Calcitonin-Negative Neuroendocrine Tumor of the Thyroid: A Distinct Clinical Entity

Background: Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor (NET) that arises from the parafollicular cells (C-cells) of the thyroid gland which produces calcitonin (CT) and is, therefore, a serum and immunohistochemical biomarker of MTC. Here, we describe a patient with another form of NET arising with the thyroid gland. Patient Findings: This is a forty-year-old woman who underwent total thyroidectomy for a thyroid nodule that had features of an NET on fine needle aspiration. Her serum CT and carcinoembryonic antigen were normal. Surgical pathology showed a well-differentiated NET with immunohistochemical stains positive for markers of follicular cells (thyroglobulin and synaptophysin), positive for neuroendocrine markers (neuron specific enolase and chromogranin A), but negative for CT, the defining marker of MTC. Conclusions: We describe a rare case of a nonmedullary NET of the thyroid gland arising from thyroid follicular cells, not parafollicular cells. We suggest that calcitonin-negative neuroendocrine tumor of the thyroid gland (CNNETT) may be an entity that has not been recognized in the literature. This distinction between MTC and CNNETT may be important, as the treatment and prognosis may differ.