#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Lymphomatoid granulomatosis – the past and present


Authors: Alice Sýkorová 1;  Vít Campr 2;  Petra Kašparová 3;  Eva Kočová 4;  David Belada 1;  Marek Trněný 5;  Pavel Žák 1
Authors‘ workplace: IV. interní hematologická klinika LF UK a FN Hradec Králové, přednosta doc. MUDr. Pavel Žák, Ph. D. 1;  Ústav patologie a molekulární medicíny 2. LF UK a FN Motol Praha, přednosta prof. MUDr. Roman Kodet, CSc. 2;  Fingerlandův ústav patologie LF UK a FN Hradec Králové, přednosta prof. MUDr. Aleš Ryška, Ph. D. 3;  Radiologická klinika LF UK a FN Hradec Králové, přednosta prof. MUDr. Antonín Krajina, CSc. 4;  I. interní klinika – klinika hematologie 1. LF UK a VFN Praha, přednosta prof. MUDr. Marek Trněný, CSc. 5
Published in: Vnitř Lék 2014; 60(3): 225-238
Category: Reviews

Overview

Background:
Lymphomatoid granulomatosis (LyG) is a rare multisystemic angiocentric and angiodestructive B lymphoproliferative disease that was first described by Liebow in 1972. Disease was then in the “gray zone” between vasculitis and lymphoproliferative disease. LyG is currently categorized as a primary B lymphoproliferative disease associated with Epstein-Barr (EB) virus according to the World Health Organization (WHO) classification of tumours.

Epidemiology, clinical course and treatment:
Lymphomatoid granulomatosis is a rare disease with unknown prevalence. It occurs more often in males (male : female ratio 2 : 1) between the 5th to 6th decade of life and is more frequent in Europe than in Asia. Lungs are typically the predominantly affected organ; the disease spreads predominantly by extralymphatic manner. Spleen and lymph nodes are affected at an advanced stage. The clinical features are often nonspecific. Dyspnea, cough, hemoptysis, chest pain are the most common features with/without B symptoms (fever, night sweats, weight loss) in the pulmonary involvement. The radiographic finding of the lung is very diverse, but when there are multiple bilateral nodular lesions with basal predominance in perilymphatic distribution, we should think of this disease, although LyG rarely occurs. The histopathologic examination of affected tissue (most commonly the lung) is necessary to confirm the diagnosis. The thoracoscopy is used mainly. When the pulmonary findings are without any response to antibiotics, the autoimmune cause and other granulomatous inflammations (tuberculosis, sarcoidosis, etc.) are excluded, this diagnostic performance is indicated. Prognosis is variable – from spontaneous remission to progressive disease, often with aggressive behavior. Median survival is 14 months from diagnosis and mortality rate is 60% in the first year – despite the treatment. Treatment strategy is chosen depending on the histological grade. The therapy is not yet standardized. Interferon α, rituximab, glucocorticoids, cyclophosphamide and combined immunochemotherapy have been used for the treatment. The disease may lead to pulmonary failure, fatal CNS (central nervous system) involvement and sometimes develops into progressive EB virus positive lymphoproliferative disorder.

Conclusion:
Improvements in understanding of the biology of LyG, especially in determining the precise role of EB virus infection in its pathogenesis may lead to optimization of treatment strategies for this disease. Novel treatment modalities are urgently needed due to unfavourable prognosis. Adoptive immunotherapy appeals to be a promising approach.

Key words:
epidemiology – Epstein-Barr virus – lymphomatoid granulomatosis


Sources

1. Pittaluga S, Wilson WH, Jaffe ES. Lymphomatoid granulomatosis. In: Swerdlow SH, Campo E, Harris NL et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. IARC Press: Lyon 2008: 247–249. ISBN 139789283224310.

2. Hare SS, Souza CA, Bain G et al. The radiological spectrum of pulmonary lymphoproliferative disease. Br J Radiol 2012; 85 (1015): 848–864.

