Endocrine Abstracts (2007) 14 P109

Histopathological and molecular studies in patients with goiter and hypercalcitoninemia: reactive or neoplastic C-cell hyperplasia?

Uberta Verga1, Stefano Ferrero3, Leonardo Vicentini2, Tatiana Brambilla3, Valentina Cirello1, Marina Muzza1, Paolo Beck-Peccoz1 & Laura Fugazzola1


1Endocrine Unit, Dept. of Medical Sciences, University of Milan and Fondazione Policlinico IRCCS, Milan, Italy, 2Endocrine Surgery Unit, Fondazione Policlinico IRCCS, Milan, Italy, 3Pathology Unit, Dept. of Medicine, Surgery and Dentistry, University of Milan, Ospedale S. Paolo, Milan, Italy.


The cut-off values able to differentiate between reactive or neoplastic C cell hyperplasia (CCH) or to predict sporadic medullary thyroid cancer (MTC) are still debated both for basal and stimulated calcitonin (bCT and sCT). Aim of the present study was to define the prevalence and the histological patterns of CCH in 15 patients with multinodular goiter (MNG), bCT>10 pg/ml and sCT levels >50 pg/ml. These data were compared with those from 16 patients with MNG and bCT levels <10 pg/ml, and with those from 4 patients with familial medullary thyroid cancer (FMTC). For each case, 6 paraffin blocks were selected, CT immunoreactive cells were counted in sixty consecutive high power fields (400x) and classified as focal, diffuse, nodular or neoplastic. RET genetic analyses were performed at the germline and tissue level in MTC and, for the first time, in CCH cases. In patients with MNG, sCT levels >50 pg/ml were associated with CCH or with MTC, being the total number of C cells/60 fields significantly higher than that found in MNG with normal bCT (P=0.0008), and comparable to that detected in FMTCs. Interestingly, in the group with sCT>50 pg/ml, the C cells displayed a neoplastic phenotype, concerning morphology, distribution and localization. No RET mutations were found neither at the germline nor at the somatic level.

In conclusion, sCT levels >50 pg/ml were associated with CCH in all cases and with MTC in 4 patients, without correlation between CT levels and the number of C cells or the final diagnosis. After serial blocking and high power field magnification, an elevated number of C cells were counted, often showing a morphology and a distribution pattern consistent with neoplastic CCH, thus strengthening the hypothesis that CCH might be the precursor also of sporadic MTC in the absence of RET mutations. Hence, sCT levels >50 pg/ml indicate the presence of CCH with a possible preneoplastic potential, suggesting the opportunity to perform a “prophylactic” surgical treatment.

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