Langerhans cell histiocytosis in adult patients – a disease with many faces
Experience of a centre and an overview of the disease symptoms

Česká verzia

Authors: Z. Adam ¹; L. Pour ¹; M. Krejčí ¹; J. Neubauer ²; J. Vaníček ³; V. Vašků ⁴; R. Hájek ¹
Authors place of work: Interní hematoonkologická klinika Lékařské fakulty MU a FN Brno, pracoviště Bohunice, zastupující přednosta prof. MUDr. Jiří Mayer, CSc. ¹; Radiologická klinika Lékařské fakulty MU a FN Brno, pracoviště Bohunice, přednosta prof. MUDr. Vlastimil A. Válek, CSc. ²; Klinika zobrazovacích metod Lékařské fakulty MU a FN u sv. Anny Brno, přednosta doc. MUDr. Petr Krupa, CSc. ³; I. dermatovenerologická klinika Lékařské fakulty MU a FN u sv. Anny Brno, přednosta doc. MUDr. Vladimír Vašků, CSc. ⁴
Published in the journal: Vnitř Lék 2008; 54(11): 1063-1080
Category: Přehledný referát

Summary

Over a period of 18 years, 17 patients with proven Langerhans cell histiocytosis (LCH) were treated at the Haematological Clinic in Brno. In 13 of them, the disease was diagnosed at adult age, and 4 patients were referred to the centre with LCH diagnosed at early child age. One of these 4 patients suffered from repeated recurrences of the disease at adult age and was diagnosed with progressive neurodegenerative damage of the CNS at the age of 25 which in its terminal phase resulted in the patient’s immobility, loss of sphincter control, incapacity to communicate and death at the age of 32. LCH was diagnosed at adult age in 13 patients. The form with primary bone involvement was detected in 8 out of 13 patients (62%). Only 2 of 13 patients (15%) had multiple bone lesions upon diagnosis, the remaining 6 patients (46%) had only one lesion at the time of diagnosis. Repeated recurrence of bone involvement was only recorded in 3 out of 13 patients (23%). The combination of recurrent bone involvement and the development of lung affection (dyspnoea, irritating cough, nodularities and cysts in HRCT images) were documented in 2 out of 13 patients (15%). One of the patients diagnosed with LCH at the age of 37 had repeated recurrence of bone involvement, which was also treated by 2 cycles of high-dose chemotherapy and autologous transplantation. He died of bronchopneumonia due to the affection of the lungs by LCH at 48 years of age. Primary extraoseal (extamedular) involvement was diagnosed in 5 out of 13 patients (38%) (mandibular gum infiltration, single cervical node infiltration, hand skin infiltration, infiltration of the perineal region and infiltration of the hypophysial infundibular and primary lung form of LCH). In the 1st case, excision was the solution applied to the infiltration of the lingual side of the gums, without further recurrence. In the 2nd case, the infiltrated region of skin over the metacarpophalangeal joint was irradiated and the infiltration disappeared. In the 3rd case, the first sign of the disease was diabetes insipidus in a 34-year old man, and an infiltrate in the anal region similar to condylomata acuminata. The diagnosis was confirmed 2 years after the development of diabetes insipidus from perianal infiltrates. After treatment with leustatin in 4 cycles (10 mg a day for 5 consecutive days), control MR showed that the infiltration in the hypophysial infundibular had disappeared, while the finding in the perianal region only regressed by 50% after therapy with leustatin, the reason for subsequent application of radiotherapy (20 Gy). The finding in the perianal region is normal one year after therapy, but substitution therapy with adiuretin is still necessary. The 4th patient was a case of LCH with primary pulmonary involvement diagnosed on the basis of HRCT and lavage with an immunohistochemical proof (expression of CD1 and of protein S-100) of a high number of Langerhans cells. The occurrence of LCH at adult age is rare and the disease may affect the skeleton as well as other organs. Therefore each new osteolytic lesion should be submitted for histological exam, as well as each pathologic formation, because diagnosing the disease without a microscopic and immunohistochemical exams is not possible. In the case of occurrence of diabetes insipidus at adult age, LCH should be considered as one of the possible underlying diseases. LCH pulmonary involvement should be considered in patients with an interstitial pulmonary process and the examinations should be focused accordingly (thoracoscopy with sampling for histological exams or bronchoalveolar lavage) plus the indispensable immunohistochemical examination.

