Mediastinal Lymphoma

  • Miguel A. Piris
  • Jorge Muñoz
  • Socorro M. Rodríguez-Pinilla
Part of the Current Clinical Pathology book series (CCPATH)


There is a group of Hodgkin and non-Hodgkin lymphoma that can initially manifest themselves as a primary mediastinal disease. These include nodular sclerosis Hodgkin lymphoma (NSHL); primary mediastinal large B-cell lymphoma (PMLBCL); B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classic Hodgkin lymphoma; thymic marginal zone B-cell lymphoma (MZL); and T-lymphoblastic lymphoma (T-LL).

Here we review the main aspects of these different conditions.


Mediastinal lymphoma Nodular sclerosis Hodgkin lymphoma Gray-zone mediastinal lymphoma Lymphoblastic T-cell lymphoma 



This work was supported by grants from the Instituto de Salud Carlos III (ISCIII) of the Spanish Ministry of Economy and Competence (MINECO, RTICC ISCIII, and CIBERONC) (SAF2013-47416-R, RD06/0020/0107-RD012/0036/0060, and Plan Nacional I + D + I: PI16/01294 and PIE15/0081) and the Asociación Española Contra el Cáncer (AECC).


  1. 1.
    Inagaki H, Chan JK, Ng JW, Okabe M, Yoshino T, Okamoto M, et al. Primary thymic extranodal marginal-zone B-cell lymphoma of mucosa-associated lymphoid tissue type exhibits distinctive clinicopathological and molecular features. Am J Pathol. 2002;160(4):1435–43.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Balakrishna JP, Jaffe ES. Crystal-storing histiocytosis associated with thymic extranodal marginal zone lymphoma. Blood. 2017;130(14):1683.PubMedGoogle Scholar
  3. 3.
    Go H, Cho HJ, Paik JH, Park CM, Oh YH, Jung KC, et al. Thymic extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue: a clinicopathological and genetic analysis of six cases. Leuk Lymphoma. 2011;52(12):2276–83.CrossRefPubMedGoogle Scholar
  4. 4.
    Kominato S, Nakayama T, Sato F, Yamada S, Xia H, Fujiyoshi Y, et al. Characterization of chromosomal aberrations in thymic MALT lymphoma. Pathol Int. 2012;62(2):93–8.CrossRefPubMedGoogle Scholar
  5. 5.
    Takino H, Li C, Yamada S, Sato F, Masaki A, Fujiyoshi Y, et al. Thymic extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue: a gene methylation study. Leuk Lymphoma. 2013;54(8):1742–6.CrossRefPubMedGoogle Scholar
  6. 6.
    Eberle FC, Mani H, Jaffe ES. Histopathology of Hodgkin’s lymphoma. Cancer J. 2009;15(2):129–37.CrossRefPubMedGoogle Scholar
  7. 7.
    Colby TV, Hoppe RT, Warnke RA. Hodgkin’s disease: a clinicopathologic study of 659 cases. Cancer. 1982;49(9):1848–58.CrossRefPubMedGoogle Scholar
  8. 8.
    Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127(20):2375–90.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Strickler JG, Michie SA, Warnke RA, Dorfman RF. The “syncytial variant” of nodular sclerosing Hodgkin’s disease. Am J Surg Pathol. 1986;10(7):470–7.CrossRefPubMedGoogle Scholar
  10. 10.
    Masih AS, Weisenburger DD, Vose JM, Bast MA, Armitage JO. Histologic grade does not predict prognosis in optimally treated, advanced-stage nodular sclerosing Hodgkin’s disease. Cancer. 1992;69(1):228–32.CrossRefPubMedGoogle Scholar
  11. 11.
    Dorfman DM, Shahsafaei A, Alonso MA. Utility of CD200 immunostaining in the diagnosis of primary mediastinal large B cell lymphoma: comparison with MAL, CD23, and other markers. Mod Pathol. 2012;25(12):1637–43.CrossRefPubMedGoogle Scholar
  12. 12.
    Wang Z, Cook JR. PDCD1LG2 (PD-L2) RNA in situ hybridization is a sensitive, specific, and practical marker of primary mediastinal large B-cell lymphoma. Br J Haematol. 2017.Google Scholar
  13. 13.
    Ritz O, Guiter C, Castellano F, Dorsch K, Melzner J, Jais JP, et al. Recurrent mutations of the STAT6 DNA binding domain in primary mediastinal B-cell lymphoma. Blood. 2009;114(6):1236–42.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Guiter C, Dusanter-Fourt I, Copie-Bergman C, Boulland ML, Le Gouvello S, Gaulard P, et al. Constitutive STAT6 activation in primary mediastinal large B-cell lymphoma. Blood. 2004;104(2):543–9.CrossRefPubMedGoogle Scholar
  15. 15.
    Mestre C, Rubio-Moscardo F, Rosenwald A, Climent J, Dyer MJ, Staudt L, et al. Homozygous deletion of SOCS1 in primary mediastinal B-cell lymphoma detected by CGH to BAC microarrays. Leukemia. 2005;19(6):1082–4.CrossRefPubMedGoogle Scholar
  16. 16.
    Mottok A, Woolcock B, Chan FC, Tong KM, Chong L, Farinha P, et al. Genomic alterations in CIITA are frequent in primary mediastinal large B cell lymphoma and are associated with diminished MHC class II expression. Cell Rep. 2015;13(7):1418–31.CrossRefPubMedGoogle Scholar
