Lymphangioleiomyomatosis: A Disease Involving the Lymphatic System
Lymphangioleiomyomatosis: A Disease Involving the Lymphatic System
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DOI：
10.1089/lrb.2009.0018
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发表时间：
2010-01-01
影响因子：
1.4
通讯作者：
Sato, Teruhiko
中科院分区：
文献类型：
--
作者：
Seyama, Kuniaki;Kumasaka, Toshio;Sato, Teruhiko
工作背景：淋巴管平滑肌瘤病（LAM）是一种罕见的肿瘤性疾病，其中异常平滑肌样细胞（LAM细胞）在肺中增殖，并沿着轴淋巴系统，包括淋巴结和胸导管。LAM细胞由于TSC 1或TSC 2肿瘤抑制基因的功能丧失型突变而转化。病理学特征包括良性LAM细胞的增殖和与乳糜漏等临床病症相关的大量淋巴管的存在。LAM细胞产生有效的淋巴管生成生长因子（VEGF-C和VEGF-D），LAM病变内的淋巴管密度与LAM的组织学严重程度相关。LAM患者血清VEGF-D水平升高，尤其是有淋巴结转移的患者。LAM细胞簇（LCC），这是假设病理上产生的淋巴管生成介导的碎片和随后脱落到淋巴循环中，观察到乳糜积液和LAM组织标本内的LAM相关的炎症。因此，如果LAM患者并发乳糜efficiency.Conclusion：LAM似乎是一种涉及淋巴系统功能障碍的疾病，并且是一种迷人的肿瘤扩散模型，完全是淋巴管炎性的，那么乳糜积液中的LCC的识别与特征性临床表现一起可以作为肺活检的替代。介导LCC脱落的LAM相关淋巴管生成似乎在LAM细胞的传播和LAM的进展中起核心作用，并且它也可能是潜在的治疗靶点以及失调的mTOR信号通路。
Background: Lymphangioleiomyomatosis (LAM) is a rare neoplastic disease in which abnormal smooth muscle-like cells (LAM cells) proliferate in the lungs and along the axial lymphatic systems, including the lymph nodes and thoracic ducts. LAM cells are transformed due to loss-of-function type mutations of either the TSC1 or TSC2 tumor suppressor genes. The pathological features include the proliferation of benign-looking LAM cells and the existence of abundant lymphatic vessels that are associated with clinical conditions such as chyle leakage. LAM cells produce potent lymphangiogenic growth factors (VEGF-C and VEGF-D) and the lymphatic vessel density within LAM lesions correlates with the histologic severity of LAM. The serum VEGF-D level increases in LAM, especially in patients with lymphatic involvement. LAM cell clusters (LCCs), which are postulated pathologically to be generated by lymphangiogenesis-mediated fragmentation and subsequent shedding into the lymphatic circulation, are observed in both chylous effusion and LAM-associated lymphatics within LAM tissue specimens. The identification of LCCs in chylous effusion together with the characteristic clinical manifestations can therefore be an alternative for a lung biopsy if LAM patients are complicated with chylous effusion.Conclusion: LAM appears to be a disease involving a dysfunction of the lymphatic system and a fascinating model of tumor dissemination that is exclusively lymphangitic. LAM-associated lymphangiogenesis that mediates the shedding of LCCs seems to play a central role in the dissemination of LAM cells and progression in LAM and it may also be a potential therapeutic target as well as the dysregulated mTOR signaling pathway.