ECEESPE2025 Poster Presentations Endocrine Related Cancer (76 abstracts)
Medullary thyroid carcinoma and c-cell hyperplasia in patients affected with neurofibromatosis type 1
Andrea Contarino 1 , 2 , Alessia Dolci 2 , Giulia Rodari 2 , Mariarosa Ferrara 3 , Gianluca Lopez 4 , 5 , Claudia Cesaretti 3 , Marica Eoli 6 , Federica Natacci 3 , Silvia Tabano 3 , 7 & Giovanna Mantovani 2 & 8
1University of Milan, Department of Health Sciences, Milan, Italy; 2Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Endocrinology Unit, Milan, Italy; 3Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Medical Genetics Unit, Milan, Italy; 4University of Milan, Department of Biomedical, Surgical and Dental Sciences, Milan, Italy; 5Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Pathology Unit, Milan, Italy; 6Fondazione IRCCS Istituto Neurologico Carlo Besta, Molecular Neuro-Oncology Unit, Milan, Italy; 7University of Milan, Department of Medical-Surgical Pathophysiology and Transplants, Milan, Italy; 8University of Milan, Department of Clinical Sciences and Community Health, Milan, Italy
JOINT2573
Background: Neurofibromatosis type 1 (NF1) is an autosomal dominant cancer predisposition syndrome caused by NF1 gene mutations. Although medullary thyroid carcinoma (MTC) is not typically associated with NF1, several case reports suggest a higher prevalence of C-cell disease in this syndrome. On the other hand, somatic NF1 mutations may drive MTC in some rare cases, when mutations in RET or RAS are not present.
Methods: Clinical data from 421 adult NF1 patients, being followed up at the Medical Genetics and Endocrinology Units at our Institution, were retrospectively retrieved, selecting only those who underwent at least one Ctn measurement. Patients with confirmed elevated Ctn values (≥ 10 pg/mL) were referred for thyroid surgery, either immediately or after a positive calcium stimulation test (Ctn peak above the threshold for MTC or C-cell hyperplasia, CCH). Somatic nucleic acids were extracted from 5 formalin-fixed paraffin-embedded thyroid tissue samples, with histologically proven C-cell disease, for molecular characterization by Next Generation Sequencing (NGS).
Results: The study included 384 NF1 patients, with 332/384 testing negative after Ctn screening and 52/384 (13. 5%) with hypercalcitoninemia (median Ctn 14. 1, IQR 12. 1–18. 4 pg/mL). No statistically significant differences were found between the two groups except for male sex (P = 0. 002). After repeating Ctn measurement, 20/52 patients showed persistently elevated levels and two of them were directly referred for thyroid surgery. Nine out of 20 patients were placed under active surveillance, with mean Ctn levels not significantly changing over a median period of 32. 1 months (IQR 21–37). Calcium stimulation test was performed in 9 patients with hypercalcitoninemia, excluding C-cell disease in 2 cases but resulting positive in 7 of them. Overall, 14 NF1 patients (3. 6%) underwent thyroid surgery, with 50% of cases having a suspicious C-cell disease. Among the latter, MTC was found in 2 patients, nodular CCH in 4 (coexisting with follicular thyroid adenoma in 1 case) and thyroid follicular nodular disease in the other one. The NGS analysis identified at least one acquired somatic mutation in the NF1 gene in both cases of MTC and in 3 available cases of CCH, whereas no pathogenic mutation involving RET or RAS was found.
Conclusions: Hypercalcitoninemia is a relatively common finding in patients with NF1 and underlies a possible higher combined prevalence of MTC/CCH (1. 6%) than the general population. The molecular basis of this association is most likely to be found in NF1 gene loss of heterozygosity in thyroid C-cells.
Volume 110
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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