Key words:
Langerhans cell histiocytosis – eosinophillic bone granuloma – osteolysis – diabetes insipidus – multiple myeloma – 2-chlordeoxyadenosin – high-dose chemotherapy with autologous transplantation

Zdroje

1. Nicholson SH, Egeler M, Nesbit ME. The epidemiology of Langerhans cell histiocytosis. Hematol Oncol Clin North Amer 1998; 12: 379–348.

2. Baumgartner I, Hochstetter A, Baumert Bet al. Langerhans cell histiocytosis in adults. Med Pediatric Oncol 1997; 28: 9–14.

3. Bubanska E, Stančokova T, Dluholucky S. Histiocytóza z Langerhansových buněk. Čes Slov Pediat 1998; 53: 18–19.

4. Mottl H, Koutecký J, Ganevová M. Strategieléčby histiocytózy z Langerhansových bu-něk u dětí. Čes Slov Pediat 1994; 49: 81.

5. Mottl H, Mracek J, Kabelka Z et al. Histiocytóza z Langerhansových buněk u dětí. Čs Pediat 1992; 47: 530–533.

6. Mottl H, Rob L, Stary J et al. Langerhans cell histiocytosis of vulva in adolescent. Int J Gynecol Cancer 2000; 17: 520–524.

7. Šímová B, Mališ J, Neuwirt J. Klinické projevy histiocytózy z Langerhansových buněk. Zdrav Nov ČR Lék Listy 2003; 52: 18.

8. Tichý M jr, Tichý M, Krč I et al. Multicentrická retikulohistiocytóza. Čes Slov Derm 1999; 74: 168–171.

9. Toušovská K, Slavík Z. Histiocytóza z Langerhansových buněk v dětském věku. Lék Zprav lék Fak Univ Karlovy Hr Králové 1997; 42: 127–132.

10. Gotz G, Fichter J. Langerhans’-cell histiocytosis in 58 adults. Eur J Med Res 2004; 9: 510–514.

11. Pacovska V, Bortlova A, Homolka J et al. Granulomatóza z Langerhansových buněk. Trendy Med 2002; 4: 59–61.

12. Malpas JS. Langerhans cell histiocytosis in adults. Hematol Oncol Clin North Amer 1998; 12: 259–268.

13. Stockschlaeder M, Sucker C. Adult Langerhans cell histiocytosis. Eur J Haematol 2006; 76: 363–368.

14. 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.

15. Adam Z, Krejčí M, Vorlíček J. Maligní krevní nemoci. Praha: Grada Publishing 2008, 396 s.

16. Cheung N, Selva D, McNab AA. Orbital Langerhans cell histiocytosis in adults. Ophthalmology 2007; 114: 1569–1573.

17. Smilek P, Krejčova B, Čada K et al. Histiocytóza z Langerhansových buněk, případ postižení spánkové kosti. Otorinolaryng Foniat 1994; 43: 263–265.

18. Srikulmontree T, Massey HD, Roberts WN. Treatment of skeletal Erdheim-Chester disease with zoledronic acid: case report and proposed mechanisms of action. Rheumatol Int 2007; 27: 303–307.

19. Hoover KB, Rosenthal DI, Mankin H. Langerhans cell histiocytosis. Skeletal Radiol 2007; 36: 95–104.

20. Dogan S, Conway J, Miller JH et al. Detection of bone lesions in Langerhans cell histiocytosis. Complementary roles of scintigraphy and conventional radiograpy. J Pediatric Hematol/Oncol 1996; 18: 51–58.

21. Howarth DM, Mullan BP, Wiseman GA et al. Bone scintigraphy evaluated in diagnosis and staging Langerhans’s cell histiocytosis and related disorders. J Nuclear Med 1996; 37: 1456–1460.

