Lung Metastasis in Children with Differentiated Thyroid Cancer: Factors Associated with Diagnosis and Outcomes of Therapy

Background:Lung metastasis from differentiated thyroid cancer (DTC) in children and young adults (CAYA) is estimated at 25%, which is 3-4 times higher than in adults. Lung metastases may respond to radioactive iodine (RAI) therapy and overall survival is excellent. Associations with lung metastasis include lateral lymph node (LN) disease although CAYA data are limited. We investigated factors associated with lung metastasis in children and adolescents and described their presentation and outcome. Methods:A retrospective review of medical records from 1998 to 2017 in patients aged <18 years treated at a tertiary pediatric center was carried out. Data on age, clinical features at diagnosis, histology, biochemistry, imaging, RAI therapy, and outcome were collected. Results:Patients treated for DTC totaled 98 and 19 of 98 (19%) patients had lung metastasis; 17 of 19 (89%) patients were identified within 6 months from thyroidectomy. Patients with lung metastasis were younger (p < 0.001)-40% <13 years old had lung metastasis-and had a larger primary tumor diameter (p = 0.01). Absence of LN disease had negative predictive values >= 90% (p < 0.02). Patients with lung metastasis had a higher postoperative thyrotropin-stimulated thyroglobulin (Tg) (p < 0.001), >= 2 ng/mL in 10 of 11 (91%) patients, and 100% had an elevated preoperative Tg (>60 ng/mL). Post-therapy whole body scan (WBS) identified most metastasis (13 of 17 patients), which were mostly diffuse (11 of 19 patients). Discordant findings were found between WBS and computed tomography (CT) at diagnosis (2 patients), WBS and CT during surveillance (3 patients), and diagnostic and post-therapy WBS (2 patients). Final outcome was "excellent" in 3 of 19 (16%) patients, "biochemically persistent" in 1 of 19 (5%) patients, "structurally persistent" in 13 of 19 (68%) patients-including 1 death-and indeterminate in 2 of 19 (11%) patients. Postoperative Tg correlated with response to therapy. Lung metastasis pattern and RAI cumulative activity were not predictive of response to therapy. Conclusions:Lung metastases are mostly observed at diagnosis of DTC and higher suspicion should be maintained in CAYA who are younger, have LN disease, and have elevated postoperative Tg. Preoperative Tg shows promise as another predictive marker, but limited sample size precludes generalization. "Excellent" response to therapy is uncommon-multiple RAI courses do not necessarily improve outcome-response appears unrelated to RAI activity or metastasis pattern.