Pediatric Medullary Thyroid Carcinoma: Clinical Presentations and Long-Term Outcomes in 144 Patients Over 6 Decades

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.