Thyroid C-cell Tumors
Tumors derived from C-cells (parafollicular, ultimobranchial cells) of the thyroid gland 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 seen 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. A diffuse or nodular hyperplasia of secretory cells in the adrenal medulla often precedes the development of pheochromocytoma.
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. Distinguishing these tumors from other thyroid carcinomas is challenging with light microscopy alone, and confirmation requires immunohistologic staining. These tumors are usually well encapsulated and do not show the tendency for metastasis other thyroid carcinomas exhibit. Oversecretion of calcitonin has not been clearly documented in affected animals. Perhaps related to excessive release of prostaglandins or serotonin, diarrhea is a common clinical sign in dogs with C-cell tumors of the thyroid.
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 anterior 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. If present, metastases in anterior cervical 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.
The 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 significantly when calcium intake was reduced.
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 people, bulls, and laboratory rats with medullary (ultimobranchial) thyroid neoplasms derived from C-cells. Osteosclerotic changes have been reported in bulls with this syndrome, but the relationship of longterm excess calcitonin secretion to the pathogenesis of the skeletal lesions and their occurrence in other species is unclear.
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 and 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. Surgery is the primary therapy, but some form of adjuvant therapy 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 therapy. For the rather rare functional thyroid carcinoma in dogs, treatment with 131I would be a reasonable choice.
Merkel cells are neuroendocrine cells widely dispersed in the body and normally found in skin. Merkel cell tumors are rare but have been documented in dogs and cats. Most of the tumors in dogs are benign. In contrast, Merkel cell carcinoma in cats is associated with a poor prognosis, with frequent occurrence of metastasis to regional lymph nodes and distant organs.