3. Liebow AA, Carrington CR, Friedman PJ. Lymphomatoid granulomatosis. Hum Pathol 1972; 3(4): 457–558.

4. Katzenstein AL, Carrington CB, Liebow AA. Lymphomatoid granulomatosis: a clinicopathologic study of 152 cases. Cancer 1979; 43(1): 360–373.

5. Katzenstein AL, Doxtader E, Narendra S. Lymphomatoid granulomatosis: insights gained over 4 decades. Am J Surg Pathol 2010; 34: e35-e48. Dostupné z DOI: <http://doi: 10.1097/PAS.0b013e3181fd8781>.

6. Colby TV. Current histological diagnosis of lymphomatoid granulomatosis. Mod Pathol 2012; 25 (Suppl 1): S39-S42.

7. Lipford EH, Margolick JB, Longo DL et al. Angiocentric immunoproliferative lesions: a clinicopathologic spectrum of post-thymic T-cell proliferations. Blood 1988; 72(5): 1674–1681.

8. Nichols PW, Koss M, Levine AM et al. Lymphomatoid granulomatosis: a T-cell disorder? Am J Med 1982; 72(3): 467–471.

9. Travis WD, Colby TV, Corrin B et al. Histological Typing of Lung and Pleural Tumors. 3rd ed. Springer: Berlin/New York 1999. ISBN-13: 978–3540652199.

10. Guinee D, Jaffe ES, Kingma D et al. Pulmonary lymphamatoid granulomatosis: evidence for a proliferation of Epstein-Barr virus infected B lymphocytes with a prominent T-cell components and vasculitis. Am J Sur Pathol 1994; 18(8): 753–764.

11. Myers JL, Kurtin PL, Katzenstein AL et al. Lymphomatoid granulomatosis: Evidence of immunophenotypic diversity and relationship to Epstein-Barr virus. Am J Surg Pathol 1995; 19(11): 1300–1312.

12. Jaffe ES, Wilson WH. Lymphomatoid granulomatosis. In: Jaffe ES, Harris NL, Stein H et al. World Health Organization Classification of Tumours: Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues. IARC Press: Lyon 2001: 185–187.ISBN 92 83 22411 6..

13. Katzenstein AL, Peiper S. Detection of Epstein-Barr virus genomes in lymphomatoid granulomatosis: analysis of 29 cases using the polymerase chain reaction technique. Mod Pathol 1990; 3(4): 435–441.

14. Wilson WH, Kingma DW, Raffeld M et al. Association of lymphomatoid granulomatosis with Epstein-Barr viral infection of B lymphocytes and response to interferon-alpha 2b. Blood 1996; 87(11): 4531–4537.

15. Epstein MA, Achong BG, Barr YM. Virus particles in cultured lymphoblasts from Burkitt’s lymphoma. Lancet 1964; 1(7335):702–703.

16. Williams H, Crawford DH. Epstein-Barr virus: the impact of scientific advances on clinical practice. Blood 2006; 107(3): 862–869.

17. Young LS, Murray PG. Epstein-Barr virus and oncogenesis: from latent genes to tumours. Oncogene 2003; 22(33): 5108–5121.

18. Saha A, Robertson ES. Epstein-Barr virus-associated B-cell lymphomas: pathogenesis and clinical outcomes. Clin Cancer Res 2011; 17(10): 3056–3063.

19. Heslop HE. How I treat EBV lymphoproliferation. Blood 2009; 114(19): 4002–4008.

20. Dunleavy K, Roschewski M, Wilson WH. Lymphomatoid granulomatosis and other Epstein-Barr virus associated lymphoproliferative processes. Curr Hematol Malig Rep 2012; 7(3): 208–215.

21. LeSueur BW, Ellsworth L, Bangert JL et al. Lymphomatoid granulomatosis in a 4-year-old boy. Pediatr Dermatol 2000; 17(5): 369–372.

