Fibro-adipose vascular anomaly (FAVA): three case reports with an emphasis on the mammalian target of rapamycin (mTOR) pathway
Fibro-adipose vascular anomaly (FAVA): three case reports with an emphasis on the mammalian target of rapamycin (mTOR) pathway
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DOI：
10.1186/s13000-020-01004-z
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发表时间：
2020-07-25
影响因子：
2.6
通讯作者：
Morii, Eiichi
中科院分区：
文献类型：
--
作者：
Hori, Yumiko;Hirose, Katsutoshi;Morii, Eiichi
研究背景纤维脂肪血管异常（Fibro-adipose vascular anomaly，FAVA）是一种新型的血管异常，由磷脂酰肌醇-4，5-二磷酸3-激酶催化亚基α（phosphatidylinositol-4，5-bisphosphate 3-kinase catalytic subunit alpha，PIK3CA）的体细胞和嵌合体功能获得性突变引起，PIK3CA突变过度激活哺乳动物雷帕霉素靶蛋白（mammalian target of rapamycin，mTOR）通路，促进血管生成和淋巴管生成。组织学上，FAVA由肌内纤维和脂肪组织组成，并伴有静脉畸形（VM）。虽然西罗莫司作为mTOR抑制剂对FAVA有良好的反应，但mTOR通路的表达模式仍不清楚。在此，我们以化学方法研究了三名新的FAVA患者，重点是mTOR途径（p-S6K1、p-4EBP 1和p-AKT）。病例介绍病例1：一名10岁女性自6岁起主诉左大腿疼痛。在临床诊断为VM的情况下，她接受了病变的手术切除。病例2：一名29岁女性患者自18岁起主诉左肩不适和轻度疼痛。分娩后，她有严重的持续疼痛和挛缩的肩膀。在临床诊断为VM的情况下，进行手术切除。病例3：一名53岁女性在31岁时接受膝关节肿瘤手术治疗后主诉疼痛和膝关节受限。在临床诊断为不典型脂肪瘤或高度恶性脂肪肉瘤的情况下，进行手术切除。在组织学上，所有三名患者都表现出骨骼肌内纤维和脂肪组织的特征性特征以及异常血管，从而诊断为FAVA。虽然VM已被报道为FAVA的重要发现，但免疫组织化学结果显示，所有病例的异常血管均由VM和淋巴管畸形（LM）组成。此外，除血管畸形外，FAVA的异常纤维和脂肪组织还表达mTOR途径成分。结论我们提出了三例新的FAVA病例。组织学和免疫组化分析显示，VM和LM复合体是FAVA的重要发现，并且mTOR通路组分在异常纤维组织、脂肪组织和血管畸形中表达。这些结果表明FAVA可能是由PI3K/AKT/mTOR通路引起的间充质畸形。
Background Fibro-adipose vascular anomaly (FAVA) is a new entity of vascular anomalies with somatic and mosaic gain-of-function mutations of thephosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha(PIK3CA).PIK3CAmutation excessively activates mammalian target of rapamycin (mTOR) pathway, which promotes angiogenesis and lymphangiogenesis. Histologically, FAVA is composed of intramuscular fibrous and adipose tissues with venous malformation (VM). Although sirolimus known as a mTOR inhibitor has good response to FAVA, expression pattern of the mTOR pathway was still unclear. Herein, we immunohistochemically investigated three novel FAVA patients with an emphasis on the mTOR pathway (p-S6K1, p-4EBP1 and p-AKT). Case presentation Case 1: A 10-year-old female had complained of pain in the left thigh since she was 6-year-old. Under the clinical diagnosis of VM, she underwent surgical resection for the lesion. Case 2: A 29-year-old female patient had complained of discomfort and mild pain in the left shoulder since she was 18-year-old. After childbirth, she had severe ongoing pain and contracture of the shoulder. Under clinical diagnosis of VM, surgical resection was performed. Case 3: A 53-year-old female had complained of pain and knee restriction after surgical treatment of a knee tumor at the age of 31. Under the clinical diagnosis of atypical lipomatous tumor or high grade liposarcoma, surgical resection was performed. Histologically, all three patients presented with characteristic features of fibrous and adipose tissues with abnormal vessels within the skeletal muscle, leading to diagnosis of FAVA. Although VM has been reported as an important finding in FAVA, immunohistological findings demonstrated that abnormal vessels comprised complex of VM and lymphatic malformation (LM) in all cases. Furthermore, besides vascular malformation, abnormal fibrous and adipose tissues of FAVA expressed mTOR pathway components. Conclusions We presented three new cases of FAVA. Histological and immunohistochemical analyses revealed that VM and LM complex was an important finding in FAVA, and that the mTOR pathway components were expressed in abnormal fibrous tissue, adipose tissue and vascular malformation. These findings suggested that FAVA might be a mesenchymal malformation caused by PI3K/AKT/mTOR pathway.