Kaposi's sarcoma (KS) is a tumor caused by Human herpesvirus 8 (HHV8), also known as Kaposi's sarcoma-associated herpesvirus (KSHV). It was originally described by Moritz Kaposi(KUH-po-shee), a Hungarian dermatologist practicing at the University of Vienna in 1872.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.
HHV-8 is responsible for all varieties of KS.
Classic KS' as originally described was a relatively indolent disease affecting elderly men from the Mediterranean region, or of Eastern European descent. Countries bordering the Mediterranean basin have higher rates of KSHV/HHV-8 infection than the remainder of Europe
Endemic KS was described later in young African people, mainly from sub-Saharan Africa, as a more aggressive disease which infiltrated the skin extensively, especially on the lower limbs. This, it should be noted, is not related to HIV infection. KS is prevalent worldwide.
Transplant Related KS had been described, but only rarely until the advent of calcineurin inhibitors (such as ciclosporines, which are inhibitors of T-cell function) for transplant patients in the 1980s, when its incidence grew rapidly. The tumor arises either when an HHV 8-infected organ is transplanted into someone who has not been exposed to the virus or when the transplant recipient already harbors pre-existing HHV 8 infection.
Epidemic KS was described during the 1980s as an aggressive disease in AIDS patients (HIV also causes a defect in T-cell immunity). It is over 300 times more common in AIDS patients than in renal transplant recipients. In this case, HHV 8 is sexually transmitted among people who are also at risk for sexually transmitted HIV infection.
Since Moritz Kaposi first described this malignant neoplasm, the disease has been reported in five separate clinical settings, with different presentations, epidemiology, and prognoses:599:
- 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 and respiratory tract. Growth can range from very slow to explosively fast, and is associated with significant mortality and morbidity.
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.
Intraoral AIDS-associated Kaposi sarcoma with an overlying candidiasisinfection
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.
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.
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 and diagnosis:
Micrograph of a Kaposi's sarcomashowing the characteristic spindle cells, high vascularity and intracellular hyaline globs. H&E stain.
Despite its name, it is generally not considered a true sarcoma, which is a tumor arising frommesenchymal 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. Inflammationaround 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.
In Europe and North America KSHV is transmitted through saliva. Thus, kissing is a theoretical risk factor for transmission although transmission between heterosexuals appears to be rare. Higher rates of transmission among gay and bisexual men has been attributed to "deep kissing" . Another alternative theory suggests that use of saliva as a sexual lubricant might be a major mode for transmission. Prudent advice is to use commercial lubricants when needed and avoid deep kissing with partners who have KSHV infection or have unknown status.
KSHV is transmissible during organ transplantation and to a lesser extent through blood transfusion. Testing for the virus before these procedures is likely to effectively limit iatrogenic transmission.
Treatment and prevention:
Kaposi's sarcoma before Interferon 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 immunodeficiencyor 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.