What Is Your Neurologic Diagnosis?

Rebecca E. Sidor Department of Clinical Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS 39762.

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Jennifer Gambino Department of Clinical Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS 39762.

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Abbey Fraiser Department of Clinical Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS 39762.

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Katherine Gerken Department of Clinical Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS 39762.

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A 9-year-old 22.3-kg (49.1-lb) spayed female Shetland Sheepdog was referred for evaluation of an intrathoracic mass, which appeared radiographically as a large, ill-defined, soft tissue opacity mass associated with the cranial mediastinum and causing dorsolateral deviation of the trachea. The dog had a 2-week history of excessive panting, intermittent gagging, dysphagia, inappetence, hypodipsia, and lethargy. During physical examination, the dog was alert and responsive; heart rate and rectal temperature were within reference intervals. Intermittent panting (periods during which the respiratory rate was > 60 breaths/min) with normal respiratory effort was noted during the physical examination. Mild nonpitting edema within the submandibular and cervical subcutis was present. Bilateral crepitus of the hip joints, consistent with reported hip joint arthritis, was noted in combination with moderate bilateral hind limb weakness.

What is the problem? Where is the lesion? What are the most probable causes of this problem? What is your plan to establish a diagnosis? Please turn the page.

Assessment Anatomic diagnosis

ProblemRule out location
Ambulatory hind limb paraparesis and ataxiaNeuromuscular disease or T3-L3 spinal lesion
Gagging and tachypneaNeuromuscular disease or intrathoracic or cranial mediastinal thoracic mass
Ventral neck edemaIntrathoracic or cranial mediastinal mass or thromboembolic disease

Likely location of 1 lesion

Neuromuscular disease was considered most likely. Ventral neck edema was likely attributable to impaired craniocephalic venous return (secondary to the large intrathoracic mass) or concurrent thromboembolic disease.

Etiologic diagnosis—Organs of origin for the large, cranial intrathoracic or cranial mediastinal mass detected radiographically included the thymus, lymph node, a branchial structure, esophagus, or cardiac base. The primary differential diagnosis for the cranial mediastinal mass was neoplasia. Lesser consideration was given to a cyst, granuloma, hematoma, or abscess. Weakness resulting from spinal disease, aneurysm, anemia, aortic thromboembolic disease, or primary neuromyopathy and junctionopathy, such as with thymoma and concurrent myasthenia gravis, were all considered. Other neoplastic processes, such as ectopic thyroid carcinoma or tracheobronchial lymphadenopathy were considered, especially given the submandibular and cervical swelling and edema. Additional neoplastic processes considered included lymphoma, pulmonary carcinoma, metastatic disease, or cardiac-based neoplasia, such as chemodectoma and hemangiosarcoma with secondary weakness as a result of cardiovascular compromise. Further diagnostic investigation included a CBC, serum biochemical analysis, coagulation profile, urinalysis, and microbial urine culture. To delineate the organ of origination of the thoracic mass, ultrasonography and contrast-enhanced CT of the thorax were recommended. Given the suspicion of neoplasia, abdominal radiography and ultrasonography were recommended to rule out the presence of a primary metastatic lesion. Imaging was performed in staged fashion.

Diagnostic test findings—The CBC, serum biochemical analysis, and coagulation profile revealed no abnormalities. Urinalysis revealed 2+ proteinuria; WBCs in the urine sample were too numerous to count. Microbial culture of a urine sample and subsequent antimicrobial susceptibility testing yielded Escherichia coli that was susceptible to cephalexin. Abdominal ultrasonography revealed a moderately enlarged, diffusely hyperechoic liver with multiple round to ovoid, smoothly marginated, hypoechoic nodules, the largest dimension of which was 1.01 cm. Fine-needle aspirate samples were collected (by use of a 22-gauge, 1.5-inch needle with a 3-pass, negative pressure, with to- and fro-motion technique) from 2 small liver nodules. Cytologic evaluation of the nodules was consistent with hepatic regeneration with no evidence of neoplasia. Thoracic ultrasonography revealed a large (7 × 6-cm), heterogeneous to hypoechoic mass within the cranial mediastinal space (observed via the right and left second through seventh rib spaces). This finding prompted an abbreviated echocardiographic examination of the cardiac base. The mass was closely associated with the right auricular appendage and adjacent cardiac base and was best observed on the right parasternal long axis and left cranial parasternal long axis combined right atrial, right auricular, and left ventricular outflow tract cardiac windows. The mass caused notable caudal displacement of the pulmonary trunk, which could be seen immediately adjacent to the descending portion of the aorta. The great vessels encircled the mass and were noted to be flattened, predominantly on the right lateral margin of the mass along the medial aspect of the first ribs. The lumen of the right auricular appendage was obscured and difficult to identify. Both the left and right atria were compressed by the mass. Moderate to severe tricuspid valve insufficiency with pulmonary hypertension was detected via color flow and spectral Doppler ultrasonography. The velocity of the tricuspid regurgitant jet was 3.69 m/s and corresponded to a pressure gradient of 54.4 mm Hg. Mild mitral valve insufficiency was detected via color flow Doppler ultrasonography, but was not thoroughly investigated because of the poor angle of interrogation. Complete echocardiographic evaluation was recommended, but was declined by the owner. Ultrasound-guided fine-needle aspiration of the mass was not performed owing to the intimate association of the mass with the great vessels obscuring the approach to tumor tissue. Ultrasonographic evaluation of the cranial mediastinum and cardiac base strongly supported cardiac-based neoplasia given the displacement of the great vessels, heterogeneous cardiac base mass lesion, and suspected right auricular involvement.

