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07-SEPTEMBER-2008 03:17:44 - Kaposi's sarcoma Kaposi's sarcoma Classification and external resources Intraoral Kaposi's sarcoma lesion with an overlying candidiasis infection. ICD-10 C46. ICD-9 176 ICD-O: M9140/3 OMIM 148000 DiseasesDB 7105 MedlinePlus 000661 eMedicine med/1218 derm/203 oph/481 MeSH D012514 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, a Hungarian dermatologist practicing at the University of Vienna in 1872.1 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 to be caused by a virus infection, there is widespread lack of awareness of this even among persons at risk for KSHV/HHV-8 infection1. Contents 1 Epidemiological varieties 2 Clinical features 2.1 Skin 2.2 Mouth 2.3 Gastrointestinal tract 2.4 Respiratory tract 3 Pathophysiology and diagnosis 4 Treatment and prevention 5 History and theories 5.1 Discovery 5.2 AIDS symptom 5.2.1 Resurgence in AIDS patients 5.3 Virus caused 5.4 Unknown factors 6 KS awareness 7 References 8 External links Epidemiological varieties HHV-8 is responsible for all varieties of KS. Classic KS as originally described was a relatively indolent disease affecting elderly men from the Merranean region, or of Eastern European descent. Countries bordering the Merranean basin have higher rates of KSHV/HHV-8 infection than the remainder of Europe 23 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 unrelated to HIV infection. The high rate of KS in sub-Saharan countries is due to the high rates of HHV 8 infection in their general populations, frequently greater than 50%.45 Transplant Related KS had been described, but only rarely until the advent of calcineurin inhibitors such as ciclosporin, 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.67 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 gay and bisexual men who are also at risk for sexually transmitted HIV infection. 8 Clinical features KS lesions are nodules or blotches that may be red, purple, brown, or black, and are usually papular i.e. palpable or raised. Papular cutaneous Kaposi's Sarcoma Papular cutaneous Kaposi's Sarcoma 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.9 Skin Commonly affected areas include the lower limbs, 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.10 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.11 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.12 The diagnosis is usually confirmed by bronchoscopy when the lesions are directly seen, and often biopsied. Pathophysiology and diagnosis 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, a 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 and prevention 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 his or her 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. History and theories Discovery The disease is named after Moritz Kaposi 1837-1902, a Hungarian dermatologist who first described the symptoms in 1872. Research over the next century suggested that KS, like some other forms of cancer, might be caused by a virus or genetic factors, but no definite cause was found. AIDS symptom With the rise of the AIDS epidemic, KS, as initially one of the most common AIDS symptoms, was researched more intensively in hopes that it might reveal the cause of AIDS. Resurgence in AIDS patients San Francisco doctors reported a Kaposi's sarcoma cluster among gay men. All 15 patients undergoing treatment are long-term HIV patients whose HIV infections are firmly controlled with antiviral drugs. None appears to be in any danger. The new cases are not aggressive, invasive or lethal as was typical with uncontrolled HIV during the 1980s. The lesions are unsightly, difficult to treat and raise questions about the immune response aging of HIV patients.13 Virus caused In 1994, Yuan Chang, Patrick S. Moore, and Ethel Cesarman at Columbia University in New York isolated genetic pieces of a virus from a KS lesion. They used representational difference analysis a method to subtract out all of the human DNA from a sample to isolate the viral genes. They then used these small DNA fragments as starting points to sequence the rest of the viral genome in 1996. This, the eighth human herpesvirus HHV-8-now known as Kaposi's sarcoma-associated herpesvirus KSHV-has since been found in all KS lesions tested, and is considered the cause of the disease. KSHV is a unique human tumor virus that has incorporated cellular genes that cause tumors into its genome molecular piracy; the stolen cellular genes may help the virus escape from the immune system, but in doing so it also causes cells to proliferate. It is related to Epstein-Barr virus, a very common herpesvirus that can also cause human cancers. KSHV is readily found in all forms of KS. The virus is sexually transmitted among men having sex with men 2 and can be transmitted through organ donation 3. In Africa, high rates of KSHV infection has led to KS becoming the most common cancer in sub-Saharan Africa 4. KSHV infection is thought to be life-long so that persons infected with KSHV may develop KS years later if they develop AIDS or other immunosuppression. Unknown factors Like other tumor viruses, KSHV infection only leads to cancer in a minority of infected persons. Other factors are required, such as pre-existing immune system damage, for disease to erupt. In Africa has shown that even in the absence of HIV/AIDS, KS is more common in men than women although KSHV infection is equal between both sexes. This suggests that sex hormones may either protect from or predispose to KS in persons infected with the virus. Although older theories suggested that HIV might directly initiate KS, aside from its effects on the immune system, HIV and KSHV infect different cells and HIV is not found in KS tumors making this theory obsolete. KS awareness Only 6% of men having sex with men are aware that KS is caused by a virus different from HIV5. Thus, there is little community effort to prevent KSHV infection. Similarly, no systematic screening of organ donations is in place. In AIDS patients, Kaposi's sarcoma is considered an opportunistic infection, a disease that is able to gain a foothold in the body because the immune system has been weakened. With the rise of HIV/AIDS in Africa, where KSHV is widespread, KS has become the most frequently reported cancer in some countries, such as Zimbabwe. Nigerian bandleader Fela Kuti succumbed to the disease in 1997. Because of their highly visible nature, external lesions are sometimes the presenting symptom of AIDS. Kaposi's sarcoma entered the awareness of the general public with the release of the film Philadelphia, in which the main character was fired after his employers found out he was HIV-positive due to visible lesions. Unfortunately, by the time KS lesions appear, it is likely that the immune system has already been severely weakened. References ^ Kaposi, M 1872. Idiopathisches multiples Pigmentsarkom der Haut. Arch. Dermatol. Syph. 4: 265-273. doi:10.1007/BF01830024. ^ Iscovich, J Oct 22 1998. Classic Kaposi's sarcoma in Jews living in Israel, 1961-1989: a population-based incidence study.. AIDS 12 15: 2067-72. ^ Fenig, E Oct 1998. Classic Kaposi sarcoma: experience at Rabin Medical Center in Israel.. Am J Clin Oncol 21 5: 498-500. doi:10.1097/00000421-199810000-00016. ^ Cook-Mozaffari, P Dec 1998. The geographical distribution of Kaposi's sarcoma and of lymphomas in Africa before the AIDS epidemic. Br J Cancer 78 11: 1521-8. ^ Olsen, SJ Oct 1998. Increasing Kaposi's sarcoma-associated herpesvirus seroprevalence with age in a highly Kaposi's sarcoma endemic region, Zambia in 1985.. AIDS 12 14: 1921-5. doi:10.1097/00002030-199814000-00024. ^ Qunibi, W Feb 27 1998. Serologic association of human herpesvirus eight with posttransplant Kaposi's sarcoma in Saudi Arabia. Transplantation 65 4: 583-5. doi:10.1097/00007890-199802270-00024. ^ Luppi, Mario Nov 9 2000. Bone marrow failure associated with human herpesvirus 8 infection after transplantation. N Engl J Med 343 19: 1378-85. doi:10.1056/NEJM200011093431905. PMID 11070102. ^ Beral, V Jan 20 1990. Kaposi's sarcoma among persons with AIDS: a sexually transmitted infection?. Lancet 335 8682: 123-8. doi:10.1016/0140-67369090001-L. ^ Dezube, BJ Oct 1996. Clinical presentation and natural history of AIDS--related Kaposi's sarcoma. Hematol Oncol Clin North Am 10 5: 1023-9. doi:10.1016/S0889-85880570382-8. ^ Nichols, CM Nov 1993. Treating Kaposi's lesions in the HIV-infected patient.. J Am Dent Assoc 124 11: 78-84. PMID 8227776. Retrieved on 2007-06-11. ^ Danzig, JB Jun 1991. Gastrointestinal malignancy in patients with AIDS. Am J Gastroenterol 86 6: 715-8. Retrieved on 2007-06-11. ^ Garay, SM Jan 1987. Pulmonary manifestations of Kaposi's sarcoma. Chest 91 1: 39-43. doi:10.1378/chest.91.1.39. PMID 3792084. Retrieved on 2007-06-11. ^ Russell, Sabin 2007-10-11. Unsettling re-emergence of 'gay cancer'. San Francisco Chronicle. Retrieved on 2007-10-12. 14 Antman K, Chang Y. Kaposi's sarcoma. New Engl J Med 2000;34214:1027-38 15 Scheinfeld N. Kaposi's sarcoma mimicking a facial cyst as the presenting sign of human immunodeficiency virus. Skinmed. 2004 Mar-Apr;32:109-11. http://www.ncbi.nlm.nih.gov/pubmed/15010641?ordinalpos=2itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum 16 Chang Y, Cesarman E, Pessin M, et al. Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma. Science 1994;266:1865-9. 17 Yarchoan R, Tosato G, Little RF. Therapy insight: AIDS-related malignancies - the influence of antiviral therapy on pathogenesis and management. Nature Clin Prac Oncology 2005;28:406-15. External links http://hivinsite.ucsf.edu/InSite?page=kb-authorsdoc=kb-06-02-01 Kaposi's sarcoma photo library at Dermnet 6 Kaposi Sarcoma information v d e Vascular tumors ICD-O 9120-9179 C49/D18, 171/215 Blood Hemangioma/hemangiosarcoma - Angioma/angiosarcoma - Blue rubber bleb nevus syndrome - Hemangioendothelioma Infantile hemangioendothelioma - Kaposi's sarcoma - Hemangiopericytoma - Angiokeratoma Lymphatic Lymphangioma/lymphangiosarcoma - Lymphangioleiomyomatosis see also vascular diseases, congenital v d e Tumors: skin cancer C43-C44/D22-D23, 172-173/216 Epidermis Melanoma Superficial spreading melanoma, Nodular melanoma, Acral lentiginous melanoma, Lentigo maligna melanoma - Basal cell carcinoma - Squamous cell carcinoma Acanthoma Dermis Dermatofibroma/dermatofibrosarcoma - Dermatofibrosarcoma protuberans Sweat gland Hidrocystoma - Syringoma Other/ungrouped Bowen's disease see also non-congenital, congenital Retrieved from http://en..org/wiki/Kaposi%27s_sarcoma Categories: HIV/AIDS | Types of cancer | Ashkenazi Jews topics Views Article Discussion this page History Personal tools Log in / create account Navigation Main page Contents Featured content Current events Random article Search Go Search Interaction Community portal Recent changes Contact Donate to Help Toolbox What links here Related changes Upload file Special pages Printable version Permanent link Cite this page Languages ÄŒesky Deutsch Español Français Bahasa Indonesia Italiano עברית Latina Magyar Nederlands 日本語 Polski Português РуÑ?Ñ?кий SlovenÅ¡Ä?ina СрпÑ?ки / Srpski Suomi Svenska Türkçe This page was last modified on 25 August 2008, at 03:51
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