Advertisement

Der Pathologe

, Volume 40, Issue 2, pp 157–168 | Cite as

Revidierte Fassung der 4. Ausgabe der WHO-Klassifikation maligner Lymphome

Was ist neu?
  • G. OttEmail author
  • W. Klapper
  • A. C. Feller
  • M. L. Hansmann
  • P. Möller
  • H. Stein
  • A. Rosenwald
  • F. Fend
Übersichten
  • 471 Downloads

Zusammenfassung

Nach 8 Jahren liegt nun eine Neufassung der 4. Ausgabe der WHO-Klassifikation lymphatischer Neoplasien vor. Sie beinhaltet sowohl eine konzeptionelle Neufassung bestehender Entitäten wie auch – wenige – provisorische neue Entitäten bzw. Kategorien, vor allem unter den aggressiven B‑Zell-Lymphomen. Hier sind vor allem das High-grade-B-Zell-Lymphom, das großzellige B‑Zell-Lymphom mit IRF4-Translokation und das Burkitt-ähnliche Lymphom mit Aberrationen in 11q zu nennen. Von besonderer Bedeutung sind auch neuere Konzepte zur Taxonomie und Klassifikation früher lymphatischer Läsionen bzw. möglicher Vorstufen, wie die in-situ follikuläre Neoplasie und die in-situ Mantelzellneoplasie, die Beschreibung indolenter Lymphoproliferationen wie das Brustimplantat-assoziierte anaplastische großzellige Lymphom und die indolente T‑Zell-Lymphoproliferation des Gastrointestinaltrakts sowie generell die Schärfung diagnostischer Kriterien bestehender Entitäten.

Schlüsselwörter

Maligne Lymphome Klassifikation Biologie WHO Revidierte 4. Auflage 

Revised version of the 4th edition of the WHO classification of malignant lymphomas

What is new?

Abstract

After 8 years, the WHO has now published the updated version of the 4th edition of the classification of hematopoietic and lymphoid tumors. This update provides a conceptual rewrite of existing entities as well as some new provisional entities and categories, particularly among the aggressive B‑cell lymphomas. Important new diagnostic categories include the high-grade B‑cell lymphomas, the large B‑cell lymphoma with IRF4 rearrangement, and the Burkitt-like lymphoma with 11q aberrations. Of particular importance, new concepts concerning the taxonomy and classification of early lymphoid lesions or precursor lesions are included, such as the in situ follicular neoplasia or the in situ mantle cell neoplasia. In addition, the concept of indolent lymphoproliferations, such as breast-implant-associated anaplastic large cell lymphoma and the indolent T‑cell lymphoproliferative disorder of the gastrointestinal tract, has been strengthened. Finally, diagnostic criteria for existing lymphoma entities have been refined.

Keywords

Lymphoma Classification Biology WHO Revised 4th edition 

Notes

Einhaltung ethischer Richtlinien

Interessenkonflikt

G. Ott, W. Klapper, A. C. Feller, M. L. Hansmann, P. Möller, H. Stein, A. Rosenwald und F. Fend geben an, dass kein Interessenkonflikt besteht.

Dieser Beitrag beinhaltet keine von den Autoren durchgeführten Studien an Menschen oder Tieren.

