Lymphoma‑like course in aggressive adult multisystem Langerhans cell histiocytosis and the benefit of PET/ CT imaging in evaluation of diffuse metabolic activity of lung parenchyma

Česká verze

Authors: P. Szturz ¹; Z. Adam ¹; Z. Řehák ²; R. Koukalová ²; R. Kodet ³; T. Nebeský ⁴; J. Neubauer ⁴; M. Moulis ⁵; L. Šmardová ¹; J. Mayer ¹
Authors place of work: Interní hematoonkologická klinika Lékařské fakulty MU a FN Brno, pracoviště Bohunice, přednosta prof. MU Dr. Jiří Vorlíček, CSc. 2 PET Centrum Oddělení nukleární medicíny Masarykova onkologického ústavu Brno, přednosta prim. MU Dr. Karol Bolčák3 Ústav pat ¹
Published in the journal: Vnitř Lék 2010; 56(11): 1177-1193
Category: Kazuistiky

Summary

The case report given here describes an unusual case of a 35‑year-old otherwise healthy male diagnosed with aggressive form of Langerhans cell histiocytosis initially taking course under the form of lymphoma with expressed B symptoms (night sweats, fever and weight loss) and generalized peripheral lymphadenopathy. Also present were productive cough and perianal itching. The diagnosis was determined from lymph node and perianal skin biopsies. Furthermore, by a typical finding on HRCT (high‑resolution computed tomography), pulmonary involvement was confirmed the gradual development of which we succeeded to document through a series of several HRCT and PET/ CT scans from its initial florid phase characterized by disseminated nodularities up to the terminal phase with the decline of activity and development of cystic formations. After the collection of peripheral blood stem cells, the planned patient’s therapy started which in all consisted of three monotherapy cycles with cladribine followed by three cycles of combined chemotherapy (cladribine + cyclophosphamide + methylprednisolone) and complemented with curative radiotherapy of the perianal area. This treatment put the disease into complete remission. However, in two months the initial B‑ symptoms occurred again, along with the pulmonary symptomatology, perianal pruritus and newly also hip bone pains. The suspected LCH relapse was proved histologically by lymph node biopsy and confirmed at a restaging PET/ CT examination which also showed disease dissemination into the hip bones. Consequently, an aggressive form of the disease with early relapse had been the case, which was indicated for administering 4 cycles of CHOEP (cyclophosphamide + doxorubicin + vincristine + etoposide + prednisone) as salvage regimen completed in March 2010 with autologous peripheral blood stem cell transplantation after high‑dose BEAM (carmustine + etoposide + cytarabine + melphalan) chemotherapy. Thus, the generalized involvement of nodes doesn’t always need to be malignant lymphoma or metastatic dissemination of a tumour but also LCH may be the case. The presence of B symptoms may very likely stand for an aggressive form of the disease course. Histological evaluation of the proliferative characteristic (given by Ki‑ 67 immunohistochemical proliferative index marker and also morphologically by the number of mitosis) may draw attention to an aggressive form of this disease. However, therapy with cladribine (2-chlorodeoxyadenosine) which proves beneficial in classic forms of LCH, in cases of highly aggressive forms of LCH doesn’t need to have the same effect as in LCH with low proliferative activity, which conforms to the present experience in the treatment of indolent and aggressive lymphomas. In our study, the hybrid PET/ CT imaging proved high sensitivity in evaluating the activity of the disease, including its early relapse. We are presenting here a new method for description and evaluation of diffuse increased activity of pulmonary parenchyma by means of PET/ CT examination and for using this method within the framework of monitoring the curative response.

Key words:
Langerhans cell histiocytosis – lymphadenopathy – B symptoms – PET/ CT – HRCT – cladribine – 2- chlorodeoxyadenosine

Zdroje

1. Adam Z, Pour L, Krejčí M et al. Histiocytóza z Langerhansových buněk u osob dospělého věku – nemoc s mnoha tvářemi. Zkušenosti jednoho pracoviště a přehled projevů nemoci. Vnitř Lék 2008; 54: 1063– 1081.

2. Adam Z, Krejčí M, Vorlíček J. Hematologie: přehled maligních hematologických nemocí. Praha: Grada Publishing 2008.

3. Ščudla V, Roček V, Dušek B et al. Multifokální eozinofilní granulom v dospělosti. Vnitř Lék 1987; 33: 1078– 1086.

4. Kodet R, Elleder M, Smelhaus V et al. Disseminated histiocytosis X. Česk Patol 1984; 20: 19– 26.

5. Kodet R, Zitková M. Morphologic and roentgenologic pulmonary findings in disseminated histiocytosis X. Česk Pediatr 1985; 40: 634– 638.

6. Howarth DM, Gilchrist GS, Mullan BP et al. Langerhans cell histiocytosis: diagnosis, natural history, management, and outcome. Cancer 1999; 85: 2278– 2290.

