Kaposi's Sarcoma

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

Men are sick much more often than women. The morbidity in Africa is great: in the Congo it is 9% in relation to all malignant tumors.

Kaposi's sarcoma is affected by people between the ages of 40 and 70 years.

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

Causes of Kaposi's sarcoma

The causes and pathogenesis of Kaposi's sarcoma are not fully understood. There are reports of the alleged viral nature of the disease. There is a special, as yet unidentified, virus, which simultaneously causes an immunosuppressive and oncogenic effect. A.A. Kalamkaryan et al. (1986) observed the emergence of Kaposi's sarcoma in patients who received 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 the defeat of the internal organs, which gave grounds for isolating the immunosuppressive (immuno-dependent) form. This is also confirmed by the frequent appearance of Kaposi's sarcoma in AIDS: from 10 to 25%, according to IL Ziegler et al. (1987). From tissue tumors, the DNA of a new human herpesvirus virus, type 8, has been isolated from patients with Kaposi's sarcoma. For example, the presence of cytomegalovirus (CMV) infection is confirmed by serological and virological studies, as well as the tropicity of CMV to endothelial cells and its oncogenic potentials. On the other hand, some scientists believe that the "transformation" of endothelial cells can be mediated by the secretion of a specific tumor growth factor (TGF). Endogenous production of TGF can serve as a constant stimulus for the continuous division of cells, resulting in the formation of localized or spreading foci of endothelial proliferation.

There is an opinion on the important role of the T-lymphotropic virus (HTLV-III), which was isolated in patients with Kaposi's sarcoma and AIDS. In this case, the key role belongs to the defeat of T-lymphocytes.

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

[10], [11], [12], [13], [14], [15], [16]

Pathomorphology of Kaposi's sarcoma

The picture is polymorphic, depends on the duration of the existence of the element and on 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 one can see lymphoid elements, histiocytes, sometimes plasmocytes. In proliferates, vessels forming clusters of concentrically located elongated cells are often formed. In places, hemorrhages and hemosiderin deposits are identified, which is pathognomonic for the early stages of Kaposi's sarcoma. In more mature elements (nodules, infiltrated plaques, nodes), the histological pattern has several variants, depending on the prevalence of certain constituent components of proliferating cells and newly formed spindle-shaped cells. In the case of predominance of the vascular component (angiomatous variant), a large number of vessels, both pre-existing and newly formed, located in different stages of differentiation, is determined in the lesion site. The latter can be of various types: capillaries, arterioles, venules and lymphatic fissures. Many thin-walled vessels are sharply expanded and filled with blood, form lacunae such as "blood lakes." Sometimes proliferation of lymphatic vessels predominates, as a result of which the picture may resemble that of lymphangioma, especially if some vessels are razor-sharp.

In proliferation foci, elongated cells (fibroblastic variant) form bundles interwoven in different directions. These cells have prolate nuclei, similar in structure to those of fibroblasts. Electron microscopy revealed that a large number of ribosomes and polysomes, vacuoles, enlarged cisterns of the enoplasmic network, and lysosomal structures are found in their cytoplasm. Nuclei with large nucleoli, elongated. The heterochromatin is distributed near the nuclear envelope.

Among the cells in a significant amount there are very active forms, characterized by the presence in the cytoplasm of a large number of lysosomal structures, sharply dilated cisterns of the endoplasmic reticulum. Quite a lot of mitoses. Proliferation of the faith of yen-like cells can be diffuse, occupying the entire thickness of the dermis, or limited in the form of nodes surrounded by a connective tissue capsule. Between the spindle-shaped cells, freely lying red blood cells, lumens of newly formed vessels and hemorrhages are visible.

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

In regressing foci, fibroblastic changes gradually increase with the desolation of blood vessels, homogenization, and sometimes hyalinosis of the collagen substance. However, even in such cases, it is often possible to see perivascular fishes from young undifferentiated cells of rounded form with an admixture of lymphoid elements and plasmocytes, as well as neoplasm of vessels, which is the morphological expression of the further progression of the process.

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

Histogenesis of Kaposi's sarcoma

Despite a large number of works on the histogenesis of Kaposi's sarcoma, pro and convergence of typical spindle-shaped cells is not completely elucidated. Ultrastructural data show that the tumor consists mainly of cells with the characteristic of the endothelium and fibroblast-like elements, among which 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 free of organelles, and an electronically dense nucleus, which indicates their weak activity. The latter is also confirmed by the fact that the lymphocytes are separated from the tumor elements by light spaces and do not have contact with them.

Studies of recent years, coming from the notion of a mononuclear phagocyte system, suggest the possibility of involving endotheliocytes and stromal fibroblasts in the processes of immune response and tumor proliferation. ER Aschida et al. (1981) found that endothelial cells participate in immune responses by activating T-lymphocytes. They have receptors on their surface to the Fc fragment of IgG and the C3-component of complement. 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 marker of the endothelium - factor VIII antigen (protein specific for endotheliocytes) in many cells of Kaposi's sarcoma testifies to their endothelial origin. I.A. Kazantsev et al. (1986) confirmed the origin of tumor elements from the endothelium and perivascular fibroblast-like cells with high functional activity as a result of a complex study of biopsy specimens from the lesion site using electron microscopic, immunomorphological, and autoradiographic methods. 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 basal membranes produced by both endotheliocytes and pericytes. Radioautographic study allowed the authors to establish active inclusion of ³ H-thymidine in both endotheliocytes of proliferating capillaries and in perivascular cells, which indicates active synthesis of DNA and the possibility of them to enter mitosis.

An analysis of these data suggests that in the histogenesis of Kaposi's sarcoma both endotheliocytes and perivascular pluripotent undifferentiated cells participate.

