Kaposi Sarcoma 1_0513 Derm Clinic
Kaposi Sarcoma 2_0513 Derm Clinic
A white man, aged 35 years, was referred to dermatology for treatment of a rash of several weeks’ duration. The man initially noted dark spots on his torso that subsequently developed into firm bumps. His medical history was negative, and he was taking no medications; social history revealed a homosexual lifestyle with no illegal drug use.
Physical examination revealed numerous elliptical-to-round, violaceous, and indurated papules and plaques of various sizes. Laboratory testing showed the presence of the HIV virus with a CD4+ T-lymphocyte count of 200 cells/µL. A punch biopsy was performed.
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The punch biopsy revealed a spindle-cell tumor that was comprised of proliferated, dilated blood vessels and vascular slits blended with erythrocytes and a mixed inflammatory infiltrate. These findings are characteristic of a vascular neoplasm called Kaposi sarcoma (KS), an AIDS-defining illness in an HIV-positive individual.
AIDS-related KS was highly prevalent in the 1990s; however, the introduction and widespread use of highly active antiretroviral therapy (HAART) in the United States allowed stabilization of the immune system in many HIV-infected individuals and dramatically reduced the incidence of KS. Nevertheless, KS remains a common malignancy in AIDS patients, second only to non-Hodgkin lymphoma.1
First described in 1872 by Hungarian dermatologist Moritz Kaposi,2 KS is now known to be caused by an infectious organism, human herpesvirus 8, also referred to as Kaposi sarcoma-associated herpesvirus (HHV-8/KSHV).3 Although KS is indelibly linked with HIV and AIDS in the Western world, three of its four variants are not HIV-related: Classic KS, as described by Moritz, affects mainly elderly men of eastern European and Mediterranean descent; endemic KS (also referred to as African KS) occurs most commonly in children in sub-Saharan Africa; immunosuppressed KS develops in patients on immunosuppressive therapy following a solid-organ transplant; and epidemic KS (also referred to as AIDS-related KS), first reported in 1981, is most common in HIV-positive homosexual men.4
Present in blood, saliva, and other bodily fluids, the precise mode of transmission for KSHV remains obscure. However, epidemic KS is most prevalent in those who acquire the HIV virus through homosexual contact.4,5
Cutaneous lesions occur in virtually all individuals who have KS, but the presentation and course can be highly variable. In some individuals, the skin lesions will spontaneously remit, whereas the disease will take a more aggressive course in other patients, in part related to the individual’s immune system.
Systemic involvement occurs in approximately 50% of affected patients, some of whom develop widespread disease affecting the hematopoietic and lymphatic systems, visceral internal organs, mucosal surfaces, and subcutaneous tissues.6,7
Lesions assocated with AIDS-related KS can occur anywhere but are more common on the head and neck, upper torso, and extremities. Lesions are typically asymptomatic and pigmented with a wide variety of colors, ranging from pink to purple or brown to black.
Lesions may be innumerable or single, discrete or confluent, flat or elevated, plaque-like or nodular. They can vary greatly in size from 1 mm to 2 mm to several centimeters in diameter.7 Mucosal surfaces are frequently affected.
The differential diagnosis for lesions of KS includes bacillary angiomatosis (BA), angiosarcoma, hemangioma, and lichen planus (LP); of these, BA and LP can also be associated with HIV. A biopsy readily differentiates between these conditions.
Of the 50% of patients with KS who develop internal organ involvement, the GI tract is the most common site afflicted. Although frequently asymptomatic and detected solely by examination of the oral cavity, these patients may develop diarrhea, with or without blood, or abdominal pain.7
Pulmonary involvement is the next most prevalent site of organ involvement and may be life-threatening. Patients may note shortness of breath, cough, hemoptysis, and chest pain.7,8 Other organs may be similarly affected, and autopsy studies have revealed KS to develop in nearly every organ system.
Staging of KS is based on a tumor, immunologic status, and systemic illness system. Earlier stages have a better prognosis, with skin-limited disease having a better prognosis than systemic disease. GI and pulmonary involvement adversely affect morbidity and mortality.
Other poor prognostic factors include the presence of an opportunistic infection, thrush, and the constitutional symptoms of fever, night sweats, and weight loss.9 Data suggest that aggressive treatment with HAART, even in patients with lung disease, may be associated with a more favorable prognosis.10
As an AIDS-defining illness, KS is an indication to initiate therapy in an otherwise asymptomatic HIV-positive patient.7 HAART is considered first-line therapy to treat AIDS-related KS and may result in a 20% to 80% remission rate if an adequate immune status can be re-established. A paradoxical flare of KS can occur with the initiation of HAART. This flare is called the “immune reconstitution syndrome” and is a result of a rising CD4+ count with reactivation of the immune system and associated inflammatory response.
