open access

Vol 17, No 1 (2021)
Review paper
Published online: 2021-02-26
Get Citation

Diagnosis and treatment of lymphangioleiomyomatosis (LAM) from the PEComa group

Aleksandra Sobiborowicz, Anna M. Czarnecka, Anna Szumera-Ciećkiewicz, Piotr Rutkowski, Tomasz Świtaj
DOI: 10.5603/OCP.2020.0034
·
Oncol Clin Pract 2021;17(1):28-41.

open access

Vol 17, No 1 (2021)
REVIEW ARTICLES
Published online: 2021-02-26

Abstract

Lymphangioleiomyomatosis (LAM) is a rare, proliferative lung disease, leading to progressive damage of their structure and is a member of the PEComa neoplasm family (perivascular epithelioid cell tumors). In the patients, solid-cystic masses described as lymphangioleiomyoma or extrapulmonary LAM (E-LAM) can occur. E-LAM foci have been described in the mediastinum, supraclavicular lymph nodes, the liver, walls of the small and large intestine, the pancreas, mesentery. E-LAM masses can attain very large sizes — tumors 15–22 cm long have been described. On the basis of positive results of clinical trials sirolimus, a drug from the group of mTOR kinase inhibitors, was registered by the Food and Drug Administration (FDA) in May 2015 as the first and currently only drug for systemic LAM therapy. Sirolimus use is recommended in patients with LAM, accompanied by rapidly progressing deterioration of respiratory system function or FEV1 ≤ 70% predicted value and in patients with pleural lymph exudate before applying invasive methods of treatment.

Abstract

Lymphangioleiomyomatosis (LAM) is a rare, proliferative lung disease, leading to progressive damage of their structure and is a member of the PEComa neoplasm family (perivascular epithelioid cell tumors). In the patients, solid-cystic masses described as lymphangioleiomyoma or extrapulmonary LAM (E-LAM) can occur. E-LAM foci have been described in the mediastinum, supraclavicular lymph nodes, the liver, walls of the small and large intestine, the pancreas, mesentery. E-LAM masses can attain very large sizes — tumors 15–22 cm long have been described. On the basis of positive results of clinical trials sirolimus, a drug from the group of mTOR kinase inhibitors, was registered by the Food and Drug Administration (FDA) in May 2015 as the first and currently only drug for systemic LAM therapy. Sirolimus use is recommended in patients with LAM, accompanied by rapidly progressing deterioration of respiratory system function or FEV1 ≤ 70% predicted value and in patients with pleural lymph exudate before applying invasive methods of treatment.

Get Citation

Keywords

lymphangioleiomyomatosis; sirolimus

About this article
Title

Diagnosis and treatment of lymphangioleiomyomatosis (LAM) from the PEComa group

Journal

Oncology in Clinical Practice

Issue

Vol 17, No 1 (2021)

Article type

Review paper

Pages

28-41

Published online

2021-02-26

DOI

10.5603/OCP.2020.0034

Bibliographic record

Oncol Clin Pract 2021;17(1):28-41.

Keywords

lymphangioleiomyomatosis
sirolimus

Authors

Aleksandra Sobiborowicz
Anna M. Czarnecka
Anna Szumera-Ciećkiewicz
Piotr Rutkowski
Tomasz Świtaj

