Cancer Treatment Reviews
Volume 36, Issue 4 , Pages 354-359 , June 2010

Langerhans cell histiocytosis: Current concepts and treatments

  • Oussama Abla

      Affiliations

    • Division of Haematology/Oncology, Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada
    • Corresponding Author InformationCorresponding author. Address: Division of Haematology/Oncology, Department of Paediatrics, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada M5G 1X8. Tel.: +1 416 813 5977; fax: +1 416 813 5327.
    • ,
  • R. Maarten Egeler

      Affiliations

    • Immunology, Haematology/Oncology and Bone Marrow Transplant, Leiden University Medical Center, Leiden, The Netherlands
    • ,
  • Sheila Weitzman

      Affiliations

    • Division of Haematology/Oncology, Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada

References 

  1. Favara BE, Steele A. Langerhans cell histiocytosis of lymph nodes: a morphological assessment of 43 biopsies. Pediatr Pathol Lab Med. 1997;17(5):769–787
  2. Geissmann F. Histiocytosis and the mononuclear phagocyte system. In: Proceedings of the 24th annual meeting of the histiocyte society, October 1–3, Berlin, Germany; 2008.
  3. Karis J, Bernstrand C, Fadeel B, Henter J-I. The incidence of langerhans cell histiocytosis in children in Stockholm Count, Sweden 1992–2001. In: Proceedings of the XIX meeting of the histiocyte society, Philadelphia; 2003. p. 21.
  4. Beverley PC, Egeler RM, Arceci RJ, Pritchard J. The Nikolas symposia and histiocytosis. Nat Rev Cancer. 2005;5:488–494
  5. Jaffe R. The diagnostic histopathology of Langerhans cell histiocytosis. In:  Weitzman S,  Egeler RM editor. Histiocytic disorders of children and adults. Cambridge: Cambridge University Press; 2005;p. 14–39
  6. Valladeau J, Ravel O, Dezutter-Dambuyant C, et al. Langerin, a novel C-type lectin specific to Langerhans cell, is an endocytic receptor that induces the formation of Birbeck granules. Immunity. 2000;12:71–81
  7. Bechan GI, Egeler RM, Arceci RJ. Biology of Langerhans cells and Langerhans cell histiocytosis. Int Rev Cytol. 2006;254:1–43
  8. Ginhoux F, Tacke F, Angeli V, et al. Langerhans cells arise from monocytes in vivo. Nat Immunol. 2006;7(3):265–273
  9. Ito T, Inaba M, Inaba K, et al. A CD1a+/CD11c+ subset of human blood dendritic cells is direct precursor of Langerhans cells. J Immunol. 1999;163(3):1409–1419
  10. Valladeau J, Saeland S. Cutaneous dendritic cells. Semin Immunol. 2005;17(4):273–283
  11. Annels NE, Da Costa CET, Prins FA, et al. Aberrant chemokine receptor expression and chemokine production by langerhans cells underlies the pathogenesis of langerhans cell histiocytosis. J Exp Med. 2003;197:1385–1390
  12. Sallusto F, Palermo B, Lenig D, et al. Distinct patterns and kinetics of chemokine production regulate dendritic cell function. Eur J Immunol. 1999;29:1617–1625
  13. Egeler RM, Favara BE, Laman JD, et al. Abundant expression of CD40 and CD40-ligand (CD154) in paediatric Langerhans cell histiocytosis lesions. Eur J Cancer. 2000;36:2105–2110
  14. Tazi A, Moreau J, Bergeron A, et al. Evidence that Langerhans cells in adult pulmonary Langerhans cell histiocytosis are mature dendritic cells: importance of the cytokine microenvironment. J Immunol. 1999;163:3511–3515
  15. Egeler RM, Favara BE, van Meurs M, et al. Differential in situ cytokine profiles of Langerhans-like cells and T cells in Langerhans cell histiocytosis: Abundant expression of cytokines relevant to disease and treatment. Blood. 1999;94:4195–4201
