Skip to main content
SpringerLink
Log in

Bone Marrow in Hodgkin Lymphoma and Mimickers

  • Chapter
  • First Online:
Book cover Bone Marrow Lymphoid Infiltrates

  • 1163 Accesses

Abstract

In lymph nodes and spleen, the criteria for the diagnosis of Hodgkin lymphoma (HL) are settled since the mid sixties (1]. During the last two decades, they have undergone refinements in the Revised European American Lymphoma (REAL) Classification [2] as well as in the third and forth editions of the WHO Classification of Haematopoietic and Lymphoid Tumours [3, 4]. In particular, a clear-cut distinction has been introduced between lymphocyte predominant (LP) HL and all the remaining histotypes collectively termed classical Hodgkin lymphoma (CHL). Such distinction is based on clinical, morphologic and phenotypic findings. Thus, LPHL shows a pick in the fourth decade of life, has no relationship with Epstein Barr virus (EBV) infection, tends to relapse several years after the original diagnosis (remaining anyhow curable), can occasionally progress to diffuse large B-cell lymphoma (DLBCL) and may be preceded by, associated with or followed by progressively transformed germinal centres. The neoplastic cells display a characteristic polylobated, popcorn appearance and usually express CD20, CD79a, PAX5/BSAP, CD45, BCL6, IRF4, EMA and Immunoglobulin (Ig)-related transcription factors, while they turn negative for CD30 and CD15 (for more details see blow). On the other hand, CHL shows a bimodal age distribution (with two picks in the third and seven decade of life, respectively), is characterised by an ordered dissemination that is the base for staging procedures, and reveals variable correlation with the EBV (30–90 % of cases depending on the histotype). Four subtypes are quoted under the heading CHL: lymphocyte-rich (that in the past was included in the LP chapter), nodular sclerosing, mixed-cellularity, and lymphocyte depleted. All of them are characterised by the presence of Hodgkin and Reed-Sternberg cells (HRSC) that bear the same phenotype: CD45−, CD30+, CD15+/−, CD79a−, CD20− (partly and variably + in 20 % of cases), PAX5/BSAP+ (with a few exceptions), IRF4+, Ig-transcription factors−, BCL6−, and EMA− (for more details see below). Interestingly, neoplastic elements of both LP and CHL are related to germinal centre B-cells (GCB), LP cells residing with GC and HRSC being on the way to exit form it. This is proven by the fact that the former carry ongoing mutations of the IG@, while the latter display a high load of somatic mutations which are eventually stable. In addition, besides the Ig-encoding genes, the somatic hypermutation process does also affect C-MYC, RhoH/TTF, PIM1 and PAX5, although with different prevalence in LP and CHL. In spite of these well-defined criteria, grey-zones still exist between HL and non-Hodgkin lymphomas (NHL). Thus, for instance the borders between LPHL and Histiocyte/T-cell rich B-cell lymphoma (H/TCRBCL) are not always sharp. The same holds true for CHL and diffuse large B-cell lymphoma (DLBCL): such situation has been officially recognised in the fourth edition of the WHO Classification by the inclusion of the provisional entity “B-cell lymphoma unclassifiable with features intermediate between classical Hodgkin lymphoma and diffuse large B-cell lymphoma”.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Lukes RJ, Butler JJ. The pathology and nomenclature of Hodgkin’s disease. Cancer Res. 1966;26:1063–83.

    PubMed  CAS  Google Scholar 

  2. Harris NL, Jaffe ES, Stein H, Banks PM, Chan JK, Cleary ML, et al. A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. Blood. 1994;84:1361–92.

    PubMed  CAS  Google Scholar 

  3. Jaffe ES, Harris NL, Stein H, Vardiman JW. Pathology and genetics. Tumours of haematopoietic and lymphoid tissues. 3rd ed. Lyon: IARC Press; 2001.

    Google Scholar 

  4. Swerdlow S, Campo E, Harris N, Jaffe E, Pileri S, Stein H, Thiele J, Vardiman JW, editors. Chap.12: Hodgkin lymphoma. WHO classification of tumours of haematopoietic and lymphoid tissues. 4th ed. Lyon: IARC; 2008;321-334.

    Google Scholar 

  5. Carbone PP, Kaplan HS, Musshoff K, Smithers DW, Tubiana M. Report of the committee on Hodgkin’s disease staging classification. Cancer Res. 1971;31:1860–1.