Histopathology

Two main signs are histologically distinguished: disordered formation of vessels and proliferation of spindle-shaped cells.

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

Symptoms of Kaposi's sarcoma

The clinical symptoms of Kaposi's sarcoma are varied, depending on the duration of the course of the disease. In the initial stages appear reddish-cyanotic spots of various sizes and shapes, nodular-like elements of pink, and then cyanotic color. In the future, rashes become the appearance of infiltrated nodular elements of various sizes, reddish-cyanotic color with a brownish hue. Knots can merge, forming large hummocky foci, ulcerate with the formation of sharply painful ulcers. Often in the area of the lesion the skin is compacted, edematous, purple-cyanotic in color. The foci are localized mainly on the skin of the distal parts of the extremities, tend to settle near the superficial veins. According to A.A. Kalamkaryan and co-workers. (1986), IL Ziegler (1987), in 93.8% of cases they are on the lower limbs, mainly on the feet and the anterolateral surfaces of the shins. The symmetry of the lesion is characteristic. However, other skin areas, as well as mucous membranes, can be affected.

The course of the disease can be acute, subacute and chronic. The acute course is characterized by a rapidly progressive symptomatology with fever and generalized lesion of the skin in the form of multiple nodular-nodular lesions on the limbs, face and trunk. This is accompanied by damage to the lymph nodes and internal organs. Duration of the disease from 2 months to 2 years. In subacute flow, generalization of skin rashes occurs less frequently. In chronic course there is a gradual progression of skin rashes in the form of patchy-nodular and plaque elements. 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 (immuno-dependent, immunosuppressive). In the course of the current, the acute, subacute and chronic forms of Kaposi's sarcoma are distinguished.

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

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

Primary lesions are most often located on the skin of the extremities, especially the lower ones, on the back surfaces of the groan and the front surface of the shins. However, the elements of the rash can be located on other areas of the skin (ears, eyelids, cheeks, hard palate, penis). In the period of complete development of the disease, almost all patients (95%) have a widespread and symmetrical process. Therefore, for Kaposi's sarcoma, the characteristic features are: multichannelness, prevalence and symmetry of the rash.

Kaposi's sarcoma begins with the appearance of reddish-cyanotic or reddish-brownish distinctly delineated spots as large as lentil to 1 cm or more. Over time, they slowly increase and reach up to 5 cm in diameter, their coloring, as a rule, changes: the reddish-cyanotic color turns into dark brown. The surface of the spots is smooth, only in some cases they are covered with grayish scales. In the future, infiltrated plaques, nodules, and nodes appear on the background of spots.

The nodules forming the size of a small pea are spherical or flat, initially pink, and eventually acquire a brown color. Nodules can be located in isolation or in groups and merge into large plaques or nodes.

Infiltrative plaques from 1 cm to the size of the palm of the child and more often have a rounded. Rarely - an oval shape. The surface of plaques at the beginning of the disease is uneven, eventually becomes covered with papillomatous growths. Half-spherical tumors ranging from a large pea to a hazelnut clearly rise above the level of normal skin. Their color at the beginning of the disease is reddish-cyanotic, later acquires a bluish-brownish hue. As a result of the disintegration of tumors, rarely - infiltrative plaques, deep ulcers of irregular contours appear with slightly twisted edges of cyanotic-purple color and a tuberous bloody gangrenous bottom. Characteristic features are puffiness of the affected limb and development of lymphostasis, elephantiasis.

Sometimes swelling can be the first symptoms of the disease. Subjectively sick are concerned with itching and burning, and with ulceration of the elements - a sharp painful pain. In the pathological process, mucous membranes of the oral cavity are often involved. In this case, the rashes are located on a soft and hard sky, cheeks, lips, tongue, in the throat, larynx. Nodular-tumor-like and infiltrative formations in color sharply differ from the surrounding mucosa and have a cherry-red color. Also, there may be lesions of internal organs, lymph nodes, musculoskeletal system.

With a prolonged course of the disease, individual foci regress. Complete spontaneous remission is very rare (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 limbs; Lymph nodes are rarely affected. Lymphadenopathic variant of endemic Kaposi's sarcoma is found mainly in African children 10 years and younger. There is a malignant course with severe polyadenopathy and rapid involvement in the pathological process of internal organs. Rashes are highly sensitive to radiation and chemotherapy. Relapses occur faster than in the classical form. The prognosis is unfavorable: the patients die within the period from 5 months to 2 years.

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

The iatrogenic (immunosuppressive) form of Kaposi's sarcoma is found in cancer patients receiving cytotoxic drugs and in individuals receiving immunosuppressants after kidney transplantation.

Also described are rare and distinctive forms of Kaposi's sarcoma: hypertrophic, corn-resembling, pyogenic granuloma, and others.

The acute form of Kaposi's sarcoma is characterized by a rapid course with generalization of the process and involvement of internal organs. There is a marked violation of the general condition of the patient, a fatal outcome may occur in a few months about the onset of the disease.

In subacute form, in contrast to acute form, slow generalization of rashes is noted. The lethal outcome comes in 3-5 years.

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

[17], [18], [19], [20], [21], [22], [23],

Differential diagnosis of Kaposi's sarcoma

Kaposi's sarcoma should be differentiated from Kaposi pseudosarcoma, pyogenic granuloma, melanoma, leiomyoma, angioliomyosarcoma.

[24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35]

Treatment of Kaposi's sarcoma

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

For local treatment, radiotherapy is used, which is performed in the presence of tumor formations of a large lesion area. Single pose - 8 g, total - up to 30 g. Assign injection of cytostatics in the lesion (vinblastine - 0.1 mg of the drug per 1 cm ^{2 of} the tumor area). To remove protrusions above the surface of the site, surgical excision or cryodestruction is used.