图A显示了肺部和气道在体内的位置。插图显示健康肺的横截面。图B显示了具有LAM和肺塌陷（气胸）的肺的视图。插图显示了具有LAM的肺的横截面。
淋巴管平滑肌瘤病（LAM）是一种罕见的，进行性和全身性疾病，通常导致囊性肺破坏。它主要影响女性，特别是在育龄期间。[1]术语散发性LAM用于与结节性硬化症复合体（TSC）无关的LAM患者，而TSC-LAM是指与TSC相关的LAM [2]。
目录
1 症状和体征
2 遗传学
3 病理生理学
4 诊断
4.1 胸部X光片
4.2 计算机断层扫描
4.3 通气 - 灌注扫描
4.4 正电子发射断层扫描
4.5 腹部成像
4.6 中枢神经系统成像
4.7 肺功能研究
4.8 病理学
5 治疗
5.1 气胸
5.2 乳糜胸
5.3 血管平滑肌脂肪瘤
5.4 淋巴管平滑肌瘤
5.5 管理，其他
5.6 药物治疗
6 怀孕
7 预后
8 流行病学
9 患者支持
10 在流行文化中
11 参考
体征和症状
发病的平均年龄是30岁左右。[3] [4] [5] [6]据报道，49％和46％的患者分别表现出劳累性呼吸困难（呼吸急促）和自发性气胸（肺塌陷）作为该疾病的初始表现[6]。
诊断通常会延迟5至6年。[3] [4] [5] [6]该病症经常被误诊为哮喘或慢性阻塞性肺病。第一次气胸，或肺塌陷，在82％的患者中诊断为LAM之前[7] [8]。 LAM的共识临床定义包括多种症状：
疲劳
咳嗽
咳血（很少大量）
胸痛
淋巴阻塞引起的乳糜泻并发症，包括
乳糜胸
乳糜腹水
乳糜泻
糜烂型
乳糜尿
乳糜在阴道分泌物中
大便中的乳糜。
大约30％的散发性LAM患者和高达90％的TSC-LAM患者存在血管平滑肌脂肪瘤（脂肪性肾肿瘤）[9] [10]。血管平滑肌脂肪瘤有时会自发出血，引起疼痛或低血压。
在腹膜后，骨盆或纵隔中可发生囊性淋巴管瘤或具有低密度中心的淋巴结，其模拟坏死性淋巴瘤，卵巢癌或肾癌或其他恶性肿瘤。[11] [12] [13] [14]
LAM中的肺破坏是肿瘤性平滑肌样细胞弥漫性浸润的结果，这些细胞侵入所有肺结构，包括淋巴管，气道壁，血管和间质空间。[15]血管和气道阻塞的后果包括乳糜液积聚，咯血，气流阻塞和气胸。典型的疾病过程表现为进行性呼吸困难，由复发性气胸隔开，部分患者为乳糜性胸腔积液或腹水。[16]
大多数人在症状出现后10年内因日常活动而出现呼吸困难。许多患者需要在该间隔内补充氧气。[7]
遗传学
LAM发生在两种情况下：在疾病结节性硬化症复合体（TSC-LAM）和散发性形式中，在没有TSC（散发性LAM）的女性中[17] [18]。在这两种情况下，遗传证据表明LAM是由TSC1或TSC2基因中的失活或“功能丧失”突变引起的，这些突变分别于1997年和1993年克隆。[19] TSC1基因位于染色体9q34上，TSC2基因位于染色体16p13上。 TSC-LAM发生在TSC1或TSC2基因中具有种系突变的女性中[20]。
散发性LAM主要与体细胞TSC2基因突变有关。[21] [22] LAM中的种系和体细胞突变包括遍布基因的许多类型的突变，没有明显的“热点”，包括错义变化，框内缺失和无义突变。[20] [21] [22]由于基因的大小（它们共有超过60个外显子）并且因为突变几乎可以位于基因内的任何位置，因此突变检测通常具有挑战性。
在细胞基础上，LAM细胞携带TSC2基因的双等位基因失活，与“双击”肿瘤抑制基因模型一致[23] [24]。 LAM细胞中的第二次命中事件通常是丢失含有TSC2基因的野生型拷贝的染色体区域;这被称为杂合性缺失或LOH。[25] LOH可以在显微切割的LAM细胞中检测到，[21] [26]在血管平滑肌脂肪瘤和LAM女性的淋巴结中[27]和循环LAM细胞（血液和尿液中的细胞）[28] [29]。
