History
An 8.5-year-old spayed female Siberian Husky weighing 28.0 kg (61.6 lb) was evaluated because of a sudden onset of dyspnea. The dog was current with regard to routine vaccinations and monthly heartworm prevention and had no prior underlying medical conditions.
Clinical and Gross Findings
On physical examination, the dog was quiet, alert, and responsive; dyspneic with clear lung sounds bilaterally; and tachycardic (160 beats/min) with muffled heart sounds and weak femoral pulses. No arrhythmias or murmurs were auscultated, and the other physical examination findings were considered normal. Pleural effusion was detected during a thoracic ultrasonographic examination; 1.75 L of blood-tinged lactescent fluid was removed via thoracocentesis and submitted for analysis. Assessment of a sample of the fluid revealed a nucleated cell concentration of 8,100 cells/μL, erythrocyte count of 30,000 erythrocytes/μL, and protein concentration of 4.2 g/dL; the fluid still appeared lactescent after centrifugation. On cytologic examination, the nucleated cells included non-degenerate neutrophils (53%), macrophages (27%), and small lymphocytes (20%) and no infectious agents or neoplastic cells were seen. These findings were considered consistent with a chylous lymphorrhagic effusion, with the high proportion of neutrophils likely reflecting a chronic process. Results of a CBC and serum biochemical analysis were unremarkable, with the exception of mild thrombocytopenia (156 × 103 platelets/μL; reference interval, 220 × 103 platelets/μL to 600 × 103 platelets/μL), which was considered most consistent with some degree of peripheral platelet consumption.
Thoracic radiography (3 views) was performed. On those images, the apex of the left cranial lung lobe appeared caudally displaced, and pleural effusion was evident. In addition, echocardiography revealed a small amount of pericardial effusion, although cardiac structure and function appeared normal. Abdominal ultrasonography revealed a 1.5-cm-diameter nodule in the right adrenal gland. The dog was hospitalized, received supportive care, and was managed with intermittent thoracocentesis prior to undergoing advanced diagnostic imaging. The dog was anesthetized, and thoracic CT was performed. During that CT examination, a cranial mediastinal mass with invasion into the cranial vena cava was identified and thrombi were detected within the left and right jugular veins and caudal lobar pulmonary arteries. Samples of the mass were obtained via CT-guided fine-needle aspiration and submitted for cytologic analysis. Given that the mass did not appear surgically resectable, the owners elected euthanasia.
At necropsy, the thoracic cavity and pericardium contained 100 and 150 mL of pink, cloudy fluid, respectively. A 5 × 5 × 5-cm dark red soft spherical mass was present in the craniodorsal mediastinum. On cut surface, the mass was mottled white to tan and vascular involvement was evident (Figure 1). The thyroid gland appeared normal on gross examination. The right adrenal gland was moderately enlarged, measuring 1.5 × 2 × 2.5 cm; on cut surface, there was complete loss of corticomedullary distinction and the architecture of the normal adrenal gland was replaced by a solid tan mass.
Photographs of the mediastinum (dorsal view) and the right adrenal gland (lateral view; inset) from an 8.5-year-old spayed female Siberian Husky evaluated because of a sudden onset of dyspnea. Notice the spherical dark red mass, with mottled white to tan areas on cut surface in the cranial mediastinum and a portion of this neoplasm invading the cranial vena cava. Inset—A solid tan mass has replaced the architecture of the right adrenal gland.
Citation: Journal of the American Veterinary Medical Association 246, 3; 10.2460/javma.246.3.303
Formulate differential diagnoses from the history, clinical findings, and Figure 1—then turn the page →
Cytologic and Histopathologic Findings
Microscopic examination of the CT-guided fine-needle aspirate samples from the dog's mediastinal mass contained moderate numbers of well-preserved nucleated cells and large amounts of blood. Nucleated cells formed clusters with indistinct cell borders (Figure 2). The cells had round to oval nuclei (approx 7 to 10 μm in diameter) with clumped to smooth chromatin, no visible nucleoli, and moderate amounts of lightly basophilic cytoplasm that occasionally contained low to moderate amounts of dark blue pigment granules interpreted as likely tyrosine granules. The cytologic interpretation was neuroendocrine neoplasm of thyroid origin.
