Classic Kaposi sarcoma: Clinical features, staging, diagnosis, and treatment
- Susan E Krown, MD
Susan E Krown, MD
- Member Emerita
- Memorial Sloan-Kettering Cancer Center
- Vice-Chair for International Activities
- The AIDS Malignancy Consortium
- Jasmeet Chadha Singh, MD
Jasmeet Chadha Singh, MD
- Attending Physician
- Memorial Sloan Kettering Cancer Center
- Commack, NY
- Section Editors
- Robert Maki, MD, PhD
Robert Maki, MD, PhD
- Section Editor — Bone and Soft Tissue Tumors
- Professor of Medicine
- Monter Cancer Center
- Hofstra-Northwell School of Medicine
- Thomas F DeLaney, MD
Thomas F DeLaney, MD
- Section Editor — Bone and Soft Tissue Tumors
- Professor of Radiation Oncology
- Harvard Medical School
- June K Robinson, MD
June K Robinson, MD
- Section Editor — Nonmelanoma Skin Cancer
- Professor of Clinical Dermatology
- Northwestern University Feinberg School of Medicine
Kaposi sarcoma (KS) is an angioproliferative disorder that requires infection with human herpes virus 8 (HHV-8), also known as Kaposi sarcoma-associated Herpes virus (KSHV), for its development [1-3]. KS is classified into four types based upon the clinical circumstances in which it develops: classic (the type originally described by Kaposi, which typically presents in middle or old age), endemic (several forms described in sub-Saharan indigenous Africans prior to the AIDS epidemic), iatrogenic (a type associated with immunosuppressive drug therapy, typically seen in renal allograft recipients) and AIDS-associated (epidemic KS). The epidemiologic and clinical aspects of these four types of KS are compared in the table (table 1).
This review will focus on the clinical presentation, staging, diagnosis, and treatment of classic KS (CKS). The epidemiology, risk factors, pathology, and molecular pathogenesis of CKS are discussed elsewhere, as are AIDS-related KS and iatrogenic KS developing in the setting of immunosuppressive therapy. (See "Classic Kaposi sarcoma: Epidemiology, risk factors, pathology, and molecular pathogenesis" and "AIDS-related Kaposi sarcoma: Clinical manifestations and diagnosis" and "AIDS-related Kaposi sarcoma: Staging and treatment" and "Development of malignancy following solid organ transplantation", section on 'Kaposi sarcoma'.)
Classic Kaposi sarcoma (CKS) occurs most often in older men of Mediterranean or Central/Eastern European ancestry, in whom the lesions usually occur on the distal extremities, particularly the lower legs and feet. (See "Classic Kaposi sarcoma: Epidemiology, risk factors, pathology, and molecular pathogenesis".)
Skin lesions — CKS is characterized by the appearance of purplish, reddish blue, or dark brown/black macules, plaques, and nodules on the skin (picture 1A-C). Nodular lesions may ulcerate and bleed easily. The skin lesions range in size from very small to several centimeters in diameter, and they can remain unchanged for months to years, or grow rapidly within a few weeks and disseminate. (See 'Natural history' below.)
The dermatology literature contains reference to at least 10 different morphologic variants of the cutaneous lesions of KS, which are referred to as patch, plaque, nodular, lymphadenopathic (usually in African children), exophytic, infiltrative (the latter two in African adults with endemic KS), ecchymotic, telangiectatic, keloidal, and cavernous or lymphangioma-like variants . The cavernous- or lymphangioma-like variants are common in CKS, particularly in the setting of chronic lymphedema. In this variant, lesions develop on the lower extremities that consist of compressible nodules that appear to be fluid-filled cysts. Histologically, lymphangioma-like KS consists of anastomosing networks of smaller, irregular and compressible dilated lymphatics lined by flat and cytologically banal endothelial cells [5-7].
- Gao SJ, Kingsley L, Hoover DR, et al. Seroconversion to antibodies against Kaposi's sarcoma-associated herpesvirus-related latent nuclear antigens before the development of Kaposi's sarcoma. N Engl J Med 1996; 335:233.
