Pediatric Medullary Thyroid Carcinoma: Clinical Presentations and Long-Term Outcomes in 144 Patients Over 6 Decades
Sarah G Hensley1,2, Mimi I Hu2, Roland L Bassett3
1Baylor College of Medicine, Department of Pediatrics, Section of Pediatric Diabetes and Endocrinology, Houston, TX 77030, USA.
Insights
Sporadic medullary thyroid carcinoma (sMTC) in children is often RET-driven and presents with advanced disease, but outcomes are similar to hereditary forms when diagnosed clinically. Somatic testing is recommended for targeted therapy.
Area of Science:
- Oncology
- Genetics
- Pediatric Endocrinology
Background:
- Sporadic medullary thyroid carcinoma (sMTC) is rare in children, with limited research on its specific characteristics.
- Understanding sMTC in pediatric patients is crucial for diagnosis and treatment strategies.
Purpose of the Study:
- To compare the clinical presentation and long-term outcomes of pediatric sMTC with hereditary medullary thyroid carcinoma (hMTC).
- To identify genetic drivers and clinical features of sMTC in young individuals.
Main Methods:
- Retrospective analysis of 144 patients (≤21 years) with MTC diagnosed between 1961-2019.
- Comparison of clinical data, staging, and outcomes between sMTC and hMTC cohorts.
- Somatic molecular testing for genetic alterations in sMTC tumors.
Main Results:
- sMTC (14%) presented in older children with larger tumors and more advanced disease than hMTC (86%).
- Despite advanced presentation, sMTC patients did not have significantly worse survival than hMTC.
- Somatic testing revealed RET alterations in 91% of sMTC tumors, with one ALK fusion.
Conclusions:
- Pediatric sMTC is predominantly a RET-driven malignancy, accounting for 14% of childhood MTC.
- Clinical presentation and outcomes for sMTC are comparable to hMTC when diagnosed clinically, not by family history.
- Somatic molecular testing is recommended for pediatric sMTC to guide systemic therapy decisions.
Context:
Sporadic medullary thyroid carcinoma (sMTC) rarely occurs in childhood and no studies have specifically focused on this entity.
Objective:
To describe the clinical presentations and long-term outcomes of a large cohort of children and young adults with sMTC compared with hereditary MTC (hMTC).
Methods:
Retrospective study of 144 patients diagnosed with MTC between 1961 and 2019 at an age ≤ 21 years and evaluated at a tertiary referral center.
Results:
In contrast to hMTC (n = 124/144, 86%), patients with sMTC (n = 20/144, 14%) are older (P < .0001), have larger tumors (P < .0001), a higher initial stage grouping (P = .001) and have more structural disease (P = .0045) and distant metastases (DM) (P = .00084) at last follow-up, but are not more likely to die from MTC (P = .42). Among 77 patients diagnosed clinically, not by family history (20/20 sMTC and 57/124 hMTC), there was no difference in the initial stage (P = .27), presence of DM at diagnosis (P = 1.0), disease status at last follow-up (P = .13), overall survival (P = .57), or disease-specific survival (P = .87). Of the 12 sMTC tumors that underwent somatic testing, 11 (91%) had an identifiable alteration: 10 RET gene alterations and 1 ALK fusion.
Conclusion:
sMTC is primarily a RET-driven disease that represents 14% of childhood-onset MTC in this cohort. Pediatric sMTC patients are older, present with clinical disease at a more advanced TNM classification, and have more persistent disease at last follow-up compared with hMTC, but these differences disappear when comparing those presenting clinically. Somatic molecular testing should be considered in sMTC patients who would benefit from systemic therapy.
