Kaposi's Sarcoma |
||
|
||
|
Characteristic purplish hue is seen in multifocal Kaposi's of the palate and gingiva. |
||
Quick Review for Patients
Note: click on underlined words for more detail or photos.
Kaposi’s sarcoma is a multicentric proliferation of vascular and spindle cell components, which was first described in 1872. Now considered to be a viral-induced or viral-associated tumor, it is unclear whether the lesion is a true neoplasm or a simple hyperplasia. Today it is strongly affiliated with AIDS and its course is greatly influenced by the immune status of the affected individual. Although found predominantly in HIV-infected persons, HIV does not seem to be the direct cause of the tumorous proliferation and HIV amino acid sequences have not been identified within lesional cells. These cells produce several cytokines capable of stimulating their own growth and HIV-infected lymphocytes are also capable of producing their own set of similar cytokines.
Clinical Features
Kaposi’s sarcoma has four major clinical presentations: classic (chronic), endemic (lymphadenopathic; African), immunosuppression-associated (transplant), and AIDS-related. The classic variant affects older males of Italian, Slavic or Jewish ancestry, and is rare in the United States. It is often associated with altered immune states as well as lymphoreticular and other malignancies. It has no association with HIV- infection. Cutaneous multifocal blue-red nodules develop on the lower extremities and slowly increase in size and numbers, with some lesions regressing while new ones are forming on adjacent or distant skin. Oral involvement in this form of the disease is quite unusual but when it occurs it does so as soft, bluish nodules of the palatal mucosa or gingiva.
Lymphadenopathic Kaposi’s sarcoma is endemic to young African children and presents as a localized or generalized enlargement of lymph node chains, including the cervical nodes. The disease follows a fulminating course with visceral involvement and minimal skin or mucous membrane involvement. In the head and neck region, salivary glands may be affected. This variant does not appear to be HIV related.
Transplantation-associated Kaposi’s sarcoma is seen in 1-4% of renal transplant patients, usually becoming manifested 1-2 years after transplantation. The extent and progression of the disease correlates directly with the loss of cellular immunity of the host. Sarcomatous involvement occurs on the skin as well as internal organs, but oral mucosal lesions are decidedly rare.
AIDS-related Kaposi’s sarcoma in the United States is found primarily in male homosexuals, but in Africa heterosexual transmission and needle-stick contamination seem to be much more strongly associated. Approximately 40% of homosexual AIDS patients will develop Kaposi’s sarcoma, often as an early sign of the disease. Affected patients are usually young adults or early middle-aged males, with the average age at sarcomatous diagnosis being 39 years in the U.S. Individual lesions occur in many cutaneous locations, especially along lines of cleavage and on the tip of the nose. Oral lesions can also occur on any mucosal surface but have a strong predilection for palatal and gingival mucosa.
Early oral mucosal sarcomas are flat and slightly blue, red or purple (Figure 1). With time, lesions become more deeply discolored and surface papules and soft nodules develop, usually remaining less than 2 cm. in size (Figures 2 & 3). Individual lesions may coalesce and occasional patients never develop the nodular variant. Cervical lymph nodes and salivary gland enlargement may also be seen. The patient may have oral candidiasis and AIDS-related gingivitis as well.
Pathology and Differential Diagnosis
Kaposi’s sarcoma has a similar histopathologic appearance in all of its clinical subtypes. The early lesion (patch stage) is characterized by a proliferation of small veins and capillaries around one or more dilated vessels (Figure 4). A pronounced mononuclear inflammatory cell infiltrate, including mast cells, is often noted, as are scattered erythrocytes and hemosiderin deposits. There may be an inconspicuous perivascular proliferation of spindle cells, but cellular atypia is minimal.