    PubMed  CAS  Google Scholar 

  6. Lister TA, Crowther D, Sutcliffe SB, Glatstein E, Canellos GP, Young RC, et al. Report of a committee convened to discuss the evaluation and staging of patients with Hodgkin’s disease: Cotswolds meeting. J Clin Oncol. 1989;7:1630–6.

    PubMed  CAS  Google Scholar 

  7. Ebie N, Loew JM, Gregory SA. Bilateral trephine bone marrow biopsy for staging non-Hodgkin’s lymphoma – a second look. Hematol Pathol. 1989;3:29–33.

    PubMed  CAS  Google Scholar 

  8. Luoni M, Declich P, De Paoli A, Fava S, Marinoni P, Montalbetti L, et al. Bone marrow biopsy for the staging of non-Hodgkin’s lymphoma: bilateral or unilateral trephine biopsy? Tumori. 1995;81:410–3.

    PubMed  CAS  Google Scholar 

  9. Franco V, Tripodo C, Rizzo A, Stella M, Florena AM. Bone marrow biopsy in Hodgkin’s lymphoma. Eur J Haematol. 2004;73:149–55.

    Article  PubMed  Google Scholar 

  10. Howell SJ, Grey M, Chang J, Morgenstern GR, Cowan RA, Deakin DP, et al. The value of bone marrow examination in the staging of Hodgkin’s lymphoma: a review of 955 cases seen in a regional cancer centre. Br J Haematol. 2002;119:408–11.

    Article  PubMed  Google Scholar 

  11. Moid F, DePalma L. Comparison of relative value of bone marrow aspirates and bone marrow trephine biopsies in the diagnosis of solid tumor metastasis and Hodgkin lymphoma: institutional experience and literature review. Arch Pathol Lab Med. 2005;129:497–501.

    PubMed  Google Scholar 

  12. Elstrom RL, Tsai DE, Vergilio JA, Downs LH, Alavi A, Schuster SJ. Enhanced marrow [18F] fluorodeoxyglucose uptake related to myeloid hyperplasia in Hodgkin’s lymphoma can simulate lymphoma involvement in marrow. Clin Lymphoma. 2004;5:62–4.

    Article  PubMed  Google Scholar 

  13. Moog F, Bangerter M, Kotzerke J, Guhlmann A, Frickhofen N, Reske SN. 18-F-fluorodeoxyglucose-positron emission tomography as a new approach to detect lymphomatous bone marrow. J Clin Oncol. 1998;16:603–9.

    PubMed  CAS  Google Scholar 

  14. Moulin-Romsee G, Hindie E, Cuenca X, Brice P, Decaudin D, Benamor M, et al. (18)F-FDG PET/CT bone/bone marrow findings in Hodgkin’s lymphoma may circumvent the use of bone marrow trephine biopsy at diagnosis staging. Eur J Nucl Med Mol Imaging. 2010;37:1095–105.

    Article  PubMed  Google Scholar 

  15. Khoury JD, Jones D, Yared MA, Manning Jr JT, Abruzzo LV, Hagemeister FB, et al. Bone marrow involvement in patients with nodular lymphocyte predominant Hodgkin lymphoma. Am J Surg Pathol. 2004;28:489–95.

    Article  PubMed  Google Scholar 

  16. Brusamolino E, Bacigalupo A, Barosi G, Biti G, Gobbi PG, Levis A, et al. Classical Hodgkin’s lymphoma in adults: guidelines of the Italian Society of Hematology, the Italian Society of Experimental Hematology, and the Italian Group for Bone Marrow Transplantation on initial work-up, management, and follow-up. Haematologica. 2009;94:550–65.

    Article  PubMed  Google Scholar 

  17. Mahoney Jr DH, Schreuders LC, Gresik MV, McClain KL. Role of staging bone marrow examination in children with Hodgkin disease. Med Pediatr Oncol. 1998;30:175–7.

    Article  PubMed  Google Scholar 

  18. Simpson CD, Gao J, Fernandez CV, Yhap M, Price VE, Berman JN. Routine bone marrow examination in the initial evaluation of paediatric Hodgkin lymphoma: the Canadian perspective. Br J Haematol. 2008;141:820–6.

