Thyroid carcinoma

From Dog
Thoracic radiographs of a dog with ectopic thyroid carcinoma[1]
Alopecia in the ventral region of the neck of a beagle 3 months after completion of radiation therapy for a thyroid carcinoma[2]
Numerous neoplastic cells present within a blood vessel bordering a canine thyroid carcinoma[3]

Thyroid carcinomas are relatively common malignant thyroid gland neoplasms of dogs, constituting approximately 90% of thyroid tumors[4].

The cause of these tumors is unknown, although they are common in older dogs, suggesting a role of environmental toxins (such as acrylamide[5] found in paper, dyes and fabrics) and dietary agents in the pathogenesis of this disease.

Predisposed breeds include the Golden Retriever, Beagle, Boxer and Siberian Husky[6]. A familial autosomal-recessive medullary thyroid carcinoma characterized by multiple endocrine neoplasia including hyperadrenocorticism, hypothyroidism and chronic dermatitis has been described in the Alaskan Malamute[7].

Variants of thyroid carcinoma include:

These tumors are locally aggressive but metastases, though rare, do occur, with invasion of adjacent tissues, such as the trachea, larynx, esophagus and jugular vein[10]. Laryngeal paralysis and megaesophagus associated with a thyroid carcinoma have been reported[11]. Other more distant predilection sites include the lungs, regional lymph nodes and skull, including the pituitary gland[12]. Ectopic thyroid adenoma and carcinoma have also been diagnosed in thoracic locations such as the right atrium, periaortic area, cardiac cavity, aortic valve and heart base[13].

Affected dogs clinically present with a cranial cervical mass and subscapular lymphadenopathy[14]. These tumors usually present as discrete, bilateral growths in the ventral region of the neck; they may be minimally invasive and freely moveable, but more commonly they invade into adjacent structures and are therefore fixed in place[15]. The tumor may be present in both lobes in up to 60% of dogs with thyroid carcinoma.

Ectopic thyroid carcinoma of the heart may present as echocardiographically-evident atrial fibrillations, right ventricular outflow tract obstruction[16], pericardial effusion and fulminating congestive heart failure[17].

Paraneoplastic hyperadrenocorticism[18] and hypertension[19] has also been noted in dogs with this condition, which spontaneously resolves following treatment.

Thyroid carcinomas usually have an altered capacity to synthesize thyroid hormones and although some dogs may be euthyroid, other may have hyperthyroidism or hypothyroidism, characterized by demonstrable hypocalcemia or hypercalcemia and changes in T4 and thyroglobulin levels[20]. Determination of total thyroxine (T4) and thyroid-stimulating hormone (TSH) levels is indicated to determine the patient’s thyroid hormone status.

Clinical hyperthyroidism in dogs with thyroid carcinomas is rare, but clinical signs may include polyuria, polydipsia, weight loss, increased appetite, muscle atrophy and nervousness. Blood analyses in these dogs usually reveals markedly elevated thyroxine, alanine aminotransferase and alkaline phosphatase. Urinalysis may show hyposthenuria and proteinuria associated with concurrent hyperthyroid-related glomerulopathy[3].

Diagnosis is usually based on ultrasonography of the thyroid gland[21], percutaneous biopsies and histological analysis of sampled tissue. The cervical, retropharyngeal, mandibular, and superficial cervical (prescapular) lymph nodes should be assessed by using palpation and ultrasonography or cross-sectional imaging.

Cytologic examination of fine needle aspirates may help rule out other tumors such as mast cell tumor, lymphoma or metastasis from a malignant oral tumor, such as tonsillar squamous cell carcinoma[2].

Histologically, thyroid carcinosarcoma, which comprising varying amounts of mesenchymal components can be difficult to differentiate from anaplastic thyroid carcinoma[22] and diagnostic interpretations of biopsies should be made cautiously.

Immunohistochemistry of follicular carcinomas are usually positive for osteopontin[23], thyroglobulin, cytokeratin, vimentin and thyroid transcription factor-1[24][25].

Staging a dog with a thyroid tumor involves determining the anatomical extent of disease; it includes assessment of the primary tumor, regional lymph nodes and presence or absence of distant metastasis[26].

A differential diagnosis would include thyroid adenoma[27], thyroid fibrosarcoma, thyroid squamous cell carcinoma[28], carotid body tumor, parathyroid carcinoma and paraesophageal abscess[29].

Treatment usually requires thyroidectomy and/or parathyroidectomy and is usually curative. Adjuvant radiation therapy and chemotherapy with chlorambucil[30], doxorubicin or carboplatin have significantly improved survival rates in treated patients. External beam radiation therapy has produced more consistent results in affording local tumor control when surgery is not possible[31].

Post-thyroidectomy complications included hemorrhage and laryngeal nerve trauma, but without serious consequences[32].

Experimental use of radioactive iodine (I131) has shown efficacy in some studies with non-resectable thyroid carcinomas[33].

Metastatic thyroid carcinomas may respond to boron neutron capture therapy[34] or immunotherapy with drugs such as toceranib[35][36] or ganetespib[37].


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