22. Blum R, Seymour JF, Hicks RJ. Role of FDG-positron emission tomography scanning in the management of histiocytosis. Leukem Lymphoma 2002; 43: 2155–2157.

23. Kaste SC, Rodriguez-Galindo C et al. PET-CT in pediatric Langerhans cell his-tiocytosis. Pediatr Radiol 2007; 37: 615–622.

24. Weiss SE, O’Connor L, Welsh JS. Refinement of radiation therapy based on PET data in an adult with Langerhans cell histiocytosis of soft tissues. Clin Adv Hematol Oncol 2006; 4: 290–292; discussion 292–294.

25. Furmanczyk PS, Bruckner JD, Gillespy T 3rd et al. An unusual case of Erdheim-Chester disease with features of Langerhans cell histiocytosis. Skeletal Radiol 2007; 36: 885–889.

26. Goo HW, Yang DH, Ra YS et al. MRI of Langerhans cell histiocytosis: comparison with radiography and bone scintigraphy. Pediatr Radiol 2006; 36: 1019–1031.

27. Olschewski T, Seegenschmiedt MH. Radiotherapy of Langerhans’ Cell Histiocytosis : Results and Implications of a National Patterns-of-Care Study. Strahlenther Onkol 2006; 182: 629–634.

28. Fernandez Flores A, Mallo S. Langerhans cell histiocytosis of vulva. Dermatol Online J 2006; 12: 15.

29. Ferreli C, Aste N, Pinna LA et al. Langerhans cell histiocytosis in an adult. J Eur Acad Dermatol Venereol 1997; 9: 253–255.

30. Ferringer T, Banks PM, Metcalf JS. Langerhans cell sarcoma. Am J Dermatopathol 2006; 28: 36–39.

31. Hagiuda J, Ueno M, Ashimine S et al. Langerhans cell histiocytosis on the penis: a case report. BMC Urol 2006; 6: 28.

32. Mlyncek M, Uharcek P, Durcanský D. Vulvar Langerhans’ cell histiocytosis: a case report. Acta Obstet Gynecol Scand 2006; 85: 753–755.

33. Tzung TY, Wu JC. Nonhealing perianal ulcers. Arch Dermatol 2005; 141: 1161–1166.

34. Venizelos ID, Mandala E, Tatsiou ZA et al. Primary langerhans cell histiocytosis of the vulva. Int J Gynecol Pathol 2006; 25: 48–51.

35. Fluri S, Nievergelt H, Kernland K et al. When atopic dermatitis doesn’t heal – an interesting case from the medical university polyclinic. Schweiz Rundsch Med Prax 2006; 95: 945–948.

36. Punia RS, Bagai M, Mohan H et al. Langerhans cell histiocytosis of skin: a clinicopathologic analysis of five cases. Indian J Dermatol Venereol Leprol 2006; 72: 211–214.

37. Imafuku S, Shibata S, Tashiro A. Cutaneous Langerhans cell histiocytosis in an elderly man successfully treated with narrow-band ultraviolet B. Br J Dermatol 2007; 157: 1277–1279.

38. Lan Ma H, Metze D, Luger TA et al. Successful treatment of generalized eruptive histiocytoma with PUVA. J Dtsch Dermatol Ges 2007; 5: 131–134.

39. Newman B, Hu W, Nigro K et al. Aggressive histiocytic disorders that can involve the skin. J Am Acad Dermatol 2007; 56: 302–316.

40. Munn S, Chu AC. Langerhans cell histiocytosis of the skin. Hematol Oncol Clin North Amer 1998; 12: 269–286.

41. Ashena Z, Alavi S, Arzanian MT et al. Nail involvement in langerhans cell histiocytosis. Pediatr Hematol Oncol 2007; 24: 45–51.

42. Mataix J, Betlloch I, Lucas-Costa A et al. Nail changes in Langerhans cell histiocytosis: a possible marker of multisystem disease. Pediatr Dermatol 2008; 25: 247–251.

