The histopathology of KS is nearly identical in the various epidemiologic types. However, some studies have reported minor histopathologic differences between patients with AIDS-related KS and those with non-HIV KS. AIDS-related KS lesions exhibit more extensive dissecting vessels whereas mitoses and cellular anaplasia are more common in HIV-negative KS. Early KS skin lesions (also called the patch stage) are characterized by abnormal vessels lined with thin endothelial cells dissecting the dermis. Sparse chronic inflammatory cells, red blood cells, and hemosiderin-laden macrophages are often present in these lesions. This presentation can also be seen in other vascular disorders and therefore is not pathognomonic for KS. Advanced KS lesions are characterized by proliferation of spindle cells and blood vessels and can consist of several fascicles of these spindle-shaped tumor cells mixed with chronic inflammatory infiltrate and hemosiderin-laden macrophages. KS nodules often display a sieve-like appearance because of transection of spindle cells with intervening slit-like spaces. Hyaline globules positive for periodic acid-Schiff reagent are commonly seen in advanced KS lesions. Analysis by electron microscopy can reveal occasional Weibel-Palade bodies in the lesional cells and fragmented erythrocytes intracellularly, which are believed to correspond to hyaline globules seen on light microscopy. Typical lesions of KS usually lack significant cellular pleomorphism, necrosis, and marked mitotic figures. Immunohistochemically, KS lesional cells stain positive for CD31 (platelet/endothelial cell adhesion molecule 1, PECAM-1), CD34, and factor VIII-related antigen. In advanced lesions of KS, CD34 expression is stronger than CD31 expression. KS spindle cells also express lymphatic markers such as LYVE-1 (lymphatic vessel endothelial hyaluronan receptor 1), VEGFR-3 (vascular endothelial growth factor receptor-3), M2A, and Prox-1 (Prospero-related homeobox 1). HHV8 identification and localization within KS lesional cells by immunostaining for LANA-1 (or LNA-1) is the most helpful diagnostic test in differentiating KS from other KS-mimicking diseases. However, LANA-1 (or LNA-1) can also be expressed at high levels in body cavity lymphoma and Castleman disease. HHV8 has also been detected in certain angiosarcomas, dermatofibromas, and hemangiomas. Interestingly, HAART can lead to partial or complete regression of KS lesions, and spindle cells might be absent in completely regressed lesions.