  16. Geissmann F, Lepelletier Y, Fraitag S, et al. Differentiation of Langerhans cells in langerhans cell histiocytosis. Blood. 2001;97:1241–1248
  17. Da Costa CE, Annels NE, Faaij CM, et al. Presence of osteoclast-like multinucleated giant cells in the bone and nonostotic lesions of Langerhans cell histiocytosis. J Exp Med. 2005;201:687–693
  18. Coury F, Annels N, Rivollier A, et al. Langerhans cell histiocytosis reveals a new IL-17A-dependent pathway of dendritic cell fusion. Nat Med. 2008;14(1):81–87
  19. Allen CE, Yu A, Leung E, et al. Cell-specific gene expression in Langerhans cell histiocytosis lesions. In: Proceedings of the 24th annual meeting of the histiocyte society, October 1–3, Berlin, Germany; 2008.
  20. Senechal B, Elain G, Jezioeski E, et al. Expansion of regulatory T cells in patients with Langerhans cell histiocytosis. PLoS Med. 2007;4(8):1374–1384
  21. Bechan GI, van Nederveen F, den Broeder B, et al. The role of beta-catenin in the development of Langerhans cell histiocytosis. In: Proceedings of the 24th annual meeting of the histiocyte society, October 1–3, Berlin, Germany; 2008.
  22. Willman CL, Busque L, Griffiths BB, et al. Langerhans cell histiocytosis – a clonal proliferation of Langerhans cells. New Engl J Med. 1994;331:154–160
  23. Yousem SA, Colby TV, Chen YY, et al. Pulmonary Langerhans’ cell histiocytosis: molecular analysis of clonality. Am J Surg Pathol. 2001;25:630–636
  24. Arico’ M, Scappaticci S, Danesino C. The genetics of Langerhans cell histiocytosis. In:  Weitzman S,  Egeler RM editor. Histiocytic disorders of children and adults. Cambridge: Cambridge University Press; 2005;p. 83–94
  25. Schouten B, Egeler RM, Leenen PJ, et al. Expression of cell cycle-related gene products in Langerhans cell histiocytosis. J Pediatr Hematol Oncol. 2002;24:727–732
  26. Betts DR, Leibundgut KE, Feldges A, et al. Cytogenetic abnormalities in Langerhans cell histiocytosis. Br J Cancer. 1998;77:552–555
  27. Murakami I, Gogusev J, Fournet JC, et al. Detection of molecular cytogenetic aberrations in Langerhans cell histiocytosis of bone. Hum Pathol. 2002;33:555–560
  28. Bechan GI, Meeker AK, De Marzo AM, et al. Telomere length shortening in Langerhans cell histiocytosis. Br J Haematol. 2008;140(4):420–428
  29. Glotzbecker MP, Carpentieri DF, Dormans JP. Langerhans cell histiocytosis: a primary viral infection of bone? Human herpes virus 6 latent protein detected in lymphocytes from tissue of children. J Pediatr Orthop. 2004;24(1):123–129
  30. McClain K, Jin H, Gresik V, Favara B. Langerhans cell histiocytosis: lack of a viral etiology. Am J Hematol. 1994;47(1):16–20
  31. Jenson HB, McClain KL, Leach CT, et al. Evaluation of human herpesvirus type 8 infection in childhood Langerhans cell histiocytosis. Am J Hematol. 2000;64:237–241
  32. Jeziorski E, Senechal B, Molina TJ, et al. Herpes-virus infection in patients with Langerhans cell histiocytosis: a case-controlled sero-epidemiological study, and in situ analysis. PLoS One. 2008;3(9):1–8
  33. Costa CET, Szuhai K, Eijk RV, et al. No genomic aberrations in langerhans cell histiocytosis as assessed by diverse molecular technologies. Genes, Chromosomes Cancer. 2009;48(3):239–249
  34. Broadbent V, Gadner H. Current therapy for Langerhans cell histiocytosis. Hematol Oncol Clin North Am. 1998;12:327–338
  35. Fernandez-Latorre F, Menor-Serrano F, Alonso-Charterina S, et al. Langerhans’ cell histiocytosis of the temporal bone in pediatric patients. Am J Roentgenol. 2000;174:217–221
