Immunohistochemistry can help distinguish reactive histiocytoses from granulomatous disease and nonepitheliotropic cutaneous
lymphoma. Histiocytes of both cutaneous and systemic histiocytosis express CD1b, CD1c, CD11c, and MHC II surface markers,
indicative of their derivation from dendritic antigen-presenting cells.6 Additionally, both cutaneous and systemic histiocytosis are thought to be of activated dermal (interstitial) dendritic cell
origin given the expression of Thy1 and CD4 surface markers,3,6 which differentiates them from histiocytoma and histiocytic sarcoma (Table 1).13 More than 50% of the infiltrating lymphocyte population is consistent with CD8+ T cells,6 the role of which is unclear, although their presence does not appear to be associated with lesion regression as in the
case of cutaneous histiocytoma. Rather, the T cell infiltrate may be a secondary phenomenon induced by the cytokine microenvironment
or may be the primary infiltrating cell population that attracts and retains migrating dendritic cells.6
Table 1: Immunohistochemical Characteristics of Canine Histiocytic Diseases*
Treatment and prognosis
Cutaneous and systemic histiocytosis lesions tend to wax and wane, with spontaneous regression in the early stages of disease.
Partial remission (regression of some lesions) with simultaneous development of new lesions in other locations is typical.18 Because cutaneous and systemic histiocytosis likely develop as a result of immune system dysregulation, treatment in later
stages often includes immunosuppressive therapy. About 50% of dogs with cutaneous histiocytosis experience a partial or complete
response to immunosuppressive doses of cortico steroids.6,18 Similar immunosuppressive corticosteroid treatment for systemic histiocytosis is largely ineffective.13 Dogs with reactive histiocytosis (cutaneous and systemic) have responded to other immunosuppressive agents including cyclosporine,
leflunomide, and doxorubicin hydrochloride.6
Some animals can be weaned off of therapy without relapse, while others require lifelong medical management to avoid immediate
relapses and the development of new lesions.6,18 In general, the long-term prognosis is poor as disease progression typically renders most dogs nonresponsive to corticosteroids
as well as other immunosuppressive therapies. Targeted therapy designed to block dendritic cell and T cell activation may
prove useful in treating these diseases.16
The histiocytic sarcoma complex is a single disease entity referred to as localized histiocytic sarcoma, disseminated histiocytic sarcoma, and malignant histiocytosis. Localized histiocytic sarcoma refers to a neoplasm that arises from a focal site, typically the extremities.1,20 The terms disseminated histiocytic sarcoma and malignant histiocytosis are often used interchangeably to denote a histiocytic disorder that is systemic in nature with multiple sites of involvement.
Since malignant histiocytosis is an antiquated term, we use disseminated histiocytic sarcoma in the remainder of this article when referring to histiocytic sarcoma presenting with widespread lesion distribution.
Signalment and clinical findings
Although histiocytic sarcoma was first described in Bernese mountain dogs, recent reports have also demonstrated a breed predilection
for rottweilers and retriever breeds.20-22 The breed-associated risk for developing histiocytic sarcoma has been reported as 225, 26, and 3.7 times as likely for
Bernese mountain dogs, rottweilers, and golden retrievers, respectively, when compared with other breeds.23 A sex predilection has not been identified.21