22. Saxena A, Dyker KM, Angel S at al. Posttransplant diffuse large B cell lymphoma of “lymphomatoid granulomatosis” type. Virchows Arch 2002; 441(6): 622–628.

23. Beaty MW, Toro J, Sorbara L et al. Cutaneous lymphomatoid granulomatosis: correlation of clinical and biologic features. Am J Surg Pathol 2001; 25(9): 1111–1120.

24. Hořejší V, Bartůňková J. Základy imunologie. Triton: Praha 2009. 4th ed: 247–262. ISBN 978–80–7387–280–9.

25. Tran H, Nourse J, Hall S et al. Immunodeficiency-associated lymphomas. Blood Rev 2008; 22(5): 261–281.

26. Dunleavy K, Chattopadhyah P, Kawada J et al. Immune characteristics associated with lymphomatoid granulomatosis and outcome following treatment with interferon-alpha. Blood (ASH Annual Meeting Abstracts) 2010; 116: 963.

27. Karnak I, Ciftci AO, Talim B et al. Pulmonary lymphomatoid granulomatosis in a 4 year old. J Pediatr Surg 1999; 34(6): 1033–1035.

28. Hernández-Marqués C, Lassaletta A, Torrelo A et al. Rituximab in lymphomatoid granulomatosis. J Pediatr Hematol Oncol 2014; 36(2). Dostupné z DOI: <http://doi: 10.1097/MPH.0b013e31827e63a6>.

29. Araki F, Mimura T, Fukuoka S et al. Primary orbital lymphomatoid granulomatosis. Br J Ophthalmol 2009; 93(4): 554–556.

30. Bailie J, McNaughten B, Gray S et al. Unique presentation of testicular involvement in lymphomatoid granulomatosis. Onkologie 2012; 35(6): 372–375.

31. Cameron JR, Cackett P. Lymphomatoid granulomatosis associated with bilateral exudative retinal detachments. Arch Ophthalmol 2007; 125(5): 712–713.

32. Dister F, Ghaye B. Lymphomatoid granulomatosis. JBR-BTR 2012; 95(3): 140–141.

33. James WD, Odom RB, Katzenstein AL. Cutaneous manifestations of lymphomatoid granulomatosis. Report of 44 cases and a review of the literature. Arch Dermatol 1981; 117(4): 196–202.

34. Zaidi A, Kampalath B, Peltier WL et al. Successful treatment of systemic and central nervous system lymphomatoid granulomatosis with rituximab. Leuk Lymphoma 2004; 45(4): 777–780.

35. Roschewski M, Wilson WH. Lymphomatoid granulomatosis. Cancer J 2012; 18(5): 469–474.

36. Jordan K, Grothey A, Grothe W et al. Successful treatment of mediastinal lymphomatoid granulomatosis with rituximab monotherapy. Eur J Haematol 2005; 74(3): 263–266.

37. Cadranel J, Wislez M, Antoine M. Primary pulmonary lymphoma. Eur Respir J 2002; 20(3): 750–762.

38. Chung JH, Wu CC, Gilman MD et al. Lymphomatoid Granulomatosis: CT and FDG-PET findings. Korean J Radiol 2011; 12(6): 671–678.

39. Webb WR, Muller NL, Naidich DP. High-resolution CT of the lung. Lippincott Williams and Wilkins: Philadelphia 2009. 4th ed. ISBN 978078176909.

40. Roarke MC, Nguyen BD. PET/CT characterization and monitoring of disease activity in lymphomatoid granulomatosis. Clin Nucl Med 2007; 32(3): 258–259.

41. Arai H, Oshiro H, Yamanaka S et al. Grade I lymphomatoid granulomatosis with increased uptake of [18F] fluorodeoxyglucose in positron emission tomography: a case report. J Clin Exp Hematop 2009; 49(1): 39–44.

42. Suzuki H, Takeda H, Kishi H et al. Reactivation of Epstein – Barr virus is involved in the pathogenesis of lymphomatoid granulomatosis. Nihon Kokyuki Gakkai Zasshi 2006; 44(7): 492–498.