  36. Woo KI, Harris GJ. Eosinophilic granuloma of the orbit-understanding the paradox of aggressive destruction responsive to minimal intervention. Ophthal Plast Reconstr Surg. 2003;19:429–439
  37. Egeler RM, Thompson RC, Voute PA, et al. Intralesional infiltration of corticosteroids in localized Langerhans cell histiocytosis. J Pediatr Orthop. 1992;12:811–814
  38. Weitzman S, Egeler RM. Langerhans cell histiocytosis: update for the pediatrician. Curr Opin Pediatr. 2008;20:23–29
  39. Gadner H, Ladisch S. The treatment of Langerhans cell histiocytosis. In:  Weitzman S,  Egeler RM editor. Histiocytic disorders of children and adults. Cambridge: Cambridge University Press; 2005;p. 229–253
  40. Munn SE, Olliver L, Broadbent V, Pritchard J. Use of indomethacin in Langerhans cell histiocytosis. Med Pediatr Oncol. 1999;32(4):247–249
  41. Brown RE. Biphosphonates as antialveolar macrophage therapy in pulmonary Langerhans cell histiocytosis. Med Pediatr Oncol. 2001;36:641–643
  42. Farran RP, Zaretzki E, Egeler RM. Treatment of Langerhans cell histiocytosis with pamidronate. J Pediatr Hematol Oncol. 2001;23:54–56
  43. Kamizono J, Okada Y, Shirahata A, et al. Biphosphonate induces remission of refractory osteolysis in Langerhans cell histiocytosis. J Bone Joint Surg. 2002;17:1926–1928
  44. Abildgaard N, Rungby J, Glerup H, et al. Long-term pamidronate treatment inhibits osteoclastic bone resorption and bone turnover without affecting osteoblastic function in multiple myeloma. Eur J Haematol. 1998;61(2):128–134
  45. D’Souza MJ, Oettinger CW, Shah A, et al. Macrophage depletion by albumin microencapsulated clodronate: attenuation of cytokine release in macrophage-dependent glomerulonephritis. Drug Dev Ind Pharm. 1999;25(5):591–596
  46. Migliorati CA, Siegel MA, Elting LS. Biphosphonate-associated osteonecrosis: a long-term complication of biphosphonate treatment. Lancet Oncol. 2006;7(6):508–514
  47. Brumsen C, Hamdy NA, Papapoulos SE. Long-term effects of biphosphonates on the growing skeleton. Studies of young patients with severe osteoporosis. Medicine (Baltimore). 1997;76(4):266–283
  48. Lau L, Stuurman K, Weitzman S. Skeletal Langerhans cell histiocytosis in children: permanent consequences and health-related quality of life in long term survivors. Pediatr Blood Cancer. 2008;50(3):607–612
  49. Grois N, Potschger U, Prosch H, et al. Risk factors for diabetes insipidus in Langerhans cell histiocytosis. Pediatr Blood Cancer. 2006;46:228–233
  50. Lau L, Krafchik B, Trebo M, Weitzman S. Cutaneous Langerhans cell histiocytosis in children under one year. Pediatr Blood Cancer. 2006;46:66–71
  51. Munn S, Chu AC. Langerhans cell histiocytosis of the skin. Hematol Oncol Clin North Am. 1998;12:269–286
  52. Kwon OS, Cho KH, Song KY. Primary cutaneous Langerhans cell histiocytosis treated with photochemotherapy. J Dermatol. 1997;24:54–56
  53. Hoeger PH, Nanduri VR, Harper JL, et al. Long term follow up of topical mustine treatment for cutaneous Langerhans cell histiocytosis. Arch Dis Child. 2000;82:483–487
  54. Krafchik B, Pope E, Walsh SRA. Histiocytosis of the skin in children and adults. In:  Weitzman S,  Egeler RM editor. Histiocytic disorders of children and adults. Cambridge: Cambridge University Press; 2005;p. 130–153
  55. Montero AJ, Diaz-Montero CM, Malpica A, et al. Langerhans cell histiocytosis of the female genital tract: a literature review. Int J Gynecol Cancer. 2003;13:381–388
