The tumor was predominantly located within a 2.5 cm sclerotic thyroid nodule, showing capsular invasion and infiltration into the surrounding thyroid parenchyma (Fig. 1A). Histologically, it consisted of solid sheets of small round to oval cells with enlarged nuclei, scant cytoplasm, and high mitotic activity (Fig. 1B). Focal tubule-like structures were present (Fig. 1C), with partial embedding in fibrous stroma and focal continuity with thyroid follicles (Fig. 1D).

(A) A 1.8 cm tumor within a 2.5 cm sclerotic, encapsulated thyroid nodule (arrowheads), with capsular invasion and parenchymal infiltration (arrows). (B) Solid growth of small round to oval cells with enlarged nuclei, scant cytoplasm, coarse chromatin, and brisk mitoses. (C) Focal tubule-like structures of columnar cells. (D) Tumor nests partly embedded in fibrous stroma with focal connection to follicles. (E) Lymph node metastases with solid nests and multiple rosettes, lacking follicular or spindle components

Three lateral cervical lymph nodes showed metastases composed of small round cells with multifocal rosettes (Fig. 1E), abundant necrosis, and high mitotic activity, without stromal or follicular/tubular differentiation.

Immunohistochemically, tumor cells were largely cytokeratin-negative with focal CK18 positivity (Fig. 2A), and negative for TTF1, PAX8, and thyroglobulin (positive in adjacent follicles; Fig. 2B). SALL4 was strongly expressed (Fig. 2C), synaptophysin was weak and heterogeneous (Fig. 2D), and chromogranin A and INSM1 were negative.

No stromal expression of desmin (Fig. 2E) or myogenin was detected. Tumor cells were also negative for calcitonin, S100, CD99, SOX10, CD45, CEA, BRAFV600E, NUT, and OCT4. Nuclear SMARCA4 expression was retained, and p53 and retinoblastoma protein (RB1) showed a normal expression pattern. The proliferative index was very high (> 90%, Ki-67; Fig. 2F).

Immunohistochemistry: (A) Tumor cells largely CK18-negative with focal perinuclear positivity (inset); follicles strongly positive. (B) TTF1 positive in follicles, negative in tumor cells. (C) Strong nuclear SALL4 expression. (D) Weak, heterogeneous synaptophysin expression. (E) No desmin-positive stromal cells (vascular control, inset). (F) Very high Ki-67 proliferation

Targeted next-generation sequencing identified two pathogenic DICER1 variants: a splice-site mutation (c.5603 + 2T > C, variant allele frequency 40%) and an RNase IIIb hotspot mutation (c.5127T > A; p.D1709E, 37%) consistent with a typical two-hit mechanism.