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. 2003;101:93–105.

Eosinophilic granuloma of the orbit: a paradox of aggressive destruction responsive to minimal intervention.

Gerald J Harris 1, Kyung In Woo 1
PMCID: PMC1358978  PMID: 14971567

Abstract

PURPOSE: To describe the findings and outcomes in eosinophilic granuloma (unifocal Langerhans cell histiocytosis [LCH]) of the orbit, and to explain the paradox of aggressive bone destruction responsive to minimal intervention. METHODS: Retrospective, consecutive, interventional case series of patients treated from 1985 through 2001. Minimum inclusion criteria were demonstration of CD1a positivity or Birbeck granules, treatment by a single surgeon, systemic evaluation by a pediatric oncologist, and follow-up of 12 months. A pathogenetic construct was assembled from general LCH concepts and the specific orbital findings. RESULTS: Seven patients met study criteria. All were male, 2 to 16 years of age. All had eyelid or forehead swelling and osteolytic defects, with symptoms of 2 to 6 weeks' duration. All underwent incisional biopsy, with frozen-section examination suggestive of LCH in 6 of 7 cases. The 2 earliest patients received low-dose irradiation after simple biopsy. The 5 most recent patients had subtotal curettage at the time of biopsy; 4 of 5 received simultaneous intralesional corticosteroid injection. In all cases, systemic evaluation showed no other focus of LCH, reossification was timely, and no local recurrence or additional focus was noted in follow-up of 1 to 17 years. CONCLUSIONS: Transient immune dysfunction may provoke the cytokine-mediated proliferation of pathologic Langerhans cells within the hematopoietic marrow of the anterolateral frontal bone. These cells cause osteolysis through elaboration of interleukin-1 and prostaglandlin E2. Corticosteroids can inhibit the mediators. We recommend incisional biopsy, frozen-section provisional diagnosis, subtotal curettage, intralesional corticosteroid instillation, postoperative systemic evaluation, and long-term follow-up.

