Combination therapy. A similar study examined the prognosis for morphologically (but not immunohistologically) confirmed histiocytic sarcoma in
flat-coated retrievers treated with various combinations of surgery, chemotherapy (lomustine or doxorubicin hydrochloride),
radiation therapy, and corticosteroids.22 In dogs in which a response could be evaluated, there was a 94% response rate (68% complete response; 26% partial response)
after palliative radiation therapy and a 67% response rate (42% complete response; 25% partial response) to lomustine.22 The overall median survival time for all 37 dogs was 123 days.
Similarities among canine and human histiocytoses
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Pretreatment indicators of decreased survival (Table 2) were the presence of distant metastasis or metastasis of any kind.22 Treatment with radiation therapy or chemotherapy was a strong predictor of increased survival (median survival time of dogs
not receiving radiation and chemotherapy was 60 and 34 days, respectively). Dogs receiving any therapy lived significantly
longer than dogs receiving only palliative therapy (median survival time = 17 days) consisting of analgesics and corticosteroids.
Dogs treated with a combination of radiation therapy and lomustine enjoyed the longest survival times.
Overall recommendations. The combined results of these recent studies21,22 suggest that dogs treated aggressively with multimodality therapy early in the disease course before marked laboratory abnormalities
are noted may fare better than those that are treated after presenting with widespread disease dissemination. Nonspecific
clinical signs of illness in at-risk breeds should prompt diagnostic testing and facilitate the early detection and treatment
of histiocytic sarcoma.
HEMOPHAGOCYTIC HISTIOCYTIC SARCOMA
A distinct subtype of histiocytic sarcoma characterized by hemophagocytosis and Coombs' negative regenerative anemia has recently
been described.47 Hemophagocytic histiocytic sarcoma shares many characteristics with localized and disseminated histiocytic sarcoma such
as identical breed representation (Bernese mountain dogs, retrievers, and rottweilers), presenting clinical signs (lethargy,
inappetence, weight loss, and pale mucous membranes), affected organ systems (spleen, liver, bone marrow, and lungs), and
an aggressive clinical course. However, unlike localized and disseminated histiocytic sarcoma, which arises from proliferating
interstitial dendritic cells, hemophagocytic histiocytic sarcoma is the first identified canine proliferative disorder of
splenic red pulp and bone marrow macrophages.47 Immunohistochemical analysis from histologic specimens confirms splenic macrophage origin (positive expression of CD11d)
and argues against dendritic cell origin (CD1c and CD11c negative).47
Multiorgan involvement typical of other canine histiocytic diseases combined with the unique characteristic of hemophagocytosis
and regenerative anemia distinguishes hemophagocytic histiocytic sarcoma as its own clinical entity. Other clinicopathologic
findings include thrombocytopenia, hypoalbuminemia, and hypocholesterolemia in 88%, 94%, and 69% of the cases, respectively.
Disease progression is rapid, with a reported mean survival time from diagnosis until death of seven weeks.47 As treatment-related survival data for hemophagocytic histiocytic sarcoma are not currently available, we recommend treating
with chemotherapeutic agents that possess known efficacy against localized and disseminated histiocytic sarcoma.21 Given the current research focus on the ever-elusive canine histiocytic disease complex, further clinical study of this
newly defined canine histiocytic syndrome is anticipated.
SUMMARY
The canine histiocytic diseases represent a complex of diseases originating from myeloid dendritic cells.3 Although originating from a common precursor, the benign and malignant counterparts of the histiocytic disease spectrum
are vastly different in biologic behavior, recommended treatment, and prognosis. Recognizing the breed and age predilections
for this spectrum of clinical diseases is paramount to identifying cases that require a diagnostic work-up. Immunohistochemical
analysis is beneficial in solidifying an accurate diagnosis so that appropriate therapy can be instituted promptly, as aggressive
early treatment can improve survival times in dogs with histiocytic sarcoma. Recent retrospective analyses have shown promise
for combination therapy, including radiation therapy and chemotherapy to treat histiocytic sarcoma. Controlled, prospective
studies are warranted to determine the appropriate treatment of histiocytic sarcoma.
Rebecca E. Risbon, VMD
Craig A. Clifford, DVM, MS, DACVIM (oncology)
Red Bank Veterinary Hospital
197 Hance Ave.
Tinton Falls, NJ 07724
Katherine Skorupski, DVM, DACVIM (oncology)
Department of Surgical and Radiological Sciences
School of Veterinary Medicine
University of California
Davis, CA 95616
REFERENCES
1. Affolter VK, Moore PF. Localized and disseminated histiocytic sarcoma of dendritic cell origin in dogs. Vet Pathol 2002;39:74-83.
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