Photomicrograph of a CT-guided fine-needle aspirate specimen obtained from the mediastinal mass in the dog in Figure 1. Notice large clusters of epithelial cells with clumped chromatin, low degree of anisokaryosis, and indistinct cell borders. The cells have moderate amounts of lightly basophilic cytoplasm that in some clusters also contains dark blue pigment granules (inset). Wright-Giemsa stain; bar (also applies to inset) = 10 μm.
Citation: Journal of the American Veterinary Medical Association 246, 3; 10.2460/javma.246.3.303
Samples of the mediastinal mass, thyroid glands, and adrenal gland mass were collected at the time of necropsy, routinely processed, and stained with H&E stain for histologic examination. Microscopically, the mediastinal mass was a nonencapsulated multilobulated infiltrative moderately cellular neoplasm (Figure 3). Neoplastic cells were cuboidal to low columnar epithelial cells arranged in papillary projections and in acini that variably contained eosinophilic fluid, separated by fibrous connective tissue with mineralization. Neoplastic cells had round to oval nuclei, 1 to 2 small basophilic nucleoli, and abundant eosinophilic cytoplasm with distinct cell borders. Anisocytosis and anisokaryosis were moderate, and mitotic index was 2 to 3 mitotic figures/10 hpf. Multifocally, aggregates of neoplastic cells were found within blood vessels. The stroma also contained multifocal aggregates of lymphocytes and plasma cells as well as hemorrhage and necrotic foci. On sections stained with indirect immunohistochemical stains for thyroglobulin and hematoxylin, cells had intracytoplasmic immunoreactivity for thyroglobulin. Histologic lesions were not found within the thyroid gland tissues.
Photomicrographs of sections of the mediastinal mass from the dog in Figure 1. A—Notice cuboidal to low columnar neoplastic epithelial cells (asterisk) invading within the wall of a venule (V). H&E stain; bar = 20 μm. B—The cells comprising the neoplastic follicles express intracytoplasmic thyroglobulin, which is also contained within the follicular lumina. Indirect immunohistochemical stain for thyroglobulin and hematoxylin; bar = 20 μm.
Citation: Journal of the American Veterinary Medical Association 246, 3; 10.2460/javma.246.3.303
The adrenal mass was a nonencapsulated well-demarcated moderately cellular neoplasm. Neoplastic cells were polygonal, arranged in packets, and supported by a scant fibrovascular stroma. The cells had round to oval nuclei with stippled chromatin, small eosinophilic nucleoli, and abundant amounts of eosinophilic granular cytoplasm with distinct cell borders. Anisocytosis and anisokaryosis were moderate, and the mitotic index was 1 to 2 mitotic figures/10 hpf. The stroma also contained moderate numbers of lymphocytes and macrophages, few megakaryocytes, and occasional areas of hemorrhage.
Morphologic Diagnosis and Case Summary
Morphologic diagnosis and case summary: mediastinal thyroid follicular carcinoma with vascular invasion, moderate pleural and pericardial effusion (presumptive chylous effusions), and adrenal cortical carcinoma of the right adrenal gland in a dog.
Comments
Development of ectopic thyroid tissue is not uncommon among mammalian species. The tissue develops as a result of aberrant migration of the medial primordium during embryogenesis, which may result in ectopic tissue development along midline anywhere from the base of the tongue to the mediastinum and even within the heart.1 The physiologic and pathological behavior of ectopic tissue is believed to be identical to that of normal thyroid glands, and normal ectopic tissue in dogs as well as ectopic thyroid adenomas and carcinomas have all been described.2–4 Regardless of the malignant potential of the ectopic tissue, its location may cause obstruction of nearby normal structures, as occurred with lymphatic vessels in the case described in this report, contributing to the dog's pericardial and pleural effusion.
The pleural effusion in the dog of this report was classified as lymphorrhagic and chylous because it had a high proportion of small lymphocytes and lactescent appearance, although triglyceride concentration was not measured. Long-standing lymphorrhagic or chylous effusion may incite inflammation, and as such, the high numbers of neutrophils were thought to most likely reflect chronicity5; however, neutrophilic inflammation secondary to neoplasia could not be ruled out.
