Skip to main content

Early-stage diffuse large B cell lymphoma of the head and neck: clinico-biological characterization and 18 year follow-up of 488 patients (IELSG 23 study)

Annals of Hematology volume 93, pages 221–231 (2014)Cite this article

Abstract

It is known that extranodal head and neck diffuse large B cell lymphomas (eHN-DLBCL) can affect various anatomical structures what is not well-known, however, is whether they differ in terms of clinical presentation and outcome. Clinical data of the multi-institutional series, the largest of its kind as yet, has been analysed with the aim of answering these open questions and providing long-term follow-up information. Data from 488 patients affected by stage I/II eHN-DLBCL was collected: 300 of the Waldeyer’s Ring (WR), 38 of the parotid and salivary glands (PSG), 48 of the thyroid gland (TG), 53 of the nasal cavity and paranasal sinuses (NPS), 24 of the palate and oral cavity (POC) and 25 with more than one involved site. Different eHN-DLBCL arising have distinct characteristics at presentation. The intermediate high risk-modified IPI was 67 % in TG, 44 % in WR, 38 % in PSG and POC and 20 % in MS. The worst 5-year survival rate had TG-DLBCL (61 %) due to the 61 % of patients with a mIPI >1. The addition of radiotherapy (cRT) to remitters did not translate into a survival advantage (5-year disease-free survival of 67 % in the cRT group vs. 70 % in the other). Three of four central nervous system recurrences occurred in NPS-DLBCL. Survival of HN-DLBCL was inferior to nodal DLBCL. This study showed that eHN-DLBCL remitters have an inferior survival when compared to nodal DLBCL, and that the addition of cRT does not provide a survival advantage. Since the standard of care nowadays is chemo-immunotherapy, survival of these patients might have been improved.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

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

Fig. 1
Fig. 2
Fig. 3

References

  1. Vega F, Lin P, Medeiros LJ (2005) Extranodal lymphomas of the head and neck. Ann Diagn Pathol 9(6):340–350. doi:10.1016/j.anndiagpath.2005.09.020

    PubMed  Article  Google Scholar 

  2. Weber AL, Rahemtullah A, Ferry JA (2003) Hodgkin and non-Hodgkin lymphoma of the head and neck: clinical, pathologic, and imaging evaluation. Neuroimaging Clin N Am 13(3):371–392

    PubMed  Article  Google Scholar 

  3. Ferreri AJ, Guidoboni M, Ponzoni M, De Conciliis C, Dell’Oro S, Fleischhauer K, Caggiari L, Lettini AA, Dal Cin E, Ieri R, Freschi M, Villa E, Boiocchi M, Dolcetti R (2004) Evidence for an association between Chlamydia psittaci and ocular adnexal lymphomas. J Natl Cancer Inst 96(8):586–594

    PubMed  Article  Google Scholar 

  4. Voulgarelis M, Ziakas PD, Papageorgiou A, Baimpa E, Tzioufas AG, Moutsopoulos HM (2012) Prognosis and outcome of non-Hodgkin lymphoma in primary Sjogren syndrome. Medicine (Baltimore) 91(1):1–9. doi:10.1097/MD.0b013e31824125e4

    Article  Google Scholar 

  5. Saxena A, Alport EC, Moshynska O, Kanthan R, Boctor MA (2004) Clonal B cell populations in a minority of patients with Hashimoto’s thyroiditis. J Clin Pathol 57(12):1258–1263. doi:10.1136/jcp.2004.018416

    CAS  PubMed  Article  Google Scholar 

  6. Laskin JJ, Savage KJ, Voss N, Gascoyne RD, Connors JM (2005) Primary paranasal sinus lymphoma: natural history and improved outcome with central nervous system chemoprophylaxis. Leuk Lymphoma 46(12):1721–1727. doi:10.1080/17402520500182345

