Canine thyroid carcinomas: A review with emphasis on comparing the compact subtype of follicular thyroid carcinomas and medullary thyroid carcinomas.

Canine thyroid carcinomas are relatively common malignant endocrine neoplasms in dogs derived from either thyroid follicular cells (forming follicular thyroid carcinomas) or medullary cells (parafollicular, C-cells; forming medullary thyroid carcinomas). Older and recent clinical studies often fail to discriminate between compact cellular (solid) follicular thyroid carcinomas and medullary thyroid carcinomas, which may skew conclusions. The compact subtype of follicular thyroid carcinomas appears to be the least differentiated subtype of follicular thyroid carcinomas and needs to be differentiated from medullary thyroid carcinomas. This review includes information on the signalment, presentation, etiopathogenesis, classification, histologic and immunohistochemical diagnosis, clinical management, and biochemical and genetic derangements of canine follicular and medullary carcinomas, and their correlates with human medicine.

Mixed medullary and follicular cell thyroid carcinoma in a dog.

A 12-y-old, castrated male Weimaraner dog was presented for a wellness examination. A 7-cm, firm mass was palpated on the left, ventral, mid-lateral neck. The neck mass was removed surgically and submitted for histopathology. A thyroid carcinoma was diagnosed based on microscopic examination. Immunohistochemistry for chromogranin-A, calcitonin, and thyroglobulin identified dual immunoreactivity of the latter two, and a final diagnosis was of a well-differentiated, compact, mixed medullary and follicular cell thyroid carcinoma. These neoplasms are rare in humans and have not been reported in dogs, to our knowledge.

Immunohistochemical expression of potential therapeutic targets in canine thyroid carcinoma.

BACKGROUND: Thyroid carcinoma is a common endocrine tumor in the dog. Local invasive growth frequently precludes surgical excision and, in up to 38% of dogs, the tumor has already metastasized by the time of diagnosis. Therefore, it is important to investigate new treatment modalities that may be useful for the large number of dogs with inoperable tumors or metastatic disease. HYPOTHESIS/OBJECTIVES: To investigate the immunohistochemical expression of potential therapeutic targets in canine thyroid tumors. ANIMALS: 74 dogs with thyroid neoplasia. METHODS: Immunohistochemistry was performed for thyroglobulin, calcitonin, vascular endothelial growth factor (VEGF), p53, cycloxygenase-2 (cox-2), and P-glycoprotein (P-gp). RESULTS: Fifty-four (73%) tumors were classified as follicular cell thyroid carcinomas (FTCs) and 20 (27%) as medullary thyroid carcinomas (MTCs). Eighty percent of FTCs and all MTCs had a high percentage (76-100%) of neoplastic cells immunopositive for VEGF. Thirteen percent of FTCs and 50% of MTCs expressed cox-2. Seven percent of FTCs and 70% of MTCs expressed P-gp. No tumor was immunopositive for p53 expression. Expression of VEGF (P = .034), cox-2 (P = .013), and P-gp (P < .001) was significantly higher in MTCs compared to FTCs. CONCLUSIONS AND CLINICAL IMPORTANCE: VEGF is a potential therapeutic target in both FTC and MTC in dogs. Cox-2 and P-gp may be useful molecular targets in canine MTC.

Cranial mediastinal carcinomas in nine dogs.

Nine dogs were diagnosed with cranial mediastinal carcinomas. Based on histological and immunohistochemical analysis, four dogs were diagnosed with ectopic follicular cell thyroid carcinomas, one dog with ectopic medullary cell thyroid carcinoma, two dogs with neuroendocrine carcinomas and two dogs with anaplastic carcinomas. Clinical signs and physical examination findings were associated with a space-occupying mass, although one dog was diagnosed with functional hyperthyroidism. Surgical resection was attempted in eight dogs. The cranial mediastinal mass was invasive either into the heart or into the cranial vena cava in three dogs. Resection was complete in six dogs and unresectable in two dogs. All dogs survived surgery, but four dogs developed pulmonary thromboembolism and two dogs died of respiratory complications postoperatively. Adjunctive therapies included pre-operative radiation therapy (n=1) and postoperative chemotherapy (n=3). Three dogs had metastasis at the time of diagnosis, but none developed metastasis following surgery. The overall median survival time was 243 days. Local invasion, pleural effusion and metastasis did not have a negative impact on survival time in this small case series.

A dog pedigree with familial medullary thyroid cancer.

