immunological/genetic characteristics

Primary Mediastinal (Thymic) Large B-Cell Lymphoma

REVIEWS , , , , , ,

GS Tumyan, IZ Zavodnova, MYu Kichigina, EG Medvedovskaya

NN Blokhin Russian Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478

For correspondence: Gayane Sergeevna Tumyan, DSci, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; Tel: +7(499)324-98-29; e-mail: gaytum@mail.ru

For citation: Tumyan GS, Zavodnova IZ, Kichigina MYu, Medvedovskaya EG. Primary Mediastinal (Thymic) Large B-Cell Lymphoma. Clinical oncohematology. 2017;10(1):13–24 (In Russ).

DOI: 10.21320/2500-2139-2017-10-1-13-24

ABSTRACT

Primary mediastinal (thymic) large B-cell lymphoma (PMBCL) is one of the primary extranodal tumors and originates from thymic medulla B cells. The disease is more common in young women and declares itself by mainly locally advanced growth within the anterior upper mediastinum with frequent involvement of chest organs. PMBCL has specific morphological, immunological, and genetic characteristics that permit to differentiate it from other similar diseases: diffuse large В-cell lymphoma, nodular sclerosis Hodgkin’s lymphoma, and mediastinal gray zone lymphoma. Immunochemotherapy with subsequent irradiation of the residual mediastinal tumor is the standard treatment of PMBCL. No benefits of one drug therapy over another have been demonstrated to date in controlled studies. Application of new imaging techniques (PET/CT) may result in withdrawal of the radiotherapy in some PMBCL patients without impairment of delayed survival rates.

Keywords: primary mediastinal (thymic) large B-cell lymphoma, primary extranodal lymphomas, diagnosis, pathogenesis, morphological, immunological/genetic characteristics, treatment.

