History
A 9-year-old 15.1-kg castrated male Beagle dog was evaluated because of a 1-month history of cervical pain and progressive tetraparesis that was initially responsive to nonsteroidal anti-inflammatory therapy.
Clinical and Clinicopathologic Findings
Physical examination confirmed cervical pain and ambulatory tetraparesis. Neurologic examination revealed abnormalities suggestive of a C1-5 myelopathy. Serum chemistry revealed hypercalcemia (ionized Ca2+, 1.64 mmol/L; reference interval [RI], 1.17 to 1.43 mmol/L), mild hyponatremia (142 mmol/L; RI, 143 to 150 mmol/L), mild hypomagnesemia (0.69 mmol/L; RI, 0.74 to 0.99 mmol/L), and increased ALP (202 U/L; RI, 13 to 102 U/L). The CBC was within normal limits. Thoracic radiographs revealed a lobulated cranial mediastinal soft tissue mass with deviation of the trachea, cardiac silhouette, and cranial lung lobes, along with a 2.4-cm-diameter soft tissue nodule in the right caudal lung lobe. Ultrasound-guided fine-needle aspirates of the cranial mediastinal mass were performed (Figure 1).
Photomicrograph of a fine-needle aspirate from a cranial mediastinal mass in a Beagle dog that was evaluated for a 1-month history of cervical pain and progressive tetraparesis. The population predominantly consists of small mature lymphocytes, with increased intermediate and large lymphocytes. Few variably granulated mast cells and vacuolated macrophages are mixed with the lymphocytic population. Bar = 10 µm.
Citation: Journal of the American Veterinary Medical Association 262, 2; 10.2460/javma.23.05.0270
The dog was discharged under medical management with plans for cervical MRI. One week after initial presentation, the dog was reevaluated because of rapidly progressive tetraplegia. Cervical MRI revealed an aggressive lesion that partially effaced the C5 vertebral body, occluded the vertebral canal, and compressed the spinal cord. The left axillary lymph node was enlarged. Euthanasia was elected because of the poor prognosis. The body was submitted to necropsy.
Gross and Histopathologic Findings
Grossly, a 11.4 X 10.5 X 7-cm gray to white, firm, multilobulated mass effaced the thymus and filled the thoracic cavity from the level of the thoracic inlet to the heart (Figure 2). The mass was adhered to the lungs, heart, aorta, and pulmonary artery. A 2 X 2 X 2-cm gray to white, firm, well-circumscribed nodule expanded the right caudal lung lobe. There were four 1- to 3-cm-diameter white, firm, well-circumscribed nodules in the quadrate lobe of the liver. A 1.6 X 1.9 X 2.2-cm soft, red and tan mottled mass effaced the C5 vertebral body and intervertebral disk and invaded the ventral spinal canal.
Photograph of the thoracic cavity of the dog in Figure 1. A—A gray to white, firm, multilobulated mediastinal mass effaces the thymus and invades the surrounding tissues. B—The C5 vertebral body is effaced by a soft, poorly demarcated white mass.
Citation: Journal of the American Veterinary Medical Association 262, 2; 10.2460/javma.23.05.0270
Histologically (Figure 3), the mediastinal mass was composed of unencapsulated, densely cellular lobules separated by thick bands of collagen and surrounded by adipose and fibrovascular tissue. Neoplastic lobules were composed of 2 cell populations that consisted of cords and nests of pleomorphic, polygonal to spindle cells separated by sheets of small lymphocytes. The pleomorphic cell population had a scant to moderate amount of eosinophilic, wispy cytoplasm with variably distinct cell borders. Nuclei were round to irregularly elongated and had finely stippled chromatin and prominent, single, basophilic nucleoli. There were 3 mitoses in 2.37 mm2 (equivalent to 10 FN22/40X fields). There were moderate anisocytosis and anisokaryosis. Neoplastic cells and lymphocytes invaded the surrounding adipose tissue. The pulmonary, hepatic, and vertebral nodules consisted of similar neoplastic cells that compressed and displaced the adjacent parenchyma and soft tissues. In the vertebral lesion, neoplastic cells invaded the ventral aspect of the vertebral body, the transverse process was fragmented, and the bone was replaced by neoplastic cells surrounded by fibrosis. The vertebral canal contained abundant fibrin, hemorrhage, and necrotic cellular debris. The skeletal muscle fibers immediately surrounding the vertebral mass were atrophied and necrotic. There were no pathologic changes in the spinal cord.
