Evaluation and comparison of outcomes in dogs with periarticular and nonperiarticular histiocytic sarcoma

Abstract

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 Objective-To evaluate and compare the outcomes of dogs with periarticular histiocytic sarcoma (PAHS) and histiocytic sarcoma of other anatomic locations (non-PAHS) and identify factors associated with outcome for dogs with PAHS. Design-Retrospective cohort study. Animals-19 dogs with PAHS and 31 dogs with non-PAHS. Procedures-Medical records of dogs with histiocytic sarcoma that underwent definitive local treatment (surgery or radiation), chemotherapy, or a combination of these were reviewed. Patient signalment, clinical signs, staging test results, clinicopathologic data, type of treatment, response, and outcome were collected, and potential risk factors in dogs with PAHS were identified and analyzed for an association with outcome. Results-Dogs with PAHS lived significantly longer than did dogs with non-PAHS, with an overall median survival times of 391 (range, 48 to 980) and 128 (range, 14 to 918) days, respectively, despite the presence of suspected metastasis at diagnosis in 13 of 19 dogs with PAHS. Dogs with PAHS without evidence of metastasis at diagnosis lived significantly longer than did dogs with PAHS with evidence of metastasis, with median survival times of 980 (range, 83 to 980) and 253 (range, 48 to 441) days, respectively. Administration of prednisone in dogs with PAHS was associated with a significantly shorter time to tumor progression (TTP) and increased risk of tumor progression and death. Conclusions and Clinical Relevance-Results indicated that dogs with PAHS may have a favorable outcome independent of metastatic status when treated with chemotherapy or aggressive multimodal treatment. The concurrent administration of prednisone may be a negative predictive factor for survival time and TTP in dogs with PAHS. (J Am Vet Med Assoc 2011;239:90-96) involving the lung, skin, subcutaneous tissues, bones, or joints.2-6 Disseminated...

A Review of Histiocytic Diseases of Dogs and Cats

“…72 Early detection and treatment of articular HS is potentially curative, while disseminated HS has a worse prognosis. 5,34 However, articular HS is capable of widespread dissemination since histiocytes, especially those of the various DC lineages, are actively migratory cells. This is reflected in the median survival of dogs with articular HS and evidence of metastatic disease (about 5-8 months).…”

“…This is reflected in the median survival of dogs with articular HS and evidence of metastatic disease (about 5-8 months). 18,34 Articular HS has a distinctive appearance: it occurs as multiple tan nodules located beneath the synovial lining. Hence, these lesions begin outside of the synovial space either within the joint and/or in a periarticular location.…”

Survivin suppressor (YM155) enhances chemotherapeutic efficacy against canine histiocytic sarcoma in murine transplantation models

“…Dogs with HS (hereafter referred to as HS dogs) exhibit generally poor treatment outcomes because of the tumor's aggressive biological behavior, including its high cell proliferation, multidrug resistance, and metastatic potential (Yamazaki et al, 2013(Yamazaki et al, , 2014. Lomustine (CCNU) or doxorubicin have been commonly used as antitumor agents for HS dogs (Rassnick et al, 2010); however, the therapeutic benefit on the disseminated and hemophagocytic HS is insufficient because of resistance to these drugs (Klahn et al, 2011;Rassnick et al, 2010). It is suggested that overexpression of the inhibitor of apoptosis protein (IAP) and P-glycoprotein (P-gp) is able to induce multidrug resistance in breast cancer cells and its chemoresistant cells (Liu et al, 2007.…”

Influence of a survivin suppressor YM155 on the chemoresistance of canine histiocytic sarcoma cells

“…Prognosis depends on the location of primary lesions: splenic HS commonly shows poor prognosis, whereas periarticular HS shows a better prognosis compared with non-periarticular HS (Klahn et al, 2011). We have shown that non-periarticular HS dogs exhibited significantly higher survivin expression, shorter DFI and ST as compared with other periarticular HS.…”

“…Response to CCNU was assessed based on diagnostic imaging of the chest, abdomen, and each primary location according to previously reported procedures (Klahn et al, 2011) and classified as follows: (1) complete response (disappearance of all clinical signs and disease through to at least day 21); (2) partial response (>50% or <100% decreases through to at least day 21); (3) stable disease (≤50% decreases or <20% increases through to at least day 21), or (4) progressive disease (≥20% increases in tumor volume or the development of new neoplastic lesions or metastases).…”