Literatur

  1. 1.
    Adam P, Katzenberger T, Eifert M et al (2005) Presence of preserved reactive germinal centers in follicular lymphoma is a strong histopathologic indicator of limited disease stage. Am J Surg Pathol 29(12):1661–1664PubMedGoogle Scholar
  2. 2.
    Bacon CM, Ye H, Diss TC et al (2007) Primary follicular lymphoma of the testis and epididymis in adults. Am J Surg Pathol 31(7):1050–1058PubMedGoogle Scholar
  3. 3.
    Bodor C, Grossmann V, Popov N et al (2013) EZH2 mutations are frequent and represent an early event in follicular lymphoma. Blood 122(18):3165–3168PubMedPubMedCentralGoogle Scholar
  4. 4.
    Bruscaggin A, Monti S, Arcaini L et al (2014) Molecular lesions of signalling pathway genes in clonal B‑cell lymphocytosis with marginal zone features. Br J Haematol 167(5):718–720PubMedGoogle Scholar
  5. 5.
    Cairns RA, Iqbal J, Lemonnier F et al (2012) IDH2 mutations are frequent in angioimmunoblastic T‑cell lymphoma. Blood 119(8):1901–1903PubMedPubMedCentralGoogle Scholar
  6. 6.
    Carvajal-Cuenca A, Sua LF, Silva NM et al (2012) In situ mantle cell lymphoma. Haematologica 97(2):270–278PubMedPubMedCentralGoogle Scholar
  7. 7.
    Clemens MW, Medeiros LJ, Butler CE et al (2016) Complete surgical excision is essential for the management of patients with breast implant-associated anaplastic large-cell lymphoma. J Clin Oncol 34(2):160–168PubMedGoogle Scholar
  8. 8.
    Fan Z, Natkunam Y, Bair E et al (2003) Characterization of variant patterns of nodular lymphocyte predominant hodgkin lymphoma with immunohistologic and clinical correlation. Am J Surg Pathol 27(10):1346–1356PubMedGoogle Scholar
  9. 9.
    Feldman AL, Dogan A, Smith DI et al (2011) Discovery of recurrent t(6;7)(p25.3;q32.3) translocations in ALK-negative anaplastic large cell lymphomas by massively parallel genomic sequencing. Blood 117(3):915–919PubMedPubMedCentralGoogle Scholar
  10. 10.
    Gibson SE, Swerdlow SH, Ferry JA et al (2011) Reassessment of small lymphocytic lymphoma in the era of monoclonal B‑cell lymphocytosis. Haematologica 96(8):1144–1152PubMedPubMedCentralGoogle Scholar
  11. 11.
    Gine E, Martinez A, Villamor N et al (2010) Expanded and highly active proliferation centers identify a histological subtype of chronic lymphocytic leukemia (“accelerated” chronic lymphocytic leukemia) with aggressive clinical behavior. Haematologica 95(9):1526–1533PubMedPubMedCentralGoogle Scholar
  12. 12.
    Green TM, Nielsen O, de Stricker K et al (2012) High levels of nuclear MYC protein predict the presence of MYC rearrangement in diffuse large B‑cell lymphoma. Am J Surg Pathol 36(4):612–619PubMedGoogle Scholar
  13. 13.
    Hans CP, Weisenburger DD, Greiner TC et al (2004) Confirmation of the molecular classification of diffuse large B‑cell lymphoma by immunohistochemistry using a tissue microarray. Blood 103(1):275–282PubMedGoogle Scholar
  14. 14.
    Hartmann S, Doring C, Jakobus C et al (2013) Nodular lymphocyte predominant hodgkin lymphoma and T cell/histiocyte rich large B cell lymphoma – endpoints of a spectrum of one disease? PLoS ONE 8(11):e78812PubMedPubMedCentralGoogle Scholar
  15. 15.
    Hartmann S, Eichenauer DA, Plutschow A et al (2013) The prognostic impact of variant histology in nodular lymphocyte-predominant Hodgkin lymphoma. Blood 122(26):4246–4252PubMedGoogle Scholar
  16. 16.
    Hartmann S, Doring C, Vucic E et al (2015) Array comparative genomic hybridization reveals similarities between nodular lymphocyte predominant Hodgkin lymphoma and T cell/histiocyte rich large B cell lymphoma. Br J Haematol 169(3):415–422PubMedGoogle Scholar
  17. 17.
    Horn H, Ziepert M, Becher C et al (2013) MYC status in concert with BCL2 and BCL6 expression predicts outcome in diffuse large B‑cell lymphoma. Blood 121(12):2253–2263PubMedGoogle Scholar
  18. 18.
    Horn H, Ziepert M, Wartenberg M et al (2015) Different biological risk factors in young poor-prognosis and elderly patients with diffuse large B‑cell lymphoma. Leukemia 29(7):1564–1570PubMedGoogle Scholar
  19. 19.
    Iqbal J, Wright G, Wang C et al (2014) Gene expression signatures delineate biological and prognostic subgroups in peripheral T‑cell lymphoma. Blood 123(19):2915–2923PubMedPubMedCentralGoogle Scholar
  20. 20.
    Jegalian AG, Eberle FC, Pack SD et al (2011) Follicular lymphoma in situ. Blood 118(11):2976–2984PubMedPubMedCentralGoogle Scholar