    Article  PubMed  Google Scholar 

  19. Ponzoni M, Ciceri F, Crocchiolo R, Famoso G, Doglioni C. Isolated bone marrow occurrence of classic Hodgkin’s lymphoma in an HIV-negative patient. Haematologica. 2006;91:ECR04.

    PubMed  Google Scholar 

  20. Ponzoni M, Fumagalli L, Rossi G, Freschi M, Re A, Vigano MG, et al. Isolated bone marrow manifestation of HIV-associated Hodgkin lymphoma. Mod Pathol. 2002;15:1273–8.

    Article  PubMed  Google Scholar 

  21. Rappaport H, Berard CW, Butler JJ, Dorfman RF, Lukes RJ, Thomas LB. Report of the committee on histopathological criteria contributing to staging of Hodgkin’s disease. Cancer Res. 1971;31:1864–5.

    PubMed  CAS  Google Scholar 

  22. Agostinelli C, Sabattini E, Gjorret JO, Righi S, Rossi M, Mancini M, et al. Characterization of a new monoclonal antibody against PAX5/BASP in 1525 paraffin-embedded human and animal tissue samples. Appl Immunohistochem Mol Morphol. 2010;18:561–72.

    Article  PubMed  CAS  Google Scholar 

  23. Torlakovic E, Torlakovic G, Nguyen PL, Brunning RD, Delabie J. The value of anti-pax-5 immunostaining in routinely fixed and paraffin-embedded sections: a novel pan pre-B and B-cell marker. Am J Surg Pathol. 2002;26:1343–50.

    Article  PubMed  Google Scholar 

  24. Stein H, Delsol G, Pileri SA, Weiss L, Poppema S, Jaffe ES. Classical, Hodgkin lymphoma. In: Swerdlow S, Campo E, Harris N, Jaffe E, Pileri S, Stein H, Thiele J, Vardima J, editors. WHO classification of tumours of haematopoietic and lymphoid tissues. 4th ed. Lyon: IARC; 2008. p. 326.

    Google Scholar 

  25. Asano N, Oshiro A, Matsuo K, Kagami Y, Ishida F, Suzuki R, et al. Prognostic significance of T-cell or cytotoxic molecules phenotype in classical Hodgkin’s lymphoma: a clinicopathologic study. J Clin Oncol. 2006;24:4626–33.

    Article  PubMed  Google Scholar 

  26. Naresh KN, O’Conor GT, Soman CS, Johnson J, Advani SH, Magrath IT, et al. A study of p53 protein, proliferating cell nuclear antigen, and p21 in Hodgkin’s disease at presentation and relapse. Hum Pathol. 1997;28:549–55.

    Article  PubMed  CAS  Google Scholar 

  27. Smolewski P, Robak T, Krykowski E, Blasinska-Morawiec M, Niewiadomska H, Pluzanska A, et al. Prognostic factors in Hodgkin’s disease: multivariate analysis of 327 patients from a single institution. Clin Cancer Res. 2000;6:1150–60.

    PubMed  CAS  Google Scholar 

  28. Steidl C, Lee T, Shah SP, Farinha P, Han G, Nayar T, et al. Tumor-associated macrophages and survival in classic Hodgkin’s lymphoma. N Engl J Med. 2010;362:875–85.

    Article  PubMed  CAS  Google Scholar 

  29. Muenst S, Hoeller S, Dirnhofer S, Tzankov A. Increased programmed death-1+ tumor-infiltrating lymphocytes in classical Hodgkin lymphoma substantiate reduced overall survival. Hum Pathol. 2009;40:1715–22.

    Article  PubMed  CAS  Google Scholar 

  30. Poppema S, Delsol G, Pileri SA, Swerdlow S, Warnke R, Jaffe ES. Nodular lymphocyte predominant Hodgkin lymphoma. In: Swerdlow S, Campo E, Harris N, Jaffe E, Pileri S, Stein H, Thiele J, Vardima J, editors. WHO classification of tumours of haematopoietic and lymphoid tissues. 4th ed. Lyon: IARC; 2008. p. 326.

    Google Scholar 

  31. Marafioti T, Mancini C, Ascani S, Sabattini E, Zinzani PL, Pozzobon M, et al. Leukocyte-specific phosphoprotein-1 and PU.1: two useful markers for distinguishing T-cell-rich B-cell lymphoma from lymphocyte-predominant Hodgkin’s disease. Haematologica. 2004;89:957–64.

