["Physiological" and "neoplastic" C-cell hyperplasia of the thyroid. Morphologically and biologically distinct...

C-cell hyperplasia (CCH) occurs regularly in the setting of type 2 multiple endocrine neoplasia (MEN2), either separately or in association with medullary thyroid carcinoma (MTC). It can also accompany sporadic MTC and appear without any tumour association. To test the practicability of the terms "physiologic" and "neoplastic", 18 cases with incidental sporadic, non-MTC associated CCH were investigated and the morphological patterns were described. We found CCH of various degrees, including so-called neoplastic CCH. In 16 of the 18 cases, a MEN2 setting could be ruled out by mutation analysis of the RET proto-oncogene. Morphologically, one can not distinguish with certainty between sporadic and hereditary or reactive and tumour-associated CCH. While MEN2-associated CCH can be regarded as true preneoplasia, sporadic CCH possesses variable biologic potential. The preneoplastic potential of sporadic CCH is still obscure. A pure morphological distinction between "physiologic" and "neoplastic" CCH regardless of the RET status should not be used.