References (133)
  1. Martignoni G, Pea M, Reghellin D, et al. Molecular pathology of lymphangioleiomyomatosis and other perivascular epithelioid cell tumors. Arch Pathol Lab Med. 2010; 134(1): 33–40.
  2. Matsui K, Tatsuguchi A, Valencia J, et al. Extrapulmonary lymphangioleiomyomatosis (LAM): clinicopathologic features in 22 cases. Hum Pathol. 2000; 31(10): 1242–1248.
  3. Pontes M, Barbosa C, Coelho ML, et al. Probable initial pulmonary lymphangioleiomyomatosis and mediastinal lymphangioleiomyoma. Rev Port Pneumol. 2014; 20(2): 101–106.
  4. Derweduwen AM, Verbeken E, Stas M, et al. Extrapulmonary lymphangioleiomyomatosis: a wolf in sheep's clothing. Thorax. 2013; 68(1): 111–113.
  5. Kamitani T, Yabuuchi H, Soeda H, et al. A case of lymphangioleiomyomatosis affecting the supraclavicular lymph nodes. J Comput Assist Tomogr. 2006; 30(2): 279–282.
  6. Fu W, Li Y, Li H, et al. Solitary extrapulmonary lymphangioleiomyomatosis of the liver: A case report and literature review. Exp Ther Med. 2016; 12(3): 1499–1502.
  7. Goh SG, Ho JM, Chuah KL, et al. Leiomyomatosis-like lymphangioleiomyomatosis of the colon in a female with tuberous sclerosis. Mod Pathol. 2001; 14(11): 1141–1146.
  8. Possekel AK, Katenkamp D, Brambs HJ, et al. Lymphangioleiomyomatosis: solitary abdominal manifestation (2009: 9b). Eur Radiol. 2009; 19(12): 3015–3018.
  9. Abdelkader A, Lam CA, Shahir KS, et al. Retroperitoneal lymphangioleiomyoma with lymph node involvement: A pathologic-radiologic correlation of a rare form of myomelanocytic tumor. Ann Diagn Pathol. 2017; 27: 69–73.
  10. Singh M, Saroha V, Wadhwa R, et al. Solitary lymphangioleiomyoma of pancreas mimicking pancreatic pseudocyst -- a case report. J Gastrointest Cancer. 2012; 43(2): 336–339.
  11. Jun Y, Jang S, Han H, et al. Extrapulmonary lymphangioleiomyoma presenting as a mesenteric cystic mass. Basic and Applied Pathology. 2011; 4(2): 63–65.
  12. Ascher KB. Glassberg Csete MK. Lymhangioleiomyomatosis (LAM) of the Uterus: Risk of Pulmonary LAM? D32 ILD: CASE REPORTS II. American Thoracic Society International Conference Abstracts: American Thoracic Society. 2018: A6507–A.
  13. de Groot JWB, Vecht J, van den Bergen HA, et al. Extrapulmonary lymphangioleiomyomatosis: an unusual cause of biliary tract obstruction. Neth J Med. 2008; 66(1): 31–34.
  14. Atallah D, Checrallah A, Rouzier R, et al. Retroperitoneal lymphangioleiomyoma mimicking ovarian tumor emerging after tamoxifen therapy. Obstet Gynecol. 2006; 108(3 Pt 2): 762–764.
  15. Avila NA, Bechtle J, Dwyer AJ, et al. Lymphangioleiomyomatosis: CT of diurnal variation of lymphangioleiomyomas. Radiology. 2001; 221(2): 415–421.
  16. McCormack F, Gupta N, Finlay G, et al. Official American Thoracic Society/Japanese Respiratory Society Clinical Practice Guidelines: Lymphangioleiomyomatosis Diagnosis and Management. American Journal of Respiratory and Critical Care Medicine. 2016; 194(6): 748–761.
  17. Klimczak A, Pękul M, Wiater K, et al. PEComa – grupa rzadkich nowotworów pochodzenia mezenchymalnego. NOWOTWORY Journal of Oncology. 2011; 61(1): 52–56.
  18. Thway K, Fisher C. PEComa: morphology and genetics of a complex tumor family. Ann Diagn Pathol. 2015; 19(5): 359–368.
  19. Słowińska M, Jóźwiak S, Peron A, et al. Early diagnosis of tuberous sclerosis complex: a race against time. How to make the diagnosis before seizures? Orphanet J Rare Dis. 2018; 13(1): 25.
  20. Johnson SR, Cordier JF, Lazor R, et al. Review Panel of the ERS LAM Task Force. European Respiratory Society guidelines for the diagnosis and management of lymphangioleiomyomatosis. Eur Respir J. 2010; 35(1): 14–26.