Other treatment approaches are only palliative in nature and include various regimens for localized disease and systemic cytotoxic drugs.
Local therapy options include radiation, cryosurgery, laser surgery, excisional surgery, electrocauterization, topical alitretinoin, and intralesional injection of various chemotherapeutic agents. Of the listed ablative modes, radiation is the most effective and most widely used; electron-beam radiation may even be effective for widespread cutaneous disease.
Topical alitretinoin may reduce tumor size in up to 50% of patients. Intralesional injections of vinca alkaloids (vinblastine, vincristine) may also minimize tumors, but significant localized adverse effects, including ulceration and pain, are common. Unfortunately, all local treatment options are inconsequential for systemic disease.
Various systemic cytotoxic drugs can induce rapid tumor regression but are typically reserved for extensive or life-threatening KS.11 Unfortunately, these agents carry significant side effects, including neuropathy, pulmonary fibrosis, depression, cardiotoxicity, and bone-marrow suppression, which may be unacceptable for some patients due to HIV status, age, immunosuppression, or other comorbidities.
Systemic agents include bleomycin, etoposide, paclitaxel, pegylated liposomal doxorubicin, pegylated interferon, the vinca alkaloids, and anthracyclines (doxorubicin and daunorubicin).7,11,12 Studies have shown a synergistic effect with adding zidovudine when treating epidemic KS with interferon.1
In this case, a treatment-naïve HIV patient with a low CD 4+ count, HAART was indicated. In addition to triple-drug HAART, short-term prophylactic trimethoprim/sulfamethoxazole was initiated to combat opportunistic infections during the immune reconstitution phase. Several months into therapy, the cutaneous lesions slowly involuted, and the man’s CD4+ count rose to 500 cells/µL, with an undetectable HIV viral load.
Navid Malakouti is a third-year medical student at Medical College of Virginia Hospitals, Virginia Commonwealth University, in Richmond, where Julia R. Nunley, MD, is professor of dermatology.
- Aversa SM, Cattelan AM, Salvagno L, et al. Treatments of AIDS-related Kaposi’s sarcoma. Crit Rev Oncol Hematol. 2005;53:253-265.
- Kaposi M. Idiopatisches multiples Pigmentsarkom der Haut. Arch Dermatol Syphilis. 1872;4:265-73.
- Nawar E, Mbulaiteye SM, Gallant JE, et al. Risk factors for Kaposi’s sarcoma among HHV-8 seropositive homosexual men with AIDS. Int J Cancer. 2005;115:296-300.
- Friedman-Kien AE, Laubenstein LJ, Rubinstein P, et al. Disseminated Kaposi’s sarcoma in homosexual men. Ann Intern Med. 1982;96:693-700.
- Biggar RJ, Rabkin CS. The epidemiology of AIDS-related neoplasms. Hematol Oncol Clin North Am. 1996;10:997-1010.
- Sanders CJ, Canninga-van Dijk MR, Borleffs JC. Kaposi’s sarcoma. Lancet. 2004;364:1549-1552.
- Levine AM, Tulpule A. Clinical aspects and management of AIDS-related Kaposi’s sarcoma. Eur J Cancer. 2001;37:1288-1295.
- Aboulafia DM. The epidemiologic, pathologic, and clinical features of AIDS-associated pulmonary Kaposi’s sarcoma. Chest. 2000;117:1128-1145.
- Krown SE, Testa MA, Huang J. AIDS-related Kaposi’s sarcoma: prospective validation of the AIDS Clinical Trials Group staging classification. AIDS Clinical Trials Group Oncology Committee. J Clin Oncol. 1997;15:3085-3092.
- Holkova B, Takeshita K, Cheng DM, et al. Effect of highly active antiretroviral therapy on survival in patients with AIDS-associated pulmonary Kaposi’s sarcoma treated with chemotherapy. J Clin Oncol. 2001;19:3848-3851.
- Di Lorenzo G, Konstantinopoulos PA, Pantanowitz L, et al. Management of AIDS-related Kaposi’s sarcoma. Lancet Oncol. 2007;8:167-176.
- Sgadari C, Bacigalupo I, Barillari G, Ensoli B. Pharmacological management of Kaposi’s sarcoma. Expert Opin Pharmacother. 2011;12:1669-1690.