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Selected References

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  1. Arceci R. J. The histiocytoses: the fall of the Tower of Babel. Eur J Cancer. 1999 May;35(5):747–769. doi: 10.1016/s0959-8049(99)00039-8. [DOI] [PubMed] [Google Scholar]
  2. Arenzana-Seisdedos F., Barbey S., Virelizier J. L., Kornprobst M., Nezelof C. Histiocytosis X. Purified (T6+) cells from bone granuloma produce interleukin 1 and prostaglandin E2 in culture. J Clin Invest. 1986 Jan;77(1):326–329. doi: 10.1172/JCI112296. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bealer L. A., Cibis G. W., Barker B. F., Egelhoff J. C., Freeman A. I., Zwick D. A. Aneurysmal bone cyst: report of a case mimicking orbital tumor. J Pediatr Ophthalmol Strabismus. 1993 May-Jun;30(3):199–200. doi: 10.3928/0191-3913-19930501-15. [DOI] [PubMed] [Google Scholar]
  4. Bockman R. S., Repo M. A. Lymphokine-mediated bone resorption requires endogenous prostaglandin synthesis. J Exp Med. 1981 Aug 1;154(2):529–534. doi: 10.1084/jem.154.2.529. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Broadbent V., Gadner H. Current therapy for Langerhans cell histiocytosis. Hematol Oncol Clin North Am. 1998 Apr;12(2):327–338. doi: 10.1016/s0889-8588(05)70513-x. [DOI] [PubMed] [Google Scholar]
  6. Capanna R., Springfield D. S., Ruggieri P., Biagini R., Picci P., Bacci G., Giunti A., Lorenzi E. G., Campanacci M. Direct cortisone injection in eosinophilic granuloma of bone: a preliminary report on 11 patients. J Pediatr Orthop. 1985 May-Jun;5(3):339–342. doi: 10.1097/01241398-198505000-00016. [DOI] [PubMed] [Google Scholar]
  7. Chu T., Jaffe R. The normal Langerhans cell and the LCH cell. Br J Cancer Suppl. 1994 Sep;23:S4–10. [PMC free article] [PubMed] [Google Scholar]
  8. Cohen M., Zornoza J., Cangir A., Murray J. A., Wallace S. Direct injection of methylprednisolone sodium succinate in the treatment of solitary eosinophilic granuloma of bone: a report of 9 cases. Radiology. 1980 Aug;136(2):289–293. doi: 10.1148/radiology.136.2.7403498. [DOI] [PubMed] [Google Scholar]
  9. Demirci Hakan, Shields Carol L., Shields Jerry A., Eagle Ralph C., Jr Bilateral sequential orbital involvement by eosinophilic granuloma. Arch Ophthalmol. 2002 Jul;120(7):978–979. [PubMed] [Google Scholar]
  10. Dewhirst F. E., Stashenko P. P., Mole J. E., Tsurumachi T. Purification and partial sequence of human osteoclast-activating factor: identity with interleukin 1 beta. J Immunol. 1985 Oct;135(4):2562–2568. [PubMed] [Google Scholar]
  11. Favara B. E., Jaffe R. Pathology of Langerhans cell histiocytosis. Hematol Oncol Clin North Am. 1987 Mar;1(1):75–97. [PubMed] [Google Scholar]
  12. Favara B. E. Langerhans cell histiocytosis: an identity crisis. Med Pediatr Oncol. 2001 Dec;37(6):545–545. doi: 10.1002/mpo.1250. [DOI] [PubMed] [Google Scholar]
  13. Glover A. T., Grove A. S., Jr Eosinophilic granuloma of the orbit with spontaneous healing. Ophthalmology. 1987 Aug;94(8):1008–1012. doi: 10.1016/s0161-6420(87)33352-4. [DOI] [PubMed] [Google Scholar]
  14. Gonzalez-Crussi F., Hsueh W., Wiederhold M. D. Prostaglandins in histiocytosis-X. PG synthesis by histiocytosis-X cells. Am J Clin Pathol. 1981 Feb;75(2):243–253. doi: 10.1093/ajcp/75.2.243. [DOI] [PubMed] [Google Scholar]
  15. Gowen M., Wood D. D., Ihrie E. J., McGuire M. K., Russell R. G. An interleukin 1 like factor stimulates bone resorption in vitro. Nature. 1983 Nov 24;306(5941):378–380. doi: 10.1038/306378a0. [DOI] [PubMed] [Google Scholar]