- Gao SJ, Kingsley L, Li M, et al. KSHV antibodies among Americans, Italians and Ugandans with and without Kaposi's sarcoma. Nat Med 1996; 2:925.
- Martin JN, Ganem DE, Osmond DH, et al. Sexual transmission and the natural history of human herpesvirus 8 infection. N Engl J Med 1998; 338:948.
- Schwartz RA. Kaposi's sarcoma: an update. J Surg Oncol 2004; 87:146.
- Mohanna S, Sanchez J, Ferrufino JC, et al. Lymphangioma-like Kaposi's sarcoma: report of four cases and review. J Eur Acad Dermatol Venereol 2006; 20:1010.
- RONCHESE F, KERN AB. Lymphangioma-like tumors in Kaposi's sarcoma. AMA Arch Derm 1957; 75:418.
- Pantanowitz L, Duke WH. Lymphoedematous variants of Kaposi's sarcoma. J Eur Acad Dermatol Venereol 2008; 22:118.
- Balachandra B, Tunitsky E, Dawood S, et al. Classic Kaposi's sarcoma presenting first with gastrointestinal tract involvement in a HIV-negative Inuit male--a case report and review of the literature. Pathol Res Pract 2006; 202:623.
- Neff R, Kremer S, Voutsinas L, et al. Primary Kaposi's sarcoma of the ileum presenting as massive rectal bleeding. Am J Gastroenterol 1987; 82:276.
- Weprin L, Zollinger R, Clausen K, Thomas FB. Kaposi's sarcoma: endoscopic observations of gastric and colon involvement. J Clin Gastroenterol 1982; 4:357.
- Stratigos JD, Potouridou I, Katoulis AC, et al. Classic Kaposi's sarcoma in Greece: a clinico-epidemiological profile. Int J Dermatol 1997; 36:735.
- Jaimovich L, Calb I, Kaminsky A. Kaposi's sarcoma of the conjunctiva. J Am Acad Dermatol 1986; 14:589.
- Cottoni F, Masala MV, Piras P, et al. Mucosal involvement in classic Kaposi's sarcoma. Br J Dermatol 2003; 148:1273.
- Kolios G, Kaloterakis A, Filiotou A, et al. Gastroscopic findings in Mediterranean Kaposi's sarcoma (non-AIDS). Gastrointest Endosc 1995; 42:336.
- Caponetti G, Dezube BJ, Restrepo CS, Pantanowitz L. Kaposi sarcoma of the musculoskeletal system: a review of 66 patients. Cancer 2007; 109:1040.
- Bordelon TR, Burton GV, Grafton WD, Mills GM. Kaposi's sarcoma involvement of the bone marrow. Am J Med Sci 1990; 300:383.
- Coll J, Pedro-Botet J, Pallas JO, et al. Classic Kaposi's sarcoma with pulmonary involvement in an HIV-negative woman. Clin Exp Dermatol 1995; 20:410.
- Brenner B, Rakowsky E, Katz A, et al. Tailoring treatment for classical Kaposi's sarcoma: comprehensive clinical guidelines. Int J Oncol 1999; 14:1097.
- Zurrida S, Bartoli C, Nolé F, et al. Classic Kaposi's sarcoma: a review of 90 cases. J Dermatol 1992; 19:548.
- Di Lorenzo G, Kreuter A, Di Trolio R, et al. Activity and safety of pegylated liposomal doxorubicin as first-line therapy in the treatment of non-visceral classic Kaposi's sarcoma: a multicenter study. J Invest Dermatol 2008; 128:1578.
- Hiatt KM, Nelson AM, Lichy JH, Fanburg-Smith JC. Classic Kaposi Sarcoma in the United States over the last two decades: a clinicopathologic and molecular study of 438 non-HIV-related Kaposi Sarcoma patients with comparison to HIV-related Kaposi Sarcoma. Mod Pathol 2008; 21:572.
- Potouridou I, Katsambas A, Pantazi V, et al. Classic Kaposi's sarcoma in two young heterosexual men. J Eur Acad Dermatol Venereol 1998; 10:48.