具有散发形式LAM的女性的血管平滑肌脂肪瘤和肺LAM细胞在TSC2中携带相同的突变。[21]这与肺移植后复发性LAM携带与原始LAM相同的TSC2突变这一事​​实[30]导致了“良性转移”假设，即LAM细胞可以从一个位点迁移或转移到另一个位点。[17] [18]
病理生理学
LAM病变中可变百分比的细胞含有Tuberous Sclerosis Complex（TSC1或TSC2）肿瘤抑制基因的突变失活[21] [27] [31]。与TSC2突变相比，TSC1突变导致临床表型不太严重[32]。发现TSC1 / 2基因作为雷帕霉素复合物1（mTORC1）哺乳动物靶标的负调节因子[33] [34]导致雷帕霉素类似物西罗莫司在临床试验中的成功应用[35] [36]和FDA批准西罗莫司用于治疗LAM。
TSC1和TSC2形成肿瘤抑制复合物，其通过经由TSC2的GTP酶活化蛋白（GAP）结构域直接控制小GTP酶Rheb的活性来调节哺乳动物雷帕霉素靶蛋白（mTOR）信号传导复合物。 Rheb与Raptor结合并控制直接磷酸化p70 S6激酶（S6K1）和4E-BP1的mTOR复合物1（mTORC1）的活性。 mTOR形成两种物理和功能上不同的多蛋白复合物：雷帕霉素敏感的mTORC1和雷帕霉素不敏感的mTORC2。[37] MTORC1由五种蛋白质组成，包括正向调节mTOR活性的Raptor。[38] [39] [40] MTORC2由六种蛋白质组成，包括mTOR和Rictor，它们定义mTORC2的激活水平[41] [42] [43]并通过Rho GTPases调节肌动蛋白细胞骨架的组装，[44] [45] [46]和Rac1是mTOR激活所需。[47]在TSC2-null和人类LAM细胞中，Rho GTP酶活性是细胞粘附，运动，增殖和存活所必需的[48] [49] [50]。 LAM中TSC1 / TSC2的缺失诱导不受控制的LAM细胞生长并增加LAM细胞活力。 STAT1和STAT3的上调[51] [52] [53] [54]和自噬[55]是已知的LAM细胞活力和存活的介质。
LAM细胞在许多方面表现像转移性肿瘤细胞。[56] LAM细胞似乎来自肺外来源并迁移到肺部。[21] TSC2重新表达挽救了LAM细胞迁移和侵袭性的增加[49]。 LAM细胞的肿瘤转化和肺实质破坏的细胞和分子机制仍然未知。肺重塑可能是由基质降解金属蛋白酶（MMPs）与其内源性抑制剂TIMPs之间的不平衡所调节的。[57] LAM中的侵袭性细胞表型与TIMP-3下调[58]和依赖TSC2依赖的MMPs上调有关[59] [60] [61] [62]。
临床和组织病理学证据表明LAM的淋巴受累[14] [57] [63] [64] [65] [66] [67] [68]普遍的假设是LAM病变分泌淋巴管生成因子VEGF-D，募集淋巴管内皮细胞（LECs），形成淋巴管并诱导肺囊肿[57]。与其他囊性肺病相比，LAM [69]中VEGF-D血清水平升高，包括肺朗格汉斯细胞组织细胞增生症，肺气肿，干燥综合征或Birt-Hogg-Dubé综合征[70]。 VEGF-D水平与LAM的严重程度相关，评估为CT等级（乳糜积液和淋巴受累的丰度）[71]。 VEGF-D是一种分泌型同源二聚体糖蛋白，是生长因子VEGF家族的一员，因其在癌症淋巴管生成和转移中的作用而闻名。[72] [73] [74] VEGF-D的蛋白水解加工影响同源物与VEGFR3的结合[75]。组织病理学上，LAM病变周围有染色VEGFR3的细胞，淋巴管内皮透明质酸受体1（LYVE-1）和podoplanin。[63] [76] VEGF-D与人类中的受体蛋白酪氨酸激酶VEGFR-2和VEGFR-349结合，并与小鼠中的VEGFR3结合[74] [77]。令人惊讶的是，小鼠体内VEGF-D的敲除对淋巴系统的发育几乎没有影响。[78]然而，在肿瘤发生过程中，VEGF-D促进肿瘤淋巴管的形成并促进癌细胞的转移性扩散[73] [74]。然而，关于LAM发病机制中异常淋巴管和VEGF-D的作用知之甚少。
