Medullary Carcinoma

Abstract

Medullary thyroid cancer (MTC) is a rare neuroendocrine tumor that can be either sporadic or familial. In both cases, the pathogenesis is due to constitutively activating mutations, somatic or germline, of RET oncogene. The familial form of MTC can be associated with other endocrine neoplasias such as pheochromocytoma (PHEO) and/or multiple adenomatosis of parathyroids (PTHAd). According to the phenotype, three different syndromes are distinguished: the multiple endocrine neoplasia (MEN) type 2A, characterized by the association of MTC, PHEO, and PTHAd; the MEN 2B in which MTC and PHEO are associated with other nonendocrine diseases such as multiple mucosal neuromas, marfanoid habitus, and megacolon; and the familial form of MTC (FMTC) with hereditary MTC not associated with other neoplasias. The familial form, but not the sporadic, can affect children, and the RET genetic screening is the only diagnostic tool able to identify gene carriers when the tumor is not yet developed. As all thyroid tumors, MTC clinical manifestation is represented by a thyroid nodule, either isolated or in the context of a multinodular goiter. The cytological diagnosis is not always straightforward and can be facilitated by the measurement of serum calcitonin (Ct) that when >100 pg/ml is the most specific and sensitive serum marker of MTC. An early diagnosis of MTC, when the tumor is still intrathyroid, is needed to definitively cure the patient with the first surgical treatment. The presence of distant metastases at diagnosis is, together with the presence of a somatic RET mutation in the tumor tissue, the most important prognostic factor for a poor outcome. If the first surgery will not be curative, other local or systemic therapies are currently available, and their use can have a positive impact on the progression-free survival of MTC patients. Since MTC is a rare tumor, with several peculiarities such as the possibility to be hereditary, the management of MTC patients should be performed in referral centers and by a multidisciplinary team.