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

8. Takahashi T, Yoshimoto M, Kondoh N. Spontaneously regressed Langerhans cell histiocytosis of lymph nodes in an elderly patient. Intern Med 2007; 46: 1757– 1760.

9. Vassallo R, Ryu JH. Pulmonary Langerhans’ cell histiocytosis. Clin Chest Med 2004; 25: 561– 571.

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

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

12. 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.

13. Dogan AS, Conway JJ, Miller JH et al. Detection of bone lesions in Langerhans cell histiocytosis: complementary roles of scintigraphy and conventional radiography. J Pediatr Hematol Oncol 1996; 18: 51– 58.

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

15. Olschewski T, Seegenschmiedt MH. Radiotherapy for bony manifestations of Langerhans cell histiocytosis. Review and proposal for an international registry. Strahlenther Onkol 2006; 182: 72– 79.

16. Blum R, Seymour JF, Hicks RJ. Role of 18FDG‑ positron emission tomography scanning in the management of histiocytosis. Leukem Lymphoma 2002; 43: 2155– 2157.

17. 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– 294.

18. Kaste SC, Rodriguez‑ Galindo C, McCarville ME et al. PET‑ CT in pediatric Langerhans cell histiocytosis. Pediatr Radiol 2007; 37: 615– 622.

19. Hance AJ, Basset F, Saumon G et al. Smoking and interstitial lung disease. The effect of cigarette smoking on the incidence of pulmonary histiocytosis X and sarcoidosis. Ann N Y Acad Sci 1986; 465: 643– 656.

20. Mogulkoc N, Veral A, Bishop PW et al. Pulmonary Langerhans’ cell histiocytosis: radiologic resolution following smoking cessation. Chest 1999; 115: 1452– 1455.

21. Habib SB, Congleton J, Carr D et al. Recurrence of recipient Langerhans’ cell histiocytosis following bilateral lung transplantation. Thorax 1998; 53: 323– 325.

22. Brauner MW, Grenier P, Mouelhi MM et al. Pulmonary histiocytosis X: evaluation with high‑resolution CT. Radiology 1989; 172: 255– 258.

23. Soler P, Bergeron A, Kambouchner M et al. Is high‑resolution computed tomography a reliable tool to predict the histopathological activity of pulmonary Langerhans cell histiocytosis? Am J Respir Crit Care Med 2000; 162: 264– 270.

24. 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.’

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

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

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

28. 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.

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

30. 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.

31. Bittenglova R, Pešek M, Mukenšnabl P et al. Granulomatóza z Langerhansových buněk. Stud Pneumol Phtiseol 2002; 62: 196– 202.

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

33. 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.

34. 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.

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

36. 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.

37. Auerswald U, Barth J, Magnussen H. Value of CD‑ 1- positive cells in bronchoalveolar lavage fluid for the diagnosis of pulmonary histiocytosis X. Lung 1991; 169: 305– 309.

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

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

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

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

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

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

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

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

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

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

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

49. 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.

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

51. 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.

52. 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.

53. 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.

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

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

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

57. 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 Metab 2004; 89: 604– 609.

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

59. 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.

60. 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.

61. Ornvold K, Ralfkiaer E, Carstensen H. Immunohistochemical study of the abnormal cells in Langerhans cell histiocytosis (histiocytosis x). Virchows Arch A Pathol Anat Histopathol 1990; 416: 403– 410.

62. Goh NS, McDonald CE, MacGregor DP et al. Successful treatment of Langerhans cell histiocytosis with 2-chlorodeoxyadenosine. Respirology 2003; 8: 91– 94.

63. Lazor R, Etienne‑ Mastroianni B, Khouatra C et al. Progressive diffuse pulmonary Langerhans cell histiocytosis improved by cladribine chemotherapy. Thorax 2009; 64: 274– 275.

64. Büchler T, Cervinek L, Belohlavek O et al. Langerhans cell histiocytosis with central nervous system involvement: follow‑up by FDG‑ PET during treatment with cladribine. Pediatr Blood Cancer 2005; 44: 286– 288.

65. Krajicek BJ, Ryu JH, Hartman TE et al. Abnormal fluorodeoxyglucose PET in pulmonary Langerhans cell histiocytosis. Chest 2009; 135: 1542– 1549.

66. Weitzman S, Braier J, Donadieu J et al. 2’ chlordeoxyadenosine (2- Cda) as salvage therapy for Langerhans cell histiocytosis (LCH). Result of LCH‑ S‑ 98 protocol of the histiocyte society. Pediatr Blood Cancer 2009; 53: 1271– 1276.

67. George JC, Buckwalter KA, Cohen MD et al. Langerhans cell histiocytosis of bone: MR imaging. Pediatr Radiol 1994; 24: 29– 32.

68. Bruno MC, Del Basso De Caro ML, Panagiotopoulos K et al. Aggressive eosinophilic granuloma of the parietal bone. An immunohystochemical study of Ki‑ 67 expression. J Neurosurg Sci 2006; 50: 111– 117.