  21. Muzykewicz DA, Sharma A, Muse V, et al. TSC1 and TSC2 mutations in patients with lymphangioleiomyomatosis and tuberous sclerosis complex. J Med Genet. 2009; 46(7): 465–468.
  22. Freitas CSG, Baldi BG, Jardim C, et al. Pulmonary hypertension in lymphangioleiomyomatosis: prevalence, severity and the role of carbon monoxide diffusion capacity as a screening method. Orphanet J Rare Dis. 2017; 12(1): 74.
  23. Ando K, Kurihara M, Kataoka H, et al. Efficacy and safety of low-dose sirolimus for treatment of lymphangioleiomyomatosis. Respir Investig. 2013; 51(3): 175–183.
  24. Chu SC, Horiba K, Usuki J, et al. Comprehensive evaluation of 35 patients with lymphangioleiomyomatosis. Chest. 1999; 115(4): 1041–1052.
  25. Johnson SR, Tattersfield AE. Clinical experience of lymphangioleiomyomatosis in the UK. Thorax. 2000; 55(12): 1052–1057.
  26. Kebria M, Black D, Borelli C, et al. Primary retroperitoneal lymphangioleiomyomatosis in a postmenopausal woman: a case report and review of the literature. Int J Gynecol Cancer. 2007; 17(2): 528–532.
  27. Liu Yi, Guo Z, Zhao C, et al. Lymphangioleiomyomatosis: a case report and review of diagnosis and treatment. Onco Targets Ther. 2018; 11: 5339–5347.
  28. Takia L, Jat KR, Mandal A, et al. Lymphangioleiomyomatosis (LAM) presenting as recurrent pneumothorax in an infant with tuberous sclerosis: treated successfully with sirolimus. BMJ Case Rep. 2018; 2018.
  29. Fiore MG, Sanguedolce F, Lolli I, et al. Abdominal lymphangioleiomyomatosis in a man with Klinefelter syndrome: the first reported case. Ann Diagn Pathol. 2005; 9(2): 96–100.
  30. Zhang C, Chen X, Wen T, et al. Computed tomography lymphangiography findings in 27 cases of lymphangioleiomyomatosis. Acta Radiol. 2017; 58(11): 1342–1348.
  31. Avila NA, Kelly JA, Chu SC, et al. Lymphangioleiomyomatosis: abdominopelvic CT and US findings. Radiology. 2000; 216(1): 147–153.
  32. Torres VE, Björnsson J, King BF, et al. Extrapulmonary lymphangioleiomyomatosis and lymphangiomatous cysts in tuberous sclerosis complex. Mayo Clin Proc. 1995; 70(7): 641–648.
  33. Hayashi T, Kumasaka T, Mitani K, et al. Prevalence of uterine and adnexal involvement in pulmonary lymphangioleiomyomatosis: a clinicopathologic study of 10 patients. Am J Surg Pathol. 2011; 35(12): 1776–1785.
  34. Kuno I, Yoshida H, Shimizu H, et al. Incidental lymphangioleiomyomatosis in the lymph nodes of gynecologic surgical specimens. Eur J Obstet Gynecol Reprod Biol. 2018; 231: 93–97.
  35. Schoolmeester JK, Park KJ. Incidental Nodal Lymphangioleiomyomatosis Is Not a Harbinger of Pulmonary Lymphangioleiomyomatosis: A Study of 19 Cases With Evaluation of Diagnostic Immunohistochemistry. Am J Surg Pathol. 2015; 39(10): 1404–1410.
  36. Ando H, Ogawa M, Watanabe Y, et al. Lymphangioleiomyoma of the uterus and pelvic lymph nodes: a report of 3 cases, including the potentially earliest manifestation of extrapulmonary lymphangioleiomyomatosis. Int J Gynecol Pathol. 2020; 39(3): 227–232.
  37. Rabban JT, Firetag B, Sangoi AR, et al. Incidental pelvic and para-aortic lymph node lymphangioleiomyomatosis detected during surgical staging of pelvic cancer in women without symptomatic pulmonary lymphangioleiomyomatosis or tuberous sclerosis complex. Am J Surg Pathol. 2015; 39(8): 1015–1025.
  38. Avila NA, Dwyer AJ, Murphy-Johnson DV, et al. Sonography of lymphangioleiomyoma in lymphangioleiomyomatosis: demonstration of diurnal variation in lesion size. AJR Am J Roentgenol. 2005; 184(2): 459–464.
