History
A 7-year-old 31.2-kg (68.6-lb) sexually intact male Belgian Malinois was evaluated on an emergency basis because of respiratory distress with a history of sudden collapse. The dog had been evaluated by the primary care veterinarian 1 month earlier because of a nonproductive cough, exercise intolerance, and weight loss; no abnormalities were identified on physical examination. Laboratory testing performed at the referring clinic included serologic testing for heartworm disease and tick-borne diseases,a a CBC, a serum biochemical panel, and a urinalysis. The dog was negative for circulating Dirofilaria immitis antigen and negative for antibodies against Ehrlichia canis, Anaplasma phagocytophilum, and Borrelia burgdorferi. The only hematologic abnormality was marked eosinophilia (12.1 × 103 eosinophils/μL; reference interval, 0.1 × 103 eosinophils/μL to 1.2 × 103 eosinophils/μL); no notable abnormalities were revealed by serum biochemical analysis or urinalysis. At that time, once-daily treatment with cefpodoxime proxetil (300 mg), prednisone (15 mg), and hydrocodone bitartrate (15 mg) with homatropine methylbromide (4.5 mg) was instituted and resulted in partial amelioration of clinical signs.
Clinical and Gross Findings
On examination at the emergency service, the dog was quiet, alert, and responsive. Although physical examination findings were largely unremarkable, the dog was thin (body condition score, 3/9) and dyspneic with bilaterally increased expiratory lung sounds. Pulse oximetry revealed hypoxemia (oxygen saturation, 84%). The dog was hospitalized overnight and treated with supplemental 40% oxygen and IV administration of butorphanol tartrate (156 mg) and acepromazine maleate (9.4 mg). Additional diagnostic testing, including a CBC, plasma biochemical panel, and diagnostic imaging, were performed the following day.
Results of the CBC and plasma biochemical panel were within reference intervals with the exception of mild eosinophilia (1.3 × 103 eosinophils/μL). Three-view thoracic radiography revealed a well-defined, round (≤ 6-cm-diameter), soft tissue mass in the left caudal lung field, an interstitial pattern in the same lung field, and marked tracheobronchial lymphadenopathy. Thoracic ultrasonography revealed that the left cranial lung lobe was diffusely hyperechoic and mottled, with fluid bronchograms and a large mass at the periphery of the left caudal lung lobe.
At the time of the thoracic ultrasonographic assessment, fine-needle aspirate biopsy specimens were obtained from the pulmonary masses for examination; findings suggested that the dog's prognosis was poor to guarded, and euthanasia (by IV administration of pentobarbital sodium) with full postmortem examination was elected. At necropsy, the tracheobronchial and mediastinal lymph nodes were enlarged, firm, multilobulated, and mottled red to black and the lungs were diffusely consolidated and mottled red to black (Figure 1). The cranial portion of the left cranial lung lobe contained a firm mass measuring 17.5 × 9.5 × 4 cm and a firm, umbilicated, oval mass measuring 8 × 7 × 4.5 cm was present in the left caudal lung lobe. On cut section, these masses oozed green, caseous exudate.
Photograph (dorsal view) of the lungs from a 7-year-old sexually intact male Belgian Malinois that was evaluated on an emergency basis because of respiratory distress with a history of sudden collapse. Notice the multilobulated, enlarged, and mottled red to black hilar lymph nodes and the similarly mottled appearance of the lungs. Two nodular masses can be seen in the cranial portion of the left cranial lung lobe and the left caudal lung lobe. The cut section of 1 mass (top right) illustrates the green caseous exudate inside the masses.
Citation: Journal of the American Veterinary Medical Association 254, 4; 10.2460/javma.254.4.479
Photograph (dorsal view) of the lungs from a 7-year-old sexually intact male Belgian Malinois that was evaluated on an emergency basis because of respiratory distress with a history of sudden collapse. Notice the multilobulated, enlarged, and mottled red to black hilar lymph nodes and the similarly mottled appearance of the lungs. Two nodular masses can be seen in the cranial portion of the left cranial lung lobe and the left caudal lung lobe. The cut section of 1 mass (top right) illustrates the green caseous exudate inside the masses.
Citation: Journal of the American Veterinary Medical Association 254, 4; 10.2460/javma.254.4.479
Photograph (dorsal view) of the lungs from a 7-year-old sexually intact male Belgian Malinois that was evaluated on an emergency basis because of respiratory distress with a history of sudden collapse. Notice the multilobulated, enlarged, and mottled red to black hilar lymph nodes and the similarly mottled appearance of the lungs. Two nodular masses can be seen in the cranial portion of the left cranial lung lobe and the left caudal lung lobe. The cut section of 1 mass (top right) illustrates the green caseous exudate inside the masses.
