肺淋巴管平滑肌瘤5例报道及文献复习

doi:10.3877/cma.j.issn.1674-6902.2023.03.008

目的

分析肺淋巴管平滑肌瘤病(pulmonary lymphangioleiomyomatosis, PLAM)的临床表现、高分辨率体层摄影(high-resolution tomography, HRCT)的特点、诊断、鉴别诊断及治疗方法。

方法

选择2017年12月至2022年2月青海大学附属医院收治的5例肺淋巴管平滑肌瘤病患者，分析相关资料及文献。

结果

5例肺淋巴管平滑肌瘤病患者中，平均年龄40.6岁，女性，育龄期占60%(3/5)，绝经期占40%(2/5)。HRCT表现为双肺弥漫分布的多发囊状影。主要临床症状为活动后气促、呼吸困难、咳嗽等。5例PLAM患者中，散发型淋巴管肌瘤病(S-LAM)占80%(4/5) ，其中1例仅肺脏受累，3例为多系统受累，表现为肺、肾、肝、腹盆腔等病变。结节硬化症相关淋巴管肌瘤病(TSC-LAM)占20%(1/5) ，合并肺外表现：肝、肾、骨、皮肤等病变，为多系统受累。

结论

PLAM是一种罕见的肺部疾病，HRCT具有特异性，为本病的诊断和鉴别提供重要的影像学依据，本文5例患者胸部CT有共同点，表现为双肺弥漫分布的含气囊腔，边缘可见周围血管征，目前尚无有效治疗方法，免疫抑制剂可以使一些患者的病情改善，病例1患者服用依维莫司，可抑制由于mTOR(哺乳动物雷帕霉素靶蛋白)被激活后引起的LAM细胞过度增值，延缓病情进展，终末期时可考虑肺移植。

关键词: 肺淋巴管肌瘤病, 高分辨率体层摄影, 结节性硬化症

Objective

To explore the clinical manifestations, features, diagnosis, differential diagnosis and treatment methods of pulmonary lymphangioleiomyomatosis (PLAM), high-resolution tomography (HRCT).

Methods

The relevant data and literature of 5 patients with pulmonary lymphangioleiomyomatosis admitted by the Affiliated Hospital of Qinghai University from December 2017 to February 2022 were collected for case analysis.

Results

In this study, the average age of 5 patients with pulmonary lymphangioleiomyomatosis was 40.6 years, all of whom were female, accounting for 60%(3/5) of childbearing age and 40%(2/5) of menopausal women. HRCT all showed multiple cystic opacities with diffuse distribution in both lungs. The main clinical symptoms are shortness of breath after activity, dyspnea, cough, etc. Among the 5 patients with PLAM, sporadic lymphangiomyomatosis (S-LAM) accounted for 80% (4/5), of which 1 case was only lung involvement, and 3 cases were multisystem involvement, showing lung, kidney, liver, abdominal-pelvic cavity and other lesions. Tuberrosclerosis-associated lymphangiomyopathy (TSC-LAM) accounts for 20% (1/5), with extrapulmonary manifestations: liver, kidney, bone, skin and other lesions, which are multisystem involvement.

Conclusions

PLAM is a rare lung disease, HRCT has specificity, providing an important imaging basis for the diagnosis and identification of this disease, Chest CT in all 5 patients in this study had common features, all manifested as diffuse distribution of both lungs containing air cyst cavity, peripheral vascular signs can be seen at the edge, there is currently no effective treatment, immunosuppressants can improve the condition of some patients, case 1 patients take everolimus, It can inhibit the hyperplasia of LAM cells caused by activation of mTOR (mammalian target protein of rapamycin), delay disease progression, and consider lung transplantation in the terminal stage.

Key words: Pulmonary lymphangiomyoma, High-resolution tomography, Tuberous sclerosis

图1 胸部CT。注：双肺弥漫分布大小不等薄壁囊性病变(箭头所示)

图2 皮肤及趾甲的改变。注：A：背部鲨鱼皮样斑(箭头所示)；B：面部血管纤维(≥3处箭头所示)；C：双手皮肤色素脱失斑(≥3处，直径≥5 mm箭头所示)；D：趾甲纤维瘤(≥2处箭头所示)

图3 胸部CT。注：双肺多发大小不等的透亮影，边缘可见血管贴边征(箭头所示)

图4 胸部CT。注：双肺多发大小不等的透亮影，周围可见血管征(箭头所示)

图5 胸部CT。注：双肺多发类囊性病变，血管影位于囊壁边缘(箭头所示)

图6 胸部CT。注：弥漫随机分布的薄壁囊性影，血管影位于囊壁边缘(箭头所示)

