Histiocytic sarcoma is a round-cell neoplasm associated with a poor prognosis in dogs. Advances in veterinary pathology and immunohistochemical techniques have enabled identification of the putative cell of origin and have resulted in the reclassification of HS in dogs.1,2 Currently, there are 3 recognized clinical manifestations of HS. Hemophagocytic HS is thought to arise from macrophages of the splenic red pulp and bone marrow and is definitively diagnosed by positive CD18 and CD11d antibody immunohistochemical staining. Clinically, it is characterized by diffuse splenomegaly, regenerative anemia, thrombocytopenia, hypoalbuminemia, and hypocholesterolemia. Hemophagocytic HS follows a rapidly progressive clinical course despite treatment; the reported MST is approximately 7 weeks.1 Localized HS and disseminated HS are thought to arise from myeloid dendritic antigen-presenting cells. The 2 are morphologically and immunohistochemically identical, with positive staining results for CD18 and CD11c antibodies and negative results for CD11d antibodies, but are distinguished on the basis of clinical presentation.2 Localized HS appears to arise from a single site, typically involving the lung, skin, subcutaneous tissues, bones, or joints.2–6 Disseminated HS involves multiple organ systems, which could indicate metastasis and progression of the localized form. Alternatively, disseminated HS may be a primary multicentric disease, in which tumors arise simultaneously in multiple locations.2
Despite reported metastatic rates of 70% to 91%, treatment consisting of surgery, radiation, chemotherapy, or a combination of these appears to improve outcome in dogs with HS.3,4 In a recent study7 of 59 dogs with gross or disseminated disease, 54% of dogs that lived longer than 7 days following the first treatment with lomustine achieved either a partial or complete response, and the patients that responded experienced an MST of 5.5 months. In a series4 of 37 Flat-Coated Retrievers with LHS, the presence of distant metastasis at diagnosis was a strong negative predictor of survival time. However, any form of treatment beyond pain management or corticosteroids significantly improved outcome regardless of metastatic status. Thirty-four of the patients had disease involving an appendicular joint,4 and prior reports3–5 indicate that a periarticular subset of LHS may exist. Eighteen of 35 dogs in which synovial cell sarcomas were previously diagnosed were reclassified as having HS on the basis of CD18 immunohistochemical expression.3 Three of the dogs in that study3 received aggressive multimodal treatment consisting of amputation and adjuvant chemotherapy and had a mean survival duration of 9 months. More recently, long-term survival in a series of 16 dogs with LHS and no measurable residual disease was reported.6 In that study, aggressive multimodal treatment consisting of definitive local treatment and lomustine chemotherapy administered in an adjuvant setting resulted in an MST of 568 days.6
On the basis of prior reports, we hypothesized that dogs with PAHS would have a longer survival time than would dogs with HS of other anatomic locations (non-PAHS), independent of metastatic disease presence, when both groups received treatment that consisted of chemotherapy, surgery, radiation, or a combination of these. The primary objective of the present study was to evaluate and compare the outcomes of dogs with PAHS and non-PAHS. The secondary objective was to identify factors associated with survival time or TTP for dogs with PAHS.
Doxorubicin, cyclophosphamide chemotherapy protocol
Cyclophosphamide, doxorubicin, vincristine, prednisone chemotherapy protocol
Localized histiocytic sarcoma
Median survival time
Periarticular histiocytic sarcoma
Time to tumor progression
Vincristine, doxorubicin, cyclophosphamide chemotherapy protocol
MedCalc, version 10.2.0.0, MedCalc Software, Mariakerke, Belgium.
Varian Clinac 2100C, Varian Medical Systems Inc, Palo Alto, Calif.
Wiley J, Walton R, Kennedy D, et al. Comparison of cytology, flow cytometry using CD18, and histopathology with immunohistochemistry (CD18) for the diagnosis of canine histiocytic sarcoma (abstr), in proceedings. 29th Annu Conf Vet Cancer Soc 2009;28.
Moore PF, Affolter VK, and Vernau W. Canine hemophagocytic histiocytic sarcoma: a proliferative disorder of CD11d+ macrophages. Vet Pathol 2006; 43:632–645.
Affolter VK, and Moore PF. Localized and disseminated histiocytic sarcoma of dendritic cell origin in dogs. Vet Pathol 2002; 39:74–83.
Craig LE, Julian ME, and Ferracone JD. The diagnosis and prognosis of synovial tumors in dogs: 35 cases. Vet pathol 2002; 39:66–73.
Fidel J, Schiller I, and Hauser B, et al. Histiocytic sarcomas in Flat-Coated Retrievers: a summary of 37 cases (November 1998–March 2005). Vet Comp Oncol 2006; 4:63–74.
Schultz RM, Puchalski SM, and Kent M, et al. Skeletal lesions of histiocytic sarcoma in nineteen dogs. Vet Radiol Ultrasound 2007; 48:539–543.
Skorupski KA, Rodriguez CO, and Krick EL, et al. Long-term survival in dogs with localized histiocytic sarcoma treated with CCNU as an adjuvant to local therapy. Vet Comp Oncol 2009; 7:139–144.
Skorupski KA, Clifford CA, and Paoloni MC, et al. CCNU for the treatment of dogs with histiocytic sarcoma. J Vet Intern Med 2007; 21:121–126.