No abstract

In this study the BRAF(V600E) mutation correlated with the worst outcome for PTC patients, who were not only at a higher risk not to be cured but also for death. In particular, the BRAF(V600E) mutation was demonstrated to be a poor prognostic factor independent from other clinicopathological features.

Anaplastic thyroid carcinoma (ATC) is a rare malignancy, accounting for 1-2% of all thyroid cancers. Although rare, ATC accounts for the majority of deaths from thyroid carcinoma. ATC often originates in a pre-existing thyroid cancer lesion, as suggested by the simultaneous presence of areas of differentiated or poorly differentiated thyroid carcinoma. ATC is characterized by the accumulation of several oncogenic alterations, and studies have shown that an increased number of oncogenic alterations equates to an increased level of dedifferentiation and aggressiveness. The clinical management of ATC requires a multidisciplinary approach; according to recent American Thyroid Association guidelines, surgery, radiotherapy and/or chemotherapy should be considered. In addition to conventional therapies, novel molecular targeted therapies are the most promising emerging treatment modalities. These drugs are often multiple receptor tyrosine kinase inhibitors, several of which have been tested in clinical trials with encouraging results so far. Accordingly, clinical trials are ongoing to evaluate the safety, efficacy and effectiveness of these new agents. This Review describes the updated clinical and pathological features of ATC and provides insight into the molecular biology of this disease. The most recent literature regarding conventional, newly available and future therapies for ATC is also discussed.

We demonstrated that the presence of a somatic RET mutation correlates with a worse outcome of MTC patients, not only for the highest probability to have persistence of the disease, but also for a lower survival rate in a long-term follow up. More interestingly, the presence of a somatic RET mutation correlates with the presence of lymph node metastases at diagnosis, which is a known bad prognostic factor for the definitive cure of MTC patients.

The survival rate of patients with medullary thyroid carcinoma (MTC) is significantly better in patients diagnosed and treated when the tumor is limited to the thyroid. In a pioneer study carried out in 1991, we demonstrated that routine measurement of serum calcitonin (CT) in nodular thyroid disease allowed the preoperative diagnosis of unsuspected sporadic MTC with better accuracy than routine fine needle aspiration cytology (FNAC). This finding has been confirmed in subsequent studies. In the present study we report the results of CT screening in 10,864 patients with thyroid nodular disease seen in the years 1991-1998 (group 1). We analyzed the prevalence of MTC and compared their outcomes with those of a historical group of patients (group 2) diagnosed before the introduction of CT screening (1970-1990). The prevalence of MTC found by CT screening in group 1 was 0.40% (44 patients). A positive CT test had a higher diagnostic sensitivity and specificity compared with FNAC. CT screening allowed the diagnosis of MTC at an earlier stage compared with group 2 (P = 0.004). Normalization of serum CT levels (undetectable) after surgery was more frequently observed in group 1. At the end of follow-up, complete remission was observed in 59% of group 1 and in 2.7% of group 2 (P = 0.0001). Our study confirms that MTC is not an infrequent finding among patients with thyroid nodules (nearly 1 in 250 patients). In addition, screening thyroid nodules with serum CT measurement allows the diagnosis and treatment of MTC at an earlier stage, resulting in a better outcome compared with MTC not detected by serum CT measurement. One of the reasons for this finding is that increasing the preoperative diagnostic accuracy of MTC prompts the surgeon to perform a more radical and possibly curative treatment. On this basis, routine measurement of basal serum CT levels should be considered an integral part of the diagnostic evaluation of thyroid nodules.