Malignant Potential of Thyroid Follicular Nodular Disease With Solid/Trabecular Components: A Case Report.

Although rare, thyroid follicular nodular disease (TFND) may exhibit a nodule-in-nodule (NN) appearance with solid/trabecular (ST) components (STc). While the STc has histologically aggressive features compared to the outer nodule (Out-N) in TFND, its pathological significance remains unclear. We present a case of TFND with STc in a 63-year-old man who developed skin implantation and lung metastases 3 years after lobectomy. Histologically, the skin tumor resembled STc with high mitotic activity. Molecular analysis revealed EZH1 mutations in both the Out-N and STc of TFND, while KRAS and TERT promoter mutations were restricted to STc and the skin tumor. These findings suggest that the STc of NN may be a precursor to poorly differentiated thyroid carcinoma arising from well-differentiated components through stepwise mutations. This case highlights the malignant potential of certain Noninvasive TFNDs and suggests the need for further analyses to clarify this hypothesis and reconsider their classification and management.