Canine histiocytic proliferative diseases represent a range of disorders with different pathologic features as well as clinical
behavior.1,2 At least three well-defined syndromes have been reported in dogs that arise from histiocyte proliferation, including cutaneous
histiocytoma, reactive histiocytosis (cutaneous and systemic), and histiocytic sarcoma (localized and disseminated).3 Malignant fibrous histiocytoma was previously grouped with canine histiocytic diseases but is now more appropriately considered
a soft tissue sarcoma (see boxed text titled "Difficult to delineate: Malignant fibrous histiocytoma and histiocytic disease").4,5 The dendritic cell lineage of this elusive complex of histiocytic disease syndromes has been recently clarified through
the use of immunohistochemical staining and specific monoclonal antibodies (Table 1).1,2,6-9
A quick guide to histiocytic disorders in dogs
In this article, we focus on how to diagnose the various histiocytic disorders by using routine imaging modalities, cytologic
and histologic examination, and immunohistochemistry when needed to accurately distinguish elusive cases. We also discuss
the recommended treatment and prognosis for each disease process.
Difficult to delineate: Malignant fibrous histiocytoma and histiocytic disease
Most histiocytes differentiate from CD34+ (CD = cluster of differentiation) stem cell precursors in the bone marrow into macrophages and one of three dendritic cell
lineages: epithelial dendritic cells or Langerhans cells in the skin, interstitial dendritic cells in many organs (Figure 1), and interdigitating dendritic cells (antigen-presenting cells located in the T cell zone in peripheral lymphoid organs).3,10 The interdigitating dendritic cells are not yet known to arise in histiocytic disease.
Figure 1. Adapted from Withrow SJ, Vail D. Histiocytic diseases. In: Small animal clinical oncology. 4th ed. St. Louis, Mo: Saunders Elsevier, 2007;814-823.
The fate of the CD34+ stem cells is largely influenced by cytokines and specific combinations of them. For example, granulocyte-macrophage colony-stimulating
factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF) induce macrophage development from CD34+ stem cells, while GM-CSF, transforming growth factor beta, tumor necrosis factor alpha, and interleukin-4 influence dendritic
Histiocytomas are benign skin tumors that occur most commonly in young dogs, accounting for 3% to 14% of skin tumors in this