Neurofibromatosis Type 1 Tumor Involving the Anterosuperior Mediastinum With a Rare c.147C>G Germline Mutation: A...

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder that affects multiple organ systems, most commonly the skin, peripheral nerves, and skeletal system. However, involvement of the anterior mediastinum is rare and has been sporadically reported in the literature. Patients with NF1 have a markedly increased risk of developing malignant peripheral nerve sheath tumors (MPNSTs), which are associated with poor 5-year survival outcomes; therefore, early diagnosis and timely intervention are essential to improving clinical outcomes. We report a case of a solitary neurofibroma located in the anterosuperior mediastinum of a 41-year-old male of Han ethnicity. The tumor was completely resected via uniportal video-assisted thoracoscopic surgery (VATS). Immunohistochemical (IHC) analysis showed positivity for SOX10, S100, CD34, and vimentin, with a Ki-67 proliferation index of < 1%. Genetic analysis of tumor tissue identified two heterozygous nonsense variants in the NF1 gene: c.147C>G (p.Tyr49Ter), a rare pathogenic variant, and c.1318C>T (p.Arg440Ter), a common pathogenic variant. Concurrently, next-generation sequencing of the patient's son's blood sample revealed only the c.147C>G (p.Tyr49Ter) variant. No evidence of recurrence was observed during a 1-year postoperative follow-up. This case underscores the importance of a comprehensive, multidisciplinary approach in the evaluation of mediastinal masses to achieve an accurate diagnosis. Furthermore, it highlights the role of genetic testing in facilitating risk stratification and informing preventive strategies aimed at reducing the risk of progression from NF1 to MPNSTs.