43. Jung KH, Sung HJ, Lee JH et al. A case of pulmonary lymphomatoid granulomatosis successfully treated by combination chemotherapy with rituximab. Chemotherapy 2009; 55(5): 386–390.

44. Kawai N, Miyake N, Nishiyama Y et al. FDG-findings of the brain in lymphomatoid granulomatosis. Ann Nucl Med 2006; 20(10): 683–687.

45. Pisani RJ, DeRemee RA. Clinical implications of the histopathologic diagnosis of pulmonary lymphomatoid granulomatosis. Mayo Clin Proc 1990; 65(2): 151–163.

46. Jaffe ES, Wilson WH. Lymphomatoid granulomatosis: pathogenesis, pathology and clinical implications. Cancer Surv 1997; 30: 233–248.

47. Jaffe ES. Pulmonary lymphocytic angiitis: a nosologic quandary. Mayo Clin Proc 1988; 63(4): 411–413.

48. Tichý T, Musilová K, Škarda J. Morfologie granulomů a základní histologie vybraných plicních granulomatóz. Program konference. Dostupné z WWW: <http://www.geum.org/sarko/3_Tichy.html>.

49. Hamilton-Dutoit SJ, Raphael M, Audouin J et al. In situ demonstration of Epstein Barr virus small RNAs (EBER1) in acquired immunodeficiency syndrome-related lymphomas: correlation with tumor morphology and primary site. Blood 1993; 82(2): 619–624.

50. McNiff JM, Cooper D, Howe G et al. Lymphomatoid granulomatosis of the skin and lung. An angiocentric T-cell-rich B cell lymphoproliferative disorder. Arch Dermatol 1996; 132(12): 1464–1470.

51. Roubalová K. Laboratorní diagnostika herpetických virů. Med Pro Praxi 2010; 7(5): 241–244.

52. Jaffre S, Jardin F, Dominique S et al. Fatal haemoptysis in a case of lymphomatoid granulomatosis treated with rituximab. Eur Respir J 2006; 27(3): 644–646.

53. Guinee DG Jr, Perkins SL, Travis WD et al. Proliferation and cellular phenotype in lymphomatoid granulomatosis: implications of a higher proliferation index in B cells. Am J Surg Pathol 1998; 22(9): 1093–1100.

54. Fauci AS, Haynes BF, Costa J et al. Lymphomatoid granulomatosis. Prospective clinical and therapeutic experience over 10 years. N Engl J Med 1982; 306(2): 68–74.

55. Armitage JO. My treatment approach to patients with diffuse large B-cell lymphoma. Mayo Clin Proc 2012; 87(2): 161–171.

56. Medeiros LJ, Peiper SC, Elwood L et al. Angiocentric immunoproliferative lesions: a molecular analysis of eight cases. Human Pathology 1991; 22(11): 1150–1157.

57. Takeishi G, Moroki K, Kawasoe T et al. Spontaneous regression and regrowth of central nervous system lymphomatoid granulomatosis: case report. Neurol Med Chir (Tokyo) 2011; 51(11): 801–804.

58. Drasga RE, Williams SD, Wills ER et al. Lymphomatoid granulomatosis. Successful treatment with CHOP combination chemotherapy. Am J Clin Oncol 1984; 7(1): 75–80.

59. Klener P (ed). Biomodulační léčba (imunoterapie). In: Klener P, Abrahámová J, Fait V et al. Klinická onkologie. Galén: Praha 2002: 223–230. ISBN 8072621513.

60. Shapiro RS, Chauvenet A, McGuire W et al. Treatment of B-cell lymphoproliferative disorders with interferon alfa and intravenous gamma globulin. N Engl J Med 1988; 318(20): 1334.

61. Dunleavy K, Chattopadhyay P, Kawada J et al. Immune characteristics associated with lymphomatoid granulomatosis and outcome following treatment with interferon-alpha. Blood 2010; 116(424): Abstrakt 963.

