Clinical History
An 8-year-old 40.5-kg (89.1-lb) neutered male Mastiff × pit bull–type dog with a history of joint problems and suspected torn cranial cruciate ligament had a sudden onset of anorexia, started vomiting bile and water, and died a day after onset of these signs. In view of the fact that this dog's death occurred shortly after a recent party in the house, the client suspected the dog could have gained access to potentially toxic substances during the event.
Gross Findings
On gross examination, the dog was in good nutritional status (body condition score, 6/9) but slightly dehydrated with mild autolysis. The liver was diffusely enlarged and dark red and had approximately fifty 2-mm- to 3-cm-diameter, round, light yellow to tan, spherical, solid nodules protruding from the capsular surface as well as extending variably deep into the hepatic parenchyma (Figure 1). The gallbladder was distended. Both kidneys had approximately 20 similar raised, firm, white to pale yellow nodules that protruded from the cortical surface. Intra-abdominal lymph nodes were variably enlarged, with the largest (pancreaticoduodenal lymph node) measuring 8 × 4 × 4 cm. The heart had a poorly delimited, infiltrative, slightly raised, multifocal to coalescing, nodular, white, transmural mass that was concentrated around the apex of the left ventricle. The mass measured approximately 7 × 10 cm on the epicardial surface and extensively effaced the myocardium in the region of the cardiac apex, the left ventricular wall (including the papillary muscles), and the interventricular septum, with small, dark red, soft areas (interpreted as hemorrhage and necrosis). Cranial mediastinal lymph nodes were slightly enlarged and firm.
Photographs of the abdominal organs (A) and heart (B) of an adult dog that died after a brief period of anorexia and vomiting. In panel A, notice the multifocal raised nodules on the surfaces of the liver and kidney. In panel B, the left ventricular wall of the heart has an infiltrative lesion extensively effacing the cardiac parenchyma (arrows).
Citation: Journal of the American Veterinary Medical Association 247, 2; 10.2460/javma.247.2.163
The medial and lateral aspects of both left and right femoral condyles had osteophyte formation. This alteration was most severe on the left hind limb, which also had a ruptured cranial cruciate ligament. The gastrointestinal tract contained scant ingesta and no foreign material.
Histopathologic Findings
Sections of the heart, lungs, liver, kidneys, pancreas, spleen, multiple lymph nodes, stomach, small and large intestines, and brain were routinely processed and examined microscopically. Within the endocardium, myocardium, and epicardium of the left cardiac ventricle and interventricular septum, including the papillary muscles, was a markedly infiltrative round cell neoplasm. Neoplastic cells were arranged in variably dense sheets, extensively effaced cardiac myofibers and vasculature, and at the margins, dissected between the myofibers of the remaining myocardium (Figure 2). The cells were pleomorphic, ranging from round to polygonal to spindle-shaped with tapering cytoplasmic processes; had distinct cell borders; and contained moderate to abundant eosinophilic cytoplasm. Nuclei of the neoplastic cells were round to oval and moderately to densely stippled, often with 1 to 4 distinct nucleoli. The degree of anisocytosis and anisokaryosis was marked, and numerous multinucleated giant cells were diffusely scattered throughout the neoplasm. Mitoses were present at 21 mitotic figures/10 hpfs (400X). Additionally, within the neoplasm, extensive areas of necrosis, hemorrhage, and fibrosis as well as a marked lymphoplasmacytic, neutrophilic, and histiocytic infiltrate were present. Scattered hemosiderin-laden macrophages and hematoidin deposits were evident within hemorrhagic, devitalized areas. Nodules in the liver and kidneys were comprised of the same neoplastic cell population. Approximately 95% of the normal architecture of a pancreaticoduodenal lymph node was completely replaced by sheets of the same neoplastic cells. Similar neoplastic cells were also present in other abdominal and thoracic lymph nodes examined histologically. No neoplastic cell infiltrate was evident in any other tissue examined histologically, including the spleen and lungs. Blood vessels of the lungs, liver, kidneys, stomach, and intestines were diffusely congested. Immunohistochemical analysis for the cell surface marker CD18 on a heart tissue section revealed strong positive perimembranous and cytoplasmic labeling of the neoplastic cells (Figure 3). Neoplastic cells also had diffuse, moderate to strong cytoplasmic and perimembranous CD11d immunolabelling but were immunonegative for CD3, CD79a, and E-cadherin.
