Lymphatic manifestations of lymphangioleiomyomatosis.
Lymphatic manifestations of lymphangioleiomyomatosis.
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发表时间：
2014-01
期刊：
影响因子：
2.5
通讯作者：
R. Gupta;M. Kitaichi;Y. Inoue;R. Kotloff;F. McCormack
中科院分区：
文献类型：
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作者：
R. Gupta;M. Kitaichi;Y. Inoue;R. Kotloff;F. McCormack
淋巴管平滑肌瘤病（LAM）是一种缓慢进展，低级别，转移性肿瘤，与细胞侵袭和肺实质囊性破坏有关。虽然浸润肺部的LAM细胞来源尚不清楚，但现有证据表明，该疾病主要通过淋巴通道传播，常累及腹部、轴向和腹膜后淋巴结，提示起源于骨盆。LAM细胞在结节性硬化症基因中含有突变，并产生淋巴管生成生长因子，促进淋巴系统的进入和运动，并可能在肺的破坏性组织重塑中发挥重要作用。LAM的淋巴表现包括胸导管壁侵犯、淋巴管油膜肌瘤形成、腹膜、胸膜和心包间隙乳糜积液、乳糜溶解、乳糜结肠漏、脐乳糜漏、肺乳糜充血和下肢淋巴水肿。LAM病变表达淋巴管生成生长因子VEGF-C和VEGF-D；生长因子受体，VEGFR-2和VEGFR-3；以及LYVE-1和podoplanin标记物，并伴有混乱的淋巴通道。血清VEGF-D在70%的LAM患者中升高，是临床上有用的诊断和预后生物标志物。西罗莫司分子靶向治疗稳定肺功能，抗淋巴管生成，对LAM的淋巴和乳糜并发症非常有效。未来对有淋巴表现或血清VEGF-D升高的LAM患者的试验可能会集中在VEGF-C/VEGF-D/VEGFR-3轴上。
Lymphangioleiomyomatosis (LAM) is a slowly progressive, low grade, metastasizing neoplasm, associated with cellular invasion and cystic destruction of the pulmonary parenchyma. Although the source of LAM cells that infiltrate the lung is unknown, available evidence indicates that the disease spreads primarily through lymphatic channels, often involving abdominal, axial, and retroperitoneal nodes, suggestive of an origin in the pelvis. LAM cells harbor mutations in tuberous sclerosis genes and produce lymphangiogenic growth factors, which facilitate access to and movement through the lymphatic system and likely play an important role in destructive tissue remodeling in the lung. Lymphatic manifestations of LAM include thoracic duct wall invasion, lymphangioleiomyoma formation, chylous fluid collections in the peritoneal, pleural, and pericardial spaces, chyloptysis, chylocolporrheal chylometrorrhea, chyle leak from the umbilicus, chylous pulmonary congestion, and lower extremity lymphedema. LAM lesions express lymphangiogenic growth factors VEGF-C and VEGF-D; growth factor receptors, VEGFR-2 and VEGFR-3; and markers LYVE-1 and podoplanin, and are laced with chaotic lymphatic channels. Serum VEGF-D is elevated in 70% of patients with LAM and is a clinically useful diagnostic and prognostic biomarker. Molecular targeted therapy with sirolimus stabilizes lung function, is anti-lymphangiogenic, and is highly effective for the lymphatic and chylous complications of LAM. Future trials in patients with LAM who have lymphatic manifestations or elevated serum VEGF-D will likely focus on the VEGF-C/VEGF-D/VEGFR-3 axis.