结节性硬化症相关型和散发型肺淋巴管肌瘤病30例临床回顾研究

doi:10.3877/cma.j.issn.1674-6902.2017.05.002

中华肺部疾病杂志(电子版) ›› 2017, Vol. 10 ›› Issue (05) : 514 -520. doi: 10.3877/cma.j.issn.1674-6902.2017.05.002

所属专题：经典病例；文献；

论著

结节性硬化症相关型和散发型肺淋巴管肌瘤病30例临床回顾研究

刘杰¹^,^†(

), 钟南山¹, 陈荣昌¹, 顾为丽¹, 安嘉颖¹, 顾莹莹²

^1. 510120　广州医科大学附属第一医院·广州呼吸疾病研究所呼吸疾病国家重点实验室　呼吸疾病国家临床研究中心　呼吸内科
^2. 510120　广州医科大学附属第一医院病理科

收稿日期:2017-07-23 出版日期:2017-10-20
通信作者: 刘杰
基金资助:
国家重点研发计划专项(2016YFC0901502); 广东省医学科学技术研究基金项目(A2015018)

Tuberous sclerosis complex associated lymphangioleiomyomatosis and sporadic lymphangioleiomyomatosis: a retrospective study of 30 cases

Jie Liu¹^,^†(), Nanshan Zhong¹, Rongchang Chen¹, Weili Gu¹, Jiaying An¹, Yingying Gu²

^1. Department of Respiratory Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Institute of Respiratory Disease, The State Key Laboratory of Respiratory Disease, The National Clinical Research Center of Respiratory Disease, Guangzhou 510120 , China
^2. Department of Pathology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Institute of Respiratory Disease, The State Key Laboratory of Respiratory Disease, The National Clinical Research Center of Respiratory Disease, Guangzhou 510120 , China

Received:2017-07-23 Published:2017-10-20
Corresponding author: Jie Liu
About author:
Corresponding author: Liu Jie, Email: ljgird001@163.com

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引用本文：

刘杰, 钟南山, 陈荣昌, 顾为丽, 安嘉颖, 顾莹莹. 结节性硬化症相关型和散发型肺淋巴管肌瘤病30例临床回顾研究[J/OL]. 中华肺部疾病杂志(电子版), 2017, 10(05): 514-520.

Jie Liu, Nanshan Zhong, Rongchang Chen, Weili Gu, Jiaying An, Yingying Gu. Tuberous sclerosis complex associated lymphangioleiomyomatosis and sporadic lymphangioleiomyomatosis: a retrospective study of 30 cases[J/OL]. Chinese Journal of Lung Diseases(Electronic Edition), 2017, 10(05): 514-520.

目的

探讨结节性硬化症相关型(TSC-LAM)和散发型肺淋巴管肌瘤病(S-LAM)的临床、影像、病理特点，提高对该病的诊治水平，减少误诊和漏诊。

方法

对2011年至2016年广州呼吸疾病研究所收治的30例TSC-LAM和S-LAM患者资料进行回顾分析。

结果

本研究纳入TSC-LAM组10例和S-LAM组20例，均为成年女性，两组平均年龄分别为38.1岁和39.2岁，TSC-LAM组常伴家族史(40%)，S-LAM组均为散发，常见临床表现发生比例两组分别为呼吸困难(60%，70%)，自发性气胸(50%，55%)，咳嗽(30%，40%)，咯血(30%，40%)，乳糜胸(20%，25%)，其中合并呼吸衰竭需要家庭氧疗(20%，15%)。TSC-LAM组皮肤损害包括面部血管纤维瘤10例，脱色素斑疹8例，甲床纤维瘤3例，鲨革斑3例。两组胸部CT均表现为弥漫性双肺囊性变并多发肺大疱；腹部增强CT显示单侧或双侧的单发或多发肾血管平滑肌脂肪瘤(AML)。TSC-LAM组头颅增强CT或MRI示皮质不典型增生6例，室管膜下结节9例。两组典型肺部组织病理示免疫组化：SMA(＋)、HMB45(＋)、ER(＋)和PR(＋)。健康对照组(20例)、TSC-LAM组和S-LAM组血清VEGF-D结果分别为268.1 pg/ml [IQR 190.8～364.1；n＝20]、2 031.9 pg/ml [IQR 1 441.3～3 124.4; n＝10]和1 476.9 pg/ml [IQR 855.3～1 861.1; n＝20]。其中，TSC-LAM组和S-LAM组均显著高于健康对照组(P<0.001)。

