Canine histiocytic sarcoma complex: recent advances (Proceedings)
Canine proliferative histiocytic disorders (PHD) include nonneoplastic or nonmalignant conditions such as the benign cutaneous histiocytoma of young dogs or the cutaneous and systemic histiocytoses (reactive histiocytic diseases), and malignant proliferations including malignant fibrous histiocytoma, splenic fibrohistiocytic nodules, and histiocytic sarcoma (localized, disseminated, hemophagocytic). This conference will focus on the various forms of canine histiocytic sarcoma (HS) and provide updates on diagnosis, prognosis, and treatment.
Determining exactly what type of PHD a dog has developed is crucial because the prognosis and therapeutic approach of the different syndromes are markedly different. It can be difficult to distinguish PHD from histiocytic inflammation, lymphoma, or other round cell tumors and sarcomas with conventional histopathologic techniques. The development of various monoclonal antibodies identifying an array of canine hematopoietic cell surface proteins (CDs or cluster of differentiation molecules) helps to diagnose PHD more precisely, and our ability to diagnose, prognosticate, and treat these diseases will only improve with time and further refinements in diagnostic techniques and therapeutic options.
Histiocytic sarcoma was initially described in Bernese mountain dogs, where it is recognized as a familial disorder and recently demonstrated to have an autosomal oligogenic mode of transmission. All forms of HS have been found to be frequent in other predisposed breeds including retrievers (golden, flat coated, Labrador) and the rottweiller. Though genetics clearly play a role in certain PHD, the exact pathogenesis and etiology currently remain unknown.The HS complex typically affects middle-age to older dogs, but may also be diagnosed in younger dogs. It is characterized by proliferation and tissue infiltration of atypical histiocytic cells that often involves multiple organs simultaneously. Canine histiocytic sarcoma may initially present as solitary tumor (localized HS – periarticular vs. other sites) or multicentric disease (disseminated HS – previously called malignant histiocytosis) but eventually widespread metastasis is observed in a majority of cases. A third form of HS, haemophagocytic HS was recently described.
Historically, PHD have been classified as diseases of histiocytes, which are tissue-based leukocytes. Histiocytes are divided into two separate phenotypic lineages, macrophages and dendritic (antigen-presenting) cells, and are found in all tissues. Both of these lineages originate from a common CD34+ precursor in the bone marrow and, with exposure to specific cytokines and growth factors, differentiate to become cells of the monocyte/macrophage lineage or of the dendritic cell type. After differentiation, macrophages and dendritic cells still share many surface antigens and receptors for immunoglobulin and complement molecules but, despite many similarities, enough differences (morphologic, phenotypic, functional) exist to categorize them as distinct cell lineages.
Macrophages are part of the innate immune system and function mainly as phagocytic cells that can digest foreign antigens intracellularly and present peptides on their cell surface in association with MHC-class II molecules. Dendritic cells, on the other hand, tend to be poorly phagocytic and mainly process foreign antigens and then present them to T lymphocytes to evoke a specific immune response. Therefore, dendritic cells are one of many types of professional antigen-presenting cells (APCs). Dendritic APCs typically coexpress the cell surface markers CD1a, b, c, CD11c, and MHC-class II, therefore canine HPD are diseases of Langerhans cells (skin dendritic cells).