Expanding Our Knowledge of DICER1 Gene Alterations and Their Role in Thyroid Diseases

Simple Summary Mutations in DICER1, a gene involved in RNA interference, have been associated with a wide range of multi-organ neoplastic and non-neoplastic conditions. Historically known for its association with pleuropulmonary blastoma, DICER1 syndrome has received more attention due to the association with newly discovered diseases and tumors. Recent studies evaluating DICER1 mutations and DICER1-driven thyroid disease in both pediatric and adult thyroid nodules revealed thyroid disease as the most common manifestation of DICER1 mutations. Thyroid follicular nodular disease and differentiated thyroid carcinomas in infancy are highly specific manifestations of germline DICER1 mutation or DICER1 syndrome. Furthermore, poorly differentiated thyroid carcinoma and thyroblastoma should raise the concern for somatic DICER1 mutations. Recognizing these manifestations should prompt clinicians to expedite genetic evaluation for this neoplastic syndrome and classify these patients as high risk for additional multi-organ malignancies. Abstract Mutations in DICER1, a gene involved in RNA interference, have been associated with a wide range of multi-organ neoplastic and non-neoplastic conditions. Historically known for its association with pleuropulmonary blastoma, DICER1 syndrome has received more attention due to the association with newly discovered diseases and tumors. Recent studies evaluating DICER1 mutations and DICER1-driven thyroid disease in both pediatric and adult thyroid nodules revealed thyroid disease as the most common manifestation of DICER1 mutations. This study undertakes a comprehensive investigation into DICER1 mutations, focusing on their role in thyroid diseases. Specific attention was given to thyroid follicular nodular disease and differentiated thyroid carcinomas in infancy as highly indicative of germline DICER1 mutation or DICER1 syndrome. Additionally, poorly differentiated thyroid carcinoma and thyroblastoma were identified as potential indicators of somatic DICER1 mutations. Recognizing these manifestations should prompt clinicians to expedite genetic evaluation for this neoplastic syndrome and classify these patients as high risk for additional multi-organ malignancies. This study comprehensively synthesizes the current knowledge surrounding this genetically associated entity, providing intricate details on histologic findings to facilitate its diagnosis.

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