Neuroendocrine tumors of the thyroid gland are generally considered to derive from parafollicular endocrine cells (C cells) and are generally referred to as medullary
thyroid carcinomas (MTC).
Calcitonin secretion is almost always detected in MTC and a prerequisite for both clinical and pathological diagnosis. Thyroid
neuroendocrine tumors without any apparent
calcitonin secretion reflect a diagnostic dilemma because non-
calcitonin-producing MTCs have virtually not been characterized. Here, we report a case of primary thyroid
neuroendocrine tumors lacking
calcitonin secretion or expression. The
tumor cells expressed cytokeratins,
chromogranin A, and
synaptophysin, all of which were consistent with epithelial and neuroendocrine differentiation. Thyroid transcription factor-1 paired box gene 8, and
carcinoembryonic antigen were also immunohistochemically detected, consistent with its thyroid origin. However, the
tumor was negative for
calcitonin both by immunohistochemistry and in situ hybridization, hence, not meeting the definition of MTC. Despite the loss of
calcitonin expression, immunoreactivity for the
calcitonin-gene-related peptide was detected in the
tumor. Somatic gene mutations of RET, H-RAS, K-RAS, or BRAF were not detected in this case. A limited number of
calcitonin non-producing thyroid
neuroendocrine tumors are available in the scientific literature available in English, and its etiology and clinical manifestations remain largely unknown. Our case, along with the rare, previously reported cases, suggests that
calcitonin non-producing
neuroendocrine tumors of the thyroid gland are most likely derived from C cells, but should be differentiated from ordinary MTCs.