  39. Ernst JC, Sohaey R, Cary JM. Pelvic lymphangioleiomyomatosis. Atypical precursor to pulmonary disease. Chest. 1994; 106(4): 1267–1269.
  40. Kim HS, Park MI, Suh KS. Lymphangiomyomatosis arising in the pelvic cavity: a case report. J Korean Med Sci. 2005; 20(5): 904–907.
  41. Lam B, Ooi GC, Wong MP, et al. Extrapulmonary presentation of asymptomatic pulmonary lymphangioleiomyomatosis. Respirology. 2003; 8(4): 544–547.
  42. Lu HC, Wang J, Tsang YM, et al. Lymphangioleiomyomatosis initially presenting with abdominal pain: a case report. Clin Imaging. 2003; 27(3): 166–170.
  43. Bahmer T, Watz H, Waschki B, et al. Reduced physical activity in lymphangioleiomyomatosis compared with COPD and healthy controls: disease-specific impact and clinical correlates. Thorax. 2016; 71(7): 662–663.
  44. Johnson SR, Whale CI, Hubbard RB, et al. Survival and disease progression in UK patients with lymphangioleiomyomatosis. Thorax. 2004; 59(9): 800–803.
  45. Matsui K, Beasley MB, Nelson WK, et al. Prognostic significance of pulmonary lymphangioleiomyomatosis histologic score. Am J Surg Pathol. 2001; 25(4): 479–484.
  46. Lama A, Ferreiro L, Golpe A, et al. Characteristics of patients with lymphangioleiomyomatosis and pleural effusion: a systematic review. Respiration. 2016; 91(3): 256–264.
  47. Favoreel N, Van Meerbeeck SF, Gosselin R. Extrapulmonary manifestation of lymphangioleiomyomatosis. JBR-BTR. 2015; 98(1): 53.
  48. Grant L, Chipwete S, Soo Hoo S, et al. Extrapulmonary uterine lymphangioleiomyomatosis (LAM) and dysfunctional uterine bleeding: the first presentation of LAM in a tuberous sclerosis complex patient. BMJ Case Rep. 2019; 12(2).
  49. Han JM, Lee KH, Kim SJ, et al. A case of lymphangioleiomyomatosis originated in the pelvic cavity. J Gynecol Oncol. 2008; 19(3): 195–198.
  50. Jaiswal VR, Baird J, Fleming J, et al. Localized retroperitoneal lymphangioleiomyomatosis mimicking malignancy. A case report and review of the literature. Arch Pathol Lab Med. 2003; 127(7): 879–882.
  51. Gray S, Carrington C, Cornog J. Lymphangiomyomatosis: Report of a case with ureteral involvement and chyluria. Cancer. 1975; 35(2): 490–498.
  52. Longacre TA, Hendrickson MR, Kapp DS, et al. Lymphangioleiomyomatosis of the uterus simulating high-stage endometrial stromal sarcoma. Gynecol Oncol. 1996; 63(3): 404–410.
  53. Sandrini A, Silverstone E, Yates DH. Menstrual cycle variation of retroperitoneal lymphangioleiomyomas in lymphangioleiomyomatosis. Intern Med J. 2011; 41(12): 832–835.
  54. Gupta N, Finlay GA, Kotloff RM, et al. ATS Assembly on Clinical Problems. 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.
  55. Koba T, Arai T, Kitaichi M, et al. Efficacy and safety of transbronchial lung biopsy for the diagnosis of lymphangioleiomyomatosis: A report of 24 consecutive patients. Respirology. 2018; 23(3): 331–338.
  56. Grzegorek I, Lenze D, Chabowski M, et al. Immunohistochemical evaluation of pulmonary lymphangioleiomyomatosis. Anticancer Res. 2015; 35(6): 3353–3360.
  57. Matsui K, Tatsuguchi A, Valencia J, et al. Lymphangioleiomyomatosis (LAM): a review of clinical and morphological features. J Nippon Med Sch. 2000; 67(5): 311–329.
  58. Taveira-DaSilva AM, Pacheco-Rodriguez G, Moss J. The natural history of lymphangioleiomyomatosis: markers of severity, rate of progression and prognosis. Lymphat Res Biol. 2010; 8(1): 9–19.
  59. Zhe X, Schuger L. Combined smooth muscle and melanocytic differentiation in lymphangioleiomyomatosis. J Histochem Cytochem. 2004; 52(12): 1537–1542.
  60. Zhang X, Travis WD. Pulmonary lymphangioleiomyomatosis. Arch Pathol Lab Med. 2010; 134(12): 1823–1828.
  61. Davis JM, Hyjek E, Husain AN, et al. Lymphatic endothelial differentiation in pulmonary lymphangioleiomyomatosis cells. J Histochem Cytochem. 2013; 61(8): 580–590.
  62. Gao L, Yue MM, Davis J, et al. In pulmonary lymphangioleiomyomatosis expression of progesterone receptor is frequently higher than that of estrogen receptor. Virchows Arch. 2014; 464(4): 495–503.
  63. Flavin R, Cook J, Fiorentino M, et al. β-Catenin Is a Useful Adjunct Immunohistochemical Marker for the Diagnosis of Pulmonary Lymphangioleiomyomatosis. American Journal of Clinical Pathology. 2011; 135(5): 776–782.
  64. Dongre A, Clements D, Fisher AJ, et al. Cathepsin k in lymphangioleiomyomatosis: LAM cell-fibroblast interactions enhance protease activity by extracellular acidification. Am J Pathol. 2017; 187(8): 1750–1762.
  65. Kobayashi K, Miki Y, Saito R, et al. Roles of human epidermal growth factor receptor family in pulmonary lymphangioleiomyomatosis. Hum Pathol. 2018; 81: 121–130.
  66. Maisel K, Merrilees MJ, Atochina-Vasserman EN, et al. Immune checkpoint ligand PD-L1 is upregulated in pulmonary lymphangioleiomyomatosis. Am J Respir Cell Mol Biol. 2018; 59(6): 723–732.
  67. Uehara K, Kawakami F, Hirose T, et al. Clinicopathological analysis of clinically occult extrapulmonary lymphangioleiomyomatosis in intra-pelvic and para-aortic lymph nodes associated with pelvic malignant tumors: A study of nine patients. Pathol Int. 2019; 69(1): 29–36.
  68. Smolarek TA, Wessner LL, McCormack FX, et al. Evidence that lymphangiomyomatosis is caused by TSC2 mutations: chromosome 16p13 loss of heterozygosity in angiomyolipomas and lymph nodes from women with lymphangiomyomatosis. Am J Hum Genet. 1998; 62(4): 810–815.
  69. Kristof AS, You Z, Han YS, et al. mTOR signaling in lymphangioleiomyomatosis. Lymphat Res Biol. 2010; 8(1): 33–42.
  70. Huang J, Manning BD. The TSC1-TSC2 complex: a molecular switchboard controlling cell growth. Biochem J. 2008; 412(2): 179–190.
  71. Strizheva GD, Carsillo T, Kruger WD, et al. The spectrum of mutations in TSC1 and TSC2 in women with tuberous sclerosis and lymphangiomyomatosis. Am J Respir Crit Care Med. 2001; 163(1): 253–258.
  72. Murphy SJ, Terra SB, Harris FR, et al. Genomic rearrangements in sporadic lymphangioleiomyomatosis: an evolving genetic story. Mod Pathol. 2017; 30(9): 1223–1233.
  73. Badri K, Gao L, Hyjek E, et al. Exonic mutations ofTSC2/TSC1Are common but not seen in all sporadic pulmonary lymphangioleiomyomatosis. American Journal of Respiratory and Critical Care Medicine. 2013; 187(6): 663–665.
  74. Fujita A, Ando K, Kobayashi E, et al. Detection of low-prevalence somatic TSC2 mutations in sporadic pulmonary lymphangioleiomyomatosis tissues by deep sequencing. Hum Genet. 2016; 135(1): 61–68.
  75. Johnson SR, Tattersfield AE. Decline in lung function in lymphangioleiomyomatosis: relation to menopause and progesterone treatment. Am J Respir Crit Care Med. 1999; 160(2): 628–633.
  76. Gupta N, Lee HS, Ryu JH, et al. NHLBI LAM Registry Group. The NHLBI LAM registry: prognostic physiologic and radiologic biomarkers emerge from a 15-year prospective longitudinal analysis. Chest. 2019; 155(2): 288–296.
  77. Amaral AF, de Oliveira MR, Dias OM, et al. Tuberous Sclerosis, Lymphangioleiomyomatosis and Angiomyolipoma Study Group, Universidade de Sao Paulo, Brazil. Concentration of Serum Vascular Endothelial Growth Factor (VEGF-D) and Its Correlation with Functional and Clinical Parameters in Patients with Lymphangioleiomyomatosis from a Brazilian Reference Center. Lung. 2019; 197(2): 139–146.
