anemia have been consistently documented in hemophagocytic HS. Lameness is often observed in periarticular HS. Treatment of HS complex Localized HS affecting skin and subcutis have been cured by early surgical excision. In the case of periarticular HS which occurs in the subsynovial tissues of the extremities, amputation of the affected limb is enforced by the inoperable nature of the primary lesion which ensnares structures vital to limb function. Disseminated HS (including MH) is not readily treated surgically, since even in the splenic form, early metastasis to the liver has often occurred. Response to chemotherapy has been at best brief, and the disease progresses rapidly (weeks to months) to death or euthanasia. Morphological Features of HS Gross appearance. Lesions of HS are typically destructive mass lesions with a uniform, smooth cut surface and are white/cream to tan in color. Lesions have a soft consistency and may contain discolored areas (typically yellow) which indicate area of necrosis, which can be extensive. Lesions can be solitary or multiple within an organ (especially spleen). Periarticular HS has a distinctive appearance: it occurs as multiple tan nodules located in the subsynovium. These lesions may encircle the affected joint. Hemophagocytic HS does not initially form mass lesions in the primary sites (spleen and bone marrow). Typically, diffuse splenomegaly is observed; the cut surface is dark red and the consistency is firm. The liver is usually bile stained (jaundice) and disruption of the lobular pattern due to metastasis is observed - marked liver involvement can occur before destructive masses are noticeable. Immunophenotypic Studies MH and HS lesions express leukocyte surface molecules characteristic of DC (CD1, CD11c and MHC II). Diffuse expression of E cadherin, Thy-1 and CD4 has not been observed in HS or MH in skin or other sites; this together with cytomorphology assists in the distinction of MH and HS from histiocytoma and reactive histiocytosis (such as cutaneous and systemic histiocytosis). In histiocytoma, the phenotype is quite similar to that of HS except for the expression of E-cadherin which occurs in histiocytoma especially in the cellular infiltrate immediately adjacent to the epidermis. In reactive histiocytosis, infiltration and proliferation of activated interstitial (dermal) DC which consistently express CD4 and Thy-1 occurs. In hemophagocytic HS, histiocytes express CD11d instead of CD11c, and MHC II. Expression of CD1 molecules is uniformly low or occasionally moderate but with a patchy distribution. This phenotype is consistent with macrophage differentiation