Skip to main content
SpringerLink
Log in

Sind primär extranodale diffuse großzellige B-Zell-Lymphome organotypische Erkrankungen?

Extranodal diffuse large B-cell lymphoma – an organotypic disease?

  • Schwerpunkt: Lymphome als Organerkrankungen
  • Published:
Der Pathologe Aims and scope Submit manuscript

Zusammenfassung

Etwa 30–40% diffuser großzelliger B-Zell-Lymphome (DLBCL) entstehen primär extranodal. Am häufigsten treten sie im Gastrointestinaltrakt auf, überwiegend im Magen, häufiger aber auch in ZNS, Hoden, Lunge oder Haut. Morphologisch zeigen die Tumorzellen das gesamte Spektrum peripherer B-Blasten: Zentroblasten, Immunoblasten oder Plasmoblasten. Von primär nodalen (häufig systemischen) DLBCL sind sie morphologisch also kaum abzugrenzen. Neuere Daten deuten aber darauf hin, dass sich extranodale DLBCL insbesondere in ihren molekularen Charakteristika von nodalen Tumoren (und auch untereinander) unterscheiden und häufig organotypische Eigenschaften aufweisen. Diese betreffen zum einen eine besondere organotypische und/oder klinische Präsentation, wie sie typisch für die in der WHO-Klassifikation definierten Subtypen der DLBCL (primär mediastinales DLBCL, intravaskuläres DLBCL, primäres Ergusslymphom) ist. Zum anderen zeigen primär extranodale DLBCL in der Regel eine gegenüber nodalen Tumoren divergente genetische Konstitution mit besonderen entitätsspezifischen Aberrationen, die wiederum mit dem besonderen Entstehungsort der Tumoren assoziiert scheint, wie z. B. die häufige Deletion des HLA-Genlocus in DLBCL immunprivilegierter Lokalisationen wie ZNS oder Hoden. Schließlich sprechen z. T. sicherlich noch präliminäre Daten für eine besondere organotypische Genexpressionssignatur primär extranodaler DLBCL und damit für offenbar organotypische – unterschiedliche – Transformationswege.

Abstract

Roughly 30–40% of diffuse large B-cell lymphomas (DLBCL) arise primarily in extranodal sites. Most frequently, they occur in the gastrointestinal tract, especially in the gastric mucosa. They also occur in the central nervous system, as testicular lymphomas, in the lungs, or in the skin. Morphologically, they show the whole spectrum of peripheral B-blasts: centroblasts, immunoblasts, or plasmoblasts. Thus, there is no actual difference in their cytomorphological presentation compared to their nodal—and frequently systemic—counterparts. However, recent data point to profound differences in primary extranodal DLBCL compared to primary nodal tumors, as well as to each other, frequently relating to their molecular characteristics and especially implying organotypic features. These characteristics may relate to a particular organotypic site of origin, or the particular clinicopathogenetic setting in which the tumors arise. This is exemplified in the description of the DLBCL subtypes as defined by the World Health Organization classification (mediastinal or intravascular B-cell lymphoma; primary effusion lymphoma). On the other hand, primary extranodal DLBCL are frequently characterized by a particular (cyto-)genetic constitution, often related to their site of origin. Finally, some preliminary data on gene expression profiling strongly argue in favor of particular gene signatures for primary extranodal DLBCL, and hence in favor of particular organotypic transformation pathways.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Abb. 1
Abb. 2

Literatur

  1. Jaffe ES, Harris NL, Stein H, Vardiman JW (eds) (2001) World Health Organization Classification of Tumours. Pathology and genetics of tumours of haematopoietic and lymphoid tissues. IARC, Lyon

  2. Dave SS, Fu K, Wright GW et al. (2006) Molecular diagnosis of Burkitt’s lymphoma. N Engl J Med 354: 2431–2442

    Article  PubMed  Google Scholar 

  3. Hummel M, Bentink S, Berger H et al. (2006) A biologic definition of Burkitt’s lymphoma from transcriptional and genomic profiling. N Engl J Med 354: 2419–2430