Neoplasia of the right auricular appendage (eg, hemangiosarcoma or lymphoma) was considered. Neoplasia of the aortic root (eg, chemodectoma) or tracheobronchial lymph node was not excluded given that masses within the tracheobronchial lymph node in the adventitia between the aorta and pulmonary trunk have been previously reported,1 although not typically as large as those detected in the dog of this report. A large cranial mediastinal mass abutting the cardiac base was not entirely excluded, but was considered less likely based on the ultrasonographic findings. Computed tomography was recommended to determine the extent of the mass and vascular invasion. Computed tomography-guided fine-needle aspiration (or biopsy of the mass) was planned pending findings of a preliminary CT evaluation.

Following sedation with dexmedetomidinea (2.5 mg/kg [1.14 mg/lb]; total dose, 55.7 μg) and butorphanol tartrateb (0.1 mg/kg [0.045 mg/lb]; total dose, 2.23 mg), noncontrast- and contrast-enhanced CT was performed with a multidetector 4-slice CT scanner.c Images were acquired in the transverse plane with multiplanar reconstructions evaluated in the sagittal and dorsal planes. Images were acquired following IV administration of the nonionic iodinated contrast agent ioversold (704 mg/kg [320 mg/lb]; total dose, 15,699 mg). The CT images confirmed the radiographic findings. A 7-cm-wide × 7.5-cm-high × 9.6-cm-long, ovoid, irregularly marginated, heterogeneously enhancing, soft tissue attenuating mass was seen intimately associated with the patient's cardiac base (Figure 1).

Figure 1—
Figure 1—

Representative images obtained by various diagnostic imaging techniques that were used to diagnose a cardiac-based neoplasm in a 9-year-old Shetland Sheepdog that was initially evaluated because of a 2-week history of excessive panting, intermittent gagging, dysphagia, inappetence, hypodipsia, and lethargy. A—Ventrodorsal thoracic radiographic view. A large, cranial mediastinal soft-tissue opacity mass is displacing the cardiac silhouette caudally, with deviation of the cardiac apex toward the left. B—Ultrasonographic image obtained through the left cranial parasternal long axis combined right atrial, right auricular, and left ventricular outflow tract cardiac window. This view is easily obtained by placing the transducer along the long axis of the dog, in the left axilla, with the probe's reference marker oriented cranially. Notice the large heterogeneous to hyperechoic mass (white asterisk) in the region of the right auricle (RAU). AO = Aorta. RA = Right atrium. C—Transverse plane thoracic CT image. Notice the large heterogeneous mass (asterisk) intimately associated with the AO and main pulmonary artery (right ventricular outflow tract [RVOT]) and cranial vena cava (CrVC). D—Dorsal plane CT reconstruction. Notice the attenuation of the lumen of the CrVC at the third rib space; the more cranial aspect of the CrVC is severely distended. The caudal vena cava and hepatic veins were also severely distended (not shown). In panels C and D, images were obtained with a window width of 41 HU and window level of 479 HU; the white dashed line depicts the trajectory of the needle for uncomplicated, minimally invasive, CT-guided fine-needle aspiration of the mass. A CT scan performed immediately after the procedure was negative for pneumothorax, pleural or pericardial effusion, and intralesional active hemorrhage (not shown).

Citation: Journal of the American Veterinary Medical Association 250, 12; 10.2460/javma.250.12.1367

On the basis of CT sectional imaging, the most likely tissue of origin was the wall of the right auricular appendage. The rightward and dorsal displacement of the intrathoracic portion of the trachea detected radiographically was evident. Right-ward displacement and severe attenuation of the cranial vena cava with caudal displacement of the pulmonary trunk observed ultrasonographically were confirmed. The presence of the mass caused a severe caudal and leftward mediastinal shift of the heart. Following CT image acquisition, a second dose of dexmedetomidinee (1.25 mg/kg [0.57 mg/lb]; total dose, 28 μg) provided adequate additional sedation for single-attempt collection of a CT-guided fine-needle aspirate of the mass originating from the right auricular appendage. This was performed with a 22-gauge 3.5-inch spinal needle (with stylet) through the right third rib space and through the attenuated cranial vena cava. The needle was inserted to the hub because of a large fat-density subcutaneous mass (previously confirmed to be lipomatous) directly over the avenue of approach. A more cranial approach was not possible owing to the depth of the dog's subcutaneous fat, limited physical access due to positioning, and limitations in the lengths of available needles. The stylet was withdrawn, and a 5-mL syringe with 1 mL of room air within the syringe chamber was attached to the needle. Additional negative pressure to 5 mL was applied. The collected material was submitted for evaluation by a board-certified veterinary clinical pathologist. Immediately following the interventional procedure, repeated CT revealed no pneumothorax, pleural or pericardial effusion, or active hemorrhage. Cytologic features of the aspirate sample were consistent with a neuroendocrine tumor such as malignant chemodectoma. The mass sample had moderate cellularity and was composed of small clusters of cuboidal epithelial cells admixed with numerous free nuclei. The epithelial cells had round nuclei with stippled chromatin and a large blue nucleolus. There was mild anisokaryosis. When cytoplasm was present, it was moderately abundant, granular, and eosinophilic.