- Kaposi M. Idiopathic multiple pigmented sarcoma of the skin. [English translation from Archiv Für Dermatolgie Und Syphillis 1872; 4:265-273]. CA Cancer J Clin 1982; 32:342.
- Brambilla L, Boneschi V, Taglioni M, Ferrucci S. Staging of classic Kaposi's sarcoma: a useful tool for therapeutic choices. Eur J Dermatol 2003; 13:83.
- Brambilla L, Labianca R, Boneschi V, et al. Mediterranean Kaposi's sarcoma in the elderly. A randomized study of oral etoposide versus vinblastine. Cancer 1994; 74:2873.
- Brambilla L, Tourlaki A, Ferrucci S, et al. Treatment of classic Kaposi's sarcoma-associated lymphedema with elastic stockings. J Dermatol 2006; 33:451.
- Weintraub CM, Skudowitz RB. Excision of 1,674 classic Kaposi's sarcomas. S Afr J Surg 2002; 40:80.
- Tombolini V, Osti MF, Bonanni A, et al. Radiotherapy in classic Kaposi's sarcoma (CKS): experience of the Institute of Radiology of University "La Sapienza" of Rome. Anticancer Res 1999; 19:4539.
- Cooper JS, Sacco J, Newall J. The duration of local control of classic (non-AIDS-associated) Kaposi's sarcoma by radiotherapy. J Am Acad Dermatol 1988; 19:59.
- Nisce LZ, Safai B, Poussin-Rosillo H. Once weekly total and subtotal skin electron beam therapy for Kaposi's sarcoma. Cancer 1981; 47:640.
- Stein ME, Lakier R, Spencer D, et al. Radiation therapy for non-AIDS associated (classic and endemic African) and epidemic Kaposi's sarcoma. Int J Radiat Oncol Biol Phys 1994; 28:613.
- Huang KM, Hsu CH, Cheng JC, et al. Radiotherapy of classic Kaposi's sarcoma in Taiwan, an area where classic Kaposi's sarcoma is not prevalent. Anticancer Res 2006; 26:4659.
- Chang LF, Reddy S, Shidnia H. Comparison of radiation therapy of classic and epidemic Kaposi's sarcoma. Am J Clin Oncol 1992; 15:200.
- Caccialanza M, Marca S, Piccinno R, Eulisse G. Radiotherapy of classic and human immunodeficiency virus-related Kaposi's sarcoma: results in 1482 lesions. J Eur Acad Dermatol Venereol 2008; 22:297.
- Yildiz F, Ozyar E, Uzal D, et al. Kaposi's sarcoma: the efficacy of a single fraction of 800 cGy. Dermatology 1997; 195:142.
- Hauerstock D, Gerstein W, Vuong T. Results of radiation therapy for treatment of classic Kaposi sarcoma. J Cutan Med Surg 2009; 13:18.
- Kirova YM, Belembaogo E, Frikha H, et al. Radiotherapy in the management of epidemic Kaposi's sarcoma: a retrospective study of 643 cases. Radiother Oncol 1998; 46:19.
- Hamilton CR, Cummings BJ, Harwood AR. Radiotherapy of Kaposi's sarcoma. Int J Radiat Oncol Biol Phys 1986; 12:1931.
- Weshler Z, Loewinger E, Loewenthal E, et al. Megavoltage radiotherapy using water bolus in the treatment of Kaposi's sarcoma. Int J Radiat Oncol Biol Phys 1986; 12:2029.
- Tappero JW, Berger TG, Kaplan LD, et al. Cryotherapy for cutaneous Kaposi's sarcoma (KS) associated with acquired immune deficiency syndrome (AIDS): a phase II trial. J Acquir Immune Defic Syndr 1991; 4:839.
- Von Roenn JH, Cianfrocca M. Treatment of Kaposi's sarcoma. Cancer Treat Res 2001; 104:127.
- Webster GF. Local therapy for mucocutaneous Kaposi's sarcoma in patients with acquired immunodeficiency syndrome. Dermatol Surg 1995; 21:205.