  16. Grois N. G., Favara B. E., Mostbeck G. H., Prayer D. Central nervous system disease in Langerhans cell histiocytosis. Hematol Oncol Clin North Am. 1998 Apr;12(2):287–305. doi: 10.1016/s0889-8588(05)70511-6. [DOI] [PubMed] [Google Scholar]
  17. Grois N. G., Favara B. E., Mostbeck G. H., Prayer D. Central nervous system disease in Langerhans cell histiocytosis. Hematol Oncol Clin North Am. 1998 Apr;12(2):287–305. doi: 10.1016/s0889-8588(05)70511-6. [DOI] [PubMed] [Google Scholar]
  18. Grois N., Flucher-Wolfram B., Heitger A., Mostbeck G. H., Hofmann J., Gadner H. Diabetes insipidus in Langerhans cell histiocytosis: results from the DAL-HX 83 study. Med Pediatr Oncol. 1995 Apr;24(4):248–256. doi: 10.1002/mpo.2950240407. [DOI] [PubMed] [Google Scholar]
  19. Heuer H. E. Eosinophilic granuloma of the orbit. Acta Ophthalmol (Copenh) 1972;50(2):160–165. doi: 10.1111/j.1755-3768.1972.tb03773.x. [DOI] [PubMed] [Google Scholar]
  20. Hidayat A. A., Mafee M. F., Laver N. V., Noujaim S. Langerhans' cell histiocytosis and juvenile xanthogranuloma of the orbit. Clinicopathologic, CT, and MR imaging features. Radiol Clin North Am. 1998 Nov;36(6):1229-40, xii. doi: 10.1016/s0033-8389(05)70242-6. [DOI] [PubMed] [Google Scholar]
  21. Hildebrandt G., Seed M. P., Freemantle C. N., Alam C. A., Colville-Nash P. R., Trott K. R. Mechanisms of the anti-inflammatory activity of low-dose radiation therapy. Int J Radiat Biol. 1998 Sep;74(3):367–378. doi: 10.1080/095530098141500. [DOI] [PubMed] [Google Scholar]
  22. Hoopes P. C., Anderson R. L., Blodi F. C. Giant cell (reparative) granuloma of the orbit. Ophthalmology. 1981 Dec;88(12):1361–1366. doi: 10.1016/s0161-6420(81)34851-9. [DOI] [PubMed] [Google Scholar]
  23. Jakobiec F. A., Trokel S. L., Aron-Rosa D., Iwamoto T., Doyon D. Localized eosinophilic granuloma (Langerhans' cell histiocytosis) of the orbital frontal bone. Arch Ophthalmol. 1980 Oct;98(10):1814–1820. doi: 10.1001/archopht.1980.01020040666015. [DOI] [PubMed] [Google Scholar]
  24. Kindy-Degnan N. A., Laflamme P., Duprat G., Allaire G. S. Intralesional steroid in the treatment of an orbital eosinophilic granuloma. Arch Ophthalmol. 1991 May;109(5):617–618. doi: 10.1001/archopht.1991.01080050023015. [DOI] [PubMed] [Google Scholar]
  25. Kramer T. R., Noecker R. J., Miller J. M., Clark L. C. Langerhans cell histiocytosis with orbital involvement. Am J Ophthalmol. 1997 Dec;124(6):814–824. doi: 10.1016/s0002-9394(14)71699-x. [DOI] [PubMed] [Google Scholar]
  26. Kricun M. E. Red-yellow marrow conversion: its effect on the location of some solitary bone lesions. Skeletal Radiol. 1985;14(1):10–19. doi: 10.1007/BF00361188. [DOI] [PubMed] [Google Scholar]
  27. LaBorwit S. E., Karesh J. W., Hirschbein M. J., Dankner S. R. Multifocal Langerhans' cell histiocytosis involving the orbit. J Pediatr Ophthalmol Strabismus. 1998 Jul-Aug;35(4):234–236. doi: 10.3928/0191-3913-19980701-13. [DOI] [PubMed] [Google Scholar]
  28. Loeffler M., Hornblass A. Hematic cyst of the orbit. Arch Ophthalmol. 1990 Jun;108(6):886–887. doi: 10.1001/archopht.1990.01070080130050. [DOI] [PubMed] [Google Scholar]
  29. Marusić A., Raisz L. G. Cortisol modulates the actions of interleukin-1 alpha on bone formation, resorption, and prostaglandin production in cultured mouse parietal bones. Endocrinology. 1991 Nov;129(5):2699–2706. doi: 10.1210/endo-129-5-2699. [DOI] [PubMed] [Google Scholar]
  30. McLelland J., Pritchard J., Chu A. C. Current controversies. Histiocytosis-X. Hematol Oncol Clin North Am. 1987 Mar;1(1):147–162. [PubMed] [Google Scholar]
  31. Mercado G. V., Shields C. L., Gunduz K., Shields J. A., Eagle R. C., Jr Giant cell reparative granuloma of the orbit. Am J Ophthalmol. 1999 Apr;127(4):485–487. doi: 10.1016/s0002-9394(98)00381-x. [DOI] [PubMed] [Google Scholar]