Multiple endocrine neoplasia (MEN) is defined as concurrent neoplasia or hyperplasia in more than one endocrine gland. MEN is well known in humans and has also been reported in small animals. We report on a dog family of a mixed breed with Alaskan malamute as a major influence, where three members developed thyroid carcinomas and another dog had clinical signs mimicking the other three but without a confirmed diagnosis. The age of onset of the tumour was between 96-109 months. Clinical, biochemical and immunohistochemical examinations revealed that the affected individuals typically demonstrated symptoms including calcitonin positive thyroid cancer, hypothyroidism and chronic dermatitis. In addition, elevated serum calcium and multinodular adrenocortical hyperplasia were demonstrated in a single member. The diagnosis observed is similar to the familial form of medullary thyroid carcinoma (FMTC) in human. This is the first report of FMTC in dog. Up to 95% of FMTC and MEN2 is known to be caused by activating mutations in the RET gene. The dog Ret gene was analysed as a candidate in this pedigree. The complete dog Ret genomic sequence was predicted in silico. The lack of demonstratable Ret mutation suggests the involvement of alternative predisposing mutation in this pedigree. The unique occurrence of familial MTC makes this potentially an important model in further defining the genetic basis of MTC.

Paratracheal cervical mass in a dog.

A 14-year-old female Welsh Terrier was presented for evaluation of multiple skin masses. Two of them were diagnosed as a follicular (epidermal) cyst and a sebaceous epithelioma by cytology and histopathology. The third mass was located in the subcutis adjacent to the cervical trachea. Clinical findings, thoracic radiography, and laboratory results were otherwise unremarkable. Cytologically, the cervical mass was characterized by the presence of round to polygonal cells with distinct cell borders, mild to moderate anisocytosis, round to oval eccentric nuclei with prominent nucleoli, and a variable amount of finely granular, eosinophilic cytoplasm. Differential diagnoses included endocrine/neuroendocrine tumors such as thyroid adenocarcinoma, medullary thyroid carcinoma, carotid body chemodectoma, and parathyroid carcinoma. The mass was removed surgically and submitted for histopathologic and immunohistochemical examination. Histologically, the mass was composed of rows and nests of densely packed cells separated by thin fibrovascular stroma. Neoplastic cells had moderate to large amounts of pale eosinophilic dusty or finely vacuolated cytoplasm and round to oval nuclei with finely dispersed chromatin and 1 or 2 small nucleoli. On immunohistochemistry, neoplastic cells were positive for chromogranin A, calcitonin, and neuronspecific enolase, and were negative for cytokeratin and thyroglobulin. The final diagnosis was medullary thyroid carcinoma, an uncommon endocrine tumor of dogs that has cytologic and histopathologic features similar to other endocrine and neuroendocrine tumors. Immunohistochemistry or immunocytochemistry should be performed to differentiate medullary thyroid carcinoma from other endocrine/neuroendocrine tumors of dogs.

Unilateral thyroidectomy in 6 horses.

OBJECTIVE: To describe the surgical technique, complications, and outcome of thyroidectomy in 6 horses. STUDY DESIGN: Retrospective study. ANIMALS: Six horses, 10 to 22 years of age, with unilateral, rapidly enlarging thyroid masses. METHODS: Medical records between 1985 and 2000 were reviewed for horses that had unilateral thyroidectomy. Retrieved data included signalment, physical, clinical, and ultrasonographic examination findings, surgical technique, complications, and outcome. A minimum of 6 months follow-up was obtained. RESULTS: Six horses were identified. Three horses had tracheal compression and 2 of these also had exercise intolerance. On ultrasonography (5 horses), the enlarged thyroid ranged from 125 to 990 cm(3), and had either a heterogeneous (1 horse), cystic (2), or homogeneous (2) appearance. En bloc, unilateral thyroidectomy under general anesthesia was performed in all horses. After surgery, 3 horses had ipsilateral laryngeal hemiplegia, but tracheal compression was resolved. Thyroid masses were adenoma (3), C-cell compact carcinoma (1), and adenocarcinoma (1). No tumor recurrence or metastatic disease was reported 6 to 14 months after surgery. CONCLUSIONS: Unilateral thyroidectomy can be successfully performed in horses with large thyroid tumors, but laryngeal hemiplegia can be an important surgical complication. Ultrasonographic examination is useful to define thyroid enlargement and location but is seemingly not useful to characterize tumor type. CLINICAL RELEVANCE: Thyroidectomy is an uncommon surgical procedure and has an attendant risk for recurrent laryngeal nerve damage. Laryngoscopic examination before and after surgery and careful isolation of the recurrent laryngeal nerve during surgery is recommended.

C-cell carcinoma (medullary thyroid carcinoma) associated with multiple endocrine neoplasms in a ferret (Mustela putorius).

A firm, infiltrative mass was found in the thyroid region of an adult castrated male ferret (Mustela putorius) presenting with vague signs of weight loss, minor inappetence, and decreased activity. Efforts to surgically excise the tissue were unsuccessful, and the animal was euthanatized. Gross and histopathologic evaluation revealed multiple endocrine neoplasms, including C-cell carcinoma, adrenocortical adenoma, pheochromocytoma, and endocrine tumor of the pancreas. This is the first descriptive account of a C-cell carcinoma, also known as medullary thyroid carcinoma, in a ferret, although other endocrine neoplasms in this species have been reported with some frequency. These findings mimic features observed in human multiple endocrine neoplasia syndromes.

