Abstract
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 (NF1) and BCL6 corepressor like 1 (BCORL1), along with alterations in tumor protein p53 (TP53) and the telomerase reverse transcriptase (TERT) promoter region. Two months after R0 resection, the patient developed cervical recurrence and distant metastases involving the lungs, liver, bones, and mediastinum. In May 2025, the patient initiated intravenous chemotherapy consisting of pegylated liposomal doxorubicin and ifosfamide. The treatment response is currently being monitored during follow-up. 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 NF1 and BCORL1 mutations, along with TP53 and TERT promoter alterations, may underlie the tumor's aggressive biological behavior and supports the incorporation of molecular subtyping strategies in TLS management.