There are at least 4 well defined histiocytic proliferative disorders that have been recognized in dogs. These disorders represent a frustrating group of diseases because it may be difficult to differentiate them from granulomatous, reactive inflammatory disorders or from lympho-proliferative diseases in regular paraffin sections. The clinical presentation and behavior and responsiveness to therapy vary tremendously between the syndromes observed. Canine cutaneous histiocytoma usually occurs as a single lesion in young dogs and spontaneously regresses. Cutaneous histiocytosis (CH) presents with single or multiple lesions, which tend to wax and wane, and may even spontaneously regress. Few cases respond to corticosteroids, the remainder persist and may require more aggressive immunosuppressive therapy. Systemic histiocytosis (SH) is a familial disease of Bernese Mountain Dogs and also occurs sporadically in other breeds. SH presents with prominent skin manifestations identical to those seen in CH, but mucous membranes (ocular and nasal) and a variety of other organ systems, including lymphoid organs, lung, and bone marrow may also be involved. Although the lesions may wax and wane, SH is a progressive disease that often requires continuous immunosuppressive therapy. Histiocytic sarcoma and malignant histiocytosis (MH) occur with high incidence in Bernese Mountain Dogs, Rottweilers , Flat Coat Retrievers, Golden Retrievers and sporadically in many other breeds. Histiocytic sarcomas occur as localized lesions in spleen, lymph nodes, lung, bone marrow, skin and subcutis, brain, and periarticular tissue of large appendicular joints. Histiocytic sarcomas can also occur as multiple lesions in single organs (especially spleen), and rapidly disseminate to involve multiple organs. Hence, disseminated histiocytic sarcoma is difficult to distinguish from MH, which is a multi-system, rapidly progressive disease in which there is simultaneous involvement of multiple organs such as spleen, lymph nodes, lung, bone marrow, skin and subcutis. Response of histiocytic sarcomas and MH to chemotherapy is at best brief.

An Overview of Cell Marker Studies in Canine Histiocytic Disease
The development of canine specific monoclonal antibodies for many of the functionally important molecules on macrophages and DC has enabled the identification of the cell lineages involved in canine histiocytic disorders. Despite the large variation of clinical and pathological features of canine histiocytic diseases, the majority represent proliferations of cells of various DC lineages. Histiocytes in cutaneous histiocytoma express markers characteristic of epidermal Langerhans cells such as CD1, CD11c, MHC class II, and E-cadherin, but not Thy-1 or CD4. This disease is a localized, regressing Langerhans cell histiocytosis. Aberrant cases of histiocytoma which behave more aggressively have been observed; these cases are uncommon and behave more like some forms of human Langerhans cell histiocytosis. Cutaneous and systemic histiocytosis involve proliferation of activated interstitial DC (e.g. dermal DC in skin); these cells express CD1, CD11c, MHC class II, Thy-1 and CD4. Histiocytic sarcomas (and MH) have more varied and obscure origins. Splenic histiocytic sarcomas largely arise from cells sharing the phenotype of interdigitating DC of the white pulp and express prominent CD1, CD11c, and MHC class II. Hemophagocytic histiocytic sarcomas of spleen (and bone marrow) arise from cells sharing the phenotype of splenic red pulp (and bone marrow) macrophages (prominent CD11d expression and low expression of CD1 and CD11c). Periarticular histiocytic sarcoma likely arise from subsynovial perivascular DC which are interstitial type DC; in contrast synovial lining cells (type A cells) express markers shared by macrophages (prominent CD11b and moderate MHC class II expression, lack of CD11c and CD1 expression). Histiocytic sarcomas of lung have more obscure origins, but prominently express CD1, CD11c and MHC class II, a phenotype expected of the DC lineage.