Citation: Journal of the American Veterinary Medical Association 254, 4; 10.2460/javma.254.4.479
Formulate differential diagnoses from the history, clinical findings, and Figure 1—then turn the page →
Cytologic and Histologic Findings
Microscopic examination of the ultrasound-guided fine-needle aspirate specimens of the lung masses revealed large numbers of well-preserved nucleated cells with moderate amounts of blood (Figure 2). Nucleated cells were a mix of macrophages, eosinophils, and neutrophils with lesser numbers of plasma cells, lymphocytes, mast cells, basophils, and mesothelial cells. No infectious organisms or neoplastic cells were identified. The cytologic interpretation was pyogranulomatous and eosinophilic inflammation; differential diagnoses included eosinophilic granulomatosis; foreign body response; bacterial, parasitic, fungal, or algal disease; and less likely, a neoplastic process such as lymphomatoid granulomatosis.
Photomicrograph of an ultrasound-guided fine-needle aspirate biopsy specimen obtained from a lung mass in the dog in Figure 1. Notice large numbers of macrophages admixed with eosinophils and low numbers of neutrophils. Wright-Giemsa stain; bar = 20 μm. Inset—In thinner areas of the smear, low to moderate numbers of granules are visible within eosinophils. Wright-Giemsa stain; bar = 20 μm.
Citation: Journal of the American Veterinary Medical Association 254, 4; 10.2460/javma.254.4.479
Photomicrograph of an ultrasound-guided fine-needle aspirate biopsy specimen obtained from a lung mass in the dog in Figure 1. Notice large numbers of macrophages admixed with eosinophils and low numbers of neutrophils. Wright-Giemsa stain; bar = 20 μm. Inset—In thinner areas of the smear, low to moderate numbers of granules are visible within eosinophils. Wright-Giemsa stain; bar = 20 μm.
Citation: Journal of the American Veterinary Medical Association 254, 4; 10.2460/javma.254.4.479
Photomicrograph of an ultrasound-guided fine-needle aspirate biopsy specimen obtained from a lung mass in the dog in Figure 1. Notice large numbers of macrophages admixed with eosinophils and low numbers of neutrophils. Wright-Giemsa stain; bar = 20 μm. Inset—In thinner areas of the smear, low to moderate numbers of granules are visible within eosinophils. Wright-Giemsa stain; bar = 20 μm.
Citation: Journal of the American Veterinary Medical Association 254, 4; 10.2460/javma.254.4.479
Tissues from the lung and lymph nodes were routinely processed and stained with H&E stain for histologic examination. Examination of lung tissue revealed multifocal to coalescing effacement and replacement of the pulmonary parenchyma by fibrous connective tissue admixed with myriad inflammatory cells including dense infiltrates of viable and degenerate eosinophils, macrophages, and multinucleated giant cells, along with cellular and karyorrhectic debris, fibroblasts, and collagen (Figure 3). The airways were markedly dilated by large numbers of similar inflammatory cells within the lumina, lamina propria, and tunica muscularis. In less affected areas, alveolar spaces were filled with a large number of alveolar macrophages, and pulmonary capillaries were congested with occasional type II pneumocyte hyperplasia. Mediastinal and tracheobronchial lymph nodes were effaced by fibrous connective tissue and dense infiltrates of inflammatory cells similar to those identified in lung tissue.
Photomicrograph of a section of a pulmonary granuloma from the dog in Figure 1. The pulmonary parenchyma is replaced by fibrous connective tissue and a dense cellular infiltrate. H&E stain; bar = 500 μm. Inset—The infiltrate is composed of many eosinophils and fewer macrophages. H&E stain; bar = 20 μm.
Citation: Journal of the American Veterinary Medical Association 254, 4; 10.2460/javma.254.4.479
Photomicrograph of a section of a pulmonary granuloma from the dog in Figure 1. The pulmonary parenchyma is replaced by fibrous connective tissue and a dense cellular infiltrate. H&E stain; bar = 500 μm. Inset—The infiltrate is composed of many eosinophils and fewer macrophages. H&E stain; bar = 20 μm.
Citation: Journal of the American Veterinary Medical Association 254, 4; 10.2460/javma.254.4.479
Photomicrograph of a section of a pulmonary granuloma from the dog in Figure 1. The pulmonary parenchyma is replaced by fibrous connective tissue and a dense cellular infiltrate. H&E stain; bar = 500 μm. Inset—The infiltrate is composed of many eosinophils and fewer macrophages. H&E stain; bar = 20 μm.
Citation: Journal of the American Veterinary Medical Association 254, 4; 10.2460/javma.254.4.479
Additional Laboratory Findings
Aerobic bacterial and fungal cultures of tissue samples of the lungs and tracheobronchial lymph node were performed, and no organisms were isolated. Results of testingb of a urine sample for Blastomyces dermatitidis and Histoplasma capsulatum antigens were negative.
Morphologic Diagnosis and Case Summary
Morphologic diagnosis: severe, chronic, multifocal to coalescing, eosinophilic and granulomatous pneumonia; and severe chronic, multifocal eosinophilic lymphadenitis (mediastinal and tracheobronchial lymph nodes), with marked fibrosis.
Case summary: eosinophilic pulmonary granulomatosis (EPG) with extension into the mediastinal and tracheobronchial lymph nodes in a dog.
