Kaposi sarcoma

ALSO KNOWN AS: Kaposi's sarcoma, KS, classic Kaposi sarcoma, epidemic Kaposi sarcoma, endemic or African Kaposi sarcoma, acquired or immunosuppressive-therapy-related Kaposi sarcoma

RELATED CONDITIONS: Human herpesvirus 8 (HHV-8), acquired immunodeficiency syndrome (AIDS), organ transplant

DEFINITION: Kaposi sarcoma is a connective tissue cancer named after dermatologist Moritz Kaposi, who first described endothelial-raised lesions in connective tissues and mucosal membranes. There are four known types of Kaposi sarcoma—classic (Mediterranean) Kaposi sarcoma, mostly found in older Italian or Eastern European Jewish men; endemic (African) Kaposi sarcoma, which mainly afflicts young men in equatorial Africa; transplant-related Kaposi sarcoma, found in posttransplant patients; and epidemic (AIDS-related) Kaposi sarcoma, which develops in patients with human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS). Epidemic Kaposi sarcoma is the most clinically aggressive and most prevalent form of the disease.

Risk factors: Risk factors differ for each type of Kaposi sarcoma but include ethnicity, age, and disease state. Men are much more prone to the disease than women. In the United States, Black American men are much more likely to develop Kaposi sarcoma than White or Hispanic men. HIV is a distinct risk factor for epidemic Kaposi sarcoma. Human herpesvirus 8 (HHV-8), a deoxyribonucleic (DNA) virus in the Epstein-Barr virus family, causes all types of Kaposi sarcoma.

Etiology and the disease process: Kaposi sarcoma develops due to HHV-8 infection, also known as the Kaposi sarcoma-associated herpesvirus (KSHV). The virus infects the endothelial cells, which line the insides of blood vessels and lymphatic vessels and causes them to live longer and divide more rapidly than they otherwise would. HHV-8 is much more common than Kaposi sarcoma. The sarcoma typically only develops when an infected person becomes or is already immunocompromised.

Lesions initially develop as flat or raised colored blotches under the skin or mucous membranes, most often on the face or legs. Swelling or bleeding may impair nearby organ function, especially in the lungs, liver, and gastrointestinal (GI) tract.

Classic, African, and immunosuppressive-therapy-related Kaposi sarcoma lesions usually occur on the skin and only occasionally spread into the mucous membranes or the lymph or gastrointestinal systems. However, aggressive African Kaposi sarcoma tumors may also penetrate bone or manifest in lymph nodes and organs. In contrast, epidemic Kaposi sarcoma lesions are nodular, widespread, and rapidly multiplying. They develop in the skin, mouth, lymph nodes, and organs, especially the GI tract, lungs, liver, and spleen. In most cases, untreated epidemic Kaposi sarcoma will spread extensively throughout the patient's organs.

Incidence: Less than 1 percent of Americans carry the HHV-8 infection. Classic Kaposi sarcoma is rare. In the 1950s, African Kaposi sarcoma accounted for approximately 9 percent of all cancers found in Ugandan men. Following the advent of HIV/AIDS, African Kaposi sarcoma and epidemic Kaposi sarcoma accounted for approximately 37,000 new cases (many in prepubescent children, usually boys) and 25,000 deaths in sub-Saharan Africa each year.

In the twenty-first century, Kaposi sarcoma impacts one in two hundred people who receive organ transplants and one in six million people with HIV or AIDS. Transplant-related Kaposi sarcoma develops in a small percentage of organ-transplant recipients. The risk increases if the transplant is performed in a country where KSHV is expected, like Italy or Saudi Arabia. 

Epidemic Kaposi sarcoma is classified as an AIDS-defining cancer, like non-Hodgkin lymphoma and cervical cancer. (An AIDS-defining condition is one whose presence in an HIV patient indicates that the disease has progressed to AIDS.) The overall incidence of epidemic sarcoma among AIDS patients in the United States was once as high as 25 percent but decreased steadily with the use of highly active antiretroviral therapy (HAART).

Symptoms: Lesions are often disfiguring, palpable, and painful when swollen. Tumors bleed easily, causing ulceration, necrosis, and tissue discoloration. Symptoms are directly related to lesion location. For example, speech and feeding problems occur with palate tumors. Common symptoms of organ lesions include bleeding from gastrointestinal lesions, nausea, vomiting, bowel obstruction, cough, dyspnea, and hemoptysis. Symptoms unique to epidemic Kaposi sarcoma include swollen lymph nodes, fever, and weight loss.

Screening and diagnosis: Although HHV-8 is directly associated with Kaposi sarcoma, routine screening is not recommended for the general population. However, people with HIV/AIDS should be screened regularly.

Endoscopies, bronchoscopies, and chest X-rays may be used to screen for KS lesions. Identifiable diagnostic features include purple nodules along skin tension lines, green-yellow discoloration secondary to hemorrhage, surrounding edema, and lesion dissemination. Diagnostic histology shows an intact epidermis, new blood vessel formation with extravasated red blood cells, hemosiderin deposits, infiltrates of spindle-shaped cells, and lymphocytic inflammatory infiltrate. Lesion biopsies are definitive but carry a bleeding risk. Detection of HHV-8 in tumor tissue can confirm an uncertain diagnosis.

Kaposi sarcoma lesions are hard to measure and cannot be staged by traditional cancer classification methods. However, the AIDS Clinical Trials Group has developed staging for HIV-related Kaposi sarcoma that accounts for lesion size and presence and HIV stability.

Treatment and therapy: Treatment for Kaposi sarcoma involves local, systemic, and antiretroviral treatments or any combination. Surgical treatment is limited to diagnostic biopsies and often requires concomitant radiation to prevent spreading.

Local treatment with radiation, cryosurgery, or topical retinoids is best for palliation, cosmetically unacceptable lesions, or refractory disease. Radiation, the primary method, has an 80 to 90 percent response rate.

Systemic treatment for progressive disease includes interferon (INF) alpha, liposomal anthracyclines or paclitaxel, and investigational signal transduction or cytokine inhibitors. INF alpha is an immunomodulatory agent associated with 45 to 70 percent remission rates. Palliative chemotherapeutics may eradicate some lesions and decrease morbidity. Ganciclovir, foscarnet, and cidofovir antivirals effectively reduce lesion size and progression.

The first-line treatment of HIV-related Kaposi sarcoma is HAART, which decreases HIV replication and thereby decreases the frequency of Kaposi sarcoma lesion development. In addition, protease inhibitors such as saquinavir, indinavir, and ritonavir have direct antitumor and antiproliferative effects that can improve Kaposi sarcoma even without an observed increase in the CD4 count. Additional treatments are reserved for visceral disease progression despite HAART.

Prognosis, prevention, and outcomes: Kaposi sarcoma may resolve spontaneously or with treatment. However, aggressive Kaposi sarcoma left untreated is fatal. Approximately 33 percent of patients with classic Kaposi sarcoma risk the development of secondary tumors, typically non-Hodgkin lymphoma. Although AIDS-related Kaposi sarcoma with respiratory failure was once associated with fatality within weeks, HIV-suppressive therapy has made stabilization, complete remission, and prevention of new lesions possible.

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