    PubMed  Article  Google Scholar 

  7. Hausdorff J, Davis E, Long G, Hoppe R, van der Pas M, Lassman C, Kamel O, Jacobs C (1997) Non-Hodgkin’s lymphoma of the paranasal sinuses: clinical and pathological features, and response to combined-modality therapy. Cancer J Sci Am 3(5):303–311

    CAS  PubMed  Google Scholar 

  8. Yu JI, Nam H, Ahn YC, Kim WS, Park K, Kim SJ (2010) Involved-lesion radiation therapy after chemotherapy in limited-stage head-and-neck diffuse large B cell lymphoma. Int J Radiat Oncol Biol Phys 78(2):507–512. doi:10.1016/j.ijrobp.2009.07.1706

    PubMed  Article  Google Scholar 

  9. Nishioka T, Tsuchiya K, Nishioka S, Kitahara T, Ohmori K, Homma A, Aoyma H, Shindoh M, Shirato H (2004) Pilot study of modified version of CHOP plus radiotherapy for early-stage aggressive non-Hodgkin’s lymphoma of the head and neck. Int J Radiat Oncol Biol Phys 60(3):847–852. doi:10.1016/j.ijrobp.2004.04.034

    CAS  PubMed  Article  Google Scholar 

  10. Hart S, Horsman JM, Radstone CR, Hancock H, Goepel JR, Hancock BW (2004) Localised extranodal lymphoma of the head and neck: the Sheffield Lymphoma Group experience (1971–2000). Clin Oncol (R Coll Radiol) 16(3):186–192. doi:10.1016/j.clon.2003.10.010

    CAS  Article  Google Scholar 

  11. Chen SW, Chang ST, Lu CL, Hwang WS, Tsao CJ, Huang WT, Chang KY, Chuang SS (2010) Upper aerodigestive tract lymphoma in Taiwan. J Clin Pathol 63(10):888–893. doi:10.1136/jcp.2010.081927

    PubMed  Article  Google Scholar 

  12. Kojima M, Shimizu K, Nishikawa M, Tamaki Y, Ito H, Tsukamoto N, Masawa N (2007) Primary salivary gland lymphoma among Japanese: a clinicopathological study of 30 cases. Leuk Lymphoma 48(9):1793–1798. doi:10.1080/10428190701528509

    PubMed  Article  Google Scholar 

  13. Dunn P, Kuo TT, Shih LY, Lin TL, Wang PN, Kuo MC, Tang CC (2004) Primary salivary gland lymphoma: a clinicopathologic study of 23 cases in Taiwan. Acta haematologica 112(4):203–208. doi:10.1159/000081273

    PubMed  Article  Google Scholar 

  14. Aviles A, Delgado S, Ruiz H, de la Torre A, Guzman R, Talavera A (1996) Treatment of non-Hodgkin’s lymphoma of Waldeyer’s ring: radiotherapy versus chemotherapy versus combined therapy. Eur J Cancer B Oral Oncol 32B(1):19–23

    CAS  PubMed  Article  Google Scholar 

  15. Ezzat AA, Ibrahim EM, El Weshi AN, Khafaga YM, AlJurf M, Martin JM, Ajarim DS, Bazarbashi SN, Stuart RK, Zucca E (2001) Localized non-Hodgkin’s lymphoma of Waldeyer’s ring: clinical features, management, and prognosis of 130 adult patients. Head Neck 23(7):547–558

    CAS  PubMed  Article  Google Scholar 

  16. Proulx GM, Caudra-Garcia I, Ferry J, Harris N, Greco WR, Kaya U, Chan A, Wang CC (2003) Lymphoma of the nasal cavity and paranasal sinuses: treatment and outcome of early-stage disease. Am J Clin Oncol 26(1):6–11

    PubMed  Article  Google Scholar 

  17. Chi HS, Lee KW, Chiang FY, Tai CF, Wang LF, Yang SF, Lin SF, Kuo WR (2012) Head and neck extranodal lymphoma in a single institute: a 17-year retrospective analysis. Kaohsiung J Med Sci 28(8):435–441. doi:10.1016/j.kjms.2012.02.014

