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

Abstract

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 1961-2019 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<0.0001), have larger tumors (p<0.0001), a higher initial stage grouping (p=0.001) and have more structural disease (p=0.0045) and distant metastases (DM) (p=0.00084) at last follow up, but are not more likely to die from MTC (p=0.42). 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=0.27), presence of DM at diagnosis (p=1.0), disease status at last follow-up (p=0.13), overall survival (p=0.57), or disease specific survival (p=0.87). Of the twelve sMTC tumors that underwent somatic testing, eleven (91%) had an identifiable alteration: ten RET gene alterations and one ALK fusion. Conclusions 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.