  56. Titgemeyer C, Grois N, Minkov M, et al. Pattern and course of single-system disease in Langerhans cell histiocytosis. Med Pediatr Oncol. 2001;37:1–7
  57. Helmbold P, Hegemann B, Holzhausen H-J, et al. Low dose oral etoposide monotherapy in adult Langerhans cell histiocytosis. Arch Dermatol. 1998;134:1275–1278
  58. Ottaviano F, Finaly JL. Diabetes Insipidus and Langerhans cell histiocytosis: a case report of reversibility with 2-chlorodeoxyadenosine. J Pediatr Hematol Oncol. 2003;25:575–577
  59. Donadieu J, Rolon MA, Pion EM, et al. For the French LCH Study Group Incidence of growth hormone deficiency in pediatric-onset Langerhans cell histiocytosis: efficacy and safety of growth hormone treatment. J Clin Endocrinol Metab. 2004;89:604–609
  60. Grois N, Potschger U, Prosch H, et al. Risk factors for diabetes insipidus in Langerhans cell histiocytosis. Pediatr Blood Cancer. 2006;46:228–233
  61. Dhall G, Finlay JL, Dunkel IJ, et al. Analysis of outcome for patients with mass lesions of the central nervous system due to Langerhans cell histiocytosis treated with 2-chlorodeoxyadenosine. Pediatr Blood Cancer. 2008;50(1):72–79
  62. Imashuku S, Ishida S, Koike K, et al. Cerebellar ataxia in pediatric patients with Langerhans cell histiocytosis. J Pediatr Hematol Oncol. 2004;26:735–739
  63. Imashuku S, Okazaki N, Nakayama M, et al. Treatment of neurodegenerative CNS disease in Langerhans cell histiocytosis with a combination of intravenous immunoglobulin and chemotherapy. Pediatr Blood Cancer. 2008;50:308–311
  64. Idbaih A, Donadieu J, Barthez MA, et al. Retinoic acid therapy in “degenerative-like” neuro-Langerhans cell histiocytosis: a prospective pilot study. Pediatr Blood Cancer. 2004;43:55–58
  65. McClain KL, Allen CE, Rauch R, et al. Cytosine arabinoside can ameliorate the symptoms of CNS-LCH In some patients. In: Proceedings of the 24th annual meeting of the histiocyte society, October 1–3, Berlin, Germany; 2008.
  66. McLelland J, Broadbent V, Yeomans E, et al. Langerhans cell histiocytosis: the case for conservative treatment. Arch Dis Child. 1990;65:301–303
  67. Ceci A, Terlizzi MD, Colella R, et al. Langerhans cell histiocytosis in childhood: results from the Italian cooperative AIEOP-CNR-HX 83 study. Med Pediatr Oncol. 1993;21:259–264
  68. Gadner H, Heitger A, Grois N, et al. Treatment strategy for disseminated Langerhans cell histiocytosis. Med Pediatr Oncol. 1994;23:72–80
  69. Grois N, Flucher-Wolfram B, Heitger A, et al. Diabetes insipidus in Langerhans cell histiocytosis: results from the DAL-HX 83 Study. Med Pediatr Oncol. 1995;24:248–256
  70. Gadner H, Grois N, Arico’ M, et al. A randomized trial of treatment for multisystem Langerhans’ cell histiocytosis. J Pediatr. 2001;138:728–734
  71. Gadner H, Grois N, Potschger U, et al. Improved outcome in multisystem Langerhans cell histiocytosis is associated with therapy intensification. Blood. 2008;111:2556–2562
  72. 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. Cancer. 2006;107:613–619
  73. Arceci RJ, Brenner MK, Pritchard J. Controversies and new approaches to treatment of LCH. Hematol Oncol Clin North Am. 1998;12:339–357
  74. Egeler RM, de kraker J, Voute PA. Cytosine–arabinoside, vincristine, and prednisone in the treatment of children with disseminated Langerhans cell histiocytosis with organ dysfunction: experience at a single institution. Med Pediatr Oncol. 1993;21:265–270
  75. Saven A, Burian C. Cladribine activity in adult Langerhans cell histiocytosis. Blood. 1999;93:4125–4130