结论

成年女性结节性硬化症患者肺部受累主要为肺淋巴管肌瘤病，典型临床表现为呼吸困难和气胸，胸部CT、肺活检和血清VEGF-D有助诊断。

关键词: 结节性硬化, 淋巴管肌瘤病, 肺

Objective

To improve the recognization of clinical, radiological and pathological characteristics of lymphangioleiomyomatosis(LAM). Plus, it can decrease missed diagnosis and diagnostic errors.

Methods

It was reviewed that clinical data of 30 patients with tuberous sclerosis complex associated lymphangioleiomyomatosis (TSC-LAM) or sporadic lymphangioleiomyomatosis (S-LAM) in Guangzhou Institute of Respiratory Disease from 2011 to 2016.

Results

All of 10 TSC-LAM individuals and 20 S-LAM individuals were enrolled to this research. All participants were female and average age of both groups were 38.1 yrs and 39.2 yrs respectively. Almost 40% TSC-LAM cases had family history and all S-LAM cases were sporadic. Clinical manifestations of both groups included respectively: dyspnea(60%, 70%), spontaneous pneumothorax(50%, 55%), cough(30%, 40%c), hemoptysis(30%, 40%), Chylothorax(20%, 25%), needed supplemental oxygen(20%, 15%). Dermatologic features of TSC-LAM patients included: facial angiofibroma(10 cases), hypomelanotic macules (8 cases), ungual bromas (3 cases)and shagreen patch(3 cases). Thoracic CT scans of all patients indicated diffuse cystic lung and bullae of lung. Enhanced CT scans of the abdomen in both groups identified renal angiomyolipomas. Cerebral CT and MRI scans included 6 cortical dysplasias cases and 9 subependymal nodules cases. Typical characteristics of immunohistochemisty of lung biopsy included SMA(+ )、HMB45(+ )、ER(+ )and PR(+ ). Mean value of serum VEGF-D concentrations of healthy control and TSC-LAM and S-LAM were 268.1 pg/ml [IQR 190.8-364.1; n=20], 2 031.9 pg/ml [IQR 1 441.3-3 124.4; n=10], 1 476.9 pg/ml [IQR 855.3-1 861.1; n=20], respectively. Besides, serum VEGF-D of TSC-LAM and S-LAM were significantly higher than healthy volunteers(P<0.001).

Conclusions

The main pulmonary involvement of tuberous sclerosis complex is lymphangioleiomyomatosis. Dyspnea and pneumothorax are main clinical features. Thoracic CT and lung biopsy and serum VEGF-D is contribute to diagnosis with lymphangioleiomyomatosis.

Key words: Tuberous sclerosis, Lymphangioleiomyomatosis, Lung

表1 肺淋巴管肌瘤病临床资料汇总

临床资料		TSC-LAM(n＝10)	S-LAM(n＝20)	统计量	P值
人口学资料		?	?	?	?
?	年龄(范围)岁	38.1(21～53)	39.2(21～54)	0.013	0.990
?	家族史	4(40)	0(0)	?	0.002^b
?	生育史	5(50)	13(65)	?	0.429
?	绝经	2(20)	3(15)	?	0.729
呼吸系统临床表现		?	?	?	?
?	咳嗽	3(30)	8(40)	?	0.592
?	咯血	3(30)	8(40)	?	0.592
?	胸痛	4(40)	9(45)	?	0.794
?	呼吸困难	6(60)	14(70)	?	0.584
?	自发性气胸	5(50)	11(55)	?	0.796
?	乳糜胸	2(20)	5(25)	?	0.760
?	呼吸衰竭	2(20)	3(15)	?	0.729
皮肤损害		?	?	?	?
?	脱色素斑疹(≥3)	8(80)	0(0)	?	<0.001^b
?	血管纤维瘤(≥3)或前额斑块	10(100)	0(0)	?	<0.001^b
?	甲床纤维瘤(≥2)	3(30)	0(0)	?	0.010^a
?	鲨革斑或多发胶原瘤	3(30)	0(0)	?	0.010^a
中枢神经系统		?	?	?	?
?	皮质不典型增生(≥3)	6(60)	0(0)	?	<0.001^b
?	室管膜下结节(≥2)	9(90)	0(0)	?	<0.001^b
?	室管膜下巨细胞性星形细胞瘤(≥2)	0(0)	0(0)	－	?
肾血管平滑肌脂肪瘤(AML)		8(80)	7(35)	?	0.020^a
?	AML单侧	0(0)	6(85.7)	?	0.001^b
?	AML双侧	10(100)	1(14.3)	?	0.001^b
治疗措施		?	?	?	?
?	支气管扩张剂	6(60)	10(50)	?	0.605
?	mTOR抑制剂	8(80)	13(65)	?	0.398

