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.

The aim of the study was to evaluate the role of neck ultrasonography in follow-up of patients with differentiated thyroid cancer. Sixty-three patients had total thyroidectomy and 131I ablation for differentiated thyroid cancer and had a negative whole body scan during follow-up. They were admitted for a high resolution neck ultrasound examination. Sixteen of 63 patients presented images suspicious for lymph node metastasis and/or for local recurrences (4 cases). Fine needle aspiration confirmed the suspicion of malignancy in 12 patients: only lymph node metastasis in 8 cases, local recurrence and lymph node metastasis in 3 cases, and in one case only local recurrence. Fine needle aspiration was suspicious for lymphadenitis in 4 cases. Thyroglobulin levels were very high in all patients with local recurrence and/or lymph node metastasis but undetectable in 2 cases presenting node metastasis and in 4 cases with lymphadenitis. All but one patient were admitted for surgery and the cytological diagnosis was confirmed. Early identification of a pathologic mass in the neck is a desirable goal; high resolution echography can play an important role in the follow-up of these patients and can detect local recurrences even when there is a negative whole body scan or undetectable thyroglobulin level.

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Codon 61 of the N-ras oncogene was screened for mutations in 99 surgically resected thyroid carcinomas by a polymerase chain resection (PCR)-based method (PCR-primer introduced restriction with enrichment of mutant alleles [PCR-PIREMA]). A point mutation of the N-ras oncogene at the codon 61 was detected in 16 of 99 (16.2%) thyroid carcinomas examined by this method. No RAS alteration was detected in the group of 11 medullary thyroid carcinomas, while 3 of 31 (10.0%) papillary carcinomas, 2 of 5 (40%) follicular carcinomas, 8 of 44 (18.2%) poorly differentiated carcinomas, and 3 of 5 (60%) undifferentiated carcinomas showed an activation of N-RAS proto-oncogene. Interestingly, two primary follicular tumors and their corresponding bone metastases, showed N-ras mutations. In the same cases we evaluated the expression of thyroglobulin by immunohistochemical analysis. Although the majority of well-differentiated carcinomas expressed a high level of thyroglobulin, the expression of the same antigen was absent or only occasional weakly positive in 33 of 44 poorly differentiated carcinomas. Interestingly, N-ras mutation was restricted to the group of tumours with low or absent thyroglobulin expression, suggesting that this genetic change is prevalent in less differentiated tumors.