Photomicrograph of a section of heart tissue from the dog described in Figure 1. A neoplastic histiocytic infiltrate extensively effaces the myocardium. Only a few degenerate and fragmented cardiac myofibers remain in this area (asterisk). Inset—The neoplastic cells have moderate to abundant eosinophilic cytoplasm and oval to pleomorphic, hypochromatic nuclei. Anisocytosis and anisokaryosis are marked. H&E stain; bar = 100 μm.
Citation: Journal of the American Veterinary Medical Association 247, 2; 10.2460/javma.247.2.163
Photomicrographs of heart tissue sections from the dog described in Figure 1 following immunohistochemical labeling for CD18 (A) and CD11d (B). In panel A, neoplastic cells have strong perimembranous and cytoplasmic immunolabelling for CD18 indicative of histiocytic origin. Inset—Higher-magnification detail of CD18-positive immunolabelling in the heart section. CD18-specific immunohistochemical stain; bar = 100 μm. In panel B, neoplastic cells have moderate to strong perimembranous and cytoplasmic immunolabelling for CD11d suggestive of bone marrow macrophage origin in the absence of splenic involvement. Inset—Higher-magnification detail of CD11d-positive immunolabelling in the heart section. CD11d-specific immunohistochemical stain; bar = 100 μm.
Citation: Journal of the American Veterinary Medical Association 247, 2; 10.2460/javma.247.2.163
Additional Laboratory Findings
General organic compound screening for the presence of any pesticides, human or veterinary drugs, industrial chemicals, and plant toxins was performed on a fresh specimen of liver via gas chromatography–mass spectrometry. No toxic organic compounds were detected.
Morphologic Diagnosis and Case Summary
Morphologic diagnosis and case summary: histiocytic sarcoma (presumably of bone marrow macrophage origin) of the heart, kidneys, liver, and lymph nodes in a dog.
Comments
The primary finding in the dog of the present report was histiocytic sarcoma that had multiorgan involvement, affecting the heart, multiple lymph nodes, liver, and kidneys. Immunohistochemical analysis of formalin-fixed tissue sections from this dog yielded the expected pattern for histiocytic sarcomas: neoplastic tissue was positive for the histiocytic marker CD18 and negative for the lymphocytic markers CD3 and CD79a and the Langerhans cell marker E-cadherin. This immunophenotype and the histomorphology of the neoplastic cells are the most useful criteria for the diagnosis of histiocytic sarcomas.1
In dogs, primary heart tumors include hemangiosarcoma, chemodectoma, rhabdomyoma, rhabdomyosarcoma, chondrosarcoma, osteosarcoma, fibroma, fibrosarcoma, mesenchymoma, lymphangiosarcoma, neurofibrosarcoma, neurofibroma, lipoma, myxoma, and mesothelioma.2,3 The liver, kidneys, and lymph nodes, as in the case described in the present report, are common metastatic sites in dogs. To the authors' knowledge, there is only a single report4 of histiocytic sarcoma in the heart of a 10-year-old Fox Terrier from 1953. In that case,4 there was no evidence of the neoplasm in organs other than the heart; diagnosis was based on the histomorphology of the neoplastic cells. In what manner, if at all, the neoplastic disease accounted for the reported clinical signs in the dog of the present report remained undetermined. Considering the extent of infiltration by the neoplasm in the heart and histologic evidence of multiorgan acute congestion, the dog most likely had terminal heart decompensation. Grossly and histologically, however, there was insufficient involvement of liver and renal parenchyma by the neoplasm for there to have been dysfunctions involving those organs.
