Pathological changes of adipose tissue in secondary lymphoedema
Pathological changes of adipose tissue in secondary lymphoedema
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DOI：
10.1111/bjd.15238
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发表时间：
2017-07-01
影响因子：
10.3
通讯作者：
Yoshimura, K.
中科院分区：
文献类型：
--
作者：
Tashiro, K.;Feng, J.;Yoshimura, K.
背景 对淋巴水肿的病理生理学知之甚少。目前的治疗方案包括压迫疗法、切除术、吸脂术和淋巴显微手术，但为每位患者确定最佳治疗方法仍然具有挑战性。目的我们对继发性淋巴水肿背景下皮肤和脂肪组织的变化进行了表征。方法对从手术后患有下肢继发性淋巴水肿的 26 名女性患者采集的 70 份标本进行形态学和组织病理学评估 妇科癌症的干预。对每位患者进行吲哚菁绿淋巴造影以评估淋巴水肿的严重程度。结果肉眼和超声检查结果显示，淋巴水肿脂肪组织具有较大的脂肪组织小叶，这些小叶被厚厚的胶原纤维和间质淋巴液包围。在淋巴水肿标本中，当使用电子显微镜、整体染色和免疫组织化学检查时，脂肪细胞表现出肥大性变化和更多胶原纤维沉积。还发现淋巴水肿四肢真皮内毛细淋巴管数量增多。冠状结构（被 M1 巨噬细胞包围的死亡脂肪细胞）在淋巴水肿样本中较少见。流式细胞术显示，在脂肪组织的细胞成分中，与正常对照相比，淋巴水肿脂肪组织中脂肪源性干/基质细胞和M2巨噬细胞的数量减少。结论这些研究结果表明，长期淋巴容量超负荷可诱发慢性组织炎症、进行性纤维化、体内平衡受损、脂肪重塑改变 组织、再生能力受损和免疫功能障碍。进一步阐明淋巴水肿的病理生理机制将带来更可靠的治疗策略。
Background The pathophysiology of lymphoedema is poorly understood. Current treatment options include compression therapy, resection, liposuction and lymphatic microsurgery, but determining the optimal treatment approach for each patient remains challenging.Objectives We characterized skin and adipose tissue alterations in the setting of secondary lymphoedema.Methods Morphological and histopathological evaluations were conducted for 70 specimens collected from 26 female patients with lower-extremity secondary lymphoedema following surgical intervention for gynaecological cancers. Indocyanine green lymphography was performed for each patient to assess lymphoedema severity.Results Macroscopic and ultrasound findings revealed that lymphoedema adipose tissue had larger lobules of adipose tissue, with these lobules surrounded by thick collagen fibres and interstitial lymphatic fluid. In lymphoedema specimens, adipocytes displayed hypertrophic changes and more collagen fibre deposits when examined using electron microscopy, whole-mount staining and immunohistochemistry. The number of capillary lymphatic channels was also found to be increased in the dermis of lymphoedema limbs. Crown-like structures (dead adipocytes surrounded by M1 macrophages) were less frequently seen in lymphoedema samples. Flow cytometry revealed that, among the cellular components of adipose tissue, adipose-derived stem/stromal cells and M2 macrophages were decreased in number in lymphoedema adipose tissue compared with normal controls.Conclusions These findings suggest that long-term lymphatic volume overload can induce chronic tissue inflammation, progressive fibrosis, impaired homeostasis, altered remodelling of adipose tissue, impaired regenerative capacity and immunological dysfunction. Further elucidation of the pathophysiological mechanisms underlying lymphoedema will lead to more reliable therapeutic strategies.