Histologic. MTC originates in calcitonin-producing cells (C-cells) of the thyroid gland. MTC is diagnosed histologically when nests of C-cells appear to extend beyond the basement membrane and to infiltrate and destroy thyroid follicles. Immunohistochemistry for calcitonin expression may be performed as a pathologic diagnostic adjunct.
CCH is diagnosed histologically by the presence of an increased number of diffusely scattered or clustered C-cells. In MEN 2, the age of transformation from CCH to MTC varies with different germline RET pathogenic variants [Machens et al 2003].