Sporadic calcitonin-negative medullary thyroid carcinoma is not more aggressive than its classic counterpart: case report and review of the literature

Objective: medullary thyroid carcinoma (MTC) with normal serum basal calcitonin (calcitonin-negative MTC) is uncommon. The exact mechanism for this paradox is unclear. It has been suggested that the loss of ability to secrete calcitonin is due to tumor cell dedifferentiation and may confer a worse prognosis.
Methods: we describe a 45-year-old woman with a sporadic 4.5-cm well-differentiated MTC, who despite having normal preoperative serum basal calcitonin and poor calcitonin immunostaining in tumor cells, remains in remission 5 years after total thyroidectomy with bilateral central neck dissection. Out of the 20 patients with calcitonin-negative MTC reported to date, we include 16 patients with clinical disease at presentation to determine if they fare worse than their classic MTC counterparts. We try to correlate the extent of calcitonin immunostaining with the degree of tumor differentiation to determine if poor tumor calcitonin immunoreactivity is an indicator of tumor cell dedifferentiation.
Results: Seven and 9 patients with calcitonin-negative MTC had poorly-differentiated and well-differentiated tumors, respectively. Four patients in the former group died from metastatic MTC within 3 years of the diagnosis. The status of the 2 living patients with known follow-up information was one with N1 disease and one in remission. In the well-differentiated group, 2 patients had N1M1 disease and 7 patients were in remission.
According to the number of tumor cells immunoreactive to calcitonin, the 15 patients with known data were classified in 3 groups: 1+ group (only few tumor cells stained weakly for calcitonin), 7 patients; 2+ group (many tumor cells stained focally for calcitonin), 2 patients; and 3+ group (most tumor cells stained strongly for calcitonin), 6 patients. The level of calcitonin immunoreactivity did not correlate with the patient’s clinical status.
Conclusion: the degree of tumor differentiation is a far better predictor of outcome than the extent of calcitonin immunoreactivity and poor tumor calcitonin staining is not necessarily an indicator of tumor cell dedifferentiation.

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Medullary thyroid carcinoma
carcinoma medular de tiroides
Calcitonine-negative
calcitonina negativa
Nonsecretory tumor
tumor no secretor
Calcitonin immunostaining
inmunotinción para calcitonina
Poorly differentiated cancer
cancer pobremente diferenciado