History
A 3-year-old 40-kg (88-lb) castrated male Doberman Pinscher (resident in New York state) was evaluated on an emergency basis because of respiratory distress. Nine months prior to the evaluation, the dog had been evaluated because of bilateral swollen carpi, and radiography had revealed an aggressive bone lesion (ABL). The condition of the carpi became progressively worse, leading to forelimb lameness; the dog had also developed coughing, sneezing, and epistaxis. Treatment with diphenhydramine (as needed) and amoxicillin (for 30 days) was initiated. Cytologic examination of a fine-needle aspirate specimen from an enlarged popliteal lymph node revealed evidence of histiocytic inflammation. The dog was administered prednisone (for 21 days) and doxycycline (for 30 days). Because the bilateral carpal swelling continued to increase at the end of this regimen, the dosage of prednisone was increased; 2 days later, the dog's respiratory signs worsened. Bronchoscopy revealed inflamed, hemorrhagic bronchi, and radiography revealed progressive bilateral periosteal reaction and lytic lesions of the distal portions of the right and left radius and ulna as well as a severe generalized miliary nodular lung pattern.
Clinical and Gross Findings
At the emergency evaluation, the dog was febrile. It was tachycardic and panting with harsh lung sounds and cyanotic mucous membranes. The capillary refill time was < 2 seconds, and femoral pulses were strong. The dog had bilateral carpal joint swelling and firm popliteal lymph nodes. Euthanasia (by IV administration of pentobarbital sodium) was elected owing to the severity of the clinical signs. A postmortem CT scan of the head, neck, and thorax confirmed the generalized miliary nodular pattern within the lungs and revealed periosteal new bone formation on the calvaria. At necropsy, the lungs were diffusely mottled dark red and light pink, noncollapsing, and mildly firm (Figure 1). Throughout all lung lobes, there were dozens of miliary, white-tan foci that extended into the parenchyma. The medial aspects of the right and left carpi had multiple cystic spaces filled with brown, cloudy fluid. On sagittal sections, the periosteum of the right distal third of the radius, the ulna, and the carpal bones was expanded up to 1.7 cm in thickness with a rough and uneven outer cortical surface.
Photographs of the lungs (A), a cut surface of a caudal lung lobe (B), and a longitudinal section of the distal third of a carpus (C) of a 3-year-old castrated male Doberman Pinscher with a 9-month history of bilateral carpal swelling and respiratory tract signs. In panel C, notice the periosteal reaction (outlined by the dashed contour) and the cortex of the bone (arrowheads). Bar = 2 cm in panel A, 2.5 cm in panel B, and 2 cm in panel C.
Citation: Journal of the American Veterinary Medical Association 254, 11; 10.2460/javma.254.11.1287
Formulate differential diagnoses from the history, clinical findings, and Figure 1—then turn the page→
Histopathologic Findings
Histologic examination of sections of the lungs revealed that 80% of lung parenchyma had multifocal to coalescing areas of central necrotic debris and degenerate inflammatory cells surrounded by macrophages, multinucleated giant cells, lymphocytes, neutrophils, and rare plasma cells. Within macrophages, but also free in the alveoli, were numerous round, 8- to 20-μm-diameter, yeast-like cells with a 2- to 3-μm-thick, clear to basophilic, double-contoured refractile wall and frequent broad-based budding, consistent with Blastomyces dermatitidis. Similar inflammatory cells and yeast-like cells were present within the lumen of airways (Figure 2). Use of periodic acid–Schiff stain (to detect polysaccharides) and Grocott-Gomori methenamine silver stain (to detect fungi) on lung tissue sections highlighted numerous intracellular and extracellular fungal organisms throughout the lung parenchyma; the fungal organisms had morphological features typical of B dermatitidis.
Photomicrographs of sections of lung tissue from the dog in Figure 1. Numerous spherical yeasts are free within alveoli (solid arrows); the organisms have a 2- to 3-μm-thick refractile capsule and are undergoing broad-based budding (open arrow). The alveoli are filled with degenerate neutrophils, necrotic debris, and fewer macrophages. H&E stain; bar = 50 μm. Inset—Higher-magnification image to illustrate the broad-based budding of the yeasts. Grocott-Gomori methenamine silver stain; bar = 50 μm.
Citation: Journal of the American Veterinary Medical Association 254, 11; 10.2460/javma.254.11.1287
The cortical bone of the distal aspects of the carpi was expanded by coalescing spaces filled with macrophages, multinucleated giant cells, and rare lymphocytes. Along the trabeculae of lamellar bone were frequent osteoclasts (Figure 3). Scattered within the inflammatory infiltrate were B dermatitidis yeasts. The periosteum was expanded by a thick layer of incompletely mineralized, woven bone (periosteal reaction) with numerous osteocytes. The inflammation dissected through the periosteal reaction and extended to the adjacent fascia and skeletal muscles. Similar findings were identified in the calvarial bones. The lymph node cortex was expanded by nodular aggregates of histocytes, occasionally centered around yeasts (histiocytic lymphadenitis). Multifocally throughout the myocardium, the cytoplasm of cardiomyocytes was intensely basophilic with granular deposits of mineral. Also, scattered throughout the myocardium were numerous swollen or fragmented cardiomyocytes that had loss of striation and nuclear details (degeneration and necrosis). Predominantly within centrilobular areas of the liver, there were small clusters of intensely eosinophilic hepatocytes with loss of cellular details (hepatocellular necrosis) surrounded by a few macrophages and occasional lymphocytes.