Thyroid C-cell carcinoma with amyloid in a red fox (Vulpes vulpes schrenchki).

An amyloid-producing medullary thyroid carcinoma (MTC) in a red fox (Vulpes vulpes schrenchki) bred in a zoo was examined using histopathologic and immunohistochemical techniques. The neoplastic cells had an ill-defined cytoplasmic membrane and abundant, finely granular eosinophilic cytoplasm, containing numerous argyrophilic granules. The neoplastic tissues were divided into various sizes by a vascular connective stroma, which was partly fibrovascular with broad areas of hyalinization containing varied amounts of amyloid. Immunohistochemically, neoplastic cells showed reactivity to anti-calcitonin, neuron-specific enolase, somatostatin, and keratin antibodies. However, amyloid in the stroma did not show immunoreactivity to the antibodies used. Histologic and immunohistochemical features of MTC in the present animal were analogous to those of the C-cell carcinoma derived from thyroid C cells (parafollicular cells) reported in humans and dogs.

Cisplatin chemotherapy for treatment of thyroid carcinoma in dogs: 13 cases.

The medical records of 13 dogs (10 spayed females, one intact male, one castrated male, and one dog of unknown gender) with histopathologically diagnosed thyroid carcinoma that were treated with cisplatin chemotherapy were reviewed. The mean age was 10.6 years. Three of the dogs were beagles. One dog had a c-cell medullary carcinoma, while the remaining 12 had follicular thyroid carcinoma. Eight of 13 dogs had tumors greater than 5 cm in diameter. In all 11 tumors for which information was available in the medical record, the masses were attached to underlying tissue. One dog underwent a complete remission, six had partial remissions, three had stable disease, and three had progressive disease. The mean time between initiation of cisplatin chemotherapy and development of progressive disease was 223.7 days (median, 202 days), with a mean survival time of 191.8 days (median, 98 days).

A comparison of medullary thyroid carcinoma and thyroid adenocarcinoma in dogs: a retrospective study of 38 cases.

The medical records of 38 dogs with thyroid neoplasia that were treated by surgical excision of the tumor, or had an incisional biopsy performed as a diagnostic procedure, were reviewed. Of the 38 dogs, 21 (55%) had resectable tumors, whereas 17 (45%) had an incisional biopsy as the tumors were nonresectable. All dogs had an initial diagnosis of thyroid carcinoma. The type of carcinoma was confirmed in 33 dogs by histological and immunohistochemical examination. Twelve dogs (36%) had medullary thyroid carcinoma, and 21 dogs (64%) had thyroid adenocarcinoma. Of the 12 dogs with medullary thyroid carcinoma, 10 (83%) had resectable tumors. Of the 10, three (30%) had at least a 1-year survival. None had radiographic evidence of metastasis at the time of surgery. Of the 21 dogs with thyroid adenocarcinoma, 11 (52%) had resectable tumors. Of the 11 dogs, five (45%) had at least a 1-year survival. Three dogs had radiographic evidence of metastasis at the time of surgery. Of 10 dogs with nonresectable thyroid adenocarcinoma, two dogs (20%) had at least a 1-year survival. In the dogs in this study, medullary thyroid carcinoma was more prevalent than previously reported. Most of the medullary thyroid carcinomas were well circumscribed and resectable. Medullary thyroid carcinoma may possess gross and histological characteristics of a less malignant nature when compared with other thyroid carcinomas.

99mTc-pertechnetate imaging of thyroid tumors in dogs: 29 cases (1980-1992).

Thyroid gland scintigraphy was performed in 29 dogs with histologically confirmed thyroid tumors. Twenty dogs were female, and 9 were male. Median age was 10 years. Of the 29 dogs, 21 were initially examined because of cervical swelling or a cervical mass. Of the 29 tumors, 24 were thyroid adenocarcinomas, 1 was a C-cell carcinoma, 3 were undifferentiated carcinomas, and 1 was a thyroid adenoma. Serum triiodothyronine and thyroxine concentrations were determined in 25 dogs. Sixteen dogs were euthyroid, 6 were hyperthyroid, and 3 were hypothyroid. In all 29 dogs, results of scintigraphy were abnormal. The most common scintigraphic appearance (13 dogs) was a unilateral thyroid mass with increased radionuclide uptake, relative to that of the parotid salivary glands. There did not appear to be an association between distribution of radionuclide uptake and histologic diagnosis, although there appeared to be an association between distribution of uptake and histologic degree of capsular invasion. All 4 dogs with extensive capsular invasion and 11 of 17 dogs with limited capsular invasion had poorly circumscribed, heterogeneous uptake of pertechnetate by the tumor. All hyperthyroid dogs had intense uptake, and 5 of 6 hyperthyroid dogs had well-circumscribed, homogenous uptake. Scintigraphy did not appear to offer any additional benefit, compared with thoracic radiography, for detection of pulmonary metastases.