Thyroid carcinoma

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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].

References

  1. Kang MH et al (2012) Ectopic thyroid carcinoma infiltrating the right atrium of the heart in a dog. Can Vet J 53(2):177-181
  2. 2.0 2.1 Mayer MN & MacDonald VS (2007) External beam radiation therapy for thyroid cancer in the dog. Can Vet J 48(7):761-763
  3. 3.0 3.1 Bezzola P (2002) Thyroid carcinoma and hyperthyroidism in a dog. Can Vet J 43(2):125-236
  4. Capen CC (2002) Tumors of the endocrine glands. In: Meuten DJ, ed. Tumors in Domestic Animals. 4th ed. Ames: Iowa State Press. pp:607–696
  5. Chico Galdo V et al (2006) Acrylamide, an in vivo thyroid carcinogenic agent, induces DNA damage in rat thyroid cell lines and primary cultures. Mol Cell Endocrinol 257-258:6-14
  6. Wucherer KL & Wilke V (2010) Thyroid cancer in dogs: an update based on 638 cases (1995-2005). J Am Anim Hosp Assoc 46(4):249-254
  7. Lee JJ et al (2006) A dog pedigree with familial medullary thyroid cancer. Int J Oncol 29(5):1173-1182
  8. Bertazzolo W et al (2003) Paratracheal cervical mass in a dog. Vet Clin Pathol 32(4):209-212
  9. Grubor B & Haynes JS (2005) Thyroid carcinosarcoma in a dog. Vet Pathol 42(1):84-87
  10. Klein MK et al (1995) Treatment of thyroid carcinoma in dogs by surgical resection alone: 20 cases (1981–1989). J Am Vet Med Assoc 206:1007–1009
  11. Harari J et al (1986) Clinical and pathological features of thyroid tumors in 26 dogs. J Am Vet Med Assoc 188:1160–1163
  12. Tamura S et al (2007) Multiple metastases of thyroid cancer in the cranium and pituitary gland in two dogs. J Small Anim Pract 48(4):237-239
  13. Roth DR & Perentes E (2012) Ectopic thyroid tissue in the periaortic area, cardiac cavity and aortic valve in a Beagle dog - a case report. Exp Toxicol Pathol 64(3):243-245
  14. Gelberg HB & Valentine BA (2011) Lymphadenopathy associated with a thyroid carcinoma in a dog. Vet Pathol 48(2):530-534
  15. Bailey DB & Page RL (2007) Tumors of the endocrine system. In: Withrow SJ, Vail DM, eds. Withrow & MacEwen’s Small Animal Clinical Oncology. 4th ed. St. Louis: Saunders Elsevier. pp:583–609
  16. Bracha S et al (2009) Ectopic thyroid carcinoma causing right ventricular outflow tract obstruction in a dog. J Am Anim Hosp Assoc 45(3):138-141
  17. MacDonald KA et al (2009) Echocardiographic and clinicopathologic characterization of pericardial effusion in dogs: 107 cases (1985-2006). J Am Vet Med Assoc 235(12):1456-1461
  18. Stassen QE et al (2007) Hyperthyroidism due to an intrathoracic tumour in a dog with test results suggesting hyperadrenocorticism. J Small Anim Pract 48(5):283-287
  19. Simpson AC & McCown JL (2009) Systemic hypertension in a dog with a functional thyroid gland adenocarcinoma. J Am Vet Med Assoc 235(12):1474-1479
  20. Pessina P et al (2012) Expression of thyroid-specific transcription factors in thyroid carcinoma, contralateral thyroid lobe and healthy thyroid gland in dogs. Res Vet Sci 93(1):108-113
  21. Liles SR et al (2010) Ultrasonography of histologically normal parathyroid glands and thyroid lobules in normocalcemic dogs. Vet Radiol Ultrasound 51(4)':447-452
  22. Fernandez NJ et al (2008) What is your diagnosis? Ventral neck mass in a dog. Vet Clin Pathol 37(4):447-451
  23. Metivier KS et al (2012) Gene expression profiling demonstrates differential expression of osteopontin in follicular thyroid carcinomas compared to normal thyroid tissue in dogs. Vet Comp Oncol Aug 25
  24. Bettini G et al (2009) Thyroid transcription factor-1 immunohistochemistry: diagnostic tool and malignancy marker in canine malignant lung tumours. Vet Comp Oncol 7(1):28-37
  25. Ramos-Vara JA et al (2002) Immunohistochemical detection of thyroid transcription factor-1, thyroglobulin, and calcitonin in canine normal, hyperplastic, and neoplastic thyroid gland. Vet Pathol 39(4):480-487
  26. Owen LN (1980) TNM Classification of Tumours in Domestic Animals. 1st ed. Geneva: World Health Organization. pp:46–47
  27. Di Palma S et al (2010) Intracardiac ectopic thyroid adenoma in a dog. Vet Rec 167(18):709-710
  28. Aupperle H et al (2003) Tumors of the thyroid gland in dogs - a local characteristic in the area of Leipzig. Dtsch Tierarztl Wochenschr 110(4):154-157
  29. Taeymans O et al (2012) Comparison between clinical, ultrasound, CT, MRI and pathology findings in dogs presented for suspected thyroid carcinoma. Vet Radiol Ultrasound Sep 18
  30. Leach TN et al (2012) Prospective trial of metronomic chlorambucil chemotherapy in dogs with naturally occurring cancer. Vet Comp Oncol '10(2):102-112
  31. Barber LG (2007) Thyroid tumors in dogs and cats. Vet Clin North Am Small Anim Pract 37(4):755-773
  32. Tuohy JL et al (2012) Outcome following simultaneous bilateral thyroid lobectomy for treatment of thyroid gland carcinoma in dogs: 15 cases (1994-2010). J Am Vet Med Assoc 241(1):95-103
  33. Turrel JM et al (2006) Sodium iodide I 131 treatment of dogs with nonresectable thyroid tumors: 39 cases (1990-2003). J Am Vet Med Assoc 229(4):542-548
  34. Pisarev MA et al (2006) Boron neutron capture therapy applied to undifferentiated thyroid carcinoma. Medicina (B Aires) 66(6):569-573
  35. Urie BK et al (2012) Evaluation of expression and function of vascular endothelial growth factor receptor 2, platelet derived growth factor receptors-alpha and -beta, KIT, and RET in canine apocrine gland anal sac adenocarcinoma and thyroid carcinoma. BMC Vet Res 8(1):67
  36. London C et al (2012) Preliminary evidence for biologic activity of toceranib phosphate (Palladia(®)) in solid tumours. Vet Comp Oncol 10(3):194-205
  37. London CA et al (2011) Phase I evaluation of STA-1474, a prodrug of the novel HSP90 inhibitor ganetespib, in dogs with spontaneous cancer. PLoS One 6(11):e27018
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