    PubMed  CAS  Google Scholar 

  32. Nam-Cha SH, Roncador G, Sanchez-Verde L, Montes-Moreno S, Acevedo A, Dominguez-Franjo P, et al. PD-1, a follicular T-cell marker useful for recognizing nodular lymphocyte-predominant Hodgkin lymphoma. Am J Surg Pathol. 2008;32:1252–7.

    Article  PubMed  Google Scholar 

  33. Prakash S, Fountaine T, Raffeld M, Jaffe ES, Pittaluga S. IgD positive L&H cells identify a unique subset of nodular lymphocyte predominant Hodgkin lymphoma. Am J Surg Pathol. 2006;30:585–92.

    Article  PubMed  Google Scholar 

  34. Wickert RS, Weisenburger DD, Tierens A, Greiner TC, Chan WC. Clonal relationship between lymphocytic predominance Hodgkin’s disease and concurrent or subsequent large-cell lymphoma of B lineage. Blood. 1995;86:2312–20.

    PubMed  CAS  Google Scholar 

  35. Jaffe ES, Zarate-Osorno A, Kingma DW, Raffeld M, Medeiros LJ. The interrelationship between Hodgkin’s disease and non-Hodgkin’s lymphomas. Ann Oncol. 1994;5 Suppl 1:7–11.

    PubMed  Google Scholar 

  36. De Wolf-Peeters C, Delabie J, Jaffe ES, Delsol G. T-cell/histiocyte-rich large B-cell lymphoma. Chap. 10: In: Swerdlow S, Campo E, Harris N, Jaffe E, Pileri S, Stein H, Thiele J, Vardiman J, editors. WHO classification of tumours of haematopoietic and lymphoid tissues. 4th ed. Lyon: IARC; 2008. p. 238–9.

    Google Scholar 

  37. Yeh YM, Chang KC, Chen YP, Kao LY, Tsai HP, Ho CL, et al. Large B cell lymphoma presenting initially in bone marrow, liver and spleen: an aggressive entity associated frequently with haemophagocytic syndrome. Histopathology. 2010;57:785–95.

    Article  PubMed  Google Scholar 

  38. Mao Z, Quintanilla-Martinez L, Raffeld M, Richter M, Krugmann J, Burek C, et al. IgVH mutational status and clonality analysis of Richter’s transformation: diffuse large B-cell lymphoma and Hodgkin lymphoma in association with B-cell chronic lymphocytic leukemia (B-CLL) represent 2 different pathways of disease evolution. Am J Surg Pathol. 2007;31:1605–14.

    Article  PubMed  Google Scholar 

  39. Timar B, Fulop Z, Csernus B, Angster C, Bognar A, Szepesi A, et al. Relationship between the mutational status of VH genes and pathogenesis of diffuse large B-cell lymphoma in Richter’s syndrome. Leukemia. 2004;18:326–30.

    Article  PubMed  CAS  Google Scholar 

  40. Went P, Agostinelli C, Gallamini A, Piccaluga PP, Ascani S, Sabattini E, et al. Marker expression in peripheral T-cell lymphoma: a proposed clinical-pathologic prognostic score. J Clin Oncol. 2006;24:2472–9.

    Article  PubMed  CAS  Google Scholar 

  41. Dupuis J, Boye K, Martin N, Copie-Bergman C, Plonquet A, Fabiani B, et al. Expression of CXCL13 by neoplastic cells in angioimmunoblastic T-cell lymphoma (AITL): a new diagnostic marker providing evidence that AITL derives from follicular helper T cells. Am J Surg Pathol. 2006;30:490–4.

    Article  PubMed  Google Scholar 

  42. Grogg KL, Morice WG, Macon WR. Spectrum of bone marrow findings in patients with angioimmunoblastic T-cell lymphoma. Br J Haematol. 2007;137:416–22.

    Article  PubMed  Google Scholar 

  43. Khokhar FA, Payne WD, Talwalkar SS, Jorgensen JL, Bueso-Ramos CE, Medeiros LJ, et al. Angioimmunoblastic T-cell lymphoma in bone marrow: a morphologic and immunophenotypic study. Hum Pathol. 2010;41:79–87.

