An unusual spindle cell variant of papillary thyroid carcinoma with KIF5B::MET fusion: report of a case.

Abstract

The spindle cell variant of papillary thyroid carcinoma (PTC) is exceptionally rare and poses significant diagnostic challenges due to its morphological overlap with other spindle cell lesions of the thyroid. We report a novel case of spindle cell variant PTC in a 66-year-old woman presenting with a TI-RADS 4 thyroid nodule, initially classified as Bethesda III on fine-needle aspiration. Histopathological examination revealed a biphasic tumor composed predominantly of bland spindle cells arranged in solid sheets and fascicles, admixed with entrapped thyroid follicles. Both components demonstrated subtle nuclear features of PTC, including mild nuclear enlargement, elongation, nuclear membrane irregularities, and occasional nuclear grooves and intranuclear pseudoinclusions. The tumor showed strong immunoreactivity for CK19, TTF-1, PAX-8, and galectin-3. Comprehensive molecular profiling by targeted next-generation sequencing identified a KIF5B::MET kinase fusion, confirmed by reverse-transcription PCR, Sanger sequencing, and MET break-apart fluorescence in situ hybridization. This case represents the first spindle cell variant PTC documented to harbor a kinase fusion. The identification of KIF5B as a novel MET fusion partner further expands the molecular spectrum of kinase-driven thyroid carcinomas. The patient exhibited no evidence of recurrence after 38 months post-thyroidectomy, suggesting indolent behavior. Our findings underscore the diagnostic utility of molecular profiling in spindle cell thyroid neoplasms and highlight MET fusions as potential therapeutic targets. This case contributes to emerging evidence that MET-rearranged thyroid carcinomas may exhibit variable clinical outcomes.