Individualization of Lymph Node Dissection in RET (Rearranged During Transfection) Carriers at Risk for Medullary Thyroid Cancer Value of Pretheropeutic Calcitonin Levels

Objective: This study sought to define the need for lymph node dissection in se Rearranged during Transfection (RET) carriers at risk for hereditary medullary thyroid cancer. Summary Background Data: Controversy surrounds the need for lymph node dissection to complement thyroidectomy in RET carriers. Methods: Integration of molecular, biochemical, histopathologic, and clinical information from 308 RET carriers referred for (re-)operation to a specialist surgical center. Results: The carriers differed significantly in age at thyroidectomy when stratified by histopathology (tumor-free thyroid, node-negative, and node-positive medullary thyroid cancer) and mutated codon (611, 618, 620, 634, 768, 790, 804, 891, and 918). The wide overlap among the 3 histopathologic groups compromised individual predictions based on age alone. There was a significant relationship between the presence of lymph node metastases and increased pretherapeutic basal calcitonin levels. All 46 carriers with node-positive medullary thyroid cancer, who harbored 1 to 68 positive nodes, exhibited increased pretherapeutic basal calcitonin levels (91.4 pg/mL or higher). Conversely, 74 (44%) of 168 carriers with normal thyroids, C-cell hyperplasia, or node-negative medullary thyroid cancer displayed normal pretherapeutic basal calcitonin levels (negative predictive value 100%). Prediction of lymph node metastasis was better in carriers of codon 918 mutations (positive predictive value, PPV, 801/100%) and those older than 20 years of age (PPV, 50%). Discussion: In the absence of clinical evidence to the contrary, RET carriers with normal pretherapeutic basal calcitonin levels may forgo lymph no e dissection. The usefulness of calcitonin thresholds to break down the block of carriers with increased calcitonin levels should be explored further.