1	Liu FB, Lunsford EP, Tong JL, et al. Real-time monitoring of tumorigenesis，dissemination, & drug response in a preclinical model of lymphangioleiomyomatosis/tuberous sclerosis complex[J]. PLoS One, 2012, 7(6): e38589.
2	刘春平，顾莹莹. 肺淋巴管平滑肌瘤病的临床病理学分析[J]. 诊断病理学杂志，2022, 29(11): 1037-1040, 1048.
3	赵天明，倪吉祥. 肺淋巴管平滑肌瘤病1例[J/CD]. 中华肺部疾病杂志(电子版), 2017. 10(4): 501-503.
4	陈雪芬，邓静敏. 肺淋巴管肌瘤病治疗的研究进展[J/CD]. 中华临床医师杂志(电子版), 2021, 15(7): 556-560.
5	Gupta N, Finlay GA, Kotloff RM, et al. Lymphangioleiomyomatosis diagnosis and management: High-resolution chest computed tomography, transbronchial lung biopsy, and pleural disease management. An official American Thoracic Society/Japanese Respiratory Society Clinical Practice Guideline[J]. Am J Respir Crit Care Med, 2017, 196(10): 1337-1348.
6	Krueger DA, Northrup H. Tuberous sclerosis complex surveillance and management: recommendations of the 2012 international tuberous sclerosis complex consensus conference[J]. Pediatr Neurol, 2013, 49(4): 255-265.
7	Northrup H, Krueger DA. Tuberous sclerosis complex diagnostic criteria update: recommendations of the 2012 Iinternational Tuberous Sclerosis Complex Consensus Conference[J]. Pediatr Neurol, 2013, 49(4): 243-254.
8	中国抗癌协会泌尿男生殖系肿瘤专业委员会结节性硬化协作组. 结节性硬化症相关肾血管平滑肌脂肪瘤诊疗与管理专家共识[J]. 中国癌症杂志，2020, 30(1): 70-78.
9	Revilla-López E, Ruiz de Miguel V, López-Meseguer M, et al. Lymphangioleiomyomatosis: Searching for potential biomarkers[J]. Front Med (Lausanne), 2023, 10: 1079317.
10	Kim J, Guan KL. mTOR as a central hub of nutrient signalling and cell growth[J]. Nat Cell Biol, 2019, 21(1): 63-71.
11	Evans JF, Obraztsova K, Lin SM, et al. CrossTORC and WNTegration in disease: Focus on lymphangioleiomyomatosis[J]. Int J Mol Sci, 2021, 22(5): 2233.
12	Liu GY, Sabatini DM. mTOR at the nexus of nutrition, growth, ageing and disease[J]. Nat Rev Mol Cell Biol, 2020, 21(4): 183-203.
13	Tee AR. The target of rapamycin and mechanisms of cell growth[J]. Int J Mol Sci, 2018, 19(3): 880.
14	Brakemeier S, Grohé C, Bachmann F, et al. Sporadic lymphangioleiomyomatosis (sLAM) and tuberous sclerosis complex (TSC)-pulmonary manifestations[J]. Pneumologie, 2017, 71(2): 86-95.
15	Hirose M, Matsumuro A, Arai T, et al. Serum vascular endothelial growth factor-D as a diagnostic and therapeutic biomarker for lymphangioleiomyomatosis[J]. PLoS One, 2019，14(2): e0212776.
16	He J, Ma J, Ren B, et al. Advances in systemic lupus erythematosus pathogenesis via mTOR signaling pathway[J]. Semin Arthritis Rheum, 2020, 50(2): 314-320.
17	姜永浩，张　蕾，张嘉铖. 不稳定性心绞痛合并干燥综合征及肺淋巴管肌瘤病1例并文献复习[J]. 重庆医学，2023, 52(4): 638-640.
18	Lu Y, Liu X, Zhang E, et al. Estrogen activates pyruvate kinase M2 and increases the growth of TSC2-deficient cells[J]. PLoS One, 2020, 15(2): e0228894.
19	Seyama K, Kumasaka T, Souma S, et al. Vascular endothelial growth factor-D is increased in serum of patients with lymphangioleiomyomatosis[J]. Lymphat Res Biol, 2006, 4(3): 143-152.
20	Glasgow CG, Avila NA, Lin JP, et al. Serum vascular endothelial growth factor-D levels in patients with lymphangioleiomyomatosis reflect lymphatic involvement[J]. Chest, 2009，135(5): 1293-1300.
21	Khokha R, Murthy A, Weiss A. Metalloproteinases and their natural inhibitors in inflammation and immunity[J]. Nat Rev Immunol, 2013, 13(9): 649-665.
22	McCormack FX, Gupta N, Finlay GR, et al. Official American Thoracic Society/Japanese Respiratory Society Clinical Practice Guidelines: Lymphangioleiomyomatosis diagnosis and management[J]. Am J Respir Crit Care Med, 2016, 194(6): 748-761.
23	Ancona S, Orpianesi E, Bernardelli C, et al. Differential modulation of matrix metalloproteinases-2 and-7 in LAM/TSC cells[J]. Biomedicines, 2021, 9(12): 1760.
24	Dong X, Jin L, Wang A, et al. A Systematic review of lymphangioleiomyomatosis on diagnosis and molecular mechanism[J]. Biomed Res Int, 2021, 2021: 6612776.
25	张龙举，梁　毅，钟小宁，等. 国内三十余年肺淋巴管肌瘤病130例临床与病理文献复习分析[J]. 中国全科医学，2015, 18(3): 329-334.
26	宋留存，李富建，秦雪青. CT诊断胸部弥漫性疾病的临床应用意义评析[J]. 中国CT和MRI杂志，2017, 15(6): 63-65.
27	贾永军，于　楠，杨创勃，等. 基于模型的迭代重建在改善胸部低剂量CT评价早期周围型肺癌中的价值[J]. 中国医学影像学杂志，2019, 27(9): 682-686.
28	朱慧媛，张　莲，王亚丽，等. 超高分辨率CT靶扫描对肺结节的诊断价值[J]. 第二军医大学学报，2017, 38(9): 1165-1170.
29	赵金勇，曹世文. 高分辨CT对肺淋巴管平滑肌瘤病与特发性肺间质纤维化的鉴别诊断意义[J]. 医学影像学杂志，2016, 26(2): 359-361.
30	He F, Zhong J, Chai R, et al. A pulmonary lymphangioleiomyomatosis with multi-site angiomyolipoma: a case report[J]. Transl Cancer Res, 2022, 11(7): 2449-2456.
31	中华医学会呼吸病学分会间质性肺疾病学组，淋巴管肌瘤病共识专家组，中国医学科学院罕见病研究中心，等. 西罗莫司治疗淋巴管肌瘤病专家共识(2018)[J]. 中华结核和呼吸杂志，2019, 42(2): 92-97.
32	Medeiros V, Gonçalves de Lima J, Rosa C, et al. Physiotherapy in lymphangioleiomyomatosis: a systematic review[J]. Ann Med, 2022, 54(1): 2744-2751.
33	Harari S, Torre O, Moss J. Lymphangioleiomyomatosis: what do we know and what are we looking for[J]. Eur Respir Rev, 2011, 20(119): 34-44.
34	Schneider BS, Maimon J, Golub LM, et al. Tetracyclines inhibit intracellular muscle proteolysis in vitro[J]. Biochem Biophys Res Commun, 1992, 188(2): 767-772.
35	Ginns LC, Roberts DH, Mark EJ, et al. Pulmonary capillary hemangiomatosis with atypical endotheliomatosis: successful antiangiogenic therapy with doxycycline[J]. Chest, 2003, 124(5): 2017-2022.
36	Yoon HY, Kim HJ, Song JW. Long-term clinical course and outcomes in patients with lymphangioleiomyomatosis[J]. Respir Res, 2022, 23(1): 158.

