Integrative diagnostic approach in a rare case of primary thyroid leiomyosarcoma with distant metastasis: a case report and literature review.

Background: Primary thyroid leiomyosarcoma (TLS) is an exceptionally rare malignant tumor, with fewer than 50 cases reported in the literature worldwide. In this case, the thyroid lesion was initially misdiagnosed as a benign nodule based on ultrasound and fine-needle aspiration (FNA), and treated with microwave ablation. However, the mass continued to enlarge. Case Description: A 69-year-old female patient was re-evaluated due to progressive enlargement of the thyroid lesion. Core needle biopsy revealed a spindle cell neoplasm. Immunohistochemistry showed positivity for smooth muscle actin (SMA), desmin, calponin, and p53. Given the presence of airway compression symptoms and the patient's strong desire for surgery, the clinical team developed an active surgical plan and performed resection of the thyroid and involved adjacent tissues to relieve local compression and control disease progression. Postoperative histopathological examination confirmed high-grade TLS, with evidence of invasion into the recurrent laryngeal nerve and internal jugular vein. High-throughput sequencing identified coexisting mutations in neurofibromin 1 ( Conclusions: When TLS initially presents with benign-appearing ultrasound and FNA findings, misdiagnosis may easily occur. This case highlights the importance of early integration of histopathological and molecular evaluation for progressive thyroid lesions. The co-occurrence of