Thyroblastoma as a manifestation of DICER1 syndrome with confirmed germline mutation and comprehensive literature review.

Thyroblastoma is listed under "embryonic thyroid neoplasms" in the 5th edition of the WHO classification of thyroid tumors. This tumor mirrors the embryonic development of the thyroid. Molecular analysis has identified frequent somatic hotspot mutations in the DICER1 gene. While thyroblastoma shares morphological features with other blastomas linked to DICER1 syndrome, previous studies have not confirmed germline pathogenic DICER1 variants in thyroblastoma. To date, thyroblastoma was still considered a tumor driven by somatic mutations. Here, we report a case of a 51-year-old woman whose thyroblastoma was initially misdiagnosed. Three years following total thyroidectomy and neck lymph node dissection, she developed distant lung metastases. Both the primary and metastatic tumors shared identical histopathological features. The tumors consisted of primitive thyroid follicular components, fetal-type glands, and round to short spindle stromal cells. In addition, cartilage differentiation was observed in the lung metastasis. Next-generation sequencing (NGS) of the primary thyroid tumor and peripheral blood revealed the somatic mutation in the DICER1 gene (p.D1810V) and heterozygous germline DICER1 mutation (p.S1076N), respectively. This evidence indicates that thyroblastoma represents a component of the DICER1 syndrome tumor spectrum. Further mechanistic studies are warranted to establish whether DICER1 germline pathogenic variants confer susceptibility to thyroblastoma. Somatic and germline DICER1 genetic testing is recommended for all patients diagnosed with thyroblastoma to identify potential DICER1 syndrome and make proper management of this inherited disease.