Kaposi's sarcoma (KS) is a tumor caused by Human herpesvirus 8 (HHV8), also known as Kaposi's sarcoma-associated herpesvirus (KSHV). It became more widely known as one of the AIDS defining illnesses in the 1980s. The viral cause for this cancer was discovered in 1994. Although KS is now well-established to be caused by a virus infection, there is widespread lack of awareness of this even among persons at risk for KSHV/HHV-8 infection.
Restated, Kaposi’s sarcoma (KS) is a systemic disease which can present with cutaneous lesions with or without internal involvement. Four subtypes have been described: Classic KS, affecting middle aged men of Mediterranean and Jewish descent, African endemic KS, KS in iatrogenically immunosuppressed patients, and AIDS-related KS. The erythematous to violaceous cutaneous lesions seen in KS have several morphologies: macular, patch, plaque, nodular, and exophytic. The cutaneous lesions can be solitary, localized or disseminated. KS can involve the oral cavity, lymph nodes, and viscera. Classic KS tends to be indolent, presenting with erythematous or violaceous patches on the lower extremities. African endemic KS and AIDS-related KS tend to be more aggressive. The AIDS-related KS lesions often rapidly progress to plaques and nodules affecting the upper trunk, face, and oral mucosa. The diagnosis can be made with a tissue biopsy and, if clinically indicated, internal imaging should be done.
Once the diagnosis of KS has been made, treatment is based on the subtype and the presence of localized versus systemic disease. Localized cutaneous disease can be treated with cryotherapy, intralesional injections of vinblastine, alitretinoin gel, radiotherapy, topical immunotherapy (imiquimod), or surgical excision. Extensive cutaneous disease and/or internal disease may require IV chemotherapy and immunotherapy. Discontinuation or reduction of immunosuppressive therapy is recommended when KS arises in the setting of iatrogenic immunosuppression. However, with AIDS-related KS, HAART has been shown to prevent or induce regression of KS. Some AIDS patients have complete resolution of the lesions and prolonged remission while continuing the therapy. Therefore, HAART should be considered first-line treatment for these patients, though they may require other concomitant treatments.
Types
Since Moritz Kaposi first described this malignant neoplasm, the disease has been reported in five separate clinical settings, with different presentations, epidemiology, and prognoses
- Classic Kaposi sarcoma
- African cutaneous Kaposi sarcoma
- African lymphadenopathic Kaposi sarcoma
- AIDS-associated Kaposi sarcoma
- Immunosuppression-associated Kaposi sarcoma
Signs and symptoms
KS lesions are nodules or blotches that may be red, purple, brown, or black, and are usually papular (i.e. palpable or raised).
They are typically found on the skin, but spread elsewhere is common, especially the mouth, gastrointestinal tract andrespiratory tract. Growth can range from very slow to explosively fast, and is associated with significant mortality andmorbidity.
Skin
Commonly affected areas include the lower limbs, back, face, mouth and genitalia. The lesions are usually as described above, but may occasionally be plaque-like (often on the soles of the feet) or even involved in skin breakdown with resulting fungating lesions. Associated swelling may be from either local inflammation or lymphoedema (obstruction of local lymphatic vessels by the lesion). Skin lesions may be quite disfiguring for the sufferer, and a cause of much psychosocial pathology.
Mouth
Is involved in about 30%, and is the initial site in 15% of AIDS related KS. In the mouth, the hard palate is most frequently affected, followed by the gums. Lesions in the mouth may be easily damaged by chewing and bleed or suffer secondary infection, and even interfere with eating or speaking.
Gastrointestinal tract
Involvement can be common in those with transplant related or AIDS related KS, and it may occur in the absence of skin involvement. The gastrointestinal lesions may be silent or cause weight loss, pain, nausea/vomiting, diarrhea, bleeding (either vomiting blood or passing it with bowel motions), malabsorption, or intestinal obstruction.
Respiratory tract
Involvement of the airway can present with shortness of breath, fever, cough, hemoptysis (coughing up blood), or chest pain, or as an incidental finding on chest x-ray. The diagnosis is usually confirmed by bronchoscopy when the lesions are directly seen, and often biopsied.
Pathophysiology
Despite its name, it is generally not considered a true sarcoma, which is a tumor arising from mesenchymal tissue. KS actually arises as a cancer of lymphatic endothelium and forms vascular channels that fill with blood cells, giving the tumor its characteristic bruise-like appearance. KSHV proteins are uniformly detected in KS cancer cells.
KS lesions contain tumor cells with a characteristic abnormal elongated shape, called spindle cells. The tumor is highly vascular, containing abnormally dense and irregular blood vessels, which leak red blood cells into the surrounding tissue and give the tumor its dark color. Inflammation around the tumor may produce swelling and pain.
Although KS may be suspected from the appearance of lesions and the patient's risk factors, definite diagnosis can only be made by biopsy and microscopic examination, which will show the presence of spindle cells. Detection of the KSHV protein LANA in tumor cells confirms the diagnosis.
Treatment
Blood tests to detect antibodies against KSHV have been developed and can be used to determine if a patient is at risk for transmitting infection to their sexual partner, or if an organ is infected prior to transplantation. Unfortunately, these tests are not available except as research tools and thus there is little screening for persons at risk for becoming infected with KSHV, such as transplant patients.
Kaposi's sarcoma is not curable (in the usual sense of the word) but it can often be effectively palliated for many years and this is the aim of treatment. In KS associated with immunodeficiency or immunosuppression, treating the cause of the immune system dysfunction can slow or stop the progression of KS. In 40% or more of patients with AIDS-associated Kaposi's sarcoma, the Kaposi lesions will shrink upon first starting highly active antiretroviral therapy (HAART). However, in a certain percentage of such patients, Kaposi's sarcoma may again grow after a number of years on HAART, especially if HIV is not completely suppressed. Patients with a few local lesions can often be treated with local measures such as radiation therapy or cryosurgery. Surgery is generally not recommended as Kaposi's sarcoma can appear in wound edges. More widespread disease, or disease affecting internal organs, is generally treated with systemic therapy with interferon alpha, liposomal anthracyclines (such as Doxil) or paclitaxel.
With the decrease in the death rate among AIDS patients receiving new treatments in the 1990s, the incidence and severity of epidemic KS also decreased. However, the number of patients living with AIDS is increasing substantially in the United States, and it is possible that the number of patients with AIDS-associated Kaposi's sarcoma will again rise as these patients live longer with HIV infection.