43. Canuet M, Kessler R, Jeung MY et al. Correlation between high‑resolution computed tomography findings and lung function in pulmonary Langerhans cell histiocytosis. Respiration 2007; 74: 640–646.

44. Leatherwood DL, Heitkamp DE, Emerson RE. Best cases from the AFIP: Pulmonary Langerhans cell histiocytosis. Radiographics 2007; 27: 265–268.

45. Kim CK, Park CB, Jin U et al. Pulmonary Langerhans’ cell histiocytosis presented with recurrent pneumothorax. Interact Cardiovasc Thorac Surg 2006; 5: 512–513.

46. Mendez JL, Nadrous HF, Vassallo R et al. Pneumothorax in pulmonary Langerhans cell histiocytosis. Chest 2004; 125: 1028–1032.

47. Adams EP, Sauceda D, Oliver J et al. Isolated pulmonary Langerhans cell histiocytosis in a 17-year-old male. J Pediatr Hematol Oncol 2007; 29: 121–124.

48. Aerni MR, Aubry MC, Myers JL et al. Complete remission of nodular pulmonary Langerhans cell histiocytosis lesions induced by 2-chlorodeoxyadenosine in a non‑smoker. Respir Med 2008; 102: 316–319.

49. Bernstrand C, Cederlund K, Sandstedt B et al. Pulmonary abnormalities at long term follow up of patients with Langerhans cell histiocytosis. Med Pediatr Oncol 2001; 36: 459–468.

50. Braier J, Latella A, Balancini B et al. Isolated pulmonary Langerhans cell histiocytosis presenting with recurrent pneumothorax. Pediatr Blood Cancer 2007; 48: 241–244.

51. Bittenglova R, Pešek M, Mukenšnabl P et al. Granulomatóza z Langerhansových buněk. Stud pneumol phtiseol 2002; 62: 196–202.

52. Brown RE. Bisphosphonates as antialveolar macrophage therapy in pulmonary Langerhans cell histiocytosis. Med Pediatr Oncol 2001; 36: 641–643.

53. Green MB, Allen JN. Cough, dyspnea,and reticulonodular opacities in a 58-year-old smoker. Chest 2007; 132: 700–703.

54. Jülg BD, Weidner S, Mayr D. Pulmonary manifestation of a Langerhans cell sarcoma: case report and review of the literature. Virchows Arch 2006; 448: 369–374.

55. Rožánek P, Molnar V, Rešl M. Tři případy plicní granulomatózy z Langerhansových buněk. Lék zpr lék Fak Univ Karlovy Hr Králové 1998; 43: 127–132.

56. Sundar KM, Gosselin MV, Chung HL et al. Pulmonary Langerhans cell histiocytosis: emerging concepts in pathobiology, radiology and clinical evolution of the disease. Chest 2003; 123: 1673–1683.

57. Tazi A. Adult pulmonary Langerhans’ cell histiocytosis. Eur Respir J. 2006; 27: 1272–1285.

58. Skacel Z, Marel M, Vraštilova P et al. Histiocytóza z Langerhansových buněk. Přehled literatury a vlastní pozorování. Stud pneumol phtiseol 2000; 60: 150–156.

59. Zeppa P, Cozzolino I, Russo M et al. Pulmonary langerhans cell histiocytosis (histiocytosis X) on bronchoalveolar lavage: a report of 2 cases. Acta Cytol 2007; 51: 480–482.

60. Tötsch M, Guzman J, Theegarten D et al. Bronchoalveolar lavage. Pathologe 2007; 28: 346–353.

61. Hidalgo A, Franquet T, Giménez A. Smoking‑related interstitial lung diseases: radiologic-pathologic correlation. Eur Radiol 2006; 16: 2463–2470.

62. Liu YH, Fan XH, Fang K. Langerhans’ cell histiocytosis with multisystem involvement in an adult. Clin Exp Dermatol 2007; 32: 765–768.

