Dedifferentiation of neoplastic cells in medullary thyroid carcinoma: Report of a case

We report herein the unusual case of a man who was diagnosed as having sporadic medullary thyroid carcinoma (MTC) at the age of 29 years, and subsequently followed up for a period of 18 years. A total thyroidectomy with radical neck dissection was initially performed, followed by a stable interval of 16 years with regional metastases. He then developed widely disseminated metastases resulting in death within 2 years at the age of 47 years. While the neoplastic tissue from localized metastases in the soft tissue of the neck expressed strong immunohistochemical positivity to calcitonin (CT), calcitonin gene-related peptide, carcinoembryonic antigen, neuron-specific enolase, and chromogranin A during the stable interval, extremely weakened immunoreactivity to those markers was observed in samples from the disseminated metastases in the subcutaneous tissue after his clinical deterioration. Furthermore, only a few neoplastic cells in specimens obtained at postmortem sampling exhibited a weak response to CT. Ultrastructurally, the characteristic secretory granules in the neoplastic cells decreased remarkably in number, consistent with the immunohistochemical findings. These granules also diminished in diameter and intracytoplasmic small lumina and intercellular clefts with microvilli, interpreted as an attribute of anaplastic thyroid carcinomas, were frequently observed in tissues obtained after his clinical deterioration or at postmortem sampling. These cytological changes might represent dedifferentiation of the neoplastic cells or the anaplastic transformation of MTC. This work was supported in part by a Grant-in-Aid for Scientific Research (#01480322 and #07457268) from the Ministry of Education, Science, Sports and Culture of Japan.