Thyroid C-cell tumors are reported most often in bulls, horses, and dogs. In bulls, tumor development has been associated with coincidental pheochromocytomas and pituitary adenomas. In dogs, these tumors are often recognized as a palpable cervical mass. They are often well encapsulated and do not have a tendency for metastasis; therefore, they are often amenable to surgical excision.
Thyroid C-cell tumors (or medullary tumors of the thyroid gland) are derived from C cells (also known as parafollicular or ultimobranchial cells) of the thyroid gland. They can be benign (C-cell adenoma) or malignant (C-cell carcinoma). In bulls, tumor development has been associated with coincidental pheochromocytomas and pituitary adenomas.
Etiology and Pathogenesis of Thyroid C-Cell Tumors in Animals
Chronic stimulation of C cells by longterm dietary intake of excess calcium may be related to the high incidence of these tumors in bulls; adult bulls frequently were fed diets with 3.5–6 times the amount of calcium normally recommended for maintenance, and incidence of the tumors declined substantially when calcium intake was decreased.
Oversecretion of calcitonin has not been clearly documented in affected patients.
In bulls, with coincidental pheochromocytomas, a diffuse or nodular hyperplasia of secretory cells in the adrenal medulla often precedes the development of pheochromocytoma.
Epidemiology of Thyroid C-Cell Tumors in Animals
In dogs, C-cell tumors of the thyroid occur as a small percentage of all thyroid tumors (estimates range from 0.1%–12%, but the incidence may be higher).
Thyroid C-cell tumors are most common in adult to aged bulls and horses and in certain strains of laboratory rats.
A high percentage of aged bulls has been reported to develop C-cell tumors (≥ 30%) or hyperplasia of C cells and ultimobranchial derivatives (≥ 15%–20%). These have not been observed in cows fed similar diets. The incidence in bulls increases with advancing age and is often associated with development of increased vertebral density.
Multiple endocrine tumors, especially bilateral pheochromocytomas and occasionally pituitary adenomas, are detected coincidentally in bulls with C-cell tumors. A high frequency of thyroid C-cell tumors and pheochromocytomas has been reported in a family of Guernsey bulls, which suggests an autosomal dominant pattern of inheritance.1
Reference
Sponenberg DP, McEntee K. Pheochromocytomas and ultimobranchial (C-cell) neoplasms in the bull: evidence of autosomal dominant inheritance in the Guernsey breed. Vet Pathol. 1983;20(4):396-400. doi:10.1177/030098588302000402
Clinical Features of Thyroid C-Cell Tumors in Animals
C-cell adenomas appear in one or both thyroid lobes as discrete, single or multiple, gray to tan nodules. Adenomas are smaller (~1–3 cm in diameter) than carcinomas and are separated from the thyroid parenchyma by a thin, fibrous connective tissue capsule. The adjacent thyroid is compressed but not invaded by the tumor.
In horses, C-cell adenomas may result in a palpable enlargement in the ventral cervical region.
Larger C-cell adenomas incorporate most of the thyroid lobe, but a rim of dark brown-red thyroid often is present on one side.
Thyroid C-cell carcinomas cause extensive multinodular enlargements of one or both thyroid lobes and may incorporate the entire thyroid gland.
Syndromes associated with abnormalities in the secretion of calcitonin are recognized much less frequently than disorders involving parathyroid hormone (PTH). Hypersecretion of calcitonin has been reported in humans, bulls, and laboratory rats with medullary (ultimobranchial) thyroid neoplasms derived from C cells. Osteosclerotic changes have been reported in bulls with this syndrome; however, the relationship of longterm excess calcitonin secretion to the pathogenesis of the skeletal lesions and their occurrence in other species is unclear.
Perhaps related to excessive release of prostaglandins or serotonin, diarrhea is a common clinical sign in dogs with C-cell tumors of the thyroid.
These tumors are usually well encapsulated and do not show the tendency for metastasis other thyroid carcinomas exhibit. If present, metastases in superficial cervical (prescapular) lymph nodes usually are large and have areas of necrosis and hemorrhage. Pulmonary metastases are infrequent and appear as discrete tan nodules throughout all lobes of the lung.
Diagnosis of Thyroid C-Cell Tumors in Animals
Distinguishing C-cell carcinoma from other thyroid carcinomas is challenging with light microscopy alone, and confirmation requires immunohistologic staining.
In dogs, the histologic grading of thyroid carcinoma has been important in prognosis, although histologic type has not. Of greater importance is the volume of tumor as well as its relation to the potential for metastasis; also, the more deeply fixed the tumor is to underlying structures, the less likely surgical resection will be complete.
Medullary thyroid carcinoma can be difficult to distinguish histologically from carcinoma originating from follicular cells.
Treatment and Prognosis of Thyroid C-Cell Tumors in Animals
Surgery is the primary treatment for C-cell tumors; however, some form of adjuvant treatment is reasonable because of the potential for metastatic spread and residual nonresectable tissue. A combination of radiotherapy and chemotherapy would be ideal in theory, and there is increasing interest in such combined treatment.
For the rather rare functional thyroid carcinoma in dogs, treatment with radioactive iodine (I 131) would be a reasonable choice.
Key Points
Medullary carcinoma of the thyroid has been reported in bulls, horses, and dogs.
Medullary carcinoma of the thyroid can be difficult to distinguish histologically from carcinoma of thyroid follicular origin.
For More Information
Hamilton-Elliot J, Finotello R, Murgia D, Blundell R, Dukes-McEwan J. Ectopic medullary (C cell) thyroid carcinoma in a dog with pericardial effusion. Vet Rec Case Rep. 2018;6(4):e000729. doi:10.1136/vetreccr-2018-000729
