This case offers the opportunity to discuss several still controversial issues related to the diagnosis and the assessment of metastatic disease in MTC patients.

MTC is a rare thyroid tumor representing only 5–7 % of all thyroid malignancies. It can be sporadic (80%) or familial (20%). Its pathogenesis is related to a molecular alteration of RET oncogene that can be present at the germline level in familial cases or at somatic level in sporadic cases [1]. MTC prognosis is strongly related to the presence of metastatic disease outside the neck, with a survival rate of about 30–35 % at 10 years when distant metastases are present at the time of diagnosis [2]. Also the presence of a somatic RET mutation has been demonstrated to be correlated to an advanced stage and a lower survival [3–5]. The detection of a somatic RET mutation in the paratracheal tissue of the patient is suggestive of a more aggressive phenotype, with a higher risk of disease-related mortality even though the absence of distant metastases at the time of diagnosis likely reduces this risk [3].

This is a typical case in which the presurgical diagnosis of MTC was missed since the serum Ct was not measured and the cytological diagnosis of the nodule was indeterminate, as it can sometimes happen in MTC. An international and multicenter study recently demonstrated that the FNAC was able to identify only 46 % of 245 sporadic MTCs evaluated in 12 centers across 7 nations in 4 continents [6]. In this case, the measurement of serum Ct could have helped to avoid this mistake and allowed the appropriate surgical procedure to have been performed, which would possibly have changed the long-term outcome.

The measurement of Ct in the washout of the needle used for aspiration is of great help in the diagnosis of both primary MTC and lymph node metastases [7]. This procedure is particularly useful when the cytology is unclear or undefined and the serum Ct is borderline. Sometimes, if the serum Ct levels are very high, blood contamination can lead to a false-positive result, but the identification of a cutoff above which metastatic disease is likely can solve this problem [8].

At a certain point during the follow-up of this patient, she could have been considered to be “cured” since the serum Ct was undetectable (<14 pg/ml) from 1999 to 2001. However, the pentagastrin stimulation test demonstrated a peak Ct of 88 pg/ml suggesting that residual disease was still present. It is still a matter of discussion if postsurgical Ct stimulation testing is worthwhile when the postsurgical basal serum Ct is undetectable or in the normal range. There are studies showing that MTC patients with a basal Ct lower than the upper limit of the reference range have a risk of recurrence of 10 %, and therefore they can be considered to be cured, and their follow-up can be less intensive [9]. However, this percentage is reduced to 3 % in patients with negative Ct stimulation test [10], and thus, we believe that at least one stimulation Ct test after surgery can be useful to better identify patients who have a higher probability of being free of disease [11].

Newly diagnosed patients with MTC are usually 45–50 years old at the time of the diagnosis, and thus our patient was rather young. However, age at presentation is not a risk factor neither for the progression of the disease nor survival. However, younger age can impact on the choice of therapy. For example, after the third surgery, external radiotherapy (ERT) might have been considered, but the patient was only 25 years old, and her young age was a relative contraindication to ERT [12]. Nevertheless, no further recurrence in the neck has been observed thus far, after 15 years from the last surgery.