- Chun YS, Chang SN, Park WH. A case of classical Kaposi's sarcoma of the penis showing a good response to high-energy pulsed carbon dioxide laser therapy. J Dermatol 1999; 26:240.
- Marchell N, Alster TS. Successful treatment of cutaneous Kaposi's sarcoma by the 585-nm pulsed dye laser. Dermatol Surg 1997; 23:973.
- Odom RB, Goette DK. Treatment of cutaneous Kaposi's sarcoma with intralesional vincristine. Arch Dermatol 1978; 114:1693.
- Brambilla L, Bellinvia M, Tourlaki A, et al. Intralesional vincristine as first-line therapy for nodular lesions in classic Kaposi sarcoma: a prospective study in 151 patients. Br J Dermatol 2010; 162:854.
- Ghyka G, Alecu M, Halalau F, Coman G. Intralesional human leukocyte interferon treatment alone or associated with IL-2 in non-AIDS related Kaposi's sarcoma. J Dermatol 1992; 19:35.
- Trattner A, Reizis Z, David M, et al. The therapeutic effect of intralesional interferon in classical Kaposi's sarcoma. Br J Dermatol 1993; 129:590.
- Morganroth GS. Topical 0.1% alitretinoin gel for classic Kaposi sarcoma. Arch Dermatol 2002; 138:542.
- Rongioletti F, Zaccaria E, Viglizzo G. Failure of topical 0.1% alitretinoin gel for classic Kaposi sarcoma: first European experience. Br J Dermatol 2006; 155:856.
- Célestin Schartz NE, Chevret S, Paz C, et al. Imiquimod 5% cream for treatment of HIV-negative Kaposi's sarcoma skin lesions: A phase I to II, open-label trial in 17 patients. J Am Acad Dermatol 2008; 58:585.
- Goiriz R, Ríos-Buceta L, De Arriba AG, et al. Treatment of classic Kaposi's sarcoma with topical imiquimod. Dermatol Surg 2009; 35:147.
- Goedert JJ, Scoppio BM, Pfeiffer R, et al. Treatment of classic Kaposi sarcoma with a nicotine dermal patch: a phase II clinical trial. J Eur Acad Dermatol Venereol 2008; 22:1101.
- Castiñeiras I, Almagro M, Rodríguez-Lozano J, et al. Disseminated classic Kaposi's sarcoma. Two cases with excellent response to pegylated liposomal doxorubicin. J Dermatolog Treat 2006; 17:377.
- Di Lorenzo G, Di Trolio R, Montesarchio V, et al. Pegylated liposomal doxorubicin as second-line therapy in the treatment of patients with advanced classic Kaposi sarcoma: a retrospective study. Cancer 2008; 112:1147.
- Kreuter A, Rasokat H, Klouche M, et al. Liposomal pegylated doxorubicin versus low-dose recombinant interferon Alfa-2a in the treatment of advanced classic Kaposi's sarcoma; retrospective analysis of three German centers. Cancer Invest 2005; 23:653.
- Potouridou I, Korfitis C, Ioannidou D, et al. Low to moderate cumulative doses of pegylated liposomal doxorubicin in the treatment of classic Kaposi sarcoma in elderly patients with comorbidities. Br J Dermatol 2008; 158:431.
- Brambilla L, Labianca R, Ferrucci SM, et al. Treatment of classical Kaposi's sarcoma with gemcitabine. Dermatology 2001; 202:119.
- Brambilla L, Boneschi V, Fossati S, et al. Oral etoposide for Kaposi's Mediterranean sarcoma. Dermatologica 1988; 177:365.
- Brambilla L, Miedico A, Ferrucci S, et al. Combination of vinblastine and bleomycin as first line therapy in advanced classic Kaposi's sarcoma. J Eur Acad Dermatol Venereol 2006; 20:1090.
- Brambilla L, Romanelli A, Bellinvia M, et al. Weekly paclitaxel for advanced aggressive classic Kaposi sarcoma: experience in 17 cases. Br J Dermatol 2008; 158:1339.
- Chao SC, Lee JY, Tsao CJ. Treatment of classical type Kaposi's sarcoma with paclitaxel. Anticancer Res 2001; 21:571.