63. Marten K. Smoking‑related interstitial lung diseases. Rofo 2007; 179: 68–75.

64. Negrin‑Dastis S, Butenda D, Dorzee J et al. Complete disappearance of lung abnormalities on high‑resolution computed tomography: a case of histiocytosis X. Respir J 2007; 14: 235–237.

65. Amato MC, Elias LL, Elias J et al. Endocrine disorders in pediatric – onset Langerhans Cell Histiocytosis. Horm Metab Res 2006; 38: 746–751.

66. Donadieu J, Rolon MA, Pion I et al. Incidence of growth hormone deficiency in pediatric onset Langerhans cell histiocytosis: Efficacy and safety of Growth hormone treatment. J Clin Endocrinol Metabolism 2004; 89: 604–609.

67. Makras P, Alexandraki KI, Chrousos GP et al. Endocrine manifestations in Langerhans cell histiocytosis. Trends Endocrinol Metab 2007; 18: 252–257.

68. Neji S, Ben Slama C, Zidi B. Hypo-tha-lamic-pituitary Langerhans cell histiocytosis in adults. Presse Med 2006; 35: 1263–1266.

69. Halefoglu AM. Magnetic resonance imaging of thickened pituitary stalk proceeding to Langerhans cell histiocytosis in a child. Australas Radiol 2006; 50: 175–178.

70. Horn EM, Coons SW, Spetzler RF et al. Isolated Langerhans cell histiocytosis of the infundibulum presenting with fulminant diabetes insipidus. Childs Nerv Syst 2006; 22: 542–544.

71. Kandpal H, Subramanian S, Hari S. Langerhans cell histiocytosis of pituitary stalk. Neurol India 2007; 55: 91–92.

72. Ouyang DL, Roberts BK, Gibbs IC et al. Isolated Langerhans cell histiocytosis in an adult with central diabetes insipidus: case report and review of literature. Endocr Pract 2006; 12: 660–663.

73. Ottaviano F, Finlay JL. Diabetes insipidus and Langerhans cell histiocytosis: a case report of reversibility with 2-chlorodeoxyadenosine. J Pediatr Hematol Oncol 2003; 25: 575–577.

74. Prosch H, Grois N, Prayer D et al. Central diabetes insipidus as presenting symptom of Langerhans cell histiocytosis. Pediatr Blood Cancer 2004; 43: 594–599.

75. Ryan P, Walterfang M, Scholes A et al. Recovery of cognitive function in neuropsychiatric Langerhan’s cell histiocytosis. Psychiatry Clin Neurosci 2006; 60: 629–632.

76. Nanduri VR, Lillywhite L, Chapman Cet al. Cognitive outcome of long term survivors of multisystem Langerhans cell histiocytosis. J Clin Oncol 2003; 21: 2961–2967.

77. Prosch H, Feldges A, Grois N et al. Demonstration of CD1a positive cells in the cerebrospinal fluid-A clue to diagnosis of isolated Langerhans cell histiocytosis of the hypothalamic-pituitary axis? Med Pediatr Oncol 2003; 41: 474–476.

78. Prosch H, Grois N, Wnorowski M et al. Long‑term MR imaging course of neurodegenerative Langerhans cell histiocytosis. AJNR Am J Neuroradiol 2007; 28: 1022–1028.

79. Bös M, Grothe C, Urbach H et al. Cerebellar syndromes in Langerhans’ cell histiocytosis. Nervenarzt 2007; 78: 437–440.

80. 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: 72–79.

81. Grois N, Prayer D, Prosch H et al. Neuropathology of CNS disease in Langerhans cell histiocytosis. Brain 2005; 128: 829–838.

82. Martin‑Duverneuil N, Idbaih A, Hoang-Xuan K et al. French Langerhans Cell Histiocytosis Study Group. MRI features of neurodegenerative Langerhans cell histiocytosis. Eur Radiol 2006; 16: 2074–2082.

83. 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: 50–56.

84. Steiner M, Prayer D, Asenbaum S et al. Modern imaging methods for the assessment of Langerhans’ cell histiocytosis‑associated neurodegenerative syndrome: case report. J Child Neurol 2005; 20: 253–257.

