The tumor was encapsulated and exhibited a yellow-brown cut surface with focal hemorrhage (Fig. 1D). Microscopically, it consisted of spindle-to-ovoid cells haphazardly arranged within a collagenous stroma, surrounded by a well-defined capsule (Fig. 1E-G). Papillary thyroid carcinoma-like nuclear features were absent. Focal cytologic atypia was present (Fig. 1H), as were numerous blood vessels with hyalinized walls interspersed among the tumor cells (Fig. 1I). No follicular architecture was identified within the tumor. There was no evidence of capsular or vascular invasion. Mitotic activity was extremely low (0–1 per 2 mm2), and no tumor necrosis was identified.

Immunohistochemically, the tumor cells were positive for TTF-1, PAX8, claudin-4, vimentin, CD56, HBME1, smooth muscle actin (focal), and β-catenin (membranous), and negative for AE1/AE3, CAM5.2, CK19, EMA, calcitonin, synaptophysin, S-100, SOX10, desmin, h-caldesmon, myogenin, CD31, ERG, CD34, estrogen receptor, thyroglobulin, STAT6, HMB45, p53, and MDM2. E-cadherin showed heterogeneous membranous staining. Ki-67 labeling index was 1.2% (Fig. 2). Genetic analysis using Sanger sequencing revealed an NRAS p.Q61R mutation.

Although no definitive evidence of invasion was identified on hematoxylin and eosin–stained sections, HBME1 positivity and nuclear atypia were noted in the tumor cells. However, in the absence of invasive features, the tumor was classified as a non-invasive follicular cell–derived thyroid neoplasm composed entirely of spindle cells.

Representative immunohistochemical results