Received: August 22, 2016

Accepted: December 17, 2016

Read in PDF (RUS)pdficon

REFERENCES

  1. Benjamin SP, McCormack LJ, Effler DB, et al. Primary lymphatic tumors of the mediastinum. Cancer. 1972;30(3):708–12. doi: 10.1002/1097-0142(197209)30:3<708::AID-CNCR2820300318>3.0.CO;2–5.
  2. Lichtenstein AK, Levine A, Taylor CR, et al. Primary mediastinal lymphoma in adults. Am J Med. 1980;68(4):509–14. doi: 10.1016/0002-343(80)90294-6.
  3. National Cancer Institute sponsored study of classifications of non-Hodgkin’s lymphomas: summary and description of a working formulation for clinical usage. The Non-Hodgkin’s Lymphoma Pathologic Classification Project. Cancer. 1982;49(10):2112–35. doi: 10.1002/1097-0142(19820515)49:10<2112::AID-CNCR2820491024>3.0.CO;2–2.
  4. Stansfeld AG, Diebold J, Noel H, et al. Updated Kiel classification for lymphomas. Lancet. 1988;1(8580):292–3. doi: 10.1016/S0140-6736(88)90367-4.
  5. Harris NL, Jaffe ES, Stein H, et al. A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. Blood. 1994;84(5):1361–92. doi: 10.1016/S0968-6053(00)80051-4.
  6. Swerdlow SH, Campo E, Harris NL, et al, eds. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th edition. Lyon: IARC Press; 2008. doi: 10.1002/9781118853771.ch51.
  7. Cazals-Hatem D, Lepage E, Brice P, et al. Primary mediastinal large B-cell lymphoma. A clinicopathologic study of 141 cases compared with 916 nonmediastinal large B-cell lymphomas, a GELA (“Groupe d’Etude des Lymphomes de l’Adulte”) study. Am J Surg Pathol. 1996;20(7):877–88. doi: 10.1097/00000478-199607000-00012.
  8. Harris NL. Shades of gray between large B-cell lymphomas and Hodgkin lymphomas: differential diagnosis and biological implications. Mod Pathol. 2013;26(Suppl 1):S57–70. doi: 10.1038/modpathol.2012.182.
  9. Kanavaros P, Gaulard P, Charlotte F, et al. Discordant expression of immunoglobulin and its associated molecule mb-1/CD79a is frequently found in mediastinal large B cell lymphomas. Am J Pathol. 1995;146(3):735–41.
  10. Pileri SA, Zinzani PL, Gaidano G, et al. Pathobiology of primary mediastinal B-cell lymphoma. Leuk Lymphoma. 2003;44(Suppl 3):S21–6. doi: 10.1080/10428190310001623810.
  11. Loddenkemper C, Anagnostopoulos I, Hummel M, et al. Differential Emu enhancer activity and expression of BOB.1/OBF.1, Oct2, PU.1, and immunoglobulin in reactive B-cell populations, B-cell non-Hodgkin lymphomas, and Hodgkin lymphomas. J Pathol. 2004;202(1):60–9. doi: 10.1002/path.1485.
  12. De Leval L, Ferry JA, Falini B, et al. Expression of bcl-6 and CD10 in primary Mediastinal large B-cell lymphoma: evidence for derivation from germinal center B cells? Am J Surg Pathol. 2001;25(10):1277–82. doi: 10.1097/00000478-200110000-00008.
  13. Rosenwald A, Wright G, Leroy K, et al. Molecular diagnosis of primary mediastinal B cell lymphoma identifies a clinically favorable subgroup of diffuse large B cell lymphoma related to Hodgkin lymphoma. J Exp Med 2003;198(6):851–62. doi: 10.1084/jem.20031074.
  14. CopieBergman C, Plonquet A, Alonso MA, et al. MAL expression in lymphoid cells: further evidence for MAL as a distinct molecular marker of primary mediastinal large B-cell lymphomas. Mod Pathol. 2002;15:1172–80. doi: 10.1097/01.MP.0000032534.81894.B3.
  15. Joos S, Otano-Joos MI, Ziegler S, et al. Primary mediastinal (thymic) B-cell lymphoma is characterized by gains of chromosomal material including 9p and amplification of the REL gene. Blood. 1996;87(4):1571–8.
  16. Feuerhake F, Kutok JL, Monti S, et al. NFkappaB activity, function, and target-gene signatures in primary mediastinal large B-cell lymphoma and diffuse large B-cell lymphoma subtypes. Blood. 2005;106(4):1392–9. doi: 10.1182/blood-2004-12-4901.
  17. Zhang B, Wang Z, Li T, et al. NF-kappaB2 mutation targets TRAF1 to induce lymphomagenesis. Blood. 2007;110(2):743–51. doi: 10.1182/blood-2006-11-058446.
  18. Meier C, Hoeller S, Bourgau C, et al. Recurrent numerical aberrations of JAK2 and deregulation of the JAK2-STAT cascade in lymphomas. Mod Pathol. 2009;22(3):476–87. doi: 10.1038/modpathol.2008.207.
  19. Rossi D, Cerri M, Capello D, et al. Aberrant somatic hypermutation in primary mediastinal large B-cell lymphoma. Leukemia. 2005;19(12):2363–6. doi: 10.1038/sj.leu.2403982.
  20. Steidl C, Gascoyne RD. The molecular pathogenesis of primary mediastial large B-cell lymphoma. Blood. 2011;118(10):2659–69. doi: 10.1182/blood-2011-05-326538.
  21. Martelli M, Di Rocco A, Russo E, et al. Primary mediastinal lymphoma: diagnosis and treatment options. Expert Rev Hematol. 2014;8(2):173–86. doi: 10.1586/17474086.2015.994604.
  22. Eberle FC, Salaverria I, Steidl C, et al. Gray zone lymphoma: chromosomal aberrations with immunophenotypic and clinical correlations. Mod Pathol. 2011;24(12):1586–97. doi: 10.1038/modpathol.2011.116.
  23. Eberle FC, Rodriguez-Canales J, Wei L, et al. Methylation profiling of mediastinal gray zone lymphoma reveals a distinctive signature with elements shared by classical Hodgkin’s lymphoma and primary mediastinal large B-cell lymphoma. Haematologica. 2011;96(4):558–66. doi: 10.3324/haematol.2010.033167.
  24. Moller P, Lammler B, Herrmann B, et al. The primary mediastinal clear cell lymphoma of B-cell type has variable defects in MHC antigen expression. Immunology. 1986;59(3):411–7. doi: 10.1007/bf00705408.
  25. Hamlin PA, Portlock CS, Straus DJ, et al. Primary mediastinal large B-cell lymphoma: optimal therapy and prognostic factor analysis in 141 consecutive patients treated at Memorial Sloan Kettering from 1980 to 1999. Br J Haematol. 2005;130(5):691–9. doi: 10.1111/j.1365-2141.2005.05661.x.
