"Atypical" medullary thyroid carcinoma with little or no calcitonin expression

In a retrospective analysis of 142 medullary thyroid carcinomas, four sporadic cases with an unusual histological and immunohistochemical appearance were found. Three cases (two males, one female) had very few calcitonin-positive tumour cells, while the fourth case (male) completely lacked calcitonin immunoreactivity at both mRNA and protein levels, whereas a variety of neuroendocrine markers were positive in at least 50% of tumour cells. The four tumours were completely devoid of carcinoembryonic antigen expression and of amyloid. Differential diagnosis and histogenetic considerations are discussed.