  21. 21.
    Johnson NA, Slack GW, Savage KJ et al (2012) Concurrent expression of MYC and BCL2 in diffuse large B‑cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. J Clin Oncol 30(28):3452–3459PubMedPubMedCentralGoogle Scholar
  22. 22.
    Katzenberger T, Kalla J, Leich E et al (2009) A distinctive subtype of t(14;18)-negative nodal follicular non-Hodgkin lymphoma characterized by a predominantly diffuse growth pattern and deletions in the chromosomal region 1p36. Blood 113(5):1053–1061PubMedGoogle Scholar
  23. 23.
    Landgren O, Albitar M, Ma W et al (2009) B‑cell clones as early markers for chronic lymphocytic leukemia. N Engl J Med 360(7):659–667PubMedGoogle Scholar
  24. 24.
    Leich E, Salaverria I, Bea S et al (2009) Follicular lymphomas with and without translocation t(14;18) differ in gene expression profiles and genetic alterations. Blood 114(4):826–834PubMedPubMedCentralGoogle Scholar
  25. 25.
    Lemonnier F, Couronné L, Parrens M et al (2012) Recurrent TET2 mutations in peripheral T‑cell lymphomas correlate with TFH-like features and adverse clinical parameters. Blood 120(7):1466–1469PubMedGoogle Scholar
  26. 26.
    Louissaint AJ, Ackerman AM, as-Santagata D et al (2012) Pediatric-type nodal follicular lymphoma. Blood 120(12):2395–2404PubMedGoogle Scholar
  27. 27.
    Mamessier E, Broussais-Guillaumot F, Chetaille B et al (2014) Nature and importance of follicular lymphoma precursors. Haematologica 99(5):802–810PubMedPubMedCentralGoogle Scholar
  28. 28.
    Masque-Soler N, Szczepanowski M, Kohler CW et al (2013) Molecular classification of mature aggressive B‑cell lymphoma using digital multiplexed gene expression on formalin-fixed paraffin-embedded biopsy specimens. Blood 122(11):1985–1986PubMedGoogle Scholar
  29. 29.
    Miranda RN, Aladily TN, Prince HM et al (2014) Breast implant-associated anaplastic large-cell lymphoma. J Clin Oncol 32(2):114–120PubMedGoogle Scholar
  30. 30.
    Morabito F, Mosca L, Cutrona G et al (2013) Clinical monoclonal B lymphocytosis versus Rai 0 chronic lymphocytic leukemia. Clin Cancer Res 19(21):5890–5900PubMedGoogle Scholar
  31. 31.
    Nicolae A, Pittaluga S, Abdullah S et al (2015) EBV-positive large B‑cell lymphomas in young patients. Blood 126(7):863–872PubMedPubMedCentralGoogle Scholar
  32. 32.
    Pasqualucci L, Dalla-Favera R (2015) The genetic landscape of diffuse large B‑cell lymphoma. Semin Hematol 52(2):67–76PubMedPubMedCentralGoogle Scholar
  33. 33.
    Perry AM, Warnke RA, Hu Q et al (2013) Indolent T‑cell lymphoproliferative disease of the gastrointestinal tract. Blood 122(22):3599–3606PubMedPubMedCentralGoogle Scholar
  34. 34.
    Petrella T, Maubec E, Cornillet-Lefebvre P et al (2007) Indolent CD8-positive lymphoid proliferation of the ear. Am J Surg Pathol 31(12):1887–1892PubMedGoogle Scholar
  35. 35.
    Pillai RK, Surti U, Swerdlow SH (2013) Follicular lymphoma-like B cells of uncertain significance (in situ follicular lymphoma) may infrequently progress, but precedes follicular lymphoma, is associated with other overt lymphomas and mimics follicular lymphoma in flow cytometric studies. Haematologica 98(10):1571–1580PubMedPubMedCentralGoogle Scholar
  36. 36.
    Rawstron AC, Shanafelt T, Lanasa MC et al (2010) Different biology and clinical outcome according to the absolute numbers of clonal B‑cells in monoclonal B‑cell lymphocytosis (MBL). Cytometry B Clin Cytom 78(Suppl 1):S19–S23PubMedGoogle Scholar
  37. 37.
    Richter J, Schlesner M, Hoffmann S et al (2012) Recurrent mutation of the ID3 gene in Burkitt lymphoma identified by integrated genome, exome and transcriptome sequencing. Nat Genet 44(12):1316–1320PubMedGoogle Scholar
  38. 38.
    Rossi D, Khiabanian H, Spina V et al (2014) Clinical impact of small TP53 mutated subclones in chronic lymphocytic leukemia. Blood 123(14):2139–2147PubMedPubMedCentralGoogle Scholar
  39. 39.
    Royo C, Navarro A, Clot G et al (2012) Non-nodal type of mantle cell lymphoma is a specific biological and clinical subgroup of the disease. Leukemia 26(8):1895–1898PubMedPubMedCentralGoogle Scholar
  40. 40.
    Sakata-Yanagimoto M, Enami T, Yokoyama Y et al (2014) Disease-specific mutations in mature lymphoid neoplasms. Cancer Sci 105(6):623–629PubMedPubMedCentralGoogle Scholar
  41. 41.