Comments

In dogs, the prevalence of cardiac neoplasia is 0.19%.2 Dyspnea, tachypnea, paraparesis, lethargy, and anorexia may be associated with cardiac-based neoplasms in dogs.2 Results of the abbreviated evaluation of the cardiac base in the dog of the present report (limited to the right parasternal long axis and left cranial parasternal long axis combined right atrial, right auricular, and left ventricular outflow windows) were integral to decision making and prompted CT evaluation of this dog. In the authors' opinion, use of these ultrasound windows (especially from the left side) is ideal for quick assessment of the cardiac base for mass lesions. Historically, tissue sample collection from cardiac-based neoplasms was deemed hazardous, and special procedures including left ventricular angiography and pleurography were used to evaluate for cardiac-based neoplasia.3,4 Inadvertent fine-needle aspiration of cardiac-based neoplasms has been reported.5 Despite some challenges associated with ultrasound-guided fine-needle aspiration of cardiac-based neoplasms, examination of those specimens can provide a definitive diagnosis of malignancy type.2

In dogs, neuroendocrine cardiac-based neoplasms (eg, chemodectoma) are uncommon, slow-growing with a low metastatic rate, locally invasive tumors that develop in the carotid or aortic body. Specifically, these tumors develop from aorticopulmonary paraganglial chemoreceptor cells that reside in the atria and atrial septum and are derived from branchial arch structures and visceral paraganglia.6 Chemoreceptor cells are sensitive to oxygen and carbon dioxide tensions in the blood and aid in regulation of respiration and heart rate; therefore, hypoxic states can increase the risk of chemodectoma formation.7 Brachycephalic breeds, specifically Boxers and Boston Terriers, are predisposed to development of chemodectomas, most likely because of chronic hypoxia.8

The attenuation of the vena cava in the dog of the present report was likely the cause of the ventral neck edema leading to caval syndrome and impaired venous return from the head. Similar to the case described in this report, mechanical compression by large, locally invasive cardiac-based chemodectoma mass lesions can result in pulmonary hypertension and right-sided heart failure.9 This drastically shortens the median survival time of affected dogs.9 Clinical signs in dogs with chemodectomas include signs of respiratory tract disease (eg, gagging and coughing), weak peripheral pulses, ataxia, muffled heart sounds, abdominal distension, and inappetence.9,10

Chemodectomas are usually diagnosed on the basis of combined findings from history, physical examination, radiography, echocardiography, and advanced imaging techniques. Often, a definitive diagnosis is made from results of examination of invasive excisional surgical biopsy or necropsy specimens.8 Excision of the mass was not considered an option in the dog of the present report because of the extensive vascular displacement and involvement. Three-dimensional stereotactic radiation therapy at a tertiary care referral center was offered on the basis of a documented 42-month survival time of a 9-year-old mixed-breed dog with a cardiac-based chemodectoma following stereotactic radiation therapy.11 Progressive episodes of gagging and dysphagia continued in the dog of the present report, and further treatment was declined. Survival time was limited to 6 weeks following referral to the specialty center.

Owing to the high morbidity and mortality rates associated with surgical excision, there is great value in minimally invasive testing for this tumor type.8 In the dog of the present report, spinal or junctional neuromuscular causes of ataxia were not definitively ruled out after advanced spinal imaging and anti-acetylcholine receptor antibody testing. However, multimodality imaging in combination with a minimally invasive collection of samples from the cardiac-based neoplasm was integral in yielding the definitive diagnosis. Limitations of this report include lack of necropsy and the potential for inaccurate cytologic diagnosis.2 For the dog of the present report, a minimally invasive approach for CT-guided fine-needle aspiration of the cardiac-based neoplasm was used with no apparent associated complications. Future work is needed to investigate the sensitivity and specificity of this test procedure and incidence of complications in a larger number of cases. In addition to thymoma with myasthenia gravis, cardiac-based neoplasia should be considered as a differential diagnosis in dogs with radiographically detected cranial mediastinal mass lesions and clinical signs of ataxia, paraparesis, gagging, and dysphagia.

Footnotes

a.

Dexdomitor, Orion Corp, Espoo, Finland.

b.

Torbugesic, Fort Dodge Animal Health, Overland Park, Kans.

c.

Toshiba Aquilion 4-slice CT scanner, Toshiba Medical Systems Corp, Tochigi, Japan.

d.

Optiray 320 (ioversol injection 68%), Liebel-Flarsheim Co, Cincinnati, Ohio.

References

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