背景:PIK3CA突变的体细胞镶嵌导致各种类型的生长障碍,在术语PROS(PIK3CA相关的过度生长谱)下进行了总结。PI3K抑制剂的靶向治疗似乎是严重PROS病例的有希望的替代方案。因此,PIK3CA测试在未来可能变得更加相关。
方法:我们报告了14名PROS患者,在大多数情况下,他们接受了巨大的手术。从患者记录中检索临床数据。回顾性回顾了宏观和微观发现。对福尔马林固定的石蜡包埋(FFPE)材料进行突变分析。
结果:患者年龄为7个月至35岁。五名患者表现出额外的异常。一名患者患有CLOVES综合征。大多数标本是以肥大脂肪组织为特征的射线切除。总的来说,显微镜是微妙的。异常脂肪组织显示小叶至少表现出局灶性纤维间隔。在每种情况下,我们可以检测到PIK3CA突变.
结论:PROS患者受累脂肪组织的组织学总体上是非特异性的。因此,突变分析代表了诊断的关键,尤其是在不清楚的临床病例中。我们证明了FFPE材料适用于PIK3CA测试,这可以被认为是PI3K抑制剂靶向治疗的基础。
BACKGROUND: Somatic mosaicism for PIK3CA mutations causes various types of growth disorders, which have been summarized under the term PROS (PIK3CA related overgrowth spectrum). Targeted therapy with PI3K inhibitors seems to be a promising alternative for severe PROS cases. Therefore, PIK3CA testing may become more relevant in the future.
METHODS: We report on 14 PROS patients, who had surgery for macrodactyly in the majority of cases. Clinical data were retrieved from the patient\'s records. Macroscopic and microscopic findings were retrospectively reviewed. Mutational analysis was performed on formalin-fixed paraffin-embedded (FFPE) material.
RESULTS: Patient age ranged from 7 months to 35 years. Five patients showed additional anomalies. One patient had CLOVES syndrome. The majority of the specimens were ray resections characterized by hypertrophic fat tissue. Overall, microscopy was subtle. The abnormal adipose tissue showed lobules exhibiting at least focally fibrous septa. In each case, we could detect a PIK3CA mutation.
CONCLUSIONS: Histology of affected fat tissue in PROS patients is overall nonspecific. Therefore, mutational analysis represents the key to the diagnosis, especially in unclear clinical cases. We demonstrated that FFPE material is suitable for PIK3CA testing, which can be considered as basis for targeted therapy with PI3K inhibitors.