    Salaverria I, Philipp C, Oschlies I et al (2011) Translocations activating IRF4 identify a subtype of germinal center-derived B‑cell lymphoma affecting predominantly children and young adults. Blood 118(1):139–147PubMedGoogle Scholar
  42. 42.
    Salaverria I, Royo C, Carvajal-Cuenca A et al (2013) CCND2 rearrangements are the most frequent genetic events in cyclin D1(-) mantle cell lymphoma. Blood 121(8):1394–1402PubMedPubMedCentralGoogle Scholar
  43. 43.
    Salaverria I, Martin-Guerrero I, Wagener R et al (2014) A recurrent 11q aberration pattern characterizes a subset of MYC-negative high-grade B‑cell lymphomas resembling Burkitt lymphoma. Blood 123(8):1187–1198PubMedPubMedCentralGoogle Scholar
  44. 44.
    Sander S, Calado DP, Srinivasan L et al (2012) Synergy between PI3K signaling and MYC in Burkitt lymphomagenesis. Cancer Cell 22(2):167–179PubMedPubMedCentralGoogle Scholar
  45. 45.
    Schmatz AI, Streubel B, Kretschmer-Chott E et al (2011) Primary follicular lymphoma of the duodenum is a distinct mucosal/submucosal variant of follicular lymphoma. J Clin Oncol 29(11):1445–1451PubMedGoogle Scholar
  46. 46.
    Schmidt J, Salaverria I, Haake A et al (2014) Increasing genomic and epigenomic complexity in the clonal evolution from in situ to manifest t(14;18)-positive follicular lymphoma. Leukemia 28(5):1103–1112PubMedGoogle Scholar
  47. 47.
    Schmidt J, Gong S, Marafioti T et al (2016) Genome-wide analysis of pediatric-type follicular lymphoma reveals low genetic complexity and recurrent alterations of TNFRSF14 gene. Blood 128(8):1101–1111PubMedPubMedCentralGoogle Scholar
  48. 48.
    Schmidt J, Ramis-Zaldivar JE, Nadeu F et al (2017) Mutations of MAP2K1 are frequent in pediatric-type follicular lymphoma and result in ERK pathway activation. Blood 130(3):323.  https://doi.org/10.1182/blood-2017-03-776278 PubMedPubMedCentralGoogle Scholar
  49. 49.
    Schmitz R, Young RM, Ceribelli M et al (2012) Burkitt lymphoma pathogenesis and therapeutic targets from structural and functional genomics. Nature 490(7418):116–120PubMedPubMedCentralGoogle Scholar
  50. 50.
    Scott DW, Wright GW, Williams PM et al (2014) Determining cell-of-origin subtypes of diffuse large B‑cell lymphoma using gene expression in formalin-fixed paraffin-embedded tissue. Blood 123(8):1214–1217PubMedPubMedCentralGoogle Scholar
  51. 51.
    Staiger AM, Ziepert M, Horn H et al (2017) Clinical impact of the cell-of-origin classification and the MYC/ BCL2 dual expresser status in diffuse large B‑cell lymphoma treated within prospective clinical trials of the German high-grade non-Hodgkin’s Lymphoma Study Group. J Clin Oncol 35(22):2515.  https://doi.org/10.1200/JCO.2016.70.3660 PubMedGoogle Scholar
  52. 52.
    Swerdlow SH, Campo E, Jaffe ES et al (Hrsg) (2008) WHO classification of tumours of haematopoetic and lymphoid tissues. IARC Press, LyonGoogle Scholar
  53. 53.
    Swerdlow SH, Campo E, Harris NL et al (Hrsg) (2017) WHO classification of tumours of haematopoietic and lymphoid tissues, 4. Aufl. International Agency for Research on Cancer, LyonGoogle Scholar
  54. 54.
    Tiacci E, Trifonov V, Schiavoni G et al (2011) BRAF mutations in hairy-cell leukemia. N Engl J Med 364(24):2305–2315PubMedPubMedCentralGoogle Scholar
  55. 55.
    Treon SP, Xu L, Yang G et al (2012) MYD88 L265P somatic mutation in Waldenstrom’s macroglobulinemia. N Engl J Med 367(9):826–833PubMedGoogle Scholar
  56. 56.
    Vardi A, Dagklis A, Scarfò L et al (2013) Immunogenetics shows that not all MBL are equal. Blood 121(22):4521–4528PubMedGoogle Scholar
  57. 57.
    Wang SA, Wang L, Hochberg EP et al (2005) Low histologic grade follicular lymphoma with high proliferation index. Am J Surg Pathol 29(11):1490–1496PubMedGoogle Scholar
  58. 58.
    Wang T, Feldman AL, Wada DA et al (2014) GATA-3 expression identifies a high-risk subset of PTCL, NOS with distinct molecular and clinical features. Blood 123(19):3007–3015PubMedPubMedCentralGoogle Scholar
  59. 59.
    Xerri L, Dirnhofer S, Quintanilla-Martinez L et al (2016) The heterogeneity of follicular lymphomas. Virchows Arch 468(2):127–139PubMedGoogle Scholar
  60. 60.
    Xochelli A, Kalpadakis C, Gardiner A et al (2014) Clonal B‑cell lymphocytosis exhibiting immunophenotypic features consistent with a marginal-zone origin. Blood 123(8):1199–1206PubMedGoogle Scholar