85. Imashuku S, Okazaki NA, 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.

86. Edelweiss M, Medeiros LJ, Suster S et al. Lymph node involvement by Langerhans cell histiocytosis: a clinicopathologic and immunohistochemical study of 20 cases. Hum Pathol 2007; 38: 1463–1469.

87. Baumann C, Reschke K, Jungehülsing M et al. Destruction of the vestibular organ by Langerhans’ cell histiocytosis. Eur Radiol 2006; 16: 1177–1178.

88. Kürten T, Groeger M, Angerstein W. Frequency of hearing disorders in children with langerhans’ cell histiocytosis. Laryngorhinootologie 2008; 87: 96–99.

89. Anton M, Holoušova M, Řehůřek J et al. Histiocytoza X a dětská očnice. Čs Ophthal 1992; 48: 176–180.

90. Bermingham N, Townley D, Fenton S et al. Ocular langerhans cell histiocytosis. Eye 2007; 21: 1127–1128.

91. D’Angio GJ. Langerhans cell histiocytosis affecting the eyes. Pediatr Blood Cancer 2006; 47: 639.

92. Tsai JH, Galaydh F, Ching SS. Anterior uveitis and iris nodules that are associated with angerhans cell histiocytosis. Am J Ophthalmol 2005; 140: 1143–1145.

93. Dina I, Copaescu C, Herlea V et al. Liver involvement in Langerhans’ cell histiocytosis. Case report. J Gastrointestin Liver Dis 2006; 15: 57–59.

94. Griffiths W, Davies S, Gibbs P et al. Liver transplantation in an adult with sclerosing cholangitis due to Langerhans cell histiocytosis. J Hepatol 2006; 44: 829–831.

95. Guthery SL, Heubi JE. Liver involvement in childhood histiocytic syndromes. Curr Opin Gastroenterol 2001; 17: 474–478.

96. Choi SW, Bangaru BS, Wu CD et al. Gastrointestinal involvement in disseminated Langerhans cell histiocytosis (LCH) with durable complete response to 2-chlorodeoxyadenosine and high‑dose cytarabine. J Pediatr Hematol Oncol 2003; 25: 503–506.

97. Hait E, Liang M, Degar B et al. Gastrointestinal tract involvement in Langerhans cell histiocytosis: case report and literature review. Pediatrics 2006; 118: 1593–1599.

98. Hait E, Liang M, Degar B et al. Gastrointestinal tract involvement in Langerhans cell histiocytosis: case report and lite-rature review. Pediatrics 2006; 118: e1593–e1599.

99. Konno S, Hizawa N, Betsuyaku T et al. Adult Langerhans cell histiocytosis with independently relapsing lung and liver lesions that was successfully treated with etoposide. Intern Med 2007; 46: 1231–1235.

100. Klein F, Krigar D, Petzoldt D et al. Periodontal manifestation of Langerhans’ cell histiocytosis in a young man: case report with a 24-month follow‑up. Quintessence Int 2006; 37: 175–182.

101. Silvestros SS, Mamalis AA, Sklavounou AD et al. Eosinophilic granuloma masquerading as aggressive periodontitis. J Periodontol 2006; 77: 917–921.

102. Querings K, Starz H, Balda BR. Clinical spectrum of cutaneous Langerhans’ cell histiocytosis mimicking various diseases. Acta Derm Venereol 2006; 86: 39–43.

103. Arizo M, Egeler M. Clinical aspectsof Langerhans cell histiocytosis. Hema-tology/Oncology Clinics North Amer 1998; 12: 247–267.

104. Chang KL, Snyder DS. Langerhans cell histiocytosis. Cancer Treat Res 2008; 142: 383–398.

105. Henter JI, Tondini C, Pritchard J. Histiocyte disorders. Crit Rev Oncol Hematol 2004; 50: 157–174.

106. Ugurel S, Pröhler G, Tilgen W et al. S100-β serum protein – a new marker in the diagnosis and monitoring of Langerhans cell histiocytosis. Brit J Dermatol 2000; 143: 201–202.