Disseminated Malignant Histiocytosis in a Golden Retriever: Clinicopathologic, Ultrastructural, and Immunohistochemical Findings

Abstract

Diagnosis of malignant histiocytosis (MH), a disorder characterized by systemic proliferation of morphologically atypical histiocytes and their precursors, in an 8-year-old neutered female Golden Retriever was based on light and electron microscopic and immunohistochemical findings. Clinically, the dog presented with unilateral forelimb lameness. Eight days after surgical exploration of a swollen brachium, the dog developed sudden onset of posterior paresis, fecal and urinary incontinence, and a flaccid tail. Necropsy revealed infiltrative and nodular lesions in the right forelimb and regional lymph nodes, thoracic and abdominal cavities, and lumbar epidural space. Gross lesions were not found in the lungs or integument. Histopathologic examination showed infiltrates of atypical histiocytes in skeletal muscle, joint, and regional lymph nodes of the right forelimb; intercostal muscle; lung; liver; spleen; pancreas; kidneys; and spinal dura. Most tumor infiltrates were nodular and composed of loosely aggregated cells that were 10-30 μm in diameter with abundant eosinophilic to foamy cytoplasm, had central or eccentric nuclei, and were periodic acid-Schiff negative. Many binucleated cells, multinucleated giant cells, and mitotic figures were seen. Tumor cells contained phagocytosed erythrocytes, mononuclear cells, and some leukocytes. Ultrastructural features of tumor cells included cytoplasmic lipid droplets, lysosomes, and phagolysosomes. Immunohistochemical studies on paraffin-embedded sections showed positive reactivity to human T-cell Ag (clone UCHL-1) and for lysozyme, α-1-antitrypsin, and cathespin B. Polyclonal intracellular immunoglobulin reactivity and lectin binding (peanut, soybean, and wheat germ agglutinins and concanavalin A) were also demonstrated. Criteria for diagnosis of malignant histiocytic tumors and differential diagnosis are discussed.

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

“…This has been reported before in canine HS (1,6,7,28,(33)(34)(35)(36)(37)(38)(39) and is also often seen in human HS, sometimes simultaneously with spindle cells (40,41). In addition, extramedullary hematopoiesis was seen more often in BMD than in FCR.…”

“…This invasive behavior was exclusively found in disseminated HS. A sinusoidal pattern has been recognized before in canine HS in lymph nodes (37) and in the liver including invasion of the portal areas (28), and has been associated with the HHS subtype (8). It is also reported in human HS (54,55).…”

“…This indicates that a canine subtype comparable to human LCH/LCS may also exist. An eccentrically located nucleus was reported in canine HS (6,37,51) and in human HS (41) and IDCS (14). Further research will shed light on possible similarities among human and canine histiocytic tumor subtypes.…”

Establishment and Biological Characterization of Canine Histiocytic Sarcoma Cell Lines

“…The diagnosis of HS is based on the pathologic findings, including diffuse proliferation of large anaplastic histiocytes, multinucleated giant cells, and occasional phagocytosis of red blood cells and/or cell debris [2,4,13]. However, a definitive diagnosis is frequently difficult to make due to the presence of infiltrated macrophages and the immature features of tumor cells [5,8].…”

“…On the other hand, it has been widely accepted that canine HS cells belong to the mononuclear phagocytic system (MPS), including monocytes, macrophages, dendritic cells, and Langerhans cells, because the tumor cells usually contain intracellular microstructures related to phagocytic functions and lysosomal enzymes [2,4,6,7]. However, the exact biological characteristics of HS tumor cells are not clearly understood, because a cell line of HS tumor cells has rarely been established [9,14].…”