    PubMed  Article  Google Scholar 

  18. de Leval L, Bonnet C, Copie-Bergman C, Seidel L, Baia M, Briere J, Molina TJ, Fabiani B, Petrella T, Bosq J, Gisselbrecht C, Siebert R, Tilly H, Haioun C, Fillet G, Gaulard P (2012) Diffuse large B-cell lymphoma of Waldeyer’s ring has distinct clinicopathologic features: a GELA study. Ann Oncol 23(12):3143–3151. doi:10.1093/annonc/mds150

    PubMed  Article  Google Scholar 

  19. Jaffe E, Harris N, Stein H, Vardiman J (2001) Pathology and genetics of tumors of haematopoietic and lymphoid tissues. World Health Organization (WHO) classification of tumors. World Health Organization, Lyon

  20. Carbone PP, Kaplan HS, Musshoff K, Smithers DW, Tubiana M (1971) Report of the Committee on Hodgkin’s Disease Staging Classification. Cancer Res 31(11):1860–1861

    CAS  PubMed  Google Scholar 

  21. Miller TP, Dahlberg S, Cassady JR, Adelstein DJ, Spier CM, Grogan TM, LeBlanc M, Carlin S, Chase E, Fisher RI (1998) Chemotherapy alone compared with chemotherapy plus radiotherapy for localized intermediate- and high-grade non-Hodgkin’s lymphoma. New England J Med 339(1):21–26. doi:10.1056/NEJM199807023390104

    CAS  Article  Google Scholar 

  22. Mian M, Gaidano G, Conconi A, Tsang R, Gospodarowicz MK, Rambaldi A, Rossi A, Oldani E, Federico M, Luminari S, Bellei M, Pogliani EM, Rossini F, Cabrera ME, Martelli M, Lopez-Guillermo A, Busetto M, Cavalli F, Zucca E, Cortelazzo S (2011) High response rate and improvement of long-term survival with combined treatment modalities in patients with poor-risk primary thyroid diffuse large B-cell lymphoma: an International Extranodal Lymphoma Study Group and Intergruppo Italiano Linfomi study. Leuk Lymphoma 52(5):823–832. doi:10.3109/10428194.2011.555888

    PubMed  Article  Google Scholar 

  23. Mian M, Ferreri AJ, Rossi A, Conconi A, Tsang R, Gospodarowicz MK, Oldani E, Federico M, Luminari S, Pogliani EM, Rossini F, Cabrera ME, Martelli M, Gutierrez-Garcia G, Busetto M, Cavalli F, Zucca E, Rambaldi A, Cortelazzo S (2012) The role of radiotherapy in patients with early-stage diffuse large B-cell lymphomas of the Waldeyer’s ring in remission after anthracycline-containing chemotherapy. Leuk Lymphoma. doi:10.3109/10428194.2012.710907

    Google Scholar 

  24. Fisher RI, Gaynor ER, Dahlberg S, Oken MM, Grogan TM, Mize EM, Glick JH, Coltman CA Jr, Miller TP (1993) Comparison of a standard regimen (CHOP) with three intensive chemotherapy regimens for advanced non-Hodgkin’s lymphoma. New England J Med 328(14):1002–1006. doi:10.1056/NEJM199304083281404

    CAS  Article  Google Scholar 

  25. Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM, Lister TA, Vose J, Grillo-Lopez A, Hagenbeek A, Cabanillas F, Klippensten D, Hiddemann W, Castellino R, Harris NL, Armitage JO, Carter W, Hoppe R, Canellos GP (1999) Report of an international workshop to standardize response criteria for non-Hodgkin’s lymphomas. NCI Sponsored International Working Group. J Clin Oncol 17(4):1244

