Kaposi's Sarcoma-A Warning Sign of HIV Infection

Kaposi's sarcoma (KS) was first described in the nineteenth century, as a neoplasm most commonly occurring in elderly middle-aged Jewish or Mediterranean men. Kaposi's sarcoma is a malignant neoplasm composed of spindle cells and vascular elements. More recently, it was seen in Africa where it is endemic, particularly in East Africa. The lesions in these groups were usually slow growing and responded readily to therapy. However, in association with HIV infection the lesions of KS may be more aggressive and sometimes quite resistant to therapy.

The causes and the course of the disease:

The pathogenesis of Kaposi's sarcoma is unknown. A viral etiology is suggested by the epidemiologic features.  Human immunodeficiency virus (HIV) itself is a cofactor in patients with AIDS, as suggested by the induction of Kaposi's sarcoma.

Kaposi's Sarcoma is characterized by multifocal, widespread lesions at the onset of the disease. In the earliest, or patch stage the lesions are small, flat, and macular and may be reddish, pink, purplish, or brown. These lesions may be so inconspicuous that they are easily overlooked.  These lesions may involve the skin, oral mucosa, lymph nodes, and visceral organs, and new lesions appear throughout the course of the disease. In rare cases the patient has a single cutaneous lesion, often on the head or neck.

Intraoral lesions may occur either alone or in association with skin, visceral and lymph node lesions. Frequently the first lesions of Kaposi's sarcoma appear inside the mouth. They can be red, blue or purple and may be flat or raised, solitary or multiple. The commonest oral site reported is the hard palate, although lesions may be found on any part of the oral mucosa including the gingiva, soft palate and buccal mucosa. KS lesions on the gingiva produce diffuse swelling of the gingival papilla, resembling periodontal disease or may sometimes resemble a parulis. The gingival lesions may be associated with considerable gingival enlargement causing periodontal pocketing. The periodontal pockets may become secondarily infected because of poor oral hygiene, and superficially the mucosa may become superinfected with Candida. When the lesions are on the tongue, usually in the midline, they may be paler in color, and several cases have been reported of KS presenting as a swelling of normal mucosal color.

Another unfortunate aspect of Kaposi's sarcoma is that about one third of patients subsequently develop a second malignancy, usually lymphoma, leukemia, or myeloma.

The clinical features:

 Four forms of Kaposi's sarcoma are recognized:

1. The classic, or European, form, first described by Kaposi in 1862, was endemic to older men of Eastern European (especially Ashkenazic Jews) or Mediterranean descent. The tumor was uncommon in the United States, accounting for only 0.02% of all malignant tumors. Clinically, this form consists of multiple red to purple skin plaques or nodules primarily in the lower extremities, slowly increasing in size and number and spreading to more proximal sites. The tumors frequently remain localized to the skin and subcutaneous tissue but are locally aggressive, with an erratic course of relapses and remissions, rarely causing death of the patient. Visceral involvement occurs in only 10% of the cases and is usually clinically asymptomatic.

2. African AIDS is clinically similar to the European form, but occurs in younger men in equatorial Africa.95 It has a very high prevalence in these regions, representing up to 10% of all tumors. In children aged 2 to 3 years in Africa, the disease is often associated with generalized involvement of lymph nodes, resembling lymphoma.

3. Kaposi's sarcoma associated with renal transplant. This form occurs in transplant recipients undergoing immunosuppressive therapy. It is reported in patients with Jewish or Mediterranean heritage, and it is either localized to the skin or results in widespread systemic involvement. The lesions often regress when immunosuppressive therapy is discontinued.

4. Epidemic Kaposi's sarcoma, associated with AIDS, is found in approximately one third of such patients, and it is more common in male homosexuals than in other groups at risk for AIDS. The cutaneous lesions have no predilection for the lower extremities, and they present as few or many pink-to-purple patches, plaques, or nodules with a propensity to become widely disseminated early in the course, involving mucous membranes, gastrointestinal tract, lymph nodes, and viscera. The tumors respond to cytotoxic chemotherapy and to therapy with a-interferon. Most patients eventually succumb to the infectious complications of AIDS rather than directly to the consequences of the tumor.

As they evolve, they enlarge and develop into papules or plaques (plaque stage). The plaque stage lesions may eventually enlarge and become nodules (nodular stage). The plaque and nodular stage lesions may be red, violet, pink, brown or various combinations of these colors.

In approximately 26% of homosexual men with AIDS, Kaposi's sarcoma is present at the time of diagnosis or develops during the course of the disease. In contrast, Kaposi's sarcoma develops in only about 3% of heterosexual intravenous drug abusers with AIDS. The incidence of the disease is equally low in persons who have acquired AIDS by other means.

The differential diagnosis:

 The differential diagnosis of patch stage Kaposi's sarcoma includes hemangiomas, venous lakes, purpura, nevi, and melanomas. Plaque and nodular stage lesions may be confused clinically with AIDS-related angiomatosis, hemangiomas, pyogenic granulomas, nevi, melanomas, cutaneous lymphomas, and angiosarcomas.

The recommended treatment:

Patients with localized, epidemic Kaposi's sarcoma are treated with local modalities such as surgical excision, electrocautery, curettage, or radiation therapy. Treatment for aggressive lesions involves radiation therapy, laser surgery and/or the use of chemotherapeutic drugs. Radiation therapy is frequently associated with a rapid onset of severe mucositis, so severe that treatment is often interrupted. The lesions sometimes recur several months after treatment. Surgical debulking may be successful for small lesions.  Patients with disseminated disease may be treated with immunomodulators and single-agent or combination chemotherapy for acquired immune deficiency syndrome (AIDS).