Epidemiology, Pathology, and Genetics of Histiocytic Sarcoma in the Bernese Mountain Dog Breed

Abstract

Histiocytic sarcoma (HS) refers to a highly aggressive and frequently disseminated neoplastic disease belonging to the class of canine histiocytic proliferative disorders. Disseminated HS (previously called malignant histiocytosis) is highly breed specific, with Bernese mountain dogs (BMDs), rottweilers, and retrievers having a high prevalence with a frequency of approximately 25% in the BMD breed. We collected DNA samples and clinical information from 800 BMDs, of which 200 are affected by HS. To better characterize the physiopathology and epidemiology, an in-depth analysis of 89 BMD cases has been performed. The mean age of onset was 6.5 years, males and females being equally affected. The clinical features, biochemical parameters, and pathological features have been determined. The life span after diagnosis has been estimated to be 49 days. A large BMD pedigree of 327 dogs, 121 of which are affected, was assembled. Using a subset of 160 BMDs, encompassing 21 complete sibships, we now propose an oligogenic transmission mode of the disease. Whole-genome linkage scans as well as association studies using a case/control analysis, in parallel with expression profiling of neoplastic versus normal histiocytes, are all underway. Altogether, these complementary approaches are expected to localize the genes for HS in the BMD, leading to advances in our knowledge of histiocyte diseases in dogs and humans.

Cytopathological diagnosis of visceral histiocytic sarcoma in five dogs

“…Virtually all tissues including the central nervous system can be affected with histiocytic sarcoma, and antemortem diagnosis in such cases can be especially difficult although it is still possible (Tzipory et al 2009, Ide et al 2011. Differentiation between localized and disseminated form of HS is crucial for choosing the method of treatment and patients' prognosis, however possibilities of effective therapies are rather poor in both forms (Abadie et al 2009, Nielsen et al 2011). On the other hand, localized and disseminated form of histiocytic sarcoma should be considered to be two clinical forms of the same entity but in various stage of advancement.…”

“…Additionally, localized form of HS quickly progresses into the disseminated form and is characterized by high metastatic potential (Vali 2007, Soare et al 2012. The life span after diagnosis has been estimated to be 49-223 days (Abadie et al 2009, Nielsen et al 2011.…”

“…Pembroke Welsh Corgi, Flat Coated Retrievers and Bernese mountain dogs are predisposed to develop the localized form of HS, disseminated form is diagnosed mainly in Bernese mountain dogs and more seldom in Doberman pinchers, golden retrievers, Rottweiler (Abadie et al 2009, Tzipory et al 2009, Constantine-Casas et al 2011, Ide et al 2011. In the present study, most of dogs affected were BMD what made cytopathological diagnosis easier, since in one large review it has been estimated that 80% of systemic histiocytoses cases reported in France were diagnosed in this breed and 25.4% of tumors diagnosed in the BMD were malignant proliferation of histiocytic cells (Padgett et al 1995, Abadie et al 2009).…”

“…Histiocytic sarcoma (HS) is a solitary malignant neoplastic proliferation of atypical histiocytes with tendency to spread, characterized by fast progression to disseminated form -disseminated histiocytic sarcoma (DHS; formerly malignant histiocytosis -MH) breed predisposition, including Bernese mountain dogs (BMD), Doberman pinchers, golden retrievers, flat coated retrievers, and Rottweiler's (Paterson et al 1995, Ramsey et al 1996, Affolter and Moore 2002, Abadie et al 2009, Constantine-Casas et al 2011, Nielsen et al 2011. The average age of onset of HS is 6-8 years but tumours were recognized in animals as young as 2 years of age and as old as 13 years of age (Affolter and Moore 2002, Abadie et al 2011, Ide et al 2011, Nielsen et al 2011.…”

Morphological Distinction of Histiocytic Sarcoma from Other Tumor Types in Bernese Mountain Dogs and Flatcoated Retrievers

“…Reports of canine HS in the literature use a variety of different inclusion criteria for HS, some of which are now outdated, and many did not utilize IHC to verify the histiocytic nature of the tumors or even included dogs as HS case without any pathological examination (16). None of the reports included a large number of dogs of the same breed.…”