Histiocytic sarcoma is a neoplasm of dendritic cells; in dogs, it develops in those that are middle-aged to old. This neoplasm has localized, disseminated, and hemophagocytic forms and is generally associated with a high rate of metastasis; affected dogs have a poor prognosis.1,5 Breeds predisposed for localized histiocytic sarcoma include Bernese Mountain Dog, Rottweiler, and Flat-Coated Retrieve r.1 Disseminated histiocytic sarcoma commonly affects Bernese Mountain Dogs, with a familial polygenic inheritance.1 The localized form of histiocytic sarcoma can develop in the subcutis, spleen, lungs, nasal cavity, brain and bone marrow, and the disseminated form generally affects the spleen, lungs, bone marrow, liver, and lymph nodes.1 Apart from these common sites, histiocytic sarcoma may rarely develop in other organs such as the urinary bladder.6 Periarticular histiocytic sarcoma has been associated with joint disease in a Bernese Mountain Dog,7 and in a recent study,8 dogs with periarticular histiocytic sarcoma had a better prognosis than had dogs with nonperiarticular histiocytic sarcomas. In the case described in the present report, no neoplastic sites other than the heart, liver, kidneys, and lymph nodes were detected. Bilateral stifle joint disease in this dog was most likely age related and grossly did not seem to be affected by the neoplasm, although histologic evaluation of the synovial lining was not performed.
Interestingly, neoplastic cells in the dog of this report were immunopositive for CD11d. This immunophenotype is characteristic of resident splenic red pulp and bone marrow macrophages and their neoplastic forms, including the hemophagocytic form of histiocytic sarcoma.5 This particular entity of histiocytic sarcomas has rapid clinical progression, characterized by regenerative anemia, thrombocytopenia, hypoalbuminemia, hypocholesterolemia, and splenomegaly.5 In the dog of the present report, splenomegaly was not grossly evident and no neoplastic cells were detected histologically in tissue samples from the spleen. Hemophagocytosis by the neoplastic cells was also not observed. Thus, although this dog's bone marrow was not examined, a primary bone marrow origin of the histiocytic sarcoma was considered highly likely.
Clinical signs of dogs with nonhemophagocytic histiocytic sarcoma are generally nonspecific and include anorexia and cachexia.9 Given that, the diagnosis of histiocytic sarcoma is often only made very near terminal stages of the disease. Unfortunately, the dog of the present report did not undergo clinical workup before it died, hence the sparse clinical data. Although results of diagnostic imaging and cytologic and histologic evaluation of affected organs are undoubtedly useful in the identification and diagnosis of histiocytic sarcomas, the assessment of blood biomarkers is currently being investigated as a screening tool for early detection of these neoplasms in Bernese Mountain Dogs.9
References
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2. Aupperle H, März I, Ellenberger C, et al. Primary and secondary heart tumours in dogs and cats. J Comp Pathol 2007; 136: 18–26.
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5. Moore PF, Affolter VK, Vernau W. Canine hemophagocytic histiocytic sarcoma: a proliferative disorder of CD11d+ macrophages. Vet Pathol 2006; 43: 632–645.
6. Amores-Fuster I, Elliott JW, Freeman AI, et al. Histiocytic sarcoma of the urinary bladder in a dog (lett). J Small Anim Pract 2011; 52: 665.
7. van Kuijk L, van Ginkel K, de Vos JP, et al. Peri-articular histiocytic sarcoma and previous joint disease in Bernese Mountain Dogs. J Vet Intern Med 2013; 27: 293–299.
8. Klahn SL, Kitchell BE, Dervisis NG. Evaluation and comparison of outcomes in dogs with peri-articular and nonperiarticular histiocytic sarcoma. J Am Vet Med Assoc 2011; 239: 90–96.
9. Nielsen LN, McEvoy F, Jessen LR, et al. Investigation of a screening programme and the possible identification of biomarkers for early disseminated histiocytic sarcoma in Bernese Mountain Dogs. Vet Comp Oncol 2012; 10: 124–134.
