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Review Article
Recent Updates in Langerhans Cell Histiocytosis
Clin Pediatr Hematol Oncol 2015;22:15-21.
Published online April 30, 2015
© 2015 Korean Society of Pediatric Hematology-Oncology

Kyung-Nam Koh, M.D., Ho Joon Im, M.D. and Jong Jin Seo, M.D.

Division of Pediatric Hematology/Oncology, Department of Pediatrics, University of Ulsan College of Medicine, Asan Medical Center Children’s Hospital, Seoul, Korea
Correspondence to: Kyung-Nam Koh
Department of Pediatrics, Asan Medical
Center Children’s Hospital, 88,
Olympic-ro 43-gil, Songpa-gu, Seoul
138-736, Korea
Tel: +82-2-3010-5994
Fax: +82-2-473-3725
E-mail: pedkkn@gmail.com
Received April 1, 2015; Revised April 15, 2015; Accepted April 16, 2015.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Langerhans cell histiocytosis (LCH) encompasses a wide range of clinical presentation and its clinical course varies widely from spontaneous regression to severe disseminated disease with the risk of permanent consequences. Although pathogenesis of LCH has been a conundrum, recent advances have led to a better understanding of the molecular pathogenesis of the disease. Especially, advanced genomic analyses have suggested that LCH is a disorder of MAPK pathway mutations. Optimal treatment for LCH has not been established yet. Histiocyte Society has launched a new international multi-center clinical trial, LCH-IV to solve remaining major issues in the treatment of LCH. The aim of this review is to provide an overview of recent understandings on the pathogenesis and treatment of LCH.
Keywords: Langerhans cell histiocytosis, Pathogenesis, Treatment
References
  1. Jaffe R, Weiss LM, Facchetti F. Tumours derived from Langerhans cell. In: Swerdlow HC, Campo E, Harris NL, et al, editors, WHO classification of tumous of haematopoietic and lymphoid tissues. 4th ed. Lyon: IARC Press, 2008;358-60.
  2. Morimoto A, Oh Y, Shioda Y, Kudo K, Imamura T. Recent advances in Langerhans cell histiocytosis. Pediatr Int 2014;56:451-61.
    Pubmed CrossRef
  3. Rizzo FM, Cives M, Simone V, Silvestris F. New insights into the molecular pathogenesis of langerhans cell histiocytosis. Oncologist 2014;19:151-63.
    Pubmed KoreaMed CrossRef
  4. Guyot-Goubin A, Donadieu J, Barkaoui M, Bellec S, Thomas C, Clavel J. Descriptive epidemiology of childhood Langerhans cell histiocytosis in France, 2000-2004. Pediatr Blood Cancer 2008;51:71-5.
    Pubmed CrossRef
  5. Salotti JA, Nanduri V, Pearce MS, Parker L, Lynn R, Windebank KP. Incidence and clinical features of Langerhans cell histiocytosis in the UK and Ireland. Arch Dis Child 2009;94:376-80.
    Pubmed CrossRef
  6. Stalemark H, Laurencikas E, Karis J, Gavhed D, Fadeel B, Henter JI. Incidence of Langerhans cell histiocytosis in children:a population-based study. Pediatr Blood Cancer 2008;51:76-81.
    Pubmed CrossRef
  7. Horibe K, Saito AM, Takimoto T, et al. Incidence and survival rates of hematological malignancies in Japanese children and adolescents (2006-2010): based on registry data from the Japanese Society of Pediatric Hematology. Int J Hematol 2013;98:74-88.
    Pubmed CrossRef
  8. Kim BE, Koh KN, Suh JK, et al. Clinical features and treatment outcomes of Langerhans cell histiocytosis: a nationwide survey from Korea histiocytosis working party. J Pediatr Hematol Oncol 2014;36:125-33.
    Pubmed CrossRef
  9. Arico M, Girschikofsky M, Genereau T, et al. Langerhans cell histiocytosis in adults. Report from the International Registry of the Histiocyte Society. Eur J Cancer 2003;39:2341-8.
    CrossRef
  10. Kim HK, Park CJ, Jang S, et al. Bone marrow involvement of Langerhans cell histiocytosis: immunohistochemical evaluation of bone marrow for CD1a, Langerin, and S100 expression. Histopathology 2014;65:742-8.
    Pubmed CrossRef
  11. Valladeau J, Ravel O, Dezutter-Dambuyant C, et al. Langerin, a novel C-type lectin specific to Langerhans cells, is an endocytic receptor that induces the formation of Birbeck granules. Immunity 2000;12:71-81.
    CrossRef
  12. Ronceray L, Potschger U, Janka G, Gadner H, Minkov M;German Society for Pediatric Hematology and Oncology, Langerhans Cell Histiocytosis Study Group. Pulmonary involvement in pediatric-onset multisystem Langerhans cell histiocytosis:effect on course and outcome. J Pediatr 2012;161:129-33.
    Pubmed CrossRef
  13. Grois N, Potschger U, Prosch H, et al. Risk factors for diabetes insipidus in langerhans cell histiocytosis. Pediatr Blood Cancer 2006;46:228-33.
    Pubmed CrossRef