Comments
Eosinophilic pulmonary granulomatosis is an idiopathic disease of dogs with no known equivalent in the human medical literature.1 Lesions consist primarily of eosinophilic granulomas within the pulmonary parenchyma, often with extension into airways and regional lymph nodes.1–9 Some authors speculate that EPG may represent a severe form of the more commonly diagnosed idiopathic condition, eosinophilic bronchopneumopathy (EBP [formerly known as pulmonary infiltrates with eosinophilia]).4,5,9 Although both diseases may be associated with eosinophilic airway inflammation and peripheral eosinophilia, EBP is distinguished morphologically by airway and pulmonary infiltrates without granuloma formation or lymph node involvement and clinically by a far better response to immunosuppressive treatment.4,6
The pathogenesis and inciting agent for EPG have yet to be confirmed.1,6 Historically, the disease has been associated with D immitis infection.1–3,7 However, similar to the case described in the present report, affected dogs do not always have gross, serologic, or histologic evidence of dirofilariasis.2,6–8 As such, it is speculated that cases of EPG not attributable to dirofilariasis largely reflect hypersensitivity reactions.3
A retrospective study4 of reported EPG cases revealed no predilection for age or sex; however, the Siberian Husky and Alaskan Malamute breeds were overrepresented among dogs with EPG or EBP. Common clinical signs and physical examination findings among dogs with EPG include progressive cough, exercise intolerance, weight loss, and dyspnea.1–3,6,7 Auscultation of the lung fields may reveal increased lung sounds, and moist rales and crackles in affected dogs have been previously documented.2,3,6,7 In dogs with EPG, the most consistent findings are pulmonary masses that are usually visible radiographically, appearing as variably sized soft tissue opacities.1–4,6–8 An interstitial or alveolar infiltrate usually accompanies the masses, along with local lymphadenopathy.2,3,6–8 These radiographic findings help distinguish EPG from EBP (which is characterized by a diffuse bronchointerstitial pattern) but not from other infectious and neoplastic processes that may be associated with development of lung nodules.2,4
Although cytologic evidence of eosinophilic and granulomatous inflammation in a sample from a lung mass may support a diagnosis of EPG, ultimately, further diagnostic testing is needed to definitively rule out neoplastic and infectious diseases. For the dog of the present report, lymphomatoid granulomatosis was considered the only neoplastic process likely to account for the radiographic and cytologic findings. Lymphomatoid granulomatosis, which is currently thought to represent an angiocentric B-cell lymphoma with reactive T-cells, is highly inflammatory, and inflammatory cells such as neutrophils and eosinophils may predominate, necessitating examination of biopsy specimens for definitive diagnosis.10 Because a variety of infectious diseases may contribute to eosinophilic lung disease and the fact that the prevalence of D immitis infection in canine EPG cases is high,2,3 testing for circulating D immitis antigen should be performed in all dogs for which EPG is a primary differential diagnosis.
In dogs with EPG, a CBC will often, but not always, reveal eosinophilia with reported ranges of 0.4 × 103 eosinophils/μL to 25.1 × 103 eosinophils/μL.2 Because dogs with EPG can have widely variable (normal to markedly high) eosinophil counts, distinguishing EPG from other causes of eosinophilia (ie, hypersensitivities of idiopathic or parasitic nature, hypereosinophilic syndrome, or chronic eosinophilic leukemia) may be difficult.11 In addition, eosinophilia can also be present in dogs with EBP; however, the degree of eosinophilia is usually < 10 × 103 eosinophils/μL.4 Although not performed in the case described in the present report, examination of collected samples of bronchoalveolar lavage fluid or a transtracheal wash may reveal an eosinophilic airway infiltrate. Also, in dogs with EPG, a predominance of eosinophils is seen in pleural effusions, when those are present.2,3,6,7
Given the multitude of differential diagnoses, definitive antemortem diagnosis of EPG is rare, but postmortem examination findings are extremely consistent among documented cases and are considered diagnostic. Gross pulmonary findings of EPG include firm, consolidated lungs with multifocal to regionally extensive, discrete nodules.2,3,7 Similar nodules have been found in local lymph nodes, liver, and spleen.2,3 The nodules may contain a yellow-green exudate, as in the dog of the present report, which is characteristic of eosinophilic inflammation because of the presence of myeloperoxidase.12 In addition, the pulmonary parenchyma is extensively obliterated by fibrous connective tissue and infiltrates predominantly of eosinophils as well as epithelioid macrophages, lymphocytes, and plasma cells.2,3,7
Treatment of dogs with EPG includes administration of immunosuppressive and cytotoxic drugs, on the basis of the presumptive immune-mediated pathogenesis.5 Immunosuppressive doses of prednisone, azathioprine, and cyclophosphamide are among the documented treatments; the efficacy of other immunosuppressive drugs (eg, cyclosporine) is not known.2,5–7 The prognosis for dogs with EPG is poor because there is typically either a partial response to treatment or rapid recurrence of respiratory clinical signs on cessation of treatment.2,7 However, prolonged remission from EPG was achieved in 1 dog following treatment with prednisolone and azathioprine.6
Footnotes
SNAP 4Dx, Idexx Laboratories, Westbrook, Me.
MVista, MiraVista Diagnostics, Indianapolis, Ind.
References
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