Copyright information

© Springer Medizin Verlag GmbH, ein Teil von Springer Nature 2018

Authors and Affiliations

  • G. Ott
    • 1
    Email author
  • W. Klapper
    • 2
  • A. C. Feller
    • 3
  • M. L. Hansmann
    • 4
  • P. Möller
    • 5
  • H. Stein
    • 6
  • A. Rosenwald
    • 7
  • F. Fend
    • 8
  1. 1.Abteilung für Klinische PathologieRobert-Bosch-Krankenhaus, und Dr. Margarete Fischer-Bosch-Institut für Klinische PharmakologieStuttgartDeutschland
  2. 2.Institut für Pathologie, Sektion HämatopathologieUniversitätsklinikum Schleswig-Holstein, Campus KielKielDeutschland
  3. 3.Hämatopathologie LübeckLübeckDeutschland
  4. 4.Senckenberg Institut für PathologieUniversitätsklinikum FrankfurtFrankfurtDeutschland
  5. 5.Institut für PathologieUniversitätsklinikum UlmUlmDeutschland
  6. 6.Pathodiagnostik BerlinBerlinDeutschland
  7. 7.Pathologisches Institut und Comprehensive Cancer Center MainfrankenUniversität WürzburgWürzburgDeutschland
  8. 8.Institut für Pathologie und NeuropathologieEberhard-Karls-UniversitätTübingenDeutschland

Personalised recommendations