  14. Haupt R, Nanduri V, Calevo MG, et al. Permanent consequences in Langerhans cell histiocytosis patients: a pilot study from the Histiocyte Society-Late Effects Study Group. Pediatr Blood Cancer 2004;42:438-44.
    Pubmed CrossRef
  15. Badalian-Very G, Vergilio JA, Degar BA, et al. Recurrent BRAF mutations in Langerhans cell histiocytosis. Blood 2010;116:1919-23.
    Pubmed KoreaMed CrossRef
  16. Chakraborty R, Hampton OA, Shen X, et al. Mutually exclusive recurrent somatic mutations in MAP2K1 and BRAF support a central role for ERK activation in LCH pathogenesis. Blood 2014;124:3007-15.
    Pubmed KoreaMed CrossRef
  17. Willis B, Ablin A, Weinberg V, Zoger S, Wara WM, Matthay KK. Disease course and late sequelae of Langerhans' cell histiocytosis:25-year experience at the University of California, San Francisco. J Clin Oncol 1996;14:2073-82.
    Pubmed
  18. Morimoto A, Ikushima S, Kinugawa N, et al. Improved outcome in the treatment of pediatric multifocal Langerhans cell histiocytosis: Results from the Japan Langerhans Cell Histiocytosis Study Group-96 protocol study. Cancer 2006;107:613-9.
    Pubmed CrossRef
  19. Minkov M, Grois N, Heitger A, Potschger U, Westermeier T, Gadner H. Treatment of multisystem Langerhans cell histiocytosis. Results of the DAL-HX 83 and DAL-HX 90 studies. DAL-HX Study Group. Klin Padiatr 2000;212:139-44.
    Pubmed CrossRef
  20. Titgemeyer C, Grois N, Minkov M, Flucher-Wolfram B, Gatterer-Menz I, Gadner H. Pattern and course of single-system disease in Langerhans cell histiocytosis data from the DAL-HX 83- and 90-study. Med Pediatr Oncol 2001;37:108-14.
    Pubmed CrossRef
  21. Lee JW, Shin HY, Kang HJ, et al. Clinical characteristics and treatment outcome of Langerhans cell histiocytosis: 22 years'experience of 154 patients at a single center. Pediatr Hematol Oncol 2014;31:293-302.
    Pubmed CrossRef
  22. Munn SE, Olliver L, Broadbent V, Pritchard J. Use of indomethacin in Langerhans cell histiocytosis. Med Pediatr Oncol 1999;32:247-9.
    CrossRef
  23. Ceci A, de Terlizzi M, Colella R, et al. Langerhans cell histiocytosis in childhood: results from the Italian Cooperative AIEOPCNR-H.X '83 study. Med Pediatr Oncol 1993;21:259-64.
    Pubmed CrossRef
  24. Gadner H, Grois N, Arico M, et al. A randomized trial of treatment for multisystem Langerhans' cell histiocytosis. J Pediatr 2001;138:728-34.
    Pubmed CrossRef
  25. Gadner H, Grois N, Potschger U, et al. Improved outcome in multisystem Langerhans cell histiocytosis is associated with therapy intensification. Blood 2008;111:2556-62.
    Pubmed CrossRef
  26. Gadner H, Minkov M, Grois N, et al. Therapy prolongation improves outcome in multisystem Langerhans cell histiocytosis. Blood 2013;121:5006-14.
    Pubmed CrossRef
  27. Weitzman S, Braier J, Donadieu J, et al. 2'-Chlorodeoxyadenosine (2-CdA) as salvage therapy for Langerhans cell histiocytosis (LCH). Results of the LCH-S-98 protocol of the Histiocyte Society. Pediatr Blood Cancer 2009;53:1271-6.
    Pubmed CrossRef
  28. Bernard F, Thomas C, Bertrand Y, et al. Multi-centre pilot study of 2-chlorodeoxyadenosine and cytosine arabinoside combined chemotherapy in refractory Langerhans cell histiocytosis with haematological dysfunction. Eur J Cancer 2005;41:2682-9.
    Pubmed CrossRef
  29. Simko SJ, Tran HD, Jones J, et al. Clofarabine salvage therapy in refractory multifocal histiocytic disorders, including Langerhans cell histiocytosis, juvenile xanthogranuloma and RosaiDorfman disease. Pediatr Blood Cancer 2014;61:479-87.
    Pubmed KoreaMed CrossRef
  30. Haroche J, Cohen-Aubart F, Emile JF, et al. Dramatic efficacy of vemurafenib in both multisystemic and refractory ErdheimChester disease and Langerhans cell histiocytosis harboring the BRAF V600E mutation. Blood 2013;121:1495-500.
    Pubmed CrossRef
  31. Steiner M, Matthes-Martin S, Attarbaschi A, et al. Improved outcome of treatment-resistant high-risk Langerhans cell histiocytosis after allogeneic stem cell transplantation with reduced-intensity conditioning. Bone Marrow Transplant 2005;36:215-25.
    Pubmed CrossRef
  32. Lau LM, Stuurman K, Weitzman S. Skeletal Langerhans cell histiocytosis in children: permanent consequences and healthrelated quality of life in long-term survivors. Pediatr Blood Cancer 2008;50:607-12.
    Pubmed CrossRef
  33. Mittheisz E, Seidl R, Prayer D, et al. Central nervous system-related permanent consequences in patients with Langerhans cell histiocytosis. Pediatr Blood Cancer 2007;48:50-6.
    Pubmed CrossRef


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