More advanced lesions are nodular and show increased numbers of small capillaries or dilated vascular channels interspersed with proliferating sheets of sarcomatous or atypical spindle cells, often with large numbers of extravasated erythrocytes and abundant hemosiderin deposition (Figures 5 & 6). Slit-like vascular channels without a visible endothelial lining are typically interspersed with the spindle cells. Lesional cells have somewhat enlarged, hyperchromatic nuclei with mild to moderate pleomorphism. Mitotic activity is quite variable but is usually minimal. Infiltration by chronic inflammatory cells is also variable. Occasional lesions show such exuberance of the spindled component that the vascular features become minimally visible. Rarely, the vascular component dominates with anastomosing channels lined by anaplastic endothelial cells, similar in appearance to angiosarcoma.
Intracellular and extracellular hyaline globules occur with some frequency in the earlier stages of this tumor. They occur in clusters of faintly eosinophilic spheres smaller than erythrocytes. These are PAS positive and diastase resistant, and probably represent partially digested or degenerated erythrocytes (ghost erythrocytes). Immunoreactivity is somewhat variable, but the spindle cells are consistently reactive for CD34 and the delicate, flattened endothelial cells lining the vascular clefts are reactive for both CD31 and CD34. The vascular channels are often reactive for Ulex europaeus agglutinin, but nonreactive for factor XIIIa.
As a proliferative vascular and spindled lesion, Kaposi’s sarcoma may mimic a variety of other soft tissue lesions, especially pyogenic granuloma, hemangioma, lymphangioma, hemangioendothelioma, hemangiopericytoma, and bacillary angiomatosis. The vascular channels of pyogenic granuloma and hemangioma are more widely spaced, seldom appear slit-like and have much more prominent endothelial cells. The hemangioma lacks the inflammatory cell infiltrate of Kaposi’s sarcoma, but the pyogenic granuloma abounds with these.
Hemangioendothelioma, especially when the spindle cell component is prominent, differs from Kaposi’s sarcoma by showing dilated vascular spaces admixed with collections of epithelioid cells with and without early lumina. The angiosarcoma typically shows more endothelial cell atypia and enlargement, even intraluminal shedding, than is found in Kaposi’s sarcoma. The reader is referred to descriptions of these lesions elsewhere in the present chapter.
Treatment and Prognosis
Various treatments have been used with oral Kaposi’s sarcoma with variable success. Small or localized lesions can be surgically excised with a small surrounding margin of clinically normal tissue, but more recent therapies have concentrated on low-dose irradiation and intralesional chemotherapy and sclerosing solutions. For larger and multifocal lesions, systemic chemotherapy is often effective.
References (Chronologic Order)
Note: General references can be found by clicking on that topic to the left.
Kaposi M. Idiopathisches multiples Pigmentsarkom der Haut. Arch Dermatol Syph 1872; 4:265-276.
Ficarra G, Berson A, Silverman S Jr, et al. Kaposi’s sarcoma of the oral cavity: a study of 134 patients with a review of the pathogenesis, epidemiology, clinical aspects, and treatment. Oral Surg Oral Med Oral Pathol 1988; 66:543-550.
Friedman-Kien AE, Saltzman BR. Clinical manifestations of classical, endemic African, and epidemic AIDS-associated Kaposi’s sarcoma. J Am Acad Dermatol 1990; 22:1237-1250.
Searles GE, Markman S, Yazdi HM. Primary oral Kaposi’s sarcoma of the hard palate. J Am Acad Dermatol 1990; 23:518-519.
Lucatorto FM, Sapp JP. Treatment of oral Kaposi’s sarcoma with a sclerosing agent in AIDS patients. Oral Surg Oral Med Oral Pathol 1993; 75:192-198.
Regezi JA, MacPhail LA, Daniels TE, Greenspan JS, et al. Oral Kaposi’s sarcoma: a 10-year retrospective histopathologic study. J Oral Pathol Med 1993; 22:292-297.
Ensoli B, Gendelman R, Markham P, et al. Synergy between basic fibroblast growth factor and HIV-1 tat protein in induction of Kaposi’s sarcoma. Nature 1994; 371:674-680.
Miles SA. Pathogenesis of AIDS-related Kaposi’s sarcoma. Evidence of a viral etiology. Hematol Oncol Clin North Am 1996; 10:1011-1021.
