Individualization of lymph node dissection in RET (rearranged during transfection) carriers at risk for medullary thyroid cancer: value of pretherapeutic calcitonin levels.
OBJECTIVE
This study sought to define the need for lymph node dissection in Rearranged during Transfection (RET) carriers at risk for hereditary medullary thyroid cancer.


BACKGROUND
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, 80%-100%) and those older than 20 years of age (PPV, 50%).


CONCLUSIONS
In the absence of clinical evidence to the contrary, RET carriers with normal pretherapeutic basal calcitonin levels may forgo lymph node dissection. The usefulness of calcitonin thresholds to break down the block of carriers with increased calcitonin levels should be explored further.
Machens
Andreas
A
Department of General, Visceral and Vascular Surgery, Martin Luther University Halle-Wittenberg, Germany. AndreasMachens@aol.com
Lorenz
Kerstin
K
Dralle
Henning
H
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D002116:Calcitonin / Q000097:blood*; D018276:Carcinoma, Medullary / Q000097:blood / Q000235:genetics* / Q000473:pathology*; D016022:Case-Control Studies; D002648:Child; D015331:Cohort Studies; D005260:Female; D006579:Heterozygote; D006801:Humans; D008197:Lymph Node Excision; D008297:Male; D009154:Mutation / Q000235:genetics; D011237:Predictive Value of Tests; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology*; D013965:Thyroidectomy; D055815:Young Adult
D002116:Calcitonin; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human