诊断
淋巴管平滑肌瘤病的显微照片。 H＆E染色。
淋巴管平滑肌瘤患者肺部CT扫描显示肺内有许多薄壁囊肿。
LAM可以通过多种方式进行医疗护理，其中大多数触发胸部CT。肺部的薄壁囊性变化可偶然发生在用于其他目的的心脏，胸部或腹部（包括肺基部的切口）的CT扫描上。 TSC患者的HRCT显示，20岁左右，约20％的女性患有囊性变，40岁以后，约80％的女性患有囊性变。[79] LAM有时通过胸部CT显示出患有明显原发性自发性气胸的患者，但更常见的是CT扫描（在美国）并未发生复发。在没有哮喘或COPD特征的恶化和缓解的情况下进行性进行性呼吸困难有时会引起胸部CT。熟悉LAM的专家对CT的回顾可能会提高诊断的准确性。[80]乳糜胸也可以引起LAM的注意。
在某些情况下，对于肺部高分辨率CT扫描的典型囊性变化和结节性硬化症，血管平滑肌脂肪瘤，淋巴管平滑肌瘤，乳糜胸或血清VEGF-D的发现，可以在临床基础上进行LAM诊断（无活组织检查） 800 pg / ml。[70] [81]
如果没有这些临床特征，则可能需要进行活组织检查以进行诊断。电视辅助胸腔镜肺活检是最明确的技术，但经支气管活检的产量超过50％，也可能有效。[82] [83]然而，对弥漫性囊性病患者的后一种手术的安全性和预测信息性活检的囊性变化的丰富性尚不完全清楚。乳糜液，吸入的腹部淋巴结或淋巴肿块的细胞学也可以诊断。[84] [85] [86] [87]
图1概述了用于诊断LAM的建议算法。
图1.概述了用于诊断LAM的建议算法。 CT：计算机断层扫描; TSC：结节性硬化症复合体; AML：血管平滑肌脂肪瘤; VEGF-D：血管内皮生长因子D; TBBx：经支气管活检; VATS：电视辅助胸腔镜手术。
胸部X光片
胸片可能看起来相对正常，甚至在疾病晚期，或者可能仅表明过度充气。随着疾病的进展，胸片通常表现为弥漫性，双侧和对称性网状结节混浊，囊肿，肺大疱或“蜂窝状”（即假性纤维化）外观。[3] [6]胸腔积液和气胸可能很明显。在间质标记增加的情况下保留肺容量是LAM的放射学标志，有助于将其与大多数其他间质性肺病区分开来，其中肺泡间隔和间质扩张倾向于增加肺的弹性回缩特性和减少肺容量。
CT检查
高分辨率计算机断层扫描（HRCT）胸部扫描比胸部X线片更好地检测囊性实质疾病，并且在诊断时几乎总是异常，即使胸片和肺功能评估正常[3] [5] ] [6] [88]典型的CT显示弥漫性圆形，双侧，薄壁囊肿，大小不等，直径从1到45毫米。[5] [6] LAM的囊肿数量从正常肺组织的几个到几乎完全替换而变化。 TSC-LAM患者的囊肿丰富程度往往比S-LAM轻，可能部分原因是TSC-LAM患者通常接受早期筛查。[11] 12％的S-LAM患者和6％的TSC-LAM患者在CT上观察到胸腔积液。其他CT特征包括线性密度（29％），肺门或纵隔淋巴结肿大（9％），气胸，淋巴管肌瘤和胸导管扩张[5] [6]。磨玻璃混浊（12％）表明由于淋巴充血而存在间质水肿。对于TSC患者，HRCT上的结节密度可能代表多灶性小结节性肺细胞增生（MMPH），由增生型II型肺细胞簇组成[79] [89] [90]。在存在或不存在LAM的情况下，MMPH可能存在于患有TSC的男性或女性中，但在患有S-LAM的患者中不存在。[91] MMPH通常不会与生理或预后相关，但有报道称MMPH引起的一例呼吸衰竭[92] [93] [94]。
