Mutations in the RET proto-oncogene are responsible for multiple endocrine neoplasia type II. Somatic RET mutations were described in 50% of medullary thyroid carcinoma (MTC). We describe here a novel germline mutation of the RET gene detected in an apparentely sporadic MTC.
The index case was a 67 years old patient who arrived at our observation for a bilateral laterocervical linfoadenopathy. The patient was clinically evaluated for thyroid function and morphology. The thyroid ultrasound showed the presence of a 10 mm anechoic nodule and a solid nodule with 6 mm iperchoic spots, both in the left lobe. The measurement of thyroid hormones revealed a normal function of the gland, while the basal calcitonin (CT), was elevated (29 pg/ml). CT after pentagastrin (PG) stimulation test showes a peak of 240 pg/ml. We suspected the presence of an MTC, that was confirmed by cytological analysis of FNAB of the 6 mm nodule. In addition a cytological evaluation of FNAB from suspicious lymphnodes showed several degrees of atypia and an histological examination was suggested. The patient underwent total thyroidectomy with central and bilateral lymphadenectomy. The histological evaluation confirmed the diagnosis of MTC in the 6 mm nodule while the laterocervival limphonodes presented the typical features of the Castlemans-syndrome. We performed genetic analysis for RET mutations by sequencing exons 10, 11, 13, 14, 15, 16. The analysis revealed the presence of a novel germline mutation ATG→ACG at the codon 848 of the exon 14.(Met848→Thr). The 28 years old daughter was also found to be positive for the same mutation, but negative for clinical/biochemical examination. In conclusion, although the lymphonode disease was unrelated to thyroid, it allowed to identify a case of familial MTC. Since the association between the Castlemans-syndrome and the MTC has been never described, it is likely that they were fortuitously associated.
01 - 05 Apr 2006
European Society of Endocrinology