  32. Moore A. T., Pritchard J., Taylor D. S. Histiocytosis X: an ophthalmological review. Br J Ophthalmol. 1985 Jan;69(1):7–14. doi: 10.1136/bjo.69.1.7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Munn S. E., Olliver L., Broadbent V., Pritchard J. Use of indomethacin in Langerhans cell histiocytosis. Med Pediatr Oncol. 1999 Apr;32(4):247–249. [PubMed] [Google Scholar]
  34. Naiman J., Green W. R., d'Heurle D., Iliff W. J., Benedict G. W., Eggleston J. C., Dorfman H. D. Brown tumor of the orbit associated with primary hyperparathyroidism. Am J Ophthalmol. 1980 Oct;90(4):565–571. doi: 10.1016/s0002-9394(14)75031-7. [DOI] [PubMed] [Google Scholar]
  35. Nezelof C., Basset F. Langerhans cell histiocytosis research. Past, present, and future. Hematol Oncol Clin North Am. 1998 Apr;12(2):385–406. doi: 10.1016/s0889-8588(05)70518-9. [DOI] [PubMed] [Google Scholar]
  36. Schmitz L., Favara B. E. Nosology and pathology of Langerhans cell histiocytosis. Hematol Oncol Clin North Am. 1998 Apr;12(2):221–246. doi: 10.1016/s0889-8588(05)70507-4. [DOI] [PubMed] [Google Scholar]
  37. Selch M. T., Parker R. G. Radiation therapy in the management of Langerhans cell histiocytosis. Med Pediatr Oncol. 1990;18(2):97–102. doi: 10.1002/mpo.2950180203. [DOI] [PubMed] [Google Scholar]
  38. Sessa S., Sommelet D., Lascombes P., Prévot J. Treatment of Langerhans-cell histiocytosis in children. Experience at the Children's Hospital of Nancy. J Bone Joint Surg Am. 1994 Oct;76(10):1513–1525. doi: 10.2106/00004623-199410000-00011. [DOI] [PubMed] [Google Scholar]
  39. Smith J. H., Fulton L., O'Brien J. M. Spontaneous regression of orbital Langerhans cell granulomatosis in a three-year-old girl. Am J Ophthalmol. 1999 Jul;128(1):119–121. doi: 10.1016/s0002-9394(99)00055-0. [DOI] [PubMed] [Google Scholar]
  40. Song Alice, Johnson Thomas E., Dubovy Sander R., Toledano Stuart. Treatment of recurrent eosinophilic granuloma with systemic therapy. Ophthal Plast Reconstr Surg. 2003 Mar;19(2):140–144. doi: 10.1097/01.IOP.0000055980.85878.26. [DOI] [PubMed] [Google Scholar]
  41. Taccone A., Oddone M., Occhi M., Dell'Acqua A. D., Ciccone M. A. MRI "road-map" of normal age-related bone marrow. I. Cranial bone and spine. Pediatr Radiol. 1995;25(8):588–595. doi: 10.1007/BF02011825. [DOI] [PubMed] [Google Scholar]
  42. 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 Aug;37(2):108–114. doi: 10.1002/mpo.1178. [DOI] [PubMed] [Google Scholar]
  43. 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 Aug;37(2):108–114. doi: 10.1002/mpo.1178. [DOI] [PubMed] [Google Scholar]
  44. 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 Aug;37(2):108–114. doi: 10.1002/mpo.1178. [DOI] [PubMed] [Google Scholar]
  45. Wirtschafter J. D., Nesbit M., Anderson P., McClain K. Intralesional methylprednisolone for Langerhans' cell histiocytosis of the orbit and cranium. J Pediatr Ophthalmol Strabismus. 1987 Jul-Aug;24(4):194–197. doi: 10.3928/0191-3913-19870701-11. [DOI] [PubMed] [Google Scholar]
  46. Yasko A. W., Fanning C. V., Ayala A. G., Carrasco C. H., Murray J. A. Percutaneous techniques for the diagnosis and treatment of localized Langerhans-cell histiocytosis (eosinophilic granuloma of bone). J Bone Joint Surg Am. 1998 Feb;80(2):219–228. doi: 10.2106/00004623-199802000-00009. [DOI] [PubMed] [Google Scholar]
  47. Zelger B. Langerhans cell histiocytosis: a reactive or neoplastic disorder? Med Pediatr Oncol. 2001 Dec;37(6):543–544. doi: 10.1002/mpo.1249. [DOI] [PubMed] [Google Scholar]

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