Knockout Mice
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carinii pneumonia. This was the beginning of the AIDS epidemic and AIDS-KS is today the most common form of KS. In HIV-infected individuals the underlying immunosuppression can lead to an aggressive disease that starts with skin or mucosal lesions, but without treatment, often develops into disseminated disease affecting various organs including lung, liver, gut and spleen.
Definition Kaposi sarcoma (KS) is a vascular tumour, often affecting the skin. Four epidemiological forms exist: *
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Classic KS occurs mainly in elderly HIV negative male patients of Southern European and Middle Eastern origin. Endemic KS: In some African countries, KS has existed for many decades, long preceding HIV. Unlike classic KS, endemic KS also occurs in children, where they often present with lymphadenopathy, rather than skin lesions. Endemic KS is generally a more aggressive disease than classic KS, though less so than African AIDS-associated KS. Post-transplant or iatrogenic KS is also known to develop after an organ transplant. Patients of Mediterranean, Jewish or Arabian ancestry are over-represented among immunosuppressed patients who develop KS after a transplant, indicating that those born in countries where classic KS occurs continue to be at risk of developing KS even if they migrate to `low-risk' countries. AIDS-KS: In 1981 the occurrence of two rare diseases in young gay men from New York City (NY, USA) and California were reported: Kaposi sarcoma and Pneumocystis
Characteristics Histology Histologically, KS is a complex lesion: in early KS lesions there are a collection of irregular endothelial lined spaces that surround normal dermal blood vessels and these are accompanied by a variable inflammatory infiltrate (patch-stage). This stage is followed by the expansion of a spindle-celled vascular process throughout the dermis. These spindle cells form slit-like, vascular channels containing erythrocytes (plaque -stage). The later nodularstage KS lesions are composed of sheets of spindle cells. The spindle cells form the bulk of established KS lesions and are therefore thought to be the neoplastic component. Most of the spindle cells in KS lesions express endothelial markers, including CD31 and CD34. Recently, it was also shown that these spindle cells express markers associated with lymphatic, rather than vascular endothelial cells including vascular endothelial growth factor receptor (VEGFR)-3 and podoplanin. This suggests that these spindle cells might belong to the lymphatic lineage of endothelial cells. Early KS (`patch stage') is probably a non-clonal proliferation of lymphatic endothelial cells or endothelial precursors, with a prominent inflam-
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Kaposi Sarcoma
matory and angiogenic response, whereas advanced disease can develop into a true clonal malignancy with metastases of clonally derived spindle cells to different sites. Studies of AIDS case surveillance support the pre-AIDS data on the existence of a sexually transmissible KS cofactor: KS occurs predominantly in gay and bisexual men with AIDS, less
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