    CAS  PubMed  Google Scholar 

  26. Cox DR (1972) Regression models and life-tables. J R Stat Soc 34(2):34

    Google Scholar 

  27. Persky DO, Unger JM, Spier CM, Stea B, LeBlanc M, McCarty MJ, Rimsza LM, Fisher RI, Miller TP (2008) Phase II study of rituximab plus three cycles of CHOP and involved-field radiotherapy for patients with limited-stage aggressive B-cell lymphoma: Southwest Oncology Group study 0014. J Clin Oncol 26(14):2258–2263. doi:10.1200/JCO.2007.13.6929

    CAS  PubMed  Article  Google Scholar 

  28. Hans CP, Weisenburger DD, Greiner TC, Gascoyne RD, Delabie J, Ott G, Muller-Hermelink HK, Campo E, Braziel RM, Jaffe ES, Pan Z, Farinha P, Smith LM, Falini B, Banham AH, Rosenwald A, Staudt LM, Connors JM, Armitage JO, Chan WC (2004) Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood 103(1):275–282. doi:10.1182/blood-2003-05-1545

    CAS  PubMed  Article  Google Scholar 

  29. Qi SN, Li YX, Wang H, Wang WH, Jin J, Song YW, Wang SL, Liu YP, Zhou LQ, Yu ZH (2009) Diffuse large B-cell lymphoma: clinical characterization and prognosis of Waldeyer ring versus lymph node presentation. Cancer 115(21):4980–4989. doi:10.1002/cncr.24557

    PubMed  Article  Google Scholar 

  30. Shenkier TN, Voss N, Fairey R, Gascoyne RD, Hoskins P, Klasa R, Klimo P, O’Reilly SE, Sutcliffe S, Connors JM (2002) Brief chemotherapy and involved-region irradiation for limited-stage diffuse large-cell lymphoma: an 18-year experience from the British Columbia Cancer Agency. J clin oncol official J Am Soc Clin Oncol 20(1):197–204

    CAS  Article  Google Scholar 

  31. Mian M, Ferreri AJM, Rossi A, Conconi A, Tsang R, Gospodarowicz MK, Oldani E, Federico M, Luminari S, Pogliani EM, Rossini F, Cabrera ME, Martelli M, Gutierrez-Garcia G, Busetto M, Cavalli F, Zucca E, Rambaldi A, Cortelazzo S, Ielsg (2013) Role of radiotherapy in patients with early-stage diffuse large B-cell lymphoma of Waldeyer’s ring in remission after anthracycline-containing chemotherapy. Leukemia & Lymphoma 54(1):62–68. doi:10.3109/10428194.2012.710907

    CAS  Article  Google Scholar 

  32. Chang DT, Amdur RJ, Pacholke H, Mendenhall NP, Morris CG, Byer GA, Olivier KR (2009) Xerostomia in long-term survivors of aggressive non-Hodgkin’s lymphoma of Waldeyer’s ring: a potential role for parotid-sparing techniques? Am J Clin Oncol 32(2):145–149. doi:10.1097/COC.0b013e3181841f42

    PubMed  Article  Google Scholar 

  33. Cortelazzo S, Rossi A, Oldani E, Motta T, Giardini R, Zinzani PL, Zucca E, Gomez H, Ferreri AJM, Pinotti G, Chini C, Devizzi L, Gianni AM, Cavalli F, Barbui T (2002) The modified International Prognostic Index can predict the outcome of localized primary intestinal lymphoma of both extranodal marginal zone B-cell and diffuse large B-cell histologies. Br J Haematol 118(1):218–228

    PubMed  Article  Google Scholar 

  34. Persky DO, Unger JM, Spier CM, Stea B, LeBlanc M, McCarty MJ, Rimsza LM, Fisher RI, Miller TP, Group SO (2008) Phase II study of rituximab plus three cycles of CHOP and involved-field radiotherapy for patients with limited-stage aggressive B-cell lymphoma: Southwest Oncology Group study 0014. 26 (14):2258–2263. doi:10.1200/JCO.2007.13.6929

Download references

Acknowledgments

The authors thank Andrés J.M. Ferreri, Annarita Conconi, Monica Bellei and Armando López-Guillermo for their support. This work was supported by the Autonomous Province of Bolzano, the local health authority and Alto Adige Bolzano-AIL “Mirco Federici” Onlus.