通气 - 灌注扫描
在一项研究中，35名LAM患者中有34名患者的通气 - 灌注扫描异常[5]。最常见的异常是非特异性弥散异质性，通常是非常匹配的。这些作者还描述了74％的患者灌注图像上的“不寻常”“斑点图案”，包括“小的，通常是外围放射性同位素的外围集合”。
正电子发射断层扫描
LAM和AML病变通常不会在正电子发射断层扫描（PET）扫描中显示18F-氟脱氧葡萄糖的摄取增加[95] [96]。因此，在已知或疑似LAM病例中应考虑其他肿瘤（或炎症来源），其中FDG-PET结果为阳性。[97]
腹部成像
腹部成像异常，如肾脏AML和淋巴结构增大，在LAM中也很常见。肾脏质量内的脂肪密度是AML的特征。在患有TS-LAM的患者中，AML比在S-LAM患者中更普遍并且更频繁地双侧和大。 AML大小与TSC患者肺囊肿的患病率相关[9]。一项研究CT成像256例S-LAM患者和67例TSC-LAM患者。在32％的S-LAM患者和93％的TSC-LAM患者中存在肾脏AML。 2％的S-LAM患者和33％的TSC-LAM患者存在肝脏AML。腹水并不常见，只有不到10％的LAM患者出现腹水。在29％的S-LAM患者和9％的TSC-LAM患者中观察到腹腔淋巴管瘤病，通常含有囊性和固体成分[11]。
中枢神经系统成像
中枢神经系统异常，如皮质或室管膜下块茎和星形细胞瘤，在TSC患者中很常见，包括TSC-LAM患者，但在患有S-LAM的女性中未发现。 Moss及其同事[98]报道，患有S-LAM和TSC-LAM的女性可能会增加脑膜瘤的发病率，但这一发现的重要性受到了挑战。[99]
肺功能研究
LAM患者的肺功能检查可能正常或可能显示阻塞性，限制性或混合性模式。阻塞性生理学是最常见的异常。质量控制的肺功能数据由NHLBI登记处前瞻性收集，这是一项为期5年的美国中心LAM患者研究。肺活量测定显示约57％的患者出现阻塞性改变，正常结果为34％[10]。限制，定义为总肺容量低于正常下限，为11％。恶性通货膨胀率约为6％。通过体积描记法测量时，平均残余体积为预测值的125％，但仅用气体稀释法测定的预测量的103％，表明在非交流空域中存在显着的空气滞留。大约25％的阻塞性生理学患者可能表现出支气管扩张反应性，但在更严重的梗阻中可能更少[100] [101]。 LAM的阻塞性生理缺陷主要归因于气流阻塞。[102]各种病例系列初始肺功能检测的最早变化是异常气体转移，通过一氧化碳扩散能力（DLCO）评估，82％至97％的患者描述[3] [3] [4] [ 6] DLCO在1秒钟内与用力呼气量减少不成比例（FEV1）并不罕见。[100] DLCO的减少和残余体积的增加通常被认为是LAM最早的生理表现。
在更大的LAM患者队列中进行的心肺运动试验显示，217名患者的最大耗氧量（VO2 max）和无氧阈值均有所降低[103] [104]。即使在FEV1和DLCO没有静息异常的患者中也发现运动诱发的低氧血症。在大多数患者中，由于气流阻塞和死腔通气增加，运动被认为是通气受限。
疾病进展通常伴有进行性阻塞性通气障碍。 FEV1的下降是监测疾病进展的最常用参数。虽然LAM中静息肺动脉高压似乎不常见，但肺动脉压通常随着运动水平的升高而升高，部分与低氧血症有关[104]。一项研究报告LAM呼吸困难患者的实质内分流增加，这可能导致静息和运动性低氧血症。[105]
病理