Photomicrographs of sections of the distal portion of a carpus from the dog in Figure 1. Notice that the cortical bone has scalloped edges lined by frequent osteoclasts (arrow) and aggregates of macrophages, neutrophils, plasma cells, and occasional lymphocytes; the aggregates occasionally surround clusters of yeasts. H&E stain; bar = 150 μm. Inset—Higher-magnification image to illustrate the yeasts surrounded by inflammatory cells. H&E stain; bar = 75 μm.
Citation: Journal of the American Veterinary Medical Association 254, 11; 10.2460/javma.254.11.1287
Results of Fungal Culture
Fungal culture of lung tissue samples from the dog was performed. Culture yielded growth of B dermatitidis.
Morphologic Diagnosis and Case Summary
Morphologic diagnosis and case summary: pyogranulomatous bronchopneumonia, osteomyelitis, fasciitis, myositis, and lymphadenitis with yeasts consistent with B dermatitidis leading to myocardial degeneration and necrosis with dystrophic mineralization and centrilobular hepatocellular necrosis in a dog.
Comments
The dog of the present report had the classic signs of disseminated blastomycosis characterized by severe lung and skeletal involvement as well as secondary lesions in peripheral lymph nodes (attributed to systemic inflammation) and the myocardium and liver (attributed to severe hypoxia). Although the myocardial damage was attributed to hypoxia, microscopic infarcts could not be ruled out as a cause of myocardial necrosis. The classic radiographic appearance of fungal pneumonia is a generalized, random, miliary nodular pattern; however, blastomycosis can have the radiographic appearance of multiple pulmonary nodules, patchy or lobar lung consolidation (alveolar pattern), or a solitary pulmonary mass.1 In the case described in the present report, histopathologic findings ruled out other potential causes of pulmonary nodules including a neoplastic process or infection with Mycobacterium spp, Coccidioides immitis, Cryptococcus neoformans, or Histoplasma capsulatum.
Blastomycosis is one of the most common systemic mycotic infections of dogs that live in areas endemic for B dermatitidis, such as the Ohio and Missouri River Valleys, southern Great Lakes, and southern mid-Atlantic states.2 In the state of New York, the incidence of blastomycosis in dogs has increased over the past 20 years.3 Blastomycosis affects dogs and humans and is rare in other animals. Young sexually intact male dogs living in B dermatitidis–endemic areas are at an increased risk of becoming infected.3 Sporting dogs, such as Labrador and Golden Retrievers and Doberman Pinschers, are affected more frequently than are other breeds.4,5
Blastomycosis is caused by infection with a saprophytic fungus that is found in moist acidic or sandy soil with high organic content.4 Blastomyces dermatitidis is a thermally dimorphic fungus that exists as septate mycelia in the environment and as yeasts within infected tissues. In its mycelial form, it produces conidia (spores) that are inhaled by the host and then phagocytized by alveolar macrophages.5 At body temperature, the spores transform into yeasts, which have broad-based budding and thick double-contoured walls.4,5 The yeasts cause a local suppurative to pyogranulomatous inflammatory response, which may be self-limiting.6 However, phagocytized yeasts can be transported into the pulmonary interstitium where they can disseminate hematogenously or through the lymphatic system to other organs.6 Inoculation directly through a skin wound is also possible, but occurs rarely.6 In contrast to other mycotic diseases, including those caused by C immitis and Aspergillus infections, wherein transmission of infectious spores occurs through aerosolization from infected tissues, B dermatitidis yeasts are not infective in this manner and, thus, additional biosafety precautions during necropsy of infected carcasses are not required.7
Clinical signs of blastomycosis depend on the organ system most severely affected; however, respiratory tract signs are most common.5,6 In dogs, blastomycosis is characterized by wide variation in disease course, ranging from subclinical infection to protracted mild clinical disease that is sometimes followed by abrupt disease progression and worsening; on occasion, the disease may be associated with death.8–10 The preferred sites of dissemination of B dermatitidis in dogs are the lungs, lymph nodes, skin, eyes, bones, reproductive system, and nervous system.6 Although the distribution of lesions in the dog of the present report was considered classic for blastomycosis, the involvement of the bones in the calvaria was an unusual finding. Lameness caused by osteomyelitis or paronychia is likely in 25% of dogs with blastomycosis, and fungal osteomyelitis develops in 10% to 15% of all affected dogs.6 In cases such as that described in the present report, distinguishing between ABLs and nonaggressive bone lesions (nABLs) is essential.11 The radiographic pattern of ABLs includes periosteal reaction, bone lysis, and zones of transition, all of which progress over time.11 The zone of transition refers to the boundary between the bone lesion and unaffected bone and is the most reliable indicator of aggressiveness.11 Continuous new bone formation and reactive new bone formation can be associated with both ABLs and nABLs. Interrupted new bone formation and tumor new bone formation are associated with ABLs. A long zone of transition between normal and abnormal bone is commonly associated with ABLs, whereas a short zone of transition can be associated with both ABLs and nABLs. Aggressive bone lesions can have similar appearance regardless of the cause; therefore, distribution of lesions (eg, focal monostotic or multifocal polyostotic) helps to determine the diagnosis.
For dogs with blastomycosis, itraconazole administered at a dosage of 5 mg/kg (2.27 mg/lb) every 24 hours for 60 days is the treatment of choice. Treatment should be continued for 30 to 60 days after resolution of clinical signs. Clinical signs often become more severe in the early phase of treatment, when the yeasts die and elicit severe inflammation.6
References
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