表1 肺淋巴管肌瘤病临床资料汇总

临床资料		TSC-LAM(n＝10)	S-LAM(n＝20)	统计量	P值
人口学资料		?	?	?	?
?	年龄(范围)岁	38.1(21～53)	39.2(21～54)	0.013	0.990
?	家族史	4(40)	0(0)	?	0.002^b
?	生育史	5(50)	13(65)	?	0.429
?	绝经	2(20)	3(15)	?	0.729
呼吸系统临床表现		?	?	?	?
?	咳嗽	3(30)	8(40)	?	0.592
?	咯血	3(30)	8(40)	?	0.592
?	胸痛	4(40)	9(45)	?	0.794
?	呼吸困难	6(60)	14(70)	?	0.584
?	自发性气胸	5(50)	11(55)	?	0.796
?	乳糜胸	2(20)	5(25)	?	0.760
?	呼吸衰竭	2(20)	3(15)	?	0.729
皮肤损害		?	?	?	?
?	脱色素斑疹(≥3)	8(80)	0(0)	?	<0.001^b
?	血管纤维瘤(≥3)或前额斑块	10(100)	0(0)	?	<0.001^b
?	甲床纤维瘤(≥2)	3(30)	0(0)	?	0.010^a
?	鲨革斑或多发胶原瘤	3(30)	0(0)	?	0.010^a
中枢神经系统		?	?	?	?
?	皮质不典型增生(≥3)	6(60)	0(0)	?	<0.001^b
?	室管膜下结节(≥2)	9(90)	0(0)	?	<0.001^b
?	室管膜下巨细胞性星形细胞瘤(≥2)	0(0)	0(0)	－	?
肾血管平滑肌脂肪瘤(AML)		8(80)	7(35)	?	0.020^a
?	AML单侧	0(0)	6(85.7)	?	0.001^b
?	AML双侧	10(100)	1(14.3)	?	0.001^b
治疗措施		?	?	?	?
?	支气管扩张剂	6(60)	10(50)	?	0.605
?	mTOR抑制剂	8(80)	13(65)	?	0.398

图1 TSC典型皮肤损害；注：A：面部血管纤维瘤；B：甲床纤维瘤；C：脱色素斑疹；D：鲨革斑

图2 影像学；注：A：TSC-LAM头颅增强CT示室管膜下多发结节；B：TSC-LAM头颅增强MRI示室管膜下结节；C：TSC-LAM胸部CT示双肺弥漫性囊性变并右侧气胸；D：S-LAM胸部CT示弥漫性双肺囊性变、双肺肺大疱和右侧气胸；E和F：TSC-LAM腹部增强CT示箭头所指左肾多发血管平滑肌脂肪瘤(AML)，右肾切除术后

图3 肺组织病理；注：A：HE×40；B：HE×200 LAM典型病理改变：肺部囊性病变及多发的不成熟的平滑肌细胞和血管周上皮细胞异常增生；C：免疫组化：SMA(＋)；D：HMB45(＋)；E：ER(＋)；F：PR(＋)(×200)

图4 血清VEGF-D组间比较

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Tuberous sclerosis complex associated lymphangioleiomyomatosis and sporadic lymphangioleiomyomatosis: a retrospective study of 30 cases

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Tuberous sclerosis complex associated lymphangioleiomyomatosis and sporadic lymphangioleiomyomatosis: a retrospective study of 30 cases