总的来说，LAM肺部肿大，弥漫性囊肿，扩张的空气间隙直径达几厘米。[106] [107]肺的显微镜检查显示肺实质，气道，淋巴管和与薄壁囊性变化区域相关的血管的平滑肌样细胞浸润的病灶。 LAM病变通常包含丰富的淋巴通道，形成由内皮细胞排列的狭缝状空间的吻合网状结构。 LAM细胞通常在不侵犯组织平面的情况下扩张间质空间，但已观察到侵入气道，肺动脉，膈肌，主动脉和腹膜后脂肪，以破坏支气管软骨和小动脉壁，并阻塞肺小动脉腔。[ 106]
LAM病变中存在两种主要的细胞形态：小纺锤形细胞和立方形上皮样细胞。[108] LAM细胞对平滑肌肌动蛋白，波形蛋白，结蛋白以及通常雌激素和孕酮受体呈阳性染色。 LAM病变内的立方细胞也与称为HMB-45的单克隆抗体发生反应，该抗体是针对前黑素体蛋白gp100（黑素生成途径中的一种酶）而开发的[108]。这种免疫组化标记在诊断上非常有用，因为肺中其他平滑肌主导的病变不会与抗体反应。[109] LAM病变的纺锤形细胞比立方细胞更常增殖细胞核抗原阳性，与增殖表型一致[108]。与雪茄形正常平滑肌细胞相比，纺锤形LAM细胞含有较少的丰富细胞质并且嗜酸性较弱。雌激素和孕激素受体也存在于LAM病变[110] [111] [112]中，但不存在于邻近的正常肺组织中[113]。 LAM病变表达淋巴标记物LYVE-1，PROX1，podoplanin和VEGFR-3。 AML的平滑肌样细胞在形态学和免疫组织化学上与LAM细胞相似，包括与针对肌动蛋白，结蛋白，波形蛋白和HMB-45以及雌激素和孕酮受体的抗体的反应性[114] [115]。与肺气肿扩张的空域不同，LAM中发现的囊性空间可能部分衬有增生的II型细胞。[116]
治疗
FDA批准的治疗LAM的药物mTOR抑制剂西罗莫司可用于稳定肺功能下降。[35]肺移植仍然是晚期疾病患者的最后手段。[117]
气胸
LAM患者的气胸倾向于复发，特别是在保守治疗后，如观察，误吸或单纯管胸腔造口术。超过65％的LAM患者在患病期间出现气胸，在至少有一次气胸的患者中平均发生3.5次气胸[8]。 LAM基金会胸膜共识组主张使用第一次气胸的胸膜联合手术，因为复发的可能性超过70％。[8]化学硬化，机械磨损，滑石粉和胸膜切除术对LAM患者有效，但对于那些可能需要肺移植的患者来说，机械磨损是首选。大约一半接受过移植手术的LAM患者先前进行了胸膜固定术，其中超过75％的患者先前进行了双侧胸膜固定术[8]。虽然胸膜固定术不是移植的禁忌症，但它可导致围手术期出血增加。
乳糜胸
Chyle通常不会引起胸膜炎症或纤维化。一旦做出LAM诊断，小的稳定性乳糜泻很少需要干预。呼吸短促可能导致可能反复引流。西罗莫司对乳糜泻有效，大多数专家认为它应该作为第一线治疗。[118]使用重度T2加权MRI或造影剂淋巴管造影成像泄漏源是建议用于难治性积液。[119]一些泄漏可通过从腹股沟淋巴结穿入胸导管的导管栓塞。可考虑进行胸导管结扎术，但由于胸腔积液有时来源于胸腔波纹作用虹吸入胸腔的腹水，因此在考虑此选项之前排除腹部来源非常重要。可能需要胸膜联合以防止由反复敲击或持续引流引起的营养和淋巴细胞缺陷。化学性胸膜固定术通常是乳糜胸的有效疗法，机械磨损和滑石粉也是如此。[120]
血管平滑肌脂肪瘤
肾血管平滑肌脂肪瘤（AMLs）可能需要栓塞或烧灼来控制出血，当肿瘤直径超过4 cm时，这种并发症被认为更常见。[121]动脉瘤变化的程度可能决定出血风险。应进行连续腹部成像，以6至12个月的间隔评估AML大小，至少直到生长趋势明确。对于非常大的肿瘤，可考虑将肾单位切除部分切除。[122]对于血管内扩展或其他原因的肿瘤，有时需要进行肾切除术，但很少是可通过微创手段治疗的AML的选择方法。依维莫司经美国食品药品管理局（FDA）批准用于AML治疗。[123]
淋巴管平滑肌瘤
淋巴管平滑肌瘤病是在约30％的LAM患者中存在于腹膜和骨盆的腹膜后区域的充满液体的低密度结构。他们通常不需要干预。活组织检查或切除术可导致长期渗漏。 mTOR抑制剂可有效缩小淋巴管平滑肌瘤病的大小，并可导致完全消退。
