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Updated: Aug 27, 2025
Spontaneous Murine Model of Anaplastic Thyroid Cancer
Published on: February 3, 2023
Medullary thyroid cancer with RET V804M mutation: more indolent than expected?
Nicholas A Frisco1, Alexander H Gunn1, Samantha M Thomas2
1Department of Surgery, Duke University Medical Center, Durham, NC; Duke University School of Medicine, Durham, NC.
Background:
Significant genotype-phenotype variability among multiple endocrine neoplasia type 2A patients with a RET V804M mutation has been reported.
Methods:
Patients with a RET V804M mutation treated at a single center were identified (January 1996-December 2020). The baseline characteristics, operative details, pathology, biochemical, and long-term data were analyzed.
Results:
There were 79 patients; none developed pheochromocytoma or hyperparathyroidism or died in the study period. The mean age was 41.5 years (range = 1.0-81.0 years); 46.8% were men. Of 68 surgical patients, 53 (77.9%) underwent total thyroidectomy and 15 (22.1%) underwent total thyroidectomy with central neck dissection with or without lateral neck dissection. Twenty-four patients had elevated preoperative calcitonin, of whom 12 underwent total thyroidectomy (median = 7.5; range = 5.0-237.0 pg/mL), 10 underwent total thyroidectomy + central neck dissection (median = 27.6; range = 5.1-147.0 pg/mL), and 2 underwent total thyroidectomy + central neck dissection + lateral neck dissection (median = 3182.0; range = 361.0-6003.0 pg/mL). Pathology was benign (27.9%), papillary thyroid cancer alone (1.5%), C-cell hyperplasia (23.5%), and medullary thyroid cancer (47.1%; median tumor size = 3.0 mm). Three patients had elevated calcitonin postoperatively (median follow-up time = 60.0 months). In adjusted modeling, a preoperative calcitonin >5 pg/mL was associated with having medullary thyroid cancer on final pathology (odds ratio = 13.3; 95% confidence interval, 3.2-56.3; P < .001).
Conclusion:
In this large United States cohort of surgical patients with a RET V804M mutation, most had indolent disease and were without classic multiple endocrine neoplasia type 2A features. Calcitonin >5 pg/mL may serve as a meaningful value to guide surveillance and timing of surgery.
Insights
Patients with the RET V804M mutation often have indolent disease, with most cases lacking classic multiple endocrine neoplasia type 2A features. A preoperative calcitonin level above 5 pg/mL may help guide surgical timing and patient surveillance.
Area of Science:
- Endocrinology
- Genetics
- Oncology
Background:
- Multiple Endocrine Neoplasia type 2A (MEN2A) exhibits significant genotype-phenotype variability.
- The RET V804M mutation is associated with this variability, necessitating further investigation into its clinical implications.
Purpose of the Study:
- To analyze the clinical characteristics and outcomes of patients with the RET V804M mutation.
- To identify potential biomarkers for disease severity and guide management strategies.
Main Methods:
- Retrospective analysis of 79 patients with RET V804M mutation treated at a single center from January 1996 to December 2020.
- Evaluation of baseline characteristics, surgical procedures, pathology reports, biochemical data, and long-term follow-up.
Main Results:
- No patients developed pheochromocytoma or hyperparathyroidism; mortality was zero during the study period.
- Medullary thyroid cancer was diagnosed in 47.1% of patients, with a median tumor size of 3.0 mm.
- Elevated preoperative calcitonin (>5 pg/mL) was significantly associated with medullary thyroid cancer (OR=13.3, P<.001).
Conclusions:
- The RET V804M mutation in this cohort primarily presented as indolent disease, often without classic MEN2A manifestations.
- A preoperative calcitonin level exceeding 5 pg/mL is a valuable indicator for guiding surveillance and surgical intervention timing.
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