 g. An injection of cytostatics into the lesion is prescribed (vinblastine - 0.1 mg of the drug per 1 cm ² of the tumor area). Surgical excision or cryodestruction is used to remove nodes protruding above the surface.