管理 - 其他
含雌激素的药物会加剧LAM [124]并且是禁忌的。拮抗雌激素作用的药物尚未被证实对治疗有效，但尚未进行适当的试验。在LAM患者中应考虑使用支气管扩张剂，因为高达17％至25％的患者有支气管扩张剂反应性气流阻塞。[5] [10]应该给予氧气，以便在休息，运动和睡眠时保持氧合血红蛋白饱和度大于90％。所有固定和/或抗雌激素治疗的患者都应考虑骨密度​​测定，并为骨质疏松症患者制定适当的治疗方案。在自然或诱发绝经后应适当注意心血管健康。肺炎球菌和流感的免疫接种应该保持最新。在患有阻塞性肺病的年轻，有动力的患者中，肺康复似乎特别有益，但是尚未进行用于评估这种干预对运动耐量，调节和生活质量的影响的研究。
药物治疗
西罗莫司是一种mTOR抑制剂，可稳定肺功能并改善LAM患者的一些生活指标。[35]根据多中心国际LAM功效和西罗莫司安全性（MILES）试验的结果，它被FDA批准用于LAM。 MILES数据支持在肺功能异常（即FEV1 <70％预测值）的患者中使用西罗莫司。治疗的益处是否超过无症状的肺功能正常的LAM患者的风险尚不清楚，但是一些医生考虑对接近FEV1异常范围的衰退患者进行治疗。西罗莫司似乎对治疗乳糜积液和淋巴管平滑肌瘤病有效。西罗莫司的益处仅在治疗持续时持续存在。尚未研究长期治疗的安全性。
mTOR抑制剂的潜在副作用包括脚踝肿胀，痤疮，口腔溃疡，消化不良，腹泻，胆固醇和甘油三酯升高，高血压和头痛。西罗莫司肺炎和潜伏性恶性肿瘤是更严重的问题，但很少发生。西罗莫司抑制伤口愈合。在需要最佳伤口愈合的选择性手术之前和之后停止用药物治疗1-2周是很重要的。必须采取预防措施，以避免因皮肤癌风险增加而长时间暴露在阳光下。
在一项小型开放性试验中报道了另一种mTOR抑制剂依维莫司治疗与FEV1和6分钟步行距离的改善有关。[125]通过治疗降低血清VEGF-D和IV型胶原的水平。不良事件通常与已知与mTOR抑制剂相关的事件一致，尽管一些是严重的并且包括外周性水肿，肺炎，心力衰竭和Pneumocystis jirovecii感染。使用渐远剂量的依维莫司，每天最多10毫克;高于LAM临床常用的药物。
血清VEGF-D浓度是有用的，预测性和预后的生物标志物。[71]较高的基线VEGF-D水平可预测更快的疾病进展和更强大的治疗反应。
激素治疗方法从未在适当的试验中进行过测试。在没有证实有益的情况下，不常规推荐用黄体酮，GnRh激动剂（例如亮丙瑞林，戈舍瑞林）和他莫昔芬治疗。在双盲试验中，强力霉素对肺功能下降率没有影响。[126]
西罗莫司经常作为乳糜胸的一线管理有效。[118]如果治疗后仍存在乳糜漏或累积，可考虑使用重度T2加权MRI，MRI淋巴管造影或胸导管淋巴管造影进行成像。在难治性病例中可考虑胸膜融合术。
怀孕
据报道，在某些情况下，妊娠会加剧LAM。[97] [127] [128] [129] [130]然而，风险尚未得到严格研究。在对318名表示至少有一次怀孕的患者的调查中，163名患者回应了第二次针对肺塌陷的调查。[131]共有38名患者报告有妊娠气胸，与妊娠期气胸发生率一致至少10％（318/38）。在三分之一的患者中，妊娠期间的气胸导致LAM诊断。右侧的气胸几乎是左侧的两倍，四名女性患有双侧自发性气胸。大多数气胸都发生在孕中期和孕晚期。本研究和其他研究[7] [6]表明妊娠与LAM患者的胸膜并发症有关。很少有已知LAM诊断的女性选择怀孕，而在怀孕期间诊断出LAM的患者很少有基线肺功能检查，这使得该问题的解决变得复杂。
预测