  76. Rodriguez-Galindo C, Kelly P, Jeng M, et al. Treatment of children with Langerhans cell histiocytosis with 2-chlorodeoxyadenosine. Am J Hematol. 2002;69:179–184
  77. Weitzman S, Wayne AS, Arceci R, et al. Nucleoside analogues in the therapy of Langerhans cell histiocytosis: a survey of members of the histiocyte society and review of the literature. Med Pediatr Oncol. 1999;33:476–481
  78. Stine KC, sailors RL, Willimas LL, et al. 2-Chlorodeoxyadenosine (2-CdA) for the treatment of refractory or recurrent Langerhans cell histiocytosis (LCH) in pediatric patients. Med Pediatr Oncol. 1997;29:288–292
  79. Bernard F, Thomas C, Bertrand Y, et al. Multicenter pilot study of 2-chlorodeoxyadenosine and cytosine–arabinoside combined chemotherapy in refractory Langerhans cell histiocytosis with hematological dysfunction. Eur J Cancer. 2005;41:2682–2689
  80. McClain KL, Allen CE. Asparaginase and cytosine arabinoside for refractory Langerhans cell histiocytosis. In: Proceedings of the 24th annual meeting of the histiocyte society, October 1–3, Berlin, Germany; 2008.
  81. Rodriguez-Galindo C, Jeng M, Khuu P, et al. Clofarabine in refractory Langerhans cell histiocytosis. Pediatr Blood Cancer. 2008;51(5):703–706
  82. Carroll C, Collier A, Malempati S, Whitlock J. Intermediate-dose methotrexate for recurrent Langerhans cell histiocytosis: a retrospective analysis. In: Proceedings of the 24th annual meeting of the histiocyte society, October 1–3, Berlin, Germany; 2008.
  83. Lair G, Marie I, Cailleux N, et al. Langerhans cell histiocytosis in adults: cutaneous and mucous lesion regression after treatment with thalidomide. Rev Med Int. 1998;19:196–198
  84. Mauro E, Fraulini C, Rigolin GM, et al. A case of disseminated Langerhans’ cell histiocytosis treated with thalidomide. Eur J Haematol. 2005;74:172–174
  85. McClain KL, Kozinetz CA. A phase II trail using thalidomide for Langerhans cell histiocytosis. Pediatr Blood Cancer. 2007;48:44–49
  86. Henter JI, Karlen J, Calming U, et al. Successful treatment of Langerhans’-cell histiocytosis with etanercept. New Engl J Med. 2001;345:1577–1578
  87. Sako M, Hosoi G, Ikemiya M, et al. Successful remission induction in a case of disseminated and refractory Langerhans cell histiocytosis (LCH) with a combination of cyclosporine (CSA) plus multiagent chemotherapy (ACOP). Med Pediatr Oncol. 1999;33:521
  88. Minkov M, Grois N, Broadbent V, et al. Cyclosporine A therapy for multisystem Langerhans cell histiocytosis. Med Pediatr Oncol. 1999;33:482–485
  89. Culic S, Jakobson A, Culik V, et al. Etoposide as the basic and interferon as the maintenance therapy for Langerhans cell histiocytosis: a RTC. Pediatr Hematol Oncol. 2001;18:291–294
  90. Caselli D. Arico’ M; EBMT paediatric working party. The role of BMT in childhood histiocytosis. Bone Marrow Transplant. 2008;41:S8–S13
  91. 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;36:215–225
  92. Tazi A, Hiltermann TJN, Vassallo R. Adult lung histiocytosis. In:  Weitzman S,  Egeler RM editor. Histiocytic disorders of children and adults. Cambridge: Cambridge University Press; 2005;p. 187–207
  93. Hadzic N, Pritchard J, Webb D, et al. Recurrence of Langerhans cell histiocytosis in the graft after pediatric liver transplantation. Transplantation. 2000;15:815–819

PII: S0305-7372(10)00032-0

doi: 10.1016/j.ctrv.2010.02.012

Cancer Treatment Reviews
Volume 36, Issue 4 , Pages 354-359 , June 2010

Article Tools