    Article  PubMed  Google Scholar 

  4. Lossos IS (2005) Molecular pathogenesis of diffuse large B-cell lymphoma. J Clin Oncol 23: 6351–6357

    Google Scholar 

  5. Katzenberger T, Ott G, Klein T et al. (2004) Cytogenetic alterations affecting BCL6 are predominantly found in follicular lymphomas grade 3B with a diffuse large B-cell component. Am J Pathol 165: 481–490

    PubMed  Google Scholar 

  6. Bea S, Zettl A, Wright G et al. (2005) Diffuse large B-cell lymphoma subgroups have distinct genetic profiles that influence tumor biology and improve gene expression-based survival prediction. Blood 106: 3183-3190

    Article  PubMed  Google Scholar 

  7. Rosenwald A, Wright G, Chan WC et al. (2002) The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N Engl J Med 346: 1937–1947

    Article  PubMed  Google Scholar 

  8. Joos S, Otano-Joos MI, Ziegler S et al. (1996) Primary mediastinal (thymic) B-cell lymphoma is characterized by gains of chromosomal material including 9p and amplification of the REL gene. Blood 87: 1571–1578

    PubMed  Google Scholar 

  9. Melzner I, Bucur AJ, Bruderlein S et al. (2005) Biallelic mutation of SOCS-1 impairs JAK2 degradation and sustains phospho-JAK2 action in the MedB-1 mediastinal lymphoma line. Blood 105: 2535–2542

    Article  PubMed  Google Scholar 

  10. Rosenwald A, Wright G, Leroy K et al. (2003) 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 198: 851–862

    Article  PubMed  Google Scholar 

  11. Koch P, del Valle F, Berdel WE et al. (2001) Primary gastrointestinal non-Hodgkin’s lymphoma: I. Anatomic and histologic distribution, clinical features, and survival data of 371 patients registered in the German Multicenter Study GIT NHL 01/92. J Clin Oncol 19: 3861–3873

    Google Scholar 

  12. Omonishi K, Yoshino T, Sakuma I et al. (1998) bcl-6 protein is identified in high-grade but not low-grade mucosa-associated lymphoid tissue lymphomas of the stomach. Mod Pathol 11: 181–185

    PubMed  Google Scholar 

  13. Ott G, Katzenberger T, Greiner A et al. (1997) The t(11;18)(q21;q21) chromosome translocation is a frequent and specific aberration in low-grade but not high-grade malignant non-Hodgkin’s lymphomas of the mucosa-associated lymphoid tissue (MALT-) type. Cancer Res 57: 3944–3948

    PubMed  Google Scholar 

  14. Chen YW, Hu XT, Liang AC et al. (2006) High BCL6 expression predicts better prognosis, independent of BCL6 translocation status, translocation partner, or BCL6-deregulating mutations, in gastric lymphoma. Blood 108: 2373–2383

    Article  PubMed  Google Scholar 

  15. Barth TF, Dohner H, Werner CA et al. (1998) Characteristic pattern of chromosomal gains and losses in primary large B-cell lymphomas of the gastrointestinal tract. Blood 91: 4321–4330

    PubMed  Google Scholar 

  16. van Krieken JH, Raffeld M, Raghoebier S et al. (1990) Molecular genetics of gastrointestinal non-Hodgkin’s lymphomas: unusual prevalence and pattern of c-myc rearrangements in aggressive lymphomas. Blood 76: 797–800

    PubMed  Google Scholar 

  17. Haralambieva E, Adam P, Ventura R et al. (2006) Genetic rearrangement of FOXP1 is predominantly detected in a subset of diffuse large B-cell lymphomas with extranodal presentation. Leukemia 20: 1300–1303

    Article  PubMed  Google Scholar 

  18. Thompsett AR, Ellison DW, Stevenson FK et al. (1999) V(H) gene sequences from primary central nervous system lymphomas indicate derivation from highly mutated germinal center B cells with ongoing mutational activity. Blood 94: 1738–1746