生存估计取决于呈现或确认的模式，并且通常趋向上升，可能是由于通过更广泛使用CT扫描的早期识别。在最近一项基于人群的队列调查中，中位生存期为29年。[132]来自早期大型病例系列的数据显示，38％至78％的患者在发病后的8。5年内存活[3] [4] [6] [133]
患者通常会出现进行性气流阻塞。在症状出现10年后的英国一群患者中，55％的77名患者在平地上行走，而10％的人在家中行走。[134]在NHLBI的单个肺功能实验室研究的275名患者中，FEV1和DLCO的年平均下降率分别为75±9 mL和0.69±0.07 mL / min / mm Hg。[135]在欧洲的其他系列中，FEV1的下降速度相当高，估计约为100至120毫升/年。[6] [136] [137]在MILES试验中，安慰剂组患者每年减少134毫升[35]。在这些研究中有一些证据表明，肺功能下降的速度与初始DLCO相关，具有绝经状态和高基线VEGF-D。
中位生存期的估计值从10年到30年不等，取决于是否研究了基于医院或基于人群的队列。[99] [132] [138]
流行病学
LAM几乎完全限于女性。[139] [140]虽然一些患有结节性硬化症的男性报告了与LAM一致的肺囊肿，但这些男性中很少出现症状。 LAM的患病率使用来自登记处和患者组的数据估算，并且在3.4-7.8 /百万妇女之间。在美国，英国和瑞士，每年新发病例数在0.23-0.31 /百万女性/年之间。美国各国之间以及相邻州之间的差异表明，大量患有LAM的妇女未被诊断或其症状归因于其他疾病。[141]患有结节性硬化症的成年女性比没有结节性硬化症的女性​​更容易患LAM。已经使用CT扫描筛查了结节性硬化症患者的LAM。在一项对患有结节性硬化症的成人进行的回顾性研究中，CT显示95名女性中有42％的肺囊肿和91名男性中的13％。一般来说，女性的肺囊肿比男性更大，更多。[142]在对接受CT扫描检测LAM的TSC女性进行的另一项回顾性研究中，20％的女性中有25％患有肺囊肿，40％的女性中有80％受到影响，这表明LAM的发展至少与年龄有关。结节性硬化症相关的LAM。[79]尽管结核性硬化症在6000例中有1例患病率远高于LAM，但大多数肺部诊所看到更多的散发性病例而不是结节性硬化症 - LAM：可能是由于结节性硬化症中LAM筛查水平低和很多，没有症状。
女性和结节性硬化症是唯一已知的危险因素。虽然补充雌激素的使用与LAM的发展无关，[143]一项研究表明，使用含雌激素的避孕药与早期发病有关。[144]
结节性硬化综合征（TSC-LAM）是一种遗传性综合征，与多发组织中的癫痫发作，认知障碍和良性肿瘤相关[30] [145] [146] [79]。大多数进行医学评估的LAM患者患有散发性疾病（S-LAM），但与结节性硬化综合征的其他表现无关。
与LAM一致的轻度囊性变化已在10-15％的TSC患者中被描述[147] [142]，但男性中有症状的LAM是罕见的[139] [140]。散发性LAM仅发生在女性身上，迄今已发布一例例外情况。[140] TSC-LAM和S-LAM都与结节性硬化基因的突变有关[21]。
患者支持
LAM基金会成立于1995年，是一个基层组织，提供患者宣传和研究经费。[148]今天，LAM基金会为有LAM的妇女及其家人提供支持和教育，让医生和科学家继续了解有关该疾病的更多信息，并为继续研究LAM筹集资金。它寻求安全有效的治疗，并最终治愈淋巴管平滑肌瘤病。它总部位于俄亥俄州辛辛那提市。
在流行文化中
在House的第五季第五集“幸运十三”中，斯宾塞（Angela Gots）被诊断出患有LAM，但后来被发现是一例Sjögren综合症。
另见
PEComa
参考
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