Photomicrographs of the mediastinal mass, vertebral mass, and metastatic lung masses with immunohistochemistry. A—The mediastinal mass was composed of multiple infiltrative lobules composed of 2 cell populations separated by thick bands of collagen, surrounded by adipose and connective tissue. The neoplastic population consisted of cords and nests of pleomorphic, polygonal to spindle cells with variably distinct cell borders and scant to moderate eosinophilic cytoplasm separated by sheets of small lymphocytes. Nuclei were round to irregularly elongated with finely stippled chromatin and prominent, single, basophilic nucleoli. H&E stain; bar = 50 µm. B—Neoplastic cells invaded the ventral aspect of the vertebral body, the transverse process was fragmented, and the bone was replaced by neoplastic cells surrounded by fibrosis (asterisk). The vertebral canal contained abundant fibrin, hemorrhage, and necrotic cellular debris (arrow), and neoplastic cells invaded the skeletal muscle. H&E stain; bar = 500 µm. C—Thymic mass. Neoplastic polygonal cells in the thymus had strong membranous and occasional cytoplasmic immunolabeling for pancytokeratin AE1/AE3. Bar = 50 µm. D—Thymic mass. Greater than 95% of the lymphocytes in the thymic and lung masses had positive immunolabeling for CD3. Bar = 50 µm. E—Thymic mass. There were rare CD21+ lymphocytes throughout the thymic and lung masses. Bar = 50 µm. F—Lung mass. Neoplastic polygonal cells in a metastatic lung mass (asterisk) had immunolabeling for pancytokeratin AE1/AE3 identical to the thymic mass. The mass compressed the surrounding alveoli. Bar = 100 µm.
Citation: Journal of the American Veterinary Medical Association 262, 2; 10.2460/javma.23.05.0270
Neoplastic polygonal cells in the thymus and lung had strong cytoplasmic immunolabeling for pancytokeratin AE1/AE3. Greater than 95% of the lymphocytes in the thymic and lung masses had positive membranous immunolabeling for CD3 (consistent with mature T-cells). There were rare CD21+ lymphocytes throughout. All positive and negative external and internal controls reacted appropriately.
Morphologic Diagnosis and Case Summary
Thymoma (type B3) with hepatic, pulmonary, and vertebral metastasis.
Comments
Differential diagnoses for a cranial mediastinal mass include thymoma, lymphoma, chemodectoma, ectopic thyroid carcinoma, lung lobe torsion, abscess, or granuloma.1 A diagnosis of thymoma (type B3) was made on the basis of the clinical, pathologic, and immunohistochemical characteristics of the neoplasm. Thymomas are uncommon, typically benign neoplasms that affect middle-aged to older dogs. Malignancy in this case was confirmed by the presence of invasion into surrounding tissues and metastases. Local invasion can be assessed clinically by CT, which can provide more accurate preoperative information for surgical planning and disease extent than traditional radiographs.1 A definitive diagnosis requires cytology and/or histology. Immunohistochemistry for pancytokeratin can help differentiate lymphocyte-rich thymomas from thymic lymphoma by highlighting the epithelial component of the thymomas. Immunohistochemistry for CD3, CD79a, PAX-5, CD18, and MAC387 can be useful to rule out other round cell neoplasms such as lymphoma or histiocytic sarcoma.2 Moderate to marked cellular pleomorphism and metastasis are associated with shorter survival time; however, surgical treatment can still prolong survival time.2
Although the large mediastinal mass was found incidentally by screening thoracic radiographs, dogs with thymoma or other cranial mediastinal masses may present with dyspnea, regurgitation, polydipsia/polyuria, lethargy, and/or weight loss mediated by local effects or paraneoplastic syndrome.3 Reported paraneoplastic syndromes associated with thymoma include hypercalcemia (which was observed in this case), as well as myasthenia gravis and megaesophagus, nonthymic malignant tumors, polymyositis, myocarditis, and lymphocytosis.1,2 Another possibility for the hypercalcemia in this case was vertebral body osteolysis, as parathyroid hormone and parathyroid hormone–related protein testing, which would have differentiated paraneoplastic and physiologic hypercalcemia, was not performed.
Distant metastasis of thymoma is rare, and there are only 2 reports of bone metastasis in dogs to our knowledge.4,5
This case highlights the importance of survey radiographs and laboratory testing, which suggested a potential paraneoplastic syndrome and identified the masses that were otherwise undetected, as the dog had no associated clinical signs. Histopathology with immunohistochemistry was further able to demonstrate that the 3 masses were related and represented metastasis of the thymoma.
Acknowledgments
The authors would like to thank the histology laboratory and clinical pathology technicians as well as hospital technicians, students, and staff who were involved in the case.
Disclosures
The authors have nothing to disclose. No AI-assisted technologies were used in the generation of this manuscript.
Funding
The authors have nothing to disclose.
References
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Day MJ. Review of thymic pathology in 30 cats and 36 dogs. J Small Anim Pract. 1997;38(9):393-403. doi:10.1111/j.1748-5827.1997.tb03492.x
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Mitcham SA, Clark EG, Mills JH. Malignant thymoma with widespread metastases in a dog: case report and brief literature review. Can Vet J. 1984;25(7):280-282.
