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

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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.