62. Johnston A, Coyle L, Nevell D. Prolonged remission of refractory lymphomatoid granulomatosis after autologous hemopoietic stem cell transplantation with post-transplantation maintenance interferon. Leuk Lymphoma 2006; 47: 323–328.

63. Shanti RM, Torres-Cabala CA, Jaffe ES et al. Lymphomatoid granulomatosis with involvement of the hard palate: a case report. J Oral Maxillofac Surg 2008; 66(10): 2161–2163.

64. Oosting-Lenstra SF, van Marwijk KM. Failure of CHOP with rituximab for lymphomatoid granulomatosis. Neth J Med 2007; 65(11): 442–447.

65. Boye J, Elter T, Engert A. An overview of the current clinical use of the anti CD-20 monoclonal antibody rituximab. Ann Oncol 2003; 14(4): 520–535.

66. Mohyuddin GR, Sultan F, Khaleeq G. A rare presentation of a rare disease: pulmonary lymphomatoid granulomatosis. Case Rep Pulmonol 2012; 2012:371490. Dostupné z DOI: <http://doi: 10.1155/2012/371490>.

67. Castrale C, El Haggan W, Chapon F et al. Lymphomatoid granulomatosis treated successfully with rituximab in a renal transplant patient. J Transplant 2011; 2011:865957. Dostupné z DOI: <http://doi: 10.1155/2011/865957>.

68. Polizzotto MN, Dawson MA, Opat SS. Failure of rituximab monotherapy in lymphomatoid granulomatosis. Eur J Haematol 2005; 75(2): 172–173.

69. Ishiura H, Morikawa M, Hamada M et al. Lymphomatoid Granulomatosis Involving Central Nervous System Successfully treated With Rituximab alone. Arch Neurol 2008; 65(5): 662–665.

70. Nair BD, Joseph MG, Catton GE et al. Radiation therapy in lymphomatoid granulomatosis. Cancer 1989; 64(4): 821–824.

71. Petrella TM, Walker IR, Jones GW et al. Radiotherapy to control CNS lymphomatoid granulomatosis: a case report and review of literature. Am J Hematol 1999; 62(4): 239–241.

72. Lemieux J, Bernier V, Martel N et al. Autologous hematopoietic stem cell transplantation for refractory lymphomatoid granulomatosis. Hematology 2002; 7(6): 355–358.

73. Friedrichs B, Thiel E. Relapsed pulmonary lymphomatoid granulomatosis grade III: curative treatment with radioimmune therapy and stem cell transplantation. Dtsch Med Wochenschr 2010; 35(38): 1857–1860.

74. Bernstein ML, Reece ER, de Chadarévian JP et al. Bone marrow transplantation in lymphomatoid granulomatosis. Report of a case. Cancer 1986; 58(4): 969–972.

75. Fassas A, Jagannath S, Desikan KR et al. Lymphomatoid granulomatosis following autologous stem cell transplantation. Bone Marrow Transplant 1999; 23(1): 79–81.

76. Wilson WH, Grossbard ML, Pittaluga S et al. Dose-adjusted EPOCH chemotherapy for untreated large B-cell lymphomas: a pharmacodynamic approach with high efficacy. Blood 2002; 99(8): 2685–2693.

77. Macsween KF, Crawford DH. Epstein-Barr virus-recent advances. The Lancet Infectious Diseases 2003; 3(3): 131–140.

78. Bollard CM, Gottschalk S, Leen AM et al. Complete responses of relapsed lymphoma following genetic modification of tumor-antigen presenting cells and T-lymphocyte transfer. Blood 2007; 110(8): 2838–2845.

Labels
Diabetology Endocrinology Internal medicine

Article was published in

Internal Medicine

Issue 3

2014 Issue 3

Most read in this issue
Topics Journals
Login
Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.

Login

Don‘t have an account?  Create new account

#ADS_BOTTOM_SCRIPTS#