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<p>Soft-tissue sarcoma (STS) is a rare malignancy that accounts for less than 1% of all cancers, and recent advances in molecular biology have led to its classification based on genomic information. Some <i>RET</i>-rearranged neoplasms have been reported to present pathological features similar to Neurotrophic Tyrosine Kinase Receptor-rearranged spindle cell neoplasms. Here, we report the first case of head and neck spindle cell sarcoma with a GOLGA5–RET fusion that demonstrated a sustained clinical response to selpercatinib, identified through targeted next-generation sequencing (NGS). The patient was a 43&#xa0;year-old man with a tumor in the arytenoid region that was resected and diagnosed as a malignant spindle cell tumor. Despite initial treatment with surgical resection alone, local recurrence was confirmed, requiring salvage therapy with total laryngectomy and bilateral cervical dissection. Surgical specimen revealed a spindle tumor with a patternless pattern and collagenous stroma. Immunohistochemistry (IHC) with positivity for CD34, bcl-2 (focally), S100, and weak nuclear staining for STAT6, with absence of expression of CK AE1/3, desmin, c-kit, smooth muscle actin, myogenin, synaptophysin, and SOX10. Trk A/B/C were also negative on IHC. Following confirmation of multiple lung metastases, the patient was treated with doxorubicin monotherapy. Targeted NGS identified <i>GOLGA5–RET</i> rearrangement, <i>FGF14</i> amplification (equivocal), <i>CDKN2B</i> loss, and <i>CDKN2A</i> loss. <i>GOLGA5–RET</i> rearrangements were validated through fluorescence in situ hybridization. The patient subsequently was enrolled in a phase 1/2 trial for the selective <i>RET</i> inhibitor selpercatinib, resulting in a sustained partial response over 5&#xa0;years. Although solitary fibrous tumor (SFT) was initially considered as a differential diagnosis based on immunohistochemical findings, the lack of strong and diffuse STAT6 expression made this diagnosis unlikely. Subsequent next-generation sequencing (NGS) revealed a RET fusion, leading to the diagnosis of an RET-rearranged spindle cell neoplasm. This case highlights the importance of genomic testing for certain spindle cell sarcomas and the potential benefit of <i>RET</i>-specific inhibitors against <i>RET</i>-altered sarcomas.</p>

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The first case of GOLGA5–RET fusion-positive malignant spindle cell sarcoma of the head and neck responsive to selpercatinib

  • 期刊论文

  • 发表日期：

    2025年9月3日

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  • Takehiro Nakao,
  • Naoki Fukuda,
  • Xiaofei Wang,
  • Ryosuke Oki,
  • Tetsuya Urasaki,
  • Kenji Nakano,
  • Makiko Ono,
  • Junichi Tomomatsu,
  • Ryo Ariyasu,
  • Yukiko Sato,
  • Ippei Fukada,
  • Toru Sasaki,
  • Kengo Takeuchi,
  • Makoto Nishio,
  • Yuji Miura,
  • Shunji Takahashi

摘要

Soft-tissue sarcoma (STS) is a rare malignancy that accounts for less than 1% of all cancers, and recent advances in molecular biology have led to its classification based on genomic information. Some RET-rearranged neoplasms have been reported to present pathological features similar to Neurotrophic Tyrosine Kinase Receptor-rearranged spindle cell neoplasms. Here, we report the first case of head and neck spindle cell sarcoma with a GOLGA5–RET fusion that demonstrated a sustained clinical response to selpercatinib, identified through targeted next-generation sequencing (NGS). The patient was a 43 year-old man with a tumor in the arytenoid region that was resected and diagnosed as a malignant spindle cell tumor. Despite initial treatment with surgical resection alone, local recurrence was confirmed, requiring salvage therapy with total laryngectomy and bilateral cervical dissection. Surgical specimen revealed a spindle tumor with a patternless pattern and collagenous stroma. Immunohistochemistry (IHC) with positivity for CD34, bcl-2 (focally), S100, and weak nuclear staining for STAT6, with absence of expression of CK AE1/3, desmin, c-kit, smooth muscle actin, myogenin, synaptophysin, and SOX10. Trk A/B/C were also negative on IHC. Following confirmation of multiple lung metastases, the patient was treated with doxorubicin monotherapy. Targeted NGS identified GOLGA5–RET rearrangement, FGF14 amplification (equivocal), CDKN2B loss, and CDKN2A loss. GOLGA5–RET rearrangements were validated through fluorescence in situ hybridization. The patient subsequently was enrolled in a phase 1/2 trial for the selective RET inhibitor selpercatinib, resulting in a sustained partial response over 5 years. Although solitary fibrous tumor (SFT) was initially considered as a differential diagnosis based on immunohistochemical findings, the lack of strong and diffuse STAT6 expression made this diagnosis unlikely. Subsequent next-generation sequencing (NGS) revealed a RET fusion, leading to the diagnosis of an RET-rearranged spindle cell neoplasm. This case highlights the importance of genomic testing for certain spindle cell sarcomas and the potential benefit of RET-specific inhibitors against RET-altered sarcomas.