Supplementary Material for: Next-Generation Sequencing: Key for Diagnosing Angiomyolipoma - A Case Report

Introduction: Renal angiomyolipomas (AML) are rare tumors categorized within the perivascular epithelial cell (PEComa) family, most of which are benign, except for epithelioid angiomyolipomas (EAML) with malignant potential. EAML develops sporadically or as part of the tuberous sclerosis complex (TSC), where mutations of the TSC1/2 genes result in increased activation of the mammalian target of rapamycin (mTOR) signaling pathway. Case Presentation: A 52-year-old female patient that experienced dyspnea and abdominal pain, leading to the discovery of a retroperitoneal tumor confirmed by tomography. She was initially diagnosed with a retroperitoneal liposarcoma (LPS) with lung metastasis. Following a first-line anthracycline-based chemotherapy, the patient achieved a complete clinical and tomographic response. Subsequent surgical resection of the primary tumor and a course of ifosfamide monotherapy yielding a 36-month progression-free survival to date. Comprehensive molecular profiling of the primary tumor by Whole Exome Sequencing (WES) revealed pathogenic mutations in TSC2 and the absence of amplifications in MDM2 and CDK4, raising the need to consider a differential diagnosis in PEComas, and contemplate the potential use of AKT/Pi3K/mTOR pathway inhibitors. Pathological reevaluation confirmed the diagnosis of a metastatic retroperitoneal angiomyolipoma with complete response and no evidence of disease (NED). Conclusion: This case underscores the invaluable role of NGS testing in the differential diagnosis of retroperitoneal tumors, as well as the ability to identify precise therapeutic targets for the treatment of rare soft tissue cancer types within the realm of precision medicine.

引言：肾血管平滑肌脂肪瘤（Renal angiomyolipomas, AML）是一类归属于血管周上皮样细胞肿瘤（perivascular epithelial cell, PEComa）家族的罕见肿瘤，多数为良性，仅具有恶性潜能的上皮样血管平滑肌脂肪瘤（epithelioid angiomyolipomas, EAML）例外。EAML可散发出现，或作为结节性硬化症复合体（tuberous sclerosis complex, TSC）的临床表现之一；TSC1/2基因突变可导致哺乳动物雷帕霉素靶蛋白（mammalian target of rapamycin, mTOR）信号通路过度激活。
病例报告：本例患者为52岁女性，因呼吸困难与腹痛就诊，影像学检查发现腹膜后肿瘤，经断层扫描证实。患者最初被诊断为伴肺转移的腹膜后脂肪肉瘤（liposarcoma, LPS），接受一线蒽环类药物化疗后，达到临床与影像学完全缓解。随后患者接受原发肿瘤切除术，并辅以一疗程异环磷酰胺单药治疗，截至目前已实现36个月的无进展生存期。通过全外显子测序（Whole Exome Sequencing, WES）对原发肿瘤开展全面分子谱分析，结果显示TSC2存在致病突变，且MDM2与CDK4无扩增，这提示需对PEComa进行鉴别诊断，并考虑采用AKT/PI3K/mTOR通路抑制剂进行治疗。病理复评最终确诊为转移性腹膜后血管平滑肌脂肪瘤，患者达到完全缓解且无病生存（no evidence of disease, NED）。
结论：本病例突显了下一代测序（Next-Generation Sequencing, NGS）检测在腹膜后肿瘤鉴别诊断中的宝贵价值，同时也印证了在精准医学领域内，识别罕见软组织肿瘤精准治疗靶点的重要意义。