Lymphangioleiomyomatosis: X-ray morphological comparisons

Lymphangioleiomyomatosis (LAM) is a rare, slowly progressing disease characterized by a tumor-like overgrowth of smooth muscle fibers in the interstitial lung tissue, around blood and lymph vessels, bronchi, bronchioles, in lymph nodes. The disease has mainly been described in women of childbearing age, with a mean age of diagnosis of about 35 years.

Methods. This retrospective, cohort study included 16 patients who were diagnosed with LAM at the age of 17 – 53 years (Me – 39, HQ – 42.5, LQ – 30.5). The calculation of the volumetric area of cystic lesion in the entire volume of the lungs was carried out using the GE aws 3.2 Thoracic VCAR software. To assess the area of cystic lesion on histological sections, we calculated area of cystic formations, in the walls of which smooth muscle nodules were found. For statistical analysis, the Kolmogorov–Smirnov test, the Mann – Whitney U-test (p < 0.05), and the Spearman correlation analysis were used.

Results. Morphometric analysis of histological preparations of the lungs showed no statistically significant difference between women of young age and older age. A correlation was found between the volumetric area of cystic lesion on CT and FEV₁ (correlation coefficient = –0.886). Baseline median area of cysts was larger in patients who later deteriorated, while condition of patients with a smaller area of cysts remained stable (2.677 vs 1.119 mm2  correspondingly).

Conclusion. The volumetric area of cystic lesions in LAM correlates with functional parameters. The size of cysts in LAM may determine the prognosis of the course of the disease, because the formation of larger cysts is an unfavorable prognostic factor that increases the risk of developing pneumothorax. 

1. Henske E.P., McCormack F.X. Lymphangioleiomyomatosis – a wolf in she ep’s clothing. J. Clin. Invest. 2012; 122 (11): 3807–3816. DOI: 10.1172/JCI58709.

2. Jones A.C., Shyamsundar M.M., Thomas M.W. et al. Comprehensive mutation analysis of TSC1 and TSC2-and phenotypic correlations in 150 families with tuberous sclerosis. Am. J. Hum. Genet. 1999; 64 (5): 1305–1315. DOI: 10.1086/302381.

3. Dabora S.L., Jozwiak S., Franz D.N. et al. Mutational analysis in a cohort of 224 tuberous sclerosis patients indicates increased severity of TSC2, compared with TSC1, disease in multiple organs. Am. J. Hum. Genet. 2001; 68 (1): 64–80. DOI: 10.1086/316951.

4. Cornog J.L., Enterline H.T. Lymphangiomyoma, a benign lesion of chyliferous lymphatics synonymous with lymphangiopericytoma. Cancer. 1966; 19 (12): 1909–1930. DOI: 10.1002/1097-0142(196612)19:12%3C1909::aid-cncr2820191219%3E3.0.co;2-r.

5. Bonetti F., Pea M., Martignoni G. et al. Cellular heterogeneity in lymphangiomyomatosis of the lung. Hum. Pathol. 1991; 22 (7): 727–728. DOI: 10.1016/0046-8177(91)90298-4.

6. Zhe X., Schuger L. Combined smooth muscle and melanocytic differentiation in lymphangioleiomyomatosis. J. Histochem. Cytochem. 2004; 52 (12): 1537–1542. DOI: 10.1369/jhc.4A6438.2004.

7. Crooks D.M., Pacheco-Rodriguez G., DeCastro R.M. et al. Molecular and genetic analysis of disseminated neoplastic cells in lymphangioleiomyomatosis. Proc. Natl. Acad. Sci. USA. 2004; 101 (50): 17462–17467. DOI: 10.1073/pnas.0407971101.

8. Henry M.T., McMahon K., Mackarel A.J. et al. Matrix metalloproteinases and tissue inhibitor of metalloproteinase-1 in sarcoidosis and IPF. Eur. Respir. J. 2002; 20 (5): 1220–1227. DOI: 10.1183/09031936.02.00022302.

9. Harari S., Torre O., Moss J. Lymphangioleiomyomatosis: what do we know and what are we looking for? Eur. Respir. Rev. 2011; 20 (119): 34–44. DOI: 10.1183/09059180.00011010.

10. Avila N.A., Chen C.C., Chu S.C. et al. Pulmonary lymphangioleiomyomatosis: correlation of ventilation-perfusion scintigraphy, chest radiography, and CT with pulmonary function tests. Radiology. 2000; 214 (2): 441–446. DOI: 10.1148/radiology.214.2.r00fe41441.

11. Avila N.A., Kelly J.A., Dwyer A.J. et al. Lymphangioleiomyomatosis: correlation of qualitative and quantitative thin-section CT with pulmonary function tests and assessment of dependence on pleurodesis. Radiology. 2002; 223 (1): 189–197. DOI: 10.1148/radiol.2231010315.

12. Avdeev S.N., Anaev E.Kh., Ananyeva L.P. et al. [Respiratory medicine: guide]. Moscow: Litterra; 2017. Vol. 3 (in Russian).

13. Gupta N., Finlay G.A., Kotloff R.M. 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. Am. J. Respir. Crit. Care Med. 2017; 196 (10): 1337–1348. DOI: 10.1164/rccm.201709-1965ST.

14. Ilkovich M. M., Novikova L. N., Dvorakovskaya I. V., Kameneva M. Yu. [Lymphangioleiomyomatosis of the lungs: diagnostic difficulties]. Doktor.Ru. 2008; 42 (5): 40–44. Available at: https://cyberleninka.ru/article/n/limfangioleyomiomatoz-legkih-trudnosti-diagnostiki/viewer (in Russian).

15. Gupta N., Meraj R., Tanase D. et al. Accuracy of chest high-resolution computed tomography in diagnosing diffuse cystic lung diseases. Eur. Respir. J. 2015; 46 (4): 1196–1199. DOI: 10.1183/13993003.00570-2015.

16. Almoosa K.F., McCormack F.X., Sahn S.A. Pleural disease in lymphangioleiomyomatosis. Clin. Chest Med. 2006; 27 (2): 355–368. DOI: 10.1016/j.ccm.2006.01.005.

17. Radzikowska E., Jaguś P., Sobiecka M. et al. Correlation of serum vascular endothelial growth factor-D concentration with clinical presentation and course of lymphangioleiomyomatosis. Respir. Med. 2015; 109 (11): 1469–1475. DOI: 10.1016/j.rmed.2015.09.005.

18. Steagall W.K., Glasgow C.G., Hathaway O.M. et al. Genetic and morphologic determinants of pneumothorax in lymphangioleiomyomatosis. Am. J. Physiol. Lung Cell. Mol. Physiol. 2007; 293 (3): L800–808. DOI: 10.1152/ajplung.00176.2007.

19. Cohen M.M., Freyer A.M., Johnson S.R. Pregnancy experiences among women with lymphangioleiomyomatosis. Respir. Med. 2009; 103 (5): 766–772. DOI: 10.1016/j.rmed.2008.11.007.

20. Ryu J.H., Moss J., Beck G.J. et al. The NHLBI lymphangioleiomyomatosis registry: characteristics of 230 patients at enrollment. Am. J. Respir. Crit. Care Med. 2006; 173 (1): 105–111. DOI: 10.1164/rccm.200409-1298OC.

21. Taveira-DaSilva A.M., Gopalakrishnan, V., Yao, J. et al. Computer grading of lung disease severity in patients with lymphangioleiomyomatosis referred for transplantation. BMC Pulm. Med. 2022; 22 (1): 362. DOI: 10.1186/s12890-02123-7.