Endocrine Abstracts (2009) 20 S20.1

C Cell neoplasia

Rossella Elisei

Department of Endocrinology and Metabolism, University of Pisa, Pisa, Italy.

Parafollicular C-Cells represent 1% of thyroid cells and differ from follicular cells for their origin from the neural crest. At variance with follicular cells, their growth and function are independent from thyrotropin stimulating hormone (TSH), they do not take up iodine and they produce and secrete calcitonin (CT) but not thyroglobulin. C-Cell Hyperplasia (CCH) is defined as an increased number of normal C-cells (i.e. 50 or more C-cells in at least one low-power field (100×)), more commonly with a diffuse pattern. Although rare, CCH has been described in normal thyroids and more than 10% of lymphocytic thyroiditis are accompanied by CCH as well as some micropapillary thyroid cancer. The pathological role of this CCH is still unclear.

Malignant transformation of C cells leads to the development of medullary thyroid carcinoma (MTC). It is a well-differentiated thyroid tumor maintaining the biochemical and pathological features of C cells and elevated concentration of serum CT are strongly suggestive of the presence of either primary MTC, before thyroidectomy, or metastatic MTC, after thyroidectomy. Only rare cases of de-differentiated MTC are associated to low or absent levels of serum CT.

The prevalence of MTC varies from 5 to 10% among all thyroid tumors and from 0.4 to 1.4% among thyroid nodules. Females and males are almost equally affected. The mean age at diagnosis is around 40 years, but a wide range of age at onset is reported. In about 25% of cases MTC is one of the components of the Multiple Endocrine Neoplasia type II syndromes, which are autosomal dominant inherited syndromes involving other endocrine glands. The pathogenic mechanism of these syndromes has been recognized in the activation of the RET protoncogene. Several germline RET mutations, mainly concentrated in exons 10–16 of the RET gene have been discovered to be associated with the hereditary MTC. Somatic RET mutations are found in about 45% of sporadic MTC and have been reported to have a poor prognostic role both for the outcome and the survival.

The biological behaviour of MTC is quite aggressive and only 50% of MTC patients are still alive after 10 years. The only possibility to improve the cure and survival is the early diagnosis and the early surgical treatment when the MTC is still intrathyroid. This can be obtained by routine measurement of serum CT in patients with thyroid nodular disease and with RET genetic screening in hereditary forms. Metastatic MTC patients have only few therapeutic options and conventional therapies have been demonstrated to be ineffective. The recent development of new targeted drugs such as tyrosine kinase inhibitors able to act against both RET and other tyrosine kinase receptors (i.e VEGFR, PDGFR ecc) are very promising and several clinical trials are already on going.

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