我们报道了一个Klippel Trenaunay综合征的病例，该病例在9年期间进行了临床和分子监测。利用cfDNA NGS液体活检和组织活检鉴定出PIK3CA（p（E545G））的体细胞嵌合突变。在56岁时，由于PIK3CA背景的干预性克隆突变，她在受影响的右腿上发展出了鳞状细胞癌，并接受了手术治疗。九年后，PIK3CA突变组织支持了不同克隆突变引起的双肺腺癌。一年后，患者死于新的FGFR3克隆引起的转移，对标准护理和免疫治疗无效。我们的结果强调了血管畸形进程中发生的肿瘤转化的分子特征，并支持PIK3CA突变组织必须被视为癌前病变的观点。重要的是，它们强调了结合cfDNA NGS液体和组织活检来监测疾病演变，并识别出可靶向个体化治疗的侵袭性克隆的有效性，这比传统方案更高效。版权所有©2023 Serio, Palmieri, Innamorato, Loberti, Fallerini, Ariani, Antolini, Covarelli, Vaghi, Frullanti, Renieri and Pinto。

We report a case of Klippel Trenaunay Syndrome that was monitored both clinically and molecularly over a period of 9 years. A somatic mosaic mutation of PIK3CA (p(E545G)) was identified using both cfDNA NGS liquid biopsy and tissue biopsy. At the age of 56, due to intervening clonal mutations in PIK3CA background, she developed a squamous cell carcinoma in the right affected leg which was treated surgically. Nine years later, lung bilateral adenocarcinoma arose on PIK3CA mutated tissues supported by different clonal mutations. One year later, the patient died from metastases led by a new FGFR3 clone unresponsive to standard-of-care, immunotherapy-based. Our results highlight the presence of a molecular hallmark underlying neoplastic transformation that occurs upon an angiodysplastic process and support the view that PIK3CA mutated tissues must be treated as precancerous lesions. Importantly, they remark the effectiveness of combining cfDNA NGS liquid and tissue biopsies to monitor disease evolution as well as to identify aggressive clones targetable by tailored therapy, which is more efficient than conventional protocols.Copyright © 2023 Serio, Palmieri, Innamorato, Loberti, Fallerini, Ariani, Antolini, Covarelli, Vaghi, Frullanti, Renieri and Pinto.