- Fardet L, Stoebner PE, Bachelez H, et al. Treatment with taxanes of refractory or life-threatening Kaposi sarcoma not associated with human immunodeficiency virus infection. Cancer 2006; 106:1785.
- Zustovich F, Lombardi G, Pastorelli D. Important role of gemcitabine in the treatment of classic Kaposi's sarcoma. Tumori 2009; 95:562.
- Zidan J, Robenstein W, Abzah A, Taman S. Treatment of Kaposi's sarcoma with vinblastine in patients with disseminated dermal disease. Isr Med Assoc J 2001; 3:251.
- Brambilla L, Labianca R, Fossati S, et al. Vinorelbine: an active drug in Mediterranean Kaposi’s sarcoma. Eur J Dermatol 1995; 5:467.
- Tas F, Sen F, Keskin S, Kilic L. Oral etoposide as first-line therapy in the treatment of patients with advanced classic Kaposi's sarcoma (CKS): a single-arm trial (oral etoposide in CKS). J Eur Acad Dermatol Venereol 2013; 27:789.
- Régnier-Rosencher E, Guillot B, Dupin N. Treatments for classic Kaposi sarcoma: a systematic review of the literature. J Am Acad Dermatol 2013; 68:313.
- Krown SE. AIDS-associated Kaposi's sarcoma: is there still a role for interferon alfa? Cytokine Growth Factor Rev 2007; 18:395.
- Costa da Cunha CS, Lebbe C, Rybojad M, et al. Long-term follow-up of non-HIV Kaposi's sarcoma treated with low-dose recombinant interferon alfa-2b. Arch Dermatol 1996; 132:285.
- Tur E, Brenner S, Michalevicz R. Low dose recombinant interferon alfa treatment for classic Kaposi's sarcoma. Arch Dermatol 1993; 129:1297.
- Krown SE. Management of Kaposi sarcoma: the role of interferon and thalidomide. Curr Opin Oncol 2001; 13:374.
- Rubegni P, Sbano P, De Aloe G, et al. Thalidomide in the treatment of Kaposi's sarcoma. Dermatology 2007; 215:240.
- Ben M'barek L, Fardet L, Mebazaa A, et al. A retrospective analysis of thalidomide therapy in non-HIV-related Kaposi's sarcoma. Dermatology 2007; 215:202.
- Dittmer DP, Krown SE. Targeted therapy for Kaposi's sarcoma and Kaposi's sarcoma-associated herpesvirus. Curr Opin Oncol 2007; 19:452.
- Ganjoo K, Jacobs C. Antiangiogenesis agents in the treatment of soft tissue sarcomas. Cancer 2010; 116:1177.
- Guenova E, Metzler G, Hoetzenecker W, et al. Classic Mediterranean Kaposi's sarcoma regression with sirolimus treatment. Arch Dermatol 2008; 144:692.
- Active protocols for treatment of Kaposi's sarcoma available online. www.cancer.gov/clinicaltrials/search (Accessed on February 29, 2012).
- Monini P, Sgadari C, Grosso MG, et al. Clinical course of classic Kaposi's sarcoma in HIV-negative patients treated with the HIV protease inhibitor indinavir. AIDS 2009; 23:534.
- Taddeo A, Presicce P, Brambilla L, et al. Circulating endothelial progenitor cells are increased in patients with classic Kaposi's sarcoma. J Invest Dermatol 2008; 128:2125.
- Merimsky O, Jiveliouk I, Sagi-Eisenberg R. Targeting mTOR in HIV-Negative Classic Kaposi's Sarcoma. Sarcoma 2008; 2008:825093.
- CLINICAL FEATURES
- Skin lesions
- Extracutaneous involvement
- Natural history
- DIAGNOSIS AND STAGING
- Differential diagnosis
- Radiographic evaluation
- Local treatments
- - Surgery
- - Radiation therapy
- - Cryotherapy and laser therapy
- - Intralesional therapy
- - Topical therapy
- Systemic treatments
- - Chemotherapy
- - Immunomodulators
- Investigational therapies
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS