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Open Access 01-12-2016 | Research

Pulmonary and pleural lymphatic endothelial cells from pediatric, but not adult, patients with Gorham-Stout disease and generalized lymphatic anomaly, show a high proliferation rate

Authors: Michiko Mori, Michael Dictor, Nicholas Brodszki, Juan Carlos López-Gutiérrez, María Beato, Jonas S. Erjefält, Erik A. Eklund

Published in: Orphanet Journal of Rare Diseases | Issue 1/2016

Abstract

Background

Gorham-Stout disease (OMIM 123880) and generalized lymphatic anomaly are two rare disorders of lymphendothelial growth in which thoracic involvement with chylothorax is a feared complication. Currently it is believed that both disorders are prenatal malformations that progress slowly after birth. Several pharmaceuticals with antiproliferative properties, including interferon-α-2b, rapamycin and propranolol, have however been shown to affect the disease course in some patients. Deeper knowledge of the growth characteristics of these malformations are therefore needed to guide the clinical approach.

Methods

Lymphatic vessels in lung and pleural tissue from both children and adult patients with generalized lymphatic anomaly or Gorham-Stout disease were studied using an immunohistochemical approach, targeting lymphendothelial markers (D2-40/Prox-1) and a proliferation marker (Ki-67).

Results

We found significant proliferation and growth in these lesions in pediatric patients but not in adults. Furthermore, the data may suggest that the disease process is at least partly reversible.

Conclusions

These malformations of the lymphatic system proliferate at a significant rate long after birth, which could suggest that the clinical approach for children should be different from adults.

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Wassef M, Blei F, Adams D, Alomari A, Baselga E, Berenstein A, et al. Vascular anomalies classification: recommendations from the international society for the study of vascular anomalies. Pediatrics. 2015;136(1):e203–14. doi:10.1542/peds.2014-3673.CrossRefPubMed

Trenor 3rd CC, Chaudry G. Complex lymphatic anomalies. Semin Pediatr Surg. 2014;23(4):186–90. doi:10.1053/j.sempedsurg.2014.07.006.CrossRefPubMed

Ozeki M, Fujino A, Matsuoka K, Nosaka S, Kuroda T, Fukao T. Clinical features and prognosis of generalized lymphatic anomaly, kaposiform lymphangiomatosis, and Gorham-Stout disease. Pediatr Blood Cancer. 2016;63(5):832–8. doi:10.1002/pbc.25914.CrossRefPubMed

Croteau SE, Kozakewich HP, Perez-Atayde AR, Fishman SJ, Alomari AI, Chaudry G, et al. Kaposiform lymphangiomatosis: a distinct aggressive lymphatic anomaly. J Pediatr. 2014;164(2):383–8. doi:10.1016/j.jpeds.2013.10.013.CrossRefPubMedPubMedCentral

Lala S, Mulliken JB, Alomari AI, Fishman SJ, Kozakewich HP, Chaudry G. Gorham-Stout disease and generalized lymphatic anomaly--clinical, radiologic, and histologic differentiation. Skeletal Radiol. 2013;42(7):917–24. doi:10.1007/s00256-012-1565-4.CrossRefPubMed

Satria MN, Pacheco-Rodriguez G, Moss J. Pulmonary lymphangiomatosis. Lymphat Res Biol. 2011;9(4):191–3. doi:10.1089/lrb.2011.0023.CrossRefPubMedPubMedCentral

Brodszki N, Lansberg JK, Dictor M, Gyllstedt E, Ewers SB, Larsson MK, et al. A novel treatment approach for paediatric Gorham-Stout syndrome with chylothorax. Acta Paediatr. 2011;100(11):1448–53. doi:10.1111/j.1651-2227.2011.02361.x.CrossRefPubMed

Hagberg H, Lamberg K, Astrom G. Alpha-2b interferon and oral clodronate for Gorham’s disease. Lancet. 1997;350(9094):1822–3. doi:10.1016/S0140-6736(05)63639-2.CrossRefPubMed

Nir V, Guralnik L, Livnat G, Bar-Yoseph R, Hakim F, Ilivitzki A, et al. Propranolol as a treatment option in Gorham-Stout syndrome: a case report. Pediatr Pulmonol. 2014;49(4):417–9. doi:10.1002/ppul.22869.CrossRefPubMed

10.

Grunewald TG, Damke L, Maschan M, Petrova U, Surianinova O, Esipenko A, et al. First report of effective and feasible treatment of multifocal lymphangiomatosis (Gorham-Stout) with bevacizumab in a child. Ann Oncol. 2010;21(8):1733–4. doi:10.1093/annonc/mdq331.CrossRefPubMed

11.

Mori M, Andersson CK, Graham GJ, Lofdahl CG, Erjefalt JS. Increased number and altered phenotype of lymphatic vessels in peripheral lung compartments of patients with COPD. Respir Res. 2013;14:65. doi:10.1186/1465-9921-14-65.CrossRefPubMedPubMedCentral

12.

Mori M, Andersson CK, Svedberg KA, Glader P, Bergqvist A, Shikhagaie M, et al. Appearance of remodelled and dendritic cell-rich alveolar-lymphoid interfaces provides a structural basis for increased alveolar antigen uptake in chronic obstructive pulmonary disease. Thorax. 2013;68(6):521–31. doi:10.1136/thoraxjnl-2012-202879.CrossRefPubMed

13.

Rossler J, Saueressig U, Kayser G, von Winterfeld M, Klement GL. Personalized therapy for generalized lymphatic anomaly/Gorham-Stout disease with a combination of sunitinib and taxol. J Pediatr Hematol Oncol. 2015;37(8):e481–5. doi:10.1097/MPH.0000000000000436.CrossRefPubMedPubMedCentral

14.

Ozeki M, Fukao T, Kondo N. Propranolol for intractable diffuse lymphangiomatosis. N Engl J Med. 2011;364(14):1380–2. doi:10.1056/NEJMc1013217.CrossRefPubMed

15.

Heyd R, Micke O, Surholt C, Berger B, Martini C, Fuller J, et al. Radiation therapy for Gorham-Stout syndrome: results of a national patterns-of-care study and literature review. Int J Radiat Oncol Biol Phys. 2011;81(3):e179–85. doi:10.1016/j.ijrobp.2011.01.006.CrossRefPubMed

16.

Noda M, Endo C, Hoshikawa Y, Ishibashi N, Suzuki T, Okada Y, et al. Successful management of intractable chylothorax in Gorham-Stout disease by awake thoracoscopic surgery. Gen Thorac Cardiovasc Surg. 2013;61(6):356–8. doi:10.1007/s11748-012-0130-3.CrossRefPubMed

17.

Bhatti MA, Ferrante JW, Gielchinsky I, Norman JC. Pleuropulmonary and skeletal lymphangiomatosis with chylothorax and chylopericardium. Ann Thorac Surg. 1985;40(4):398–401.CrossRefPubMed

18.

Tammela T, Alitalo K. Lymphangiogenesis: molecular mechanisms and future promise. Cell. 2010;140(4):460–76. doi:10.1016/j.cell.2010.01.045.CrossRefPubMed

19.

Hagendoorn J, Padera TP, Yock TI, Nielsen GP, di Tomaso E, Duda DG, et al. Platelet-derived growth factor receptor-beta in Gorham’s disease. Nat Clin Pract Oncol. 2006;3(12):693–7. doi:10.1038/ncponc0660.CrossRefPubMedPubMedCentral

20.

Yao LC, Testini C, Tvorogov D, Anisimov A, Vargas SO, Baluk P, et al. Pulmonary lymphangiectasia resulting from vascular endothelial growth factor-C overexpression during a critical period. Circ Res. 2014;114(5):806–22. doi:10.1161/CIRCRESAHA.114.303119.CrossRefPubMedPubMedCentral

Title: Pulmonary and pleural lymphatic endothelial cells from pediatric, but not adult, patients with Gorham-Stout disease and generalized lymphatic anomaly, show a high proliferation rate
Authors: Michiko Mori
Michael Dictor
Nicholas Brodszki
Juan Carlos López-Gutiérrez
María Beato
Jonas S. Erjefält
Erik A. Eklund
Publication date: 01-12-2016
Publisher: BioMed Central
Published in: Orphanet Journal of Rare Diseases / Issue 1/2016
Electronic ISSN: 1750-1172
DOI: https://doi.org/10.1186/s13023-016-0449-4

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Pulmonary and pleural lymphatic endothelial cells from pediatric, but not adult, patients with Gorham-Stout disease and generalized lymphatic anomaly, show a high proliferation rate

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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