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 spor adic medullary thyroid carcinoma (MTC) at the age of 29 years, and subseque ntly followed up for a period of 18 years. A total thyroidectomy with radic al neck dissection was initially performed, followed by a stable interval o f 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 n eck expressed strong immunohistochemical positivity to calcitonin (CT), cal citonin gene-related peptide, carcinoembryonic antigen, neuron-specific eno lase, and chromogranin A during the stable interval, extremely weakened imm unoreactivity to those markers was observed in samples from the disseminate d metastases in the subcutaneous tissue after his clinical deterioration. F urthermore, only a few neoplastic cells in specimens obtained at postmortem sampling exhibited a weak response to CT, Ultrastructurally, the character istic secretory granules in the neoplastic cells decreased remarkably in nu mber, 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 r epresent dedifferentiation of the neoplastic cells or the anaplastic transf ormation of MTC.