  78. 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.
  79. Miller S, Coveney C, Johnson J, et al. The vitamin D binding protein axis modifies disease severity in lymphangioleiomyomatosis. Eur Respir J. 2018; 52(5).
  80. Liu HJ, Henske EP. Vitamin D binding protein: a new biomarker of disease severity in lymphangioleiomyomatosis. Eur Respir J. 2018; 52(5).
  81. Lamattina AM, Taveira-Dasilva A, Goldberg HJ, et al. Circulating Biomarkers From the Phase 1 Trial of Sirolimus and Autophagy Inhibition for Patients With Lymphangioleiomyomatosis. Chest. 2018; 154(5): 1070–1082.
  82. Araujo MS, Baldi BG, Freitas CSG, et al. Pulmonary rehabilitation in lymphangioleiomyomatosis: a controlled clinical trial. Eur Respir J. 2016; 47(5): 1452–1460.
  83. Gonano C, Pasquier J, Daccord C, et al. Air travel and incidence of pneumothorax in lymphangioleiomyomatosis. Orphanet J Rare Dis. 2018; 13(1): 222.
  84. Taveira-DaSilva AM, Hathaway O, Stylianou M, et al. Changes in lung function and chylous effusions in patients with lymphangioleiomyomatosis treated with sirolimus. Ann Intern Med. 2011; 154(12): 797–805, W.
  85. Reynaud-Gaubert M, Mornex JF, Mal H, et al. Lung transplantation for lymphangioleiomyomatosis: the French experience. Transplantation. 2008; 86(4): 515–520.
  86. Baldi BG, Samano MN, Campos SV, et al. Experience of lung transplantation in patients with lymphangioleiomyomatosis at a brazilian reference centre. Lung. 2017; 195(6): 699–705.
  87. Khawar MU, Yazdani D, Zhu Z, et al. Clinical outcomes and survival following lung transplantation in patients with lymphangioleiomyomatosis. J Heart Lung Transplant. 2019; 38(9): 949–955.
  88. Chen F, Omasa M, Kondo N, et al. Sirolimus treatment for recurrent lymphangioleiomyomatosis after lung transplantation. Ann Thorac Surg. 2009; 87(1): e6–e7.
  89. Sobiecka M. Limfangioleiomiomatoza. Postępy Nauk Medycznych. 2011; 4: 295–302.
  90. Lu C, Lee HS, Pappas GP, et al. Trial of an Aromatase Inhibitor in Lymphangioleiomyomatosis Group. A Phase II Clinical Trial of an Aromatase Inhibitor for Postmenopausal Women with Lymphangioleiomyomatosis. Ann Am Thorac Soc. 2017; 14(6): 919–928.
  91. McCormack FX, Inoue Y, Moss J, et al. National Institutes of Health Rare Lung Diseases Consortium, MILES Trial Group. Efficacy and safety of sirolimus in lymphangioleiomyomatosis. N Engl J Med. 2011; 364(17): 1595–1606.
  92. Takada T, Mikami A, Kitamura N, et al. Efficacy and safety of long-term sirolimus therapy for Asian patients with lymphangioleiomyomatosis. Ann Am Thorac Soc. 2016; 13(11): 1912–1922.
  93. Neurohr C, Hoffmann AL, Huppmann P, et al. Is sirolimus a therapeutic option for patients with progressive pulmonary lymphangioleiomyomatosis? Respir Res. 2011; 12: 66.
  94. Kida Y, Burger CD. Efficacy and safety of sirolimus in lymphangioleiomyomatosis. N Engl J Med. 2011; 365(3): 271–272.
  95. Young L, Lee HS, Inoue Y, et al. MILES Trial Group. Serum VEGF-D a concentration as a biomarker of lymphangioleiomyomatosis severity and treatment response: a prospective analysis of the Multicenter International Lymphangioleiomyomatosis Efficacy of Sirolimus (MILES) trial. Lancet Respir Med. 2013; 1(6): 445–452.
  96. Zhou Li, Ouyang R, Luo H, et al. Efficacy of sirolimus for the prevention of recurrent pneumothorax in patients with lymphangioleiomyomatosis: a case series. Orphanet J Rare Dis. 2018; 13(1).
  97. Yoon HY, Hwang JJ, Kim DS, et al. Efficacy and safety of low-dose sirolimus in lymphangioleiomyomatosis. Orphanet J Rare Dis. 2018; 13(1): 204.
  98. Gao N, Zhang T, Ji J, et al. The efficacy and adverse events of mTOR inhibitors in lymphangioleiomyomatosis: systematic review and meta-analysis. Orphanet J Rare Dis. 2018; 13(1): 134.
  99. Courtwright AM, Goldberg HJ, Henske EP, et al. The effect of mTOR inhibitors on respiratory infections in lymphangioleiomyomatosis. Eur Respir Rev. 2017; 26(143).
  100. Parkhitko A, Myachina F, Morrison TA, et al. Tumorigenesis in tuberous sclerosis complex is autophagy and p62/sequestosome 1 (SQSTM1)-dependent. Proc Natl Acad Sci U S A. 2011; 108(30): 12455–12460.
  101. Taveira-DaSilva AM, Jones AM, Julien-Williams PA, et al. Retrospective review of combined sirolimus and simvastatin therapy in lymphangioleiomyomatosis. Chest. 2015; 147(1): 180–187.
  102. El-Chemaly S, Taveira-Dasilva A, Goldberg HJ, et al. Sirolimus and Autophagy Inhibition in Lymphangioleiomyomatosis: Results of a Phase I Clinical Trial. Chest. 2017; 151(6): 1302–1310.
  103. Abdelwahab EMM, Pal S, Kvell K, et al. Mitochondrial dysfunction is a key determinant of the rare disease lymphangioleiomyomatosis and provides a novel therapeutic target. Oncogene. 2019; 38(16): 3093–3101.
  104. Atochina-Vasserman EN, Abramova E, James ML, et al. Pharmacological targeting of VEGFR signaling with axitinib inhibits Tsc2-null lesion growth in the mouse model of lymphangioleiomyomatosis. Am J Physiol Lung Cell Mol Physiol. 2015; 309(12): L1447–L1454.
  105. Bissler JJ, McCormack FX, Young LR, et al. Sirolimus for angiomyolipoma in tuberous sclerosis complex or lymphangioleiomyomatosis. N Engl J Med. 2008; 358(2): 140–151.
  106. Dabora SL, Franz DN, Ashwal S, et al. Multicenter phase 2 trial of sirolimus for tuberous sclerosis: kidney angiomyolipomas and other tumors regress and VEGF- D levels decrease. PLoS One. 2011; 6(9): e23379.
  107. Davies DM, de Vries PJ, Johnson SR, et al. Sirolimus therapy for angiomyolipoma in tuberous sclerosis and sporadic lymphangioleiomyomatosis: a phase 2 trial. Clin Cancer Res. 2011; 17(12): 4071–4081.
  108. Bissler JJ, Kingswood JC, Radzikowska E, et al. Everolimus for angiomyolipoma associated with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis (EXIST-2): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet. 2013; 381(9869): 817–824.
  109. Yao J, Taveira-DaSilva AM, Jones AM, et al. Sustained effects of sirolimus on lung function and cystic lung lesions in lymphangioleiomyomatosis. Am J Respir Crit Care Med. 2014; 190(11): 1273–1282.
  110. Goldberg HJ, Harari S, Cottin V, et al. Everolimus for the treatment of lymphangioleiomyomatosis: a phase II study. Eur Respir J. 2015; 46(3): 783–794.
  111. Bee J, Fuller S, Miller S, et al. Lung function response and side effects to rapamycin for lymphangioleiomyomatosis: a prospective national cohort study. Thorax. 2018; 73(4): 369–375.
  112. Taveira-DaSilva AM, Jones AM, Julien-Williams P, et al. Long-Term effect of sirolimus on serum vascular endothelial growth factor d levels in patients with lymphangioleiomyomatosis. Chest. 2018; 153(1): 124–132.
  113. Ding Y, Yan S, Tian Y, et al. Primary abdominal lymphangioleiomyomatosis: report of a case. World J Surg Oncol. 2015; 13: 93.
  114. Słodkowska J, Patera J, Breborowicz J, et al. Extrapulmonary lymphangioleiomyomatosis presented as the asymptomatic retroperitoneal tumours -- two cases report. Pol J Pathol. 2006; 57(4): 205–207.
  115. Bhattacharyya A, Balogh K. Retroperitoneal lymphangioleiomyomatosis a 36-year benign course in a postmenopausal woman. Cancer. 1985; 56(5): 1144–1146, doi: 10.1002/1097-0142(19850901)56:5<1144::aid-cncr2820560531>3.0.co;2-f.
  116. Mboyo A, Flurin V, Foulet-Roge A, et al. Conservative treatment of a mesenteric lymphangiomyomatosis in an 11-year-old girl with a long follow-up period. J Pediatr Surg. 2004; 39(10): 1586–1589.
  117. Szpurek D, Szubert S, Zielinski P, et al. Malignant presentation of uterine lymphangioleiomyomatosis. Taiwan J Obstet Gynecol. 2015; 54(5): 603–607.
  118. Radzikowska E, Przerwa KB, SkroAska P. Lymphangioma in Patients with Pulmonary Lymphangioleiomyomatosis: Results of Sirolimus Treatment. Journal of Cancer Science & Therapy. 2016; 8(9).
  119. Tümay LV, Güner OS, Zorluoğlu A. An extrapulmonary manifestation of lymphangioleiomyomatosis: A rare case report. Int J Surg Case Rep. 2017; 41: 315–318.
  120. Mohammadieh AM, Bowler SD, Silverstone EJ, et al. Everolimus treatment of abdominal lymphangioleiomyoma in five women with sporadic lymphangioleiomyomatosis. Med J Aust. 2013; 199(2): 121–123.
  121. Rozenberg D, Thenganatt J. Dramatic response to sirolimus in lymphangioleiomyomatosis. Can Respir J. 2013; 20(6): 413–414.
  122. Freitas CS, Baldi BG, Araújo MS, et al. Use of sirolimus in the treatment of lymphangioleiomyomatosis: favorable responses in patients with different extrapulmonary manifestations. J Bras Pneumol. 2015; 41(3): 275–280.
  123. Hecimovic A, Jakopovic M, Pavlisa G, et al. SUCCESSFUL TREATMENT OF PULMONARY AND LYMPHATIC MANIFESTATIONS OF LYMPHANGIOLEIOMYOMATOSIS WITH SIROLIMUS. Lymphology. 2015; 48(2): 97–102.
  124. Cabeza L, Ruiz-Cobos M, Casanova Á. Resolution of thoracic and abdominal lymphangioleiomyomas in a patient with lymphangioleiomyomatosis treated with sirolimus. Archivos de Bronconeumología (English Edition). 2016; 52(6): 329–330.
  125. Harari S, Spagnolo P, Cocconcelli E, et al. Recent advances in the pathobiology and clinical management of lymphangioleiomyomatosis. Curr Opin Pulm Med. 2018; 24(5): 469–476.
  126. Ito T, Suno M, Sakamoto K, et al. Therapeutic effect of sirolimus for lymphangioleiomyomatosis remaining in the abdominopelvic region after lung transplantation: a case report. Transplant Proc. 2016; 48(1): 271–274.
  127. Wahid S, Chiang PC, Luo HL, et al. Pelvic lymphangioleiomyomatosis treated successfully with everolimus: Two case reports with literature review. Medicine (Baltimore). 2017; 96(10): e4562.
  128. Lecuelle D, Basille D, Renard C, et al. Highly effective sirolimus therapy for abdominal lymphangioleiomyoma. Respir Med Res. 2019; 75: 32–34.
  129. Ussavarungsi K, Laroia AT, Burger CD. Low-dose sirolimus in retroperitoneal lymphangioleiomyomas. Lung India. 2019; 36(4): 349–352.
  130. Klein M, Krieger O, Ruckser R, et al. Treatment of lymphangioleiomyomatosis by ovariectomy, interferon alpha 2b and tamoxifen -- a case report. Arch Gynecol Obstet. 1992; 252(2): 99–102.
  131. Yamashita S, Nakamura K, Shinozaki H, et al. Lymphangioleiomyomatosis suspected to be a gynecologic disease. J Obstet Gynaecol Res. 2011; 37(3): 267–269.
  132. Basnet A, Shaaban H, Kessler W. A case of recurrent retroperitoneal lymphangioleiomyomatosis treated with progesterone therapy. Urol Ann. 2015; 7(1): 127–128.
  133. Yoshizawa H, Kawai S, Hirota Y, et al. A case of uterine lymphangioleiomyomatosis in a young woman that was identified via peritonitis. J Obstet Gynaecol Res. 2019; 45(2): 482–486.

Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

Wydawcą serwisu jest  "Via Medica sp. z o.o." sp.k., ul. Świętokrzyska 73, 80–180 Gdańsk

tel.:+48 58 320 94 94, faks:+48 58 320 94 60, e-mail:  viamedica@viamedica.pl