Although well described in the veterinary medical literature, ectopic thyroid carcinomas remain a rare cause of mediastinal disease, with lymphoma and thymoma being the most common mediastinal masses in dogs.2 In a small retrospective case series2 of 9 dogs with histologically confirmed mediastinal carcinomas, thyroid carcinomas represented the majority (5/9); among those 5 tumors, there were 4 follicular carcinomas and 1 medullary carcinoma.
Cytologically, thyroid tissue has a neuroendocrine appearance, containing epithelial cells with indistinct cell borders. To differentiate thyroid tissue from other neuroendocrine tissues, distinguishing features such as blue-black cytoplasmic granules considered to represent tyrosine or amorphous eosinophilic extracellular colloid material must be identified.6 In the absence of such findings, a cytologic diagnosis of neuroendocrine neoplasm is most appropriate, considering that nonthyroidal neuroendocrine carcinomas in the mediastinum of dogs have also been reported.2 As for other neuroendocrine tissues, cytologic criteria of malignancy are often lacking in thyroid carcinomas and concern for the malignant potential of the cell population must be based on clinical judgment, which combines cytologic appearance with the known biological behavior of the aspirated tissue in a given species.6
Histologically, thyroid-related neoplasms can be further divided on the basis of cell of origin. Follicular tumors are derived from follicular epithelium and may contain cells with a follicular, compact, or mixed phenotype. Medullary or C-cell tumors are derived from parafollicular cells and have a compact cellular appearance.7 If cellular morphology is not helpful in distinguishing between the 2 entities, immunohistochemical stains can be used. Follicular neoplasms are expected to be immunoreactive for thyroglobulin, whereas medullary tumors are immunoreactive for calcitonin and the neuroendocrine marker chromogranin.2,7 Nonthyroidal neuroendocrine tumors may also develop in the mediastinum, and although these tumors are also immunoreactive for chromogranin, they should not be immunoreactive for calcitonin.2
Although thyroid tumors account for only 1% to 2% of neoplasms in dogs, they remain the most common endocrine neoplasm in this species.7 It is well-known that Golden Retrievers and Beagles have an increased risk for thyroid neoplasms; however, a recent 10-year multi-institutional retrospective study8 also identified Siberian Huskies as having an increased odds of thyroid tumor development. Most thyroid tumors are malignant (approx 90%), and the majority (75%) are follicular carcinomas.2,7,8 Metastasis rates vary from 18% to 34% at the time of initial diagnosis to as high as 60% to 80% at the time of necropsy.2,7,8 In the dog of this report, vascular invasion with thrombosis was evident prior to death, as detected by CT, and on gross and histologic postmortem examination, thereby providing evidence for the malignant potential of this tumor and a plausible explanation for the dog's mild thrombocytopenia.
An additional interesting finding in the dog of the present report was the presence of a concurrent adrenal gland cortical carcinoma. In a recent prospective study9 of 1,772 dogs with a diagnosed neoplasm, 53 (3%) had at least 1 distinct concurrent primary tumor. Dogs with thyroid tumors were significantly overrepresented, with 12 of 37 (32%) dogs with thyroid tumors having at least 1 additional distinct primary tumor.9 In that case series, 1 dog had a thyroid carcinoma and adrenocortical carcinoma, a combination of distinct endocrine neoplasms in dogs that has also been reported elsewhere in the veterinary medical literature.9,10
In human medicine, multiple endocrine neoplasia is a rare hereditary complex disorder characterized by the development of > 1 distinct endocrine neoplasm within an individual, and many variations of the disease are described, depending on the endocrine tissues affected.9,10 Although development of multiple discrete endocrine neoplasms in veterinary species is well described, no conserved genetic basis for tumor formation has yet been identified.9,10
References
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10. Proverbio D, Spada A, Perego R, et al. Potential variant of multiple endocrine neoplasia in a dog. J Am Anim Hosp Assoc 2012; 48: 132–138.
