DICER1 and Associated Conditions: Identification of At-risk Individuals and Recommended Surveillance Strategies—Response

We thank Gilmour and colleagues for their thoughtful commentary on the guidelines summarized in “DICER1 and Associated Conditions: Identification of At-risk Individuals and Recommended Surveillance Strategies.” (1) Gilmour and colleagues suggested that there may be clinical scenarios in which thyroidectomy for patients with pathogenic germline DICER1 variants would be warranted without preoperative fine-needle aspiration (FNA). The authors describe a 10-year-old male with a pathogenic DICER1 variant presenting with a large multinodular goiter (MNG) associated with symptomatic airway obstruction.

We agree with Gilmour and colleagues that for this patient, preoperative FNA was appropriately declined on the basis of patient risk.

Pathogenic variation in DICER1 is associated with familial MNG as well as an increased incidence of less invasive forms of differentiated thyroid cancer (DTC), most commonly follicular variant papillary thyroid cancer and minimally invasive follicular thyroid cancer (2). In rare circumstances, DICER1 may also be associated with solid variant PTC; ref. 3) or poorly differentiated thyroid carcinoma (4). In a cohort of 145 DICER1 mutation carriers, the cumulative incidence of MNG by 40 years of age was 75% among females and 17% among males; however, only 4 cases of DTC were reported (2). Hence, while there is a 16- to 24-fold increased risk of thyroid cancer over a patient's lifetime, MNG is more common than thyroid carcinoma in patients with DICER1.

On the basis of these observations, the current recommendation is to avoid reflexive, prophylactic thyroidectomy, a common approach for patients with pathogenic germline variants in the RET gene associated with a high penetrance for developing medullary thyroid carcinoma–a cancer for which there are limited treatment options once metastatic disease is present. Rather, the approach to patients with familial DTC syndromes is to stratify surgery based on thyroid ultrasound and FNA data (5).

For the majority of patients, FNA is a safe and reliable method to direct management. However, as Gilmour and colleagues suggest, thyroidectomy without FNA may be more appropriate in certain clinical situations. Airway compromise is a situation in which it would be reasonable to proceed to thyroidectomy without preoperative FNA. Another potential situation would be an unequivocal diagnosis of thyroid cancer with associated lymphadenopathy; however, for the latter, caution should be exercised as lymphocytic thyroiditis with associated reactive lymphadenopathy may mimic infiltrative PTC.

The case presented by Gilmour and colleagues also highlights the potential for postsurgical diagnosis of DTC. In this situation, performing surgery without FNA may not increase the risk of death from thyroid cancer; however, it may increase the risk for repeat surgery as the initial surgery would not have been performed with curative intent. In contrast, for patients with benign disease, the lack of preoperative FNA data would not allow the patient an opportunity to pursue surveillance, avoiding potential surgical complications as well as life-long thyroid hormone replacement therapy. Given these concerns, we feel that adherence to the ATA guidelines for children (5) and adults (6) with thyroid nodules is the best approach for the majority of patients, with variance from guidelines and recommendations based on individual patient circumstances and attention to the rare possibility of poorly differentiated thyroid carcinoma.

We are grateful to the authors and editors for the opportunity to discuss this timely topic. We hope that ongoing international collaboration will provide additional data on which to base clinical decisions. We learn from every individual and every family.

See the original Letter to the Editor, p. 1688