A Calcitonin Non-producing Neuroendocrine Tumor of the Thyroid Gland

Atsuko Kasajima, José Cameselle-Teijeiro, Lourdes Loidi, Yoshio Takahashi, Noriaki Nakashima, Satoko Sato, Fumiyoshi Fujishima, Mika Watanabe, Tadao Nakazawa, Hiroshi Naganuma, Tetsuo Kondo, Ryohei Kato, Hironobu Sasano

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)325-331
Number of pages7
JournalEndocrine Pathology
Issue number4
Publication statusPublished - 2016 Dec 1


  • Calcitonin
  • Medullary carcinoma
  • Neuroendocrine tumor
  • Thyroid gland

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology


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