Thyroid : official journal of the American Thyroid Association
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RET/PTC rearrangement, RAS, and BRAF mutations are considered to be mutually exclusive in papillary thyroid carcinoma (PTC). However, although concomitant mutations of RET/PTC, RAS, or BRAF have been reported recently, their significance for tumor progression and survival remains unclear. We sought to examine the prognostic value of concomitant mutations in PTC. ⋯ Our data show that concomitant mutations are a frequent event in advanced PTC and are associated with poor prognosis. The concomitant mutations may represent intratumor heterogeneity and could exert a gene dosage effect to promote disease progression. KRAS(S65N) can constitutively activate the MAPK pathway.
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Prophylactic central neck dissection (PCND) for papillary thyroid cancer (PTC) is controversial. Recent publications suggest that the number and size of nodes and the presence of extranodal extension (ENE) are important features for risk stratification of lymph node metastases. We analyzed these features in clinically unapparent nodes that would not otherwise be removed. We also investigated the impact of surgeon experience on the ability to detect metastatic lymph nodes intraoperatively. ⋯ Clinical assessment based on intraoperative inspection and palpation had poor sensitivity and specificity in identifying metastatic central nodes, regardless of the level of experience of the surgeon. There was moderate agreement between surgeons of different experience levels. Sensitivity improved significantly with larger size of positive nodes, but not with the presence of multiple positive nodes or presence of ENE. In foregoing PCND in this patient population, our results suggest that treating clinicians miss potentially virulent disease with a large number of occult positive central nodes and occult nodes with ENE. This is the first report to address the pathologic features of clinically nonevident central nodes showing a high incidence of clinically relevant, adverse histologic features, as well as the impact of surgeon experience in performing the important intraoperative determination of whether there are clinically evident nodes that require removal.