Conflicts of interest

The authors have declared no conflicts of interest.

Author information

Authors and Affiliations

  1. Division of Hematology, Azienda Ospedaliera S. Maurizio, Bolzano/Bozen, Italy

    M. Mian, D. Grazio, M. Svaldi & S. Cortelazzo

  2. Lymphoma & Genomics Research Programme, IOR—Institute of Oncology Research, Bellinzona, Switzerland

    M. Mian

  3. Department of Hematology & Oncology, Medical University of Innsbruck, Innsbruck, Austria

    M. Mian & M. Fiegl

  4. Laboratory of Biochemistry and Molecular Biology, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy

    D. Capello

  5. Unit of Lymphoid Malignancies, Department of Onco-Hematology, San Raffaele Scientific Institute, Milan, Italy

    M. B. Ventre

  6. Division of Hematology, Ospedali Riuniti, Bergamo, Italy

    A. Rossi, E. Oldani & A. Rambaldi

  7. Department of Radiation Oncology, University of Toronto, Princess Margaret Hospital, Toronto, Canada

    R. Tsang & M. K. Gospodarowicz

  8. Department of Oncology and Hematology, University of Modena and Reggio Emilia, Modena, Italy

    M. Federico, S. Luminari & L. Marcheselli

  9. Chair of Hematology, University of Milan-Bicocca, Milan, Italy

    E. M. Pogliani & F. Rossini

  10. Hospital del Salvador, Universidad de Chile, Santiago, Chile

    M. E. Cabrera

  11. Chair of Hematology, University of Rome, Rome, Italy

    M. Martelli

  12. Servicio de Hematologia, Hospital Clinic Universitar I, Barcelona, Spain

    G. Gutierrez-Garcia

  13. UOC Radioterapia, UOS Radioterapia Oncoematologica, Ospedale dell’Angelo Mestre, Venice, Italy

    M. Busetto

  14. Department of Hematology, Ospedale San Bortolo, Vicenza, Italy

    C. Visco

  15. Division of Hematology, Department of Clinical and Experimental Medicine & BRMA, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy

    D. Rossi & G. Gaidano

  16. IOSI, Bellinzona, Switzerland

    F. Cavalli & E. Zucca

  17. Department of Hematology, Hospital of Bolzano, Via Lorenz Böhler 5, 39100, Bolzano, Italy

    M. Mian

Authors
  1. M. Mian
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. D. Capello
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. B. Ventre
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. D. Grazio
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. Svaldi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A. Rossi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. R. Tsang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. M. K. Gospodarowicz
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. E. Oldani
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. M. Federico
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. S. Luminari
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. L. Marcheselli
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. E. M. Pogliani
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. F. Rossini
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. M. E. Cabrera
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. M. Martelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. G. Gutierrez-Garcia
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. M. Busetto
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. C. Visco
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. M. Fiegl
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. D. Rossi
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. G. Gaidano
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. F. Cavalli
    View author publications

    You can also search for this author in PubMed Google Scholar

  24. E. Zucca
    View author publications

    You can also search for this author in PubMed Google Scholar

  25. A. Rambaldi
    View author publications

    You can also search for this author in PubMed Google Scholar

  26. S. Cortelazzo
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

on behalf of the International Extranodal Lymphoma Study Group (IELSG)

Corresponding author

Correspondence to M. Mian.

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM 1

(DOC 2739 kb)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Mian, M., Capello, D., Ventre, M.B. et al. Early-stage diffuse large B cell lymphoma of the head and neck: clinico-biological characterization and 18 year follow-up of 488 patients (IELSG 23 study). Ann Hematol 93, 221–231 (2014). https://doi.org/10.1007/s00277-013-1856-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00277-013-1856-4

Keywords

  • DLBCL
  • Lymphoma
  • Extranodal
  • Head
  • Neck