A mixed breed (miniature schnauzer) dog, 12 years, spayed femaleThe dog was presented in 2003 with a growth in the ventral neck region (approximately 3cm diameter). The mass was excised at that time and in 2005 the mass had re-grown. Again the tumor was excised and a diagnosis similar to the 2003 evaluation was made.
A round mass, 2-2.5cm in diameter was attached to the left thyroid gland.
A soft tissue mass from the ventral neck consists of a very cellular mass, a neuroendocrine neoplasm (Fig.Â 4-1).Â The cells are in packets separated by a thin vascularized stroma.Â Peripheral to the mass are numerous satellite nodules with tumor invasion of the lymphatics.Â The lesion was immunohistochemically positive for thryocalcitonin and negative for thyroglobulin and parathormone.
Mass: Thyroid carcinoma parafollicular
CBC and chemistries were all unremarkable except for slight elevation of ALP and ALT, both in the 300s.Â The animal had slightly elevated ionized calcium at 1.5.Â Total calcium was normal.Â Urinalysis was unremarkable.Â Thoracic and abdominal radiographs and abdominal ultrasound were unremarkable.Â No evidence of metastatic disease was found.Â Sections of the neoplasm were immunostained to confirm the biologic activity of the tumor
Incidence: The C-cell thyroid parafollicular cells are seen most frequently in adult cattle2,11, aged horses9 and infrequently in other domestic species.12,22 As bulls age there is an increased incidence of neoplastic C-cells, especially where bulls are fed high calcium diets.13 Multiple endocrine tumors have been associated with pheochromocytoma in bulls with C-cell tumors.19 In the dog, a pheochromocytoma has been also associated with parathyroid chief cell hyperplasia.15 In a histochemical study of 33 thyroid carcinomas in the dog, 36% were of C-cell original and 64% were from thyroid follicle cells.4 The affect on the elevated calcium is uncertain.Â In adult bulls, various skeletal lesions have been associated with C-cell neoplasia.20 In man, prominent bone lesions have not been reported as the result of excessive calcitonin.14
Fibrovascular tissue, ventral neck (per contributor): C-cell (parafollicular) carcinoma, mixed breed dog (Canis familiaris), canine.
In domestic animals, most thyroid neoplasms are thyroid follicular cell tumors or C-cell (also called parafollicular or medullary) tumors.Â These tumors can have similar (endocrine/neuroendocrine) histologic features, ie.Â packets and trabeculae of epithelioid cells supported by a fine fibrovascular stroma.Â While C-cell carcinomas may have pallisading of columnar cells along the periphery of the lobules, dense bands of connective tissue, and/or amyloid deposits, and thyroid follicular cell tumors usually have some follicular differentiation, immunohistochemistry may be needed to differentiate between thyroid follicular cell tumors and C-cell tumors.Â One study4 suggested that C-cell tumors have been underdiagnosed when the diagnosis was based on histologic evaluation of H&E stained sections alone.
C-cell neoplasms exhibit positive cytoplasmic immunoreactivity for calcitonin and are negative for thyroglobulin.Â The sensitivity for thyroglobulin for thyroid carcinomas is 90.5% alone, but if it is combined with TTF-1, that sensitivity increases to 95.2%.16 TTF-1, thryoid transcription factor, is expressed in the thyroid, brain, and lung during early embryogenesis, and the thyroid cells and bronchioloalveolar epithelial cells following birth.Â In the lung, it activates surfactant proteins and Clara cell secretory protein gene promoters.1 In the thyroid gland, it activates many factors including thyroglobulin, thyroperoxidase, thyrotropin receptor, and thyroid peroxidase.5,6,8,10,18 When positive, TTF-1 is diffusely located within the nucleus and never in the cytoplasm.Â In one study, approximately 50% of the C-cell neoplasms also stained positive for TTF-1, therefore it is not suitable to use as a single marker.16
C-cell tumors in bulls, often occur concurrently with bilateral pheochromocytomas and pituitary adenomas.4 Multiple endocrine tumors are thought to arise due to a simultaneous neoplastic mutation of multiple endocrine cell populations of neural crest origin in the same individual.3,23 In humans, multiple endocrinen neoplasia type 2 (MEN-2) occurs in an autosomal dominant pattern, and is classified into three clinical manifestations.17 MEN-2A is characterized by the presence of a medullary thyroid carcinoma in addition to a pheochromocytoma and multiple tumors of the parathyroid gland.7 MEN-2B consists of a medullary thyroid carcinoma, a pheochromocytoma, ganglioneuromatosis, and marfanoid habitus.21 FMTC syndrome, is the third form of MEN-2 and is defined as the development of a medullary thyroid carcinoma and a low incidence of other clinical manifestations of either MEN-2A or MEN-2B.7
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