  17. 17.
    Yuan J, Wright G, Rosenwald A, Steidl C, Gascoyne RD, Connors JM, et al. Identification of primary mediastinal large B-cell lymphoma at nonmediastinal sites by gene expression profiling. Am J Surg Pathol. 2015;39(10):1322–30.CrossRefPubMedGoogle Scholar
  18. 18.
    Pelland K, Mathews S, Kamath A, Cohen P, Hudnall SD, Cotta CV, et al. Dendritic cell markers and PD-L1 are expressed in mediastinal gray zone lymphoma. Appl Immunohistochem Mol Morphol. 2017.Google Scholar
  19. 19.
    Garcia JF, Mollejo M, Fraga M, Forteza J, Muniesa JA, Perez-Guillermo M, et al. Large B-cell lymphoma with Hodgkin’s features. Histopathology. 2005;47(1):101–10.CrossRefPubMedGoogle Scholar
  20. 20.
    Traverse-Glehen A, Pittaluga S, Gaulard P, Sorbara L, Alonso MA, Raffeld M, et al. Mediastinal gray zone lymphoma: the missing link between classic Hodgkin’s lymphoma and mediastinal large B-cell lymphoma. Am J Surg Pathol. 2005;29(11):1411–21.CrossRefPubMedGoogle Scholar
  21. 21.
    Song HN, Kim SJ, Ko YH, Kim WS. Mediastinal gray zone lymphoma with features intermediate between classical Hodgkin lymphoma and primary mediastinal B-cell lymphoma. Acta Haematol. 2016;136(3):186–90.CrossRefPubMedGoogle Scholar
  22. 22.
    Sarkozy C, Molina T, Ghesquieres H, Michallet AS, Dupuis J, Damotte D, et al. Mediastinal gray zone lymphoma: clinico-pathological characteristics and outcomes of 99 patients from the Lymphoma Study Association. Haematologica. 2017;102(1):150–9.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    O’Malley DP, Fedoriw Y, Weiss LM. Distinguishing classical Hodgkin lymphoma, gray zone lymphoma, and large B-cell lymphoma: a proposed scoring system. Appl Immunohistochem Mol Morphol. 2016;24(8):535–40.CrossRefPubMedGoogle Scholar
  24. 24.
    Chihara D, Westin JR, Miranda RN, Cheah CY, Oki Y, Turturro F, et al. Dose adjusted-EPOCH-R and mediastinal disease may improve outcomes for patients with gray-zone lymphoma. Br J Haematol. 2017;179(3):503–6.CrossRefPubMedGoogle Scholar
  25. 25.
    Wilson WH, Pittaluga S, Nicolae A, Camphausen K, Shovlin M, Steinberg SM, et al. A prospective study of mediastinal gray-zone lymphoma. Blood. 2014;124(10):1563–9.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Melani C, Major A, Schowinsky J, Roschewski M, Pittaluga S, Jaffe ES, et al. PD-1 blockade in mediastinal gray-zone lymphoma. N Engl J Med. 2017;377(1):89–91.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Vitale A, Guarini A, Ariola C, Mancini M, Mecucci C, Cuneo A, et al. Adult T-cell acute lymphoblastic leukemia: biologic profile at presentation and correlation with response to induction treatment in patients enrolled in the GIMEMA LAL 0496 protocol. Blood. 2006;107(2):473–9.CrossRefPubMedGoogle Scholar
  28. 28.
    Marks DI, Paietta EM, Moorman AV, Richards SM, Buck G, DeWald G, et al. T-cell acute lymphoblastic leukemia in adults: clinical features, immunophenotype, cytogenetics, and outcome from the large randomized prospective trial (UKALL XII/ECOG 2993). Blood. 2009;114(25):5136–45.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Stein H, Petersen N, Gaedicke G, Lennert K, Landbeck G. Lymphoblastic lymphoma of convoluted or acid phosphatase type-a tumor of T precursor cells. Int J Cancer. 1976;17(3):292–5.CrossRefPubMedGoogle Scholar
  30. 30.
    Weng AP, Ferrando AA, Lee W, Morris JP IV, Silverman LB, Sanchez-Irizarry C, et al. Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia. Science. 2004;306(5694):269–71.CrossRefPubMedGoogle Scholar
  31. 31.
    Ohgami RS, Arber DA, Zehnder JL, Natkunam Y, Warnke RA. Indolent T-lymphoblastic proliferation (iT-LBP): a review of clinical and pathologic features and distinction from malignant T-lymphoblastic lymphoma. Adv Anat Pathol. 2013;20(3):137–40.CrossRefPubMedGoogle Scholar
  32. 32.
    Eberle FC, Salaverria I, Steidl C, Summers TA Jr, Pittaluga S, Neriah SB, et al. Gray zone lymphoma: chromosomal aberrations with immunophenotypic and clinical correlations. Mod Pathol. 2011;24(12):1586–97.CrossRefPubMedGoogle Scholar
  33. 33.
    Steidl C, Shah SP, Woolcock BW, Rui L, Kawahara M, Farinha P, et al. MHC class II transactivator CIITA is a recurrent gene fusion partner in lymphoid cancers. Nature. 2011;471(7338):377–81.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Miguel A. Piris
    • 1
  • Jorge Muñoz
    • 1
  • Socorro M. Rodríguez-Pinilla
    • 1
  1. 1.Pathology Service, Fundación Jiménez Díaz, CIBERONCMadridSpain

Personalised recommendations