    Article  PubMed  CAS  Google Scholar 

  44. Marafioti T, Paterson JC, Ballabio E, Chott A, Natkunam Y, Rodriguez-Justo M, et al. The inducible T-cell co-stimulator molecule is expressed on subsets of T cells and is a new marker of lymphomas of T follicular helper cell-derivation. Haematologica. 2010;95:432–9.

    Article  PubMed  CAS  Google Scholar 

  45. Yu H, Shahsafaei A, Dorfman DM. Germinal-center T-helper-cell markers PD-1 and CXCL13 are both expressed by neoplastic cells in angioimmunoblastic T-cell lymphoma. Am J Clin Pathol. 2009;131:33–341.

    Article  PubMed  Google Scholar 

  46. Geissinger E, Odenwald T, Lee SS, Bonzheim I, Roth S, Reimer P, et al. Nodal peripheral T-cell lymphomas and, in particular, their lymphoepithelioid (Lennert’s) variant are often derived from CD8(+) cytotoxic T-cells. Virchows Arch. 2004;445:334–43.

    Article  PubMed  Google Scholar 

  47. Horny H, Metcalfe D, Bennet J, Bain B, Akin C, Escribano L, et al. Mastocytosis. Chap. 2: In: Swerdlow S, Campo E, Harris N, Jaffe E, Pileri S, Stein H, Thiele J, Vardiman J, editors. WHO classification of tumours of haematopoietic and lymphoid tissues. 4th ed. Lyon: IARC; 2008. p. 54–63.

    Google Scholar 

  48. Ree HJ, Strauchen JA, Khan AA, Gold JE, Crowley JP, Kahn H, et al. Human immunodeficiency virus-associated Hodgkin’s disease. Clinicopathologic ­studies of 24 cases and preponderance of mixed cellularity type characterized by the occurrence of fibrohistiocytoid stromal cells. Cancer. 1991;67:1614–21.

    Article  PubMed  CAS  Google Scholar 

  49. Macavei I, Galatar N. Bone marrow biopsy (BMB). III. Bone marrow biopsy in Hodgkin’s disease (HD). Morphol Embryol (Bucur). 1990;36:25–32.

    CAS  Google Scholar 

  50. Comin CE, Novelli L, Boddi V, Paglierani M, Dini S. Calretinin, thrombomodulin, CEA, and CD15: a useful combination of immunohistochemical markers for differentiating pleural epithelial mesothelioma from peripheral pulmonary adenocarcinoma. Hum Pathol. 2001;32:529–36.

    Article  PubMed  CAS  Google Scholar 

  51. Liebowitz D. Nasopharyngeal carcinoma: the Epstein-Barr virus association. Semin Oncol. 1994;21:376–81.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Specialised, Diagnostic and Experimental Medicine, Chair of Pathology and Unit of Haematopathology, Bologna University School of Medicine, St. Orsola Hospital, Via Massarenti 9, 40138, Bologna, Italy

    Stefano A. Pileri M.D., Ph.D.

  2. Section of Haematopathology, Department of Haematology and Oncological Sciences “L. and A. Seràgnoli”, University of Bologna, Bologna, Italy

    Elena Sabattini M.D. & Claudio Agostinelli M.D., Ph.D.

Authors
  1. Stefano A. Pileri M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Elena Sabattini M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Claudio Agostinelli M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Stefano A. Pileri M.D., Ph.D. .

Editor information

Editors and Affiliations

  1. , Department of Hematopathology, Evangelismos Hospital, Ersis Street 9, Athens, 15452, Greece

    Dimitra Anagnostou

  2. Royal Marsden Hospital, Inst. Cancer Research, NHS Foundation Trust, Fulham Road, London, SW3 6JJ, United Kingdom

    Estella Matutes

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer-Verlag London

About this chapter

Cite this chapter

Pileri, S.A., Sabattini, E., Agostinelli, C. (2012). Bone Marrow in Hodgkin Lymphoma and Mimickers. In: Anagnostou, D., Matutes, E. (eds) Bone Marrow Lymphoid Infiltrates. Springer, London. https://doi.org/10.1007/978-1-4471-4174-7_13

Download citation

  • DOI: https://doi.org/10.1007/978-1-4471-4174-7_13

  • Published:

  • Publisher Name: Springer, London

  • Print ISBN: 978-1-4471-4173-0

  • Online ISBN: 978-1-4471-4174-7

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation