Kaposi's sarcoma

KS lesions are nodules or blotches that may be red, purple, brown, or black, and are usually papular. 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. The lesions are painless but become cosmetically disfiguring or interruptive to organs. Skin 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). Kaposi's sarcoma skin lesions may be psychologically distressing. Mouth -positive person presenting with a Kaposi's sarcoma lesion with an overlying candidiasis infection in their mouth The mouth is involved in about 30% of cases 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 develop 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 movements), malabsorption, or intestinal obstruction. Respiratory tract Involvement of the airway can present with shortness of breath, fever, cough, 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. Kaposi's sarcoma of the lung has a poor prognosis. ==Cause==

Kaposi's sarcoma-associated herpesvirus (KSHV), also called HHV-8, is present in almost 100% of Kaposi sarcoma lesions, whether HIV-related, classic, endemic, or iatrogenic. KSHV encodes oncogenes, microRNAs and circular RNAs that promote cancer cell proliferation and escape from the immune system. Transmission In Europe and North America, KSHV is transmitted through saliva. Thus, kissing is a risk factor for transmission. Higher rates of transmission among gay and bisexual men have been attributed to "deep kissing" sexual partners with KSHV. 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 with KSHV infection or whose status is unknown. KSHV is also transmissible via organ transplantation and blood transfusion. Testing for the virus before these procedures is likely to effectively limit iatrogenic transmission. ==Pathology==

of a Kaposi sarcoma showing its typical features. Despite its name, in general it is not considered a true sarcoma, which is a tumor arising from mesenchymal tissue. The histogenesis of KS remains controversial. KS may arise 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 most typical feature of Kaposi sarcoma is the presence of spindle cells forming slits containing red blood cells. Mitotic activity is only moderate and pleomorphism is usually absent. 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. Variously sized PAS positive hyaline bodies are often seen in the cytoplasm or sometimes extracellularly. The spindle cells of Kaposi sarcoma differentiate toward endothelial cells, probably of lymph vessel rather than blood vessel origin. The consistent immunoreactivity for podoplanin supports the lymphatic nature of the lesion. Kaposi sarcoma high mag.jpg|Micrograph of a Kaposi sarcoma showing the characteristic spindle cells, high vascularity, and intracellular hyaline globs. H&E stain. File:Micrograph of promontory sign of kaposi's sarcoma.jpg|Micrograph of promontory sign in Kaposi's sarcoma in patch stage. Dilated irregular vascular channels surround a pre-existing vessel. File:Micrograph of plaque stage of Kaposi's sarcoma.jpg|Micrograph of plaque stage, with bizarre vessels dissecting the upper dermis. There is erythrocyte extravasation and hemosiderin pigmentation. File:Micrograph of tumor stage of Kaposi's sarcoma.jpg|Micrograph of tumor stage. Well-circumscribed spindle-cell tumor. Erythrocytes lie within poorly defined slit-like vascular spaces. ==Diagnosis==

Although KS may be suspected from the appearance of lesions and the patient's risk factors, a definite diagnosis can be made only by biopsy and microscopic examination. Detection of the KSHV protein LANA in tumor cells confirms the diagnosis. In differential diagnosis, arteriovenous malformations, pyogenic granuloma and other vascular proliferations can be microscopically confused with KS. Differential diagnosis of Kaposi's sarcoma Source: • Naevus (moles) • Histiocytoma • Cryptococcosis • Histoplasmosis • Leishmaniasis • Pneumocystis lesions • Dermatophytosis • Angioma • Bacillary angiomatosis • Pyogenic granuloma • Melanoma Classification HHV-8 is responsible for all varieties of KS. Since Moritz Kaposi first described the cancer, the disease has been reported in five separate clinical settings, with different presentations, epidemiology, and prognoses. A small percentage of these patients may have visceral lesions. In most cases, the treatment involves surgical removal of the lesion. The condition tends to be indolent and chronic, affecting elderly men from the Mediterranean region, Arab countries, or of Eastern European descent. Israeli Jews have a higher rate of KSHV/HHV-8 infection than European peoples. • Endemic KS, which has two types. Although this may be present worldwide, it has been originally described later in young African peoples, mainly those from sub-Saharan Africa. This variant is not related to HIV infection and is a more aggressive disease that infiltrates the skin extensively. • African lymphadenopathic Kaposi sarcoma is aggressive, occurring in children under 10 years of age, presenting with lymph node involvement, with or without skin lesions. Unlike classic Kaposi sarcoma, the site of presentation is more variable. This form of KS is over 300 times more common in AIDS patients than in renal transplant recipients. In this case, HHV 8 is sexually transmitted among people also at risk for sexually transmitted HIV infection. ==Prevention==

Blood tests to detect antibodies against KSHV have been developed and can be used to determine whether a person is at risk for transmitting the infection to their sexual partner, or whether an organ is infected before transplantation. However, 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 people following a transplant. ==Treatment==

Kaposi sarcoma is not curable, but it can often be treatable for many years. 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 sarcoma, the Kaposi lesions will shrink upon first starting highly active antiretroviral therapy (HAART). Therefore, HAART is considered the cornerstone of therapy in AIDS-associated Kaposi sarcoma. However, in a certain percentage of such people, Kaposi sarcoma may recur after many years on HAART, especially if HIV is not completely suppressed. People with a few local lesions can often be treated with local measures such as radiation therapy or cryosurgery. Weak evidence suggests that antiretroviral therapy in combination with chemotherapy is more effective than either of those two therapies individually. Limited basic and clinical evidence suggest that topical beta-blockers, such as timolol, may induce regression of localized lesions in classic as well as HIV-associated Kaposi sarcoma. In general, surgery is not recommended, as Kaposi sarcoma can appear in wound edges. In general, more widespread disease, or disease affecting internal organs, is treated with systemic therapy with interferon alpha, liposomal anthracyclines (such as liposomal doxorubicin or daunorubicin), thalidomide, or paclitaxel. Alitretinoin, applied to the lesion, may be used when the lesion is not getting better with standard treatment of HIV/AIDS, and chemotherapy or radiation therapy cannot be used. ==Society==

Because of their highly visible nature, external lesions are sometimes the presenting symptom of AIDS. Kaposi 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. By the time KS lesions appear, likely, the immune system has already been severely weakened. It has been reported that only 6% of men who have sex with men are aware that KS is caused by a virus different from HIV. Thus, there is little community effort to prevent KSHV infection. Likewise, no systematic screening of organ donations is in place. In people with AIDS, Kaposi sarcoma is considered an opportunistic infection, a disease that can 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. ==References==