[1]	余旭东, 杨文忠, 夏风, 兰为顺, 夏薇, 袁先宏, 苏永学, 李琳, 陈欣林, 杨小红. 超声联合磁共振成像诊断胎儿结节性硬化症[J]. 中华医学超声杂志（电子版）, 2015, 12(11): 884-888.
[2]	杨莹, 刘艳, 王央丹. 新生儿结节性硬化症相关性癫痫1例并文献复习[J]. 中华妇幼临床医学杂志(电子版), 2023, 19(04): 464-472.
[3]	张勇, 蔡保欢. 新生儿结节性硬化症并文献复习[J]. 中华妇幼临床医学杂志(电子版), 2019, 15(01): 46-50.
[4]	刘影, 李超, 许益, 王淙锦, 杨丽. 超声心动图对胎儿心脏横纹肌瘤诊断的临床价值[J]. 中华妇幼临床医学杂志(电子版), 2018, 14(05): 503-507.
[5]	赵杰, 李杰, 刘鑫, 黄龙, 李元勋, 伍火志. 肺淋巴管肌瘤病一例报告及文献复习[J]. 中华胸部外科电子杂志, 2018, 05(01): 62-64.

阅读次数

全文

摘要

选择文件类型/文献管理软件名称

选择包含的内容

5 cases of pulmonary lymphangileiomyomatosis and literature review

模态框（Modal）标题

选择文件类型/文献管理软件名称

选择包含的内容

5 cases of pulmonary lymphangileiomyomatosis and literature review