Synchronous Differentiated Thyroid Carcinoma and Nonthyroid Malignancies in Pediatric Patients: A Registry-based Case Series.
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INTRODUCTION: Differentiated thyroid carcinoma is the most common endocrine malignancy in children and typically presents as an isolated tumor. The synchronous occurrence of differentiated thyroid carcinoma with a second, non-thyroid primary malignancy is exceptionally rare and poorly characterized in pediatric patients. PATIENTS AND METHODS: We reviewed 571 pediatric patients with histologically confirmed differentiated thyroid carcinoma and enrolled in the national German Society for Pediatric Oncology and Hematology-malignant endocrine tumor registry between January 1997 and February 2025. Synchronous tumors were defined as two distinct malignancies diagnosed within 3 months prior to disease-specific therapy. Clinical, pathological, and genetic findings were analyzed descriptively. RESULTS: Five patients (0.9%) were diagnosed with synchronous differentiated thyroid carcinoma and a second primary malignancy. All thyroid tumors were papillary thyroid carcinomas, identified in the context of Hodgkin lymphoma (n=2), pheochromocytoma, synovial sarcoma, and Ewing sarcoma. In four cases, the thyroid tumor was detected during staging or evaluation for the primary malignancy. In one patient, the papillary thyroid carcinoma was diagnosed and treated prior to the identification of Hodgkin lymphoma. One patient harbored a pathogenic succinate dehydrogenase [ubiquinone] iron-sulfur subunit variant, and two patients had coexisting Hashimoto thyroiditis. All patients achieved complete remission. CONCLUSIONS: Synchronous presentation of differentiated thyroid carcinoma and other malignancies in pediatric patients, while rare, poses significant diagnostic and therapeutic challenges. These cases warrant multidisciplinary evaluation and may reflect underlying cancer predisposition, immune dysregulation, or previously unrecognized risk factors.