Paraneoplastic syndrome in haemophagocytic histiocytic sarcoma in a dog.

A case of metastatic splenic haemophagocytic histiocytic sarcoma (HHS) in a 6-year-old neutered male flat-coated retriever is described. The main clinical findings were hypoalbuminaemia and regenerative anaemia. The diagnosis was based on histological features and expression of CD11d by the neoplastic cells. Tumour cells were shown to produce interleukin (IL)-6, to phagocytose erythrocytes and to take up albumin, as demonstrated by immunohistochemistry and ultrastructural examination. Quantitative polymerase chain reaction identified increased IL-6 gene expression in affected organs. These findings suggest that neoplastic cells are responsible for the clinical features of HHS, by removing erythrocytes and albumin from the blood and releasing cytokines, such as IL-6.

[1]  D. W. Hayden,et al.  Disseminated Malignant Histiocytosis in a Golden Retriever: Clinicopathologic, Ultrastructural, and Immunohistochemical Findings , 1993, Veterinary pathology.

[2]  M. Callan,et al.  Clinical application of a hemoglobin-based oxygen-carrying solution. , 2003, The Veterinary clinics of North America. Small animal practice.

[3]  E. Ruiz-Villamor,et al.  Changes in macrophages in spleen and lymph nodes during acute African swine fever: expression of cytokines. , 2002, Veterinary immunology and immunopathology.

[4]  T. Molina,et al.  Primary histiocytic sarcoma of the spleen associated with erythrophagocytic histiocytosis. , 2003, Pathology, research and practice.

[5]  M. Shintaku,et al.  Histiocytic sarcoma of the spleen associated with hypoalbuminemia, hypo gamma-globulinemia and thrombocytopenia as a possibly unique clinical entity--report of three cases. , 1998, Leukemia & lymphoma.

[6]  C. Dinarello,et al.  Correlations and interactions in the production of interleukin-6 (IL-6), IL-1, and tumor necrosis factor (TNF) in human blood mononuclear cells: IL-6 suppresses IL-1 and TNF. , 1990, Blood.

[7]  Thomas D. Schmittgen,et al.  Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. , 2001, Methods.

[8]  P. Day,et al.  Analysis of normal and osteoarthritic canine cartilage mRNA expression by quantitative polymerase chain reaction , 2006, Arthritis research & therapy.

[9]  P. Moore,et al.  Canine Hemophagocytic Histiocytic Sarcoma: A Proliferative Disorder of CD11d+ Macrophages , 2006, Veterinary pathology.

[10]  R. Dietz,et al.  Multiple Cytokine and Acute-Phase Protein Gene Transcription in West Greenland Sledge Dogs (Canis familiaris) Dietary Exposed to Organic Environmental Pollutants , 2007, Archives of environmental contamination and toxicology.

[11]  H. Folkesson,et al.  Cellular uptake of albumin from lungs of anesthetized rabbits. , 1995, The American journal of physiology.

[12]  J. Gauldie,et al.  IL-6 functions as an exocrine hormone in inflammation. Hepatocytes undergoing acute phase responses require exogenous IL-6. , 1990, Journal of immunology.

[13]  P. Moore,et al.  Localized and Disseminated Histiocytic Sarcoma of Dendritic Cell Origin in Dogs , 2002, Veterinary pathology.

[14]  Chengxun Xi,et al.  Effects of splenomegaly and splenic macrophage activity in hypersplenism due to cirrhosis. , 2002, The American journal of medicine.

[15]  M. Radmacher,et al.  Albumin turnover: FcRn-mediated recycling saves as much albumin from degradation as the liver produces. , 2006, American journal of physiology. Gastrointestinal and liver physiology.

[16]  G. Garratty The James Blundell Award Lecture 2007: Do we really understand immune red cell destruction? , 2008, Transfusion medicine.

[17]  H. Nakamine,et al.  Primary histiocytic sarcoma of the spleen associated with hemophagocytosis , 2008, International journal of hematology.

[18]  G. Fuller,et al.  Transcriptional Control Mechanism of Fibrinogen Gene Expression , 2001, Annals of the New York Academy of Sciences.

[19]  S. Nasraway,et al.  Concepts of fever: recent advances and lingering dogma. , 1997, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[20]  A. Baba,et al.  Degradation of oxidative stress-induced denatured albumin in rat liver endothelial cells. , 2005, American journal of physiology. Cell physiology.

[21]  P. Poredos,et al.  Idiopathic venous thrombosis is related to systemic inflammatory response and to increased levels of circulating markers of endothelial dysfunction. , 2010, International angiology : a journal of the International Union of Angiology.

[22]  G. Pinchbeck,et al.  Gene expression markers of tendon fibroblasts in normal and diseased tissue compared to monolayer and three dimensional culture systems , 2009, BMC musculoskeletal disorders.

[23]  J V Castell,et al.  Interleukin-6 and the acute phase response. , 1990, The Biochemical journal.

[24]  P. Moore Characterization of Cytoplasmic Lysozyme Immunoreactivity as a Histiocytic Marker in Normal Canine Tissues , 1986, Veterinary pathology.

[25]  W. Ettinger,et al.  Cytokines decrease apolipoprotein accumulation in medium from Hep G2 cells. , 1994, Arteriosclerosis and thrombosis : a journal of vascular biology.

[26]  T. Hunter,et al.  Nuclear export of phosphorylated C/EBPβ mediates the inhibition of albumin expression by TNF‐α , 2001 .

[27]  D. Danilenko,et al.  A novel canine leukointegrin, alpha d beta 2, is expressed by specific macrophage subpopulations in tissue and a minor CD8+ lymphocyte subpopulation in peripheral blood. , 1995, Journal of immunology.

[28]  N. Van Rooijen,et al.  Cytological basis of immune functions of the spleen. Immunocytochemical characterization of lymphoid and non-lymphoid cells involved in the 'in situ' immune response. , 1989, Progress in histochemistry and cytochemistry.