    PubMed  Google Scholar 

  19. Montesinos-Rongen M, Van Roost D, Schaller C et al. (2004) Primary diffuse large B-cell lymphomas of the central nervous system are targeted by aberrant somatic hypermutation. Blood 103: 1869–1875

    Article  PubMed  Google Scholar 

  20. Jordanova ES, Riemersma SA, Philippo K et al. (2002) Hemizygous deletions in the HLA region account for loss of heterozygosity in the majority of diffuse large B-cell lymphomas of the testis and the central nervous system. Genes Chromosomes Cancer 35: 38–48

    Article  PubMed  Google Scholar 

  21. Riemersma SA, Jordanova ES, Schop RF et al. (2000) Extensive genetic alterations of the HLA region, including homozygous deletions of HLA class II genes in B-cell lymphomas arising in immune-privileged sites. Blood 96: 3569–3577

    PubMed  Google Scholar 

  22. Rimsza LM, Roberts RA, Campo E et al. (2006) Loss of major histocompatibility class II expression in non-immune-privileged site diffuse large B-cell lymphoma is highly coordinated and not due to chromosomal deletions. Blood 107: 1101–1107

    Article  PubMed  Google Scholar 

  23. Rickert CH, Dockhorn-Dworniczak B, Simon R et al. (1999) Chromosomal imbalances in primary lymphomas of the central nervous system. Am J Pathol 155: 1445–1451

    PubMed  Google Scholar 

  24. Nakamura M, Kishi M, Sakaki T et al. (2003) Novel tumor suppressor loci on 6q22–23 in primary central nervous system lymphomas. Cancer Res 63: 737–741

    PubMed  Google Scholar 

  25. Rubenstein J, Fridlyand J, Shen A et al. (2006) Gene expression and angiotropism in primary CNS lymphoma. Blood 107: 3716–3723

    Article  PubMed  Google Scholar 

  26. Bosga-Bouwer AG, Kok K, Booman M et al. (2006) Array comparative genomic hybridization reveals a very high frequency of deletions of the long arm of chromosome 6 in testicular lymphoma. Genes Chromosomes Cancer 45: 976–981

    Article  PubMed  Google Scholar 

  27. Le Boit P BG, Weedon D, Sarasin A (2006) World Health Organization Classification of Tumours. Pathology and genetics of skin tumours. IARC, Lyon

  28. Dijkman R, Tensen CP, Jordanova ES et al. (2006) Array-based comparative genomic hybridization analysis reveals recurrent chromosomal alterations and prognostic parameters in primary cutaneous large B-cell lymphoma. J Clin Oncol 24: 296–305

    Article  PubMed  Google Scholar 

  29. Hoefnagel JJ, Dijkman R, Basso K et al. (2005) Distinct types of primary cutaneous large B-cell lymphoma identified by gene expression profiling. Blood 105: 3671–3678

    Article  PubMed  Google Scholar 

  30. Willemze R (2006) Primary cutaneous B-cell lymphoma: classification and treatment. Curr Opin Oncol 18: 425–431

    Article  PubMed  Google Scholar 

Download references

Interessenkonflikt

Es besteht kein Interessenkonflikt. Der korrespondierende Autor versichert, dass keine Verbindungen mit einer Firma, deren Produkt in dem Artikel genannt ist, oder einer Firma, die ein Konkurrenzprodukt vertreibt, bestehen. Die Präsentation des Themas ist unabhängig und die Darstellung der Inhalte produktneutral.

Author information

Authors and Affiliations

  1. Institut für Pathologie, Julius-Maximilians-Universität Würzburg, 97080, Josef-Schneider-Straße 2, Würzburg, Deutschland

    G. Ott & A. Rosenwald

Authors
  1. G. Ott
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. Rosenwald
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to G. Ott.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ott, G., Rosenwald, A. Sind primär extranodale diffuse großzellige B-Zell-Lymphome organotypische Erkrankungen?. Pathologe 28, 29–35 (2007). https://doi.org/10.1007/s00292-006-0883-5

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00292-006-0883-5

Schlüsselwörter

Keywords

Search

Navigation