  26. Jacobson JO, Aisenberg AC, Lamarre L, et al. Mediastinal large cell lymphoma. An uncommon subset of adult lymphoma curable with combined modality therapy. Cancer. 1988;62(9):1893–8. doi: 10.1002/1097-0142(19881101)62:9<1893::AID-CNCR2820620904>3.0.CO;2-X.
  27. Zinzani PL, Martelli M, Magagnoli M, et al. Treatment and clinical management of primary mediastinal large B-cell lymphoma with sclerosis: MACOP-B regimen and mediastinal radiotherapy monitored by (67)Gallium scan in 50 patients. Blood. 1999;94(10):3289–93.
  28. Bishop PC, Wilson WH, Pearson D, et al. CNS involvement in primary mediastinal large B-cell lymphoma. J Clin Oncol. 1999;17(8):2479–85.
  29. Savage K, Al-Rajhi N, Voss N, et al. Favorable outcome of primary mediastinal large B-cell lymphoma in a single institution: the British Columbia experience. Ann Oncol. 2006;17:123–30. doi: 10.1016/s0360-3016(00)80463-0.
  30. Zinzani PL, Martelli M, Bertini M, et al. Induction chemotherapy strategies for primary mediastinal large B-cell lymphoma with sclerosis: a retrospective multinational study on 426 previously untreated patients. Haematologica. 2002;87(12):1258–6. doi: 10.3816/clm.2009.n.074.
  31. Fisher RI, Gaynor ER, Dahlberg S, et al. Comparison of a standard regimen (CHOP) with three intensive chemotherapy regimens for advanced non-Hodgkin’s lymphoma. N Engl J Med. 1993;328(14):1002–6. doi: 10.1056/NEJM199304083281404.
  32. Levitt LJ, Aisenberg AC, Harris NL, et al. Primary non-Hodgkin’s lymphoma of the mediastinum. Cancer. 1982;50(11):2486–92. doi: 10.1002/1097-0142(19821201)50:11<2486::AID-CNCR2820501138>3.0.CO;2-G.
  33. Todeschini G, Ambrosetti A, Meneghini V, et al. Mediastinal large-B-cell lymphoma with sclerosis: a clinical study of 21 patients. J Clin Oncol. 1990;8(5):804–8.
  34. Bertini M, Orsucci L, Vitolo U, et al. Stage II large B-cell lymphoma with sclerosis treated with MACOP-B. Ann Oncol. 1991;2(10):733–7.
  35. Falini B, Venturi S, Martelli M, et al. Mediastinal large B-cell lymphoma: clinical and immunohistological findings in 18 patients treated with different third-generation regimens. Br J Haematol. 1995;89(4):780–9. doi: 10.1111/j.1365-2141.1995.tb08415.x.
  36. van Besien K, Kelta M, Bahaguna P. Primary mediastinal B-cell lymphoma: a review of pathology and management. J Clin Oncol. 2001;19(6):1855–64.
  37. Zinzani PL, Martelli M, Bendandi M, et al. Primary mediastinal large B-cell lymphoma with sclerosis: a clinical study of 89 patients treated with MACOP-B chemotherapy and radiation therapy. Haematologica. 2001;86(2):187–91.
  38. Zinzani PL, Stefoni V, Finolezzi E, et al. Rituximab combined with MACOP-B or VACOP-B and radiation therapy in primary mediastinal large B-cell lymphoma: a retrospective study. Clin Lymph Myel. 2009;9(5):381–5. doi: 10.3816/CLM.2009.n.074.
  39. Dunleavy K, Pittaluga S, Maeda LS, et al. Dose-adjusted EPOCH-rituximab therapy in primary mediastinal B-cell lymphoma. N Engl J Med. 2013;368(15):1408–16. doi: 10.1056/NEJMoa1214561.
  40. Moskowitz CH, Schoder H, Teruya-Feldstein J, et al. Risk-adapted dose-dense immunochemotherapy determined by interim FDG-PET in Advanced-stage diffuse large B-Cell lymphoma. J Clin Oncol. 2010;28(11):1896–903. doi: 10.1200/JCO.2009.26.5942.
  41. Savage KJ, Yenson PR, Shenkier T, et al. The outcome of primary mediastinal large B-cell lymphoma (PMBCL) in the R-CHOP treatment era. Blood. 2012;120(Suppl 1–2): Abstract 303.
  42. Martelli M, Ceriani L, Zucca E, et al. [18F]fluorodeoxyglucose positron emission tomography predicts survival after chemoimmunotherapy for primary mediastinal large B-cell lymphoma: results of the International Extranodal Lymphoma Study Group IELSG-26 Study. J Clin Oncol. 2014;32(17):1769–75. doi: 10.1200/JCO.2013.51.7524.
  43. Pinnix CC, Dabaja B, Ahmed MAet al. Single-institution experience in the treatment of primary mediastinal B cell lymphoma treated with immunochemotherapy in the setting of response assessment by 18fluorodeoxyglucose positron emission tomography. Int J Radiat Oncol Biol Phys. 2015;92(1):113–21. doi: 10.1016/j.ijrobp.2015.02.006.
  44. Sehn LH, Antin JH, Shulman LN, et al. Primary diffuse large B-cell lymphoma of the mediastinum: outcome following high-dose chemotherapy and autologous hematopoietic cell transplantation. Blood. 1998;91(2):717–23.
  45. Kuruvilla J, Pintilie M, Tsang R, et al. Salvage chemotherapy and autologous stem cell transplantation are inferior for relapsed or refractory primary mediastinal large B-cell lymphoma compared with diffuse large B-cell lymphoma. Leuk Lymphoma. 2008;49(7):1329–36. doi: 10.1080/10428190802108870.
  46. Hao Y, Chapuy B, Monti S, Sun HH. Selective JAK2 inhibition specifically decreases Hodgkin lymphoma and mediastinal large B-cell lymphoma growth in vitro and in vivo. Clin Cancer Res. 2014;20(10):2674–83. doi: 10.1158/1078-0432.CCR-13-3007.
  47. Dunleavy K, Wilson W. Primary mediastinal B-cell lymphoma and mediastinal gray zone lymphoma: do they require a unique therapeutic approach? Blood. 2015;125(1):33–9. doi: 10.1182/blood-2014-05-575092.
  48. Berger R, Rotem-Yehudar R, Slama G, et al. Phase I safety and pharmacokinetic study of CT-011, a humanized antibody interacting with PD-1, in patients with advanced hematologic malignancies. Clin Cancer Res. 2008;14(10):3044–51. doi: 10.1158/1078-0432.CCR-07-4079.