Analysis of 18F-FDG PET diffuse bone marrow uptake and splenic uptake in staging of Hodgkin’s lymphoma: a reflection of disease infiltration or just inflammation?

  • Pierre Y. Salaun
  • Thomas Gastinne
  • Caroline Bodet-Milin
  • Loïc Campion
  • Pierre Cambefort
  • Anne Moreau
  • Steven Le Gouill
  • Christian Berthou
  • Philippe Moreau
  • Françoise Kraeber-Bodéré
Original Article



18F-FDG PET has been successfully evaluated in the management of Hodgkin’s lymphoma (HL) and the most recent international guidelines recommended 18F-FDG PET for initial staging and final therapeutic assessment. However, 18F-FDG PET diffuse bone marrow uptake (BMU) and splenic uptake (SU) are frequently observed at the initial imaging and remain difficult to analyse. The aim of this retrospective study was to evaluate the significance of 18F-FDG diffuse BMU and SU in initial staging of HL.


A total of 106 patients (median age: 31 years, range: 9–81, 51 female, 55 male) underwent 18F-FDG PET/CT for initial staging of HL. BMU level was assessed visually according to liver uptake (1 = below liver uptake, 2 = corresponding to liver uptake, 3 = above liver uptake) and semi-quantitatively using the maximum standardized uptake value (SUVmax) measured in the sacral area. SU was assessed visually according to liver uptake (1 = below liver uptake, 2 = corresponding to liver uptake, 3 = above liver uptake). These data were compared with the patient’s characteristics including sex, age, Ann Arbor staging, bulky disease (tumour burden > 10 cm), presence of B symptoms, bone foci on PET (n = 106), bone marrow involvement (BMI) on biopsy (n = 75), leukocyte count (n = 74), lactic dehydrogenase (LDH) (n = 87), C-reactive protein (CRP) (n = 83) and fibrinogen (n = 60). Univariate and multivariate analyses were performed.


Multivariate analysis found an independent correlation between BMU visual grading and CRP level (p = 0.007). For semi-quantitative BMU evaluation, multivariate analysis found an independent correlation between sacral SUVs and CRP level (p = 0.032) and Ann Arbor stage (p = 0.005). No BMI was found in patients who presented with SUVmax below 3.4. For splenic evaluation, multivariate analysis found an independent correlation between SU and splenic foci (p = 0.034). No statistical link was found between SU and inflammatory markers.


Our study demonstrates that diffuse BMU at initial staging of HL could be due to bone marrow involvement but more likely to bone marrow inflammatory change and that diffuse SU in contrast is probably more associated with disease involvement than with inflammatory change.


FDG PET Hodgkin’s lymphoma Bone marrow involvement Inflammation 


  1. 1.
    Stumpe KD, Urbinelli M, Steinert HC, Glanzmann C, Buck A, von Schulthess GK. Whole-body positron emission tomography using fluorodeoxyglucose for staging of lymphoma: effectiveness and comparison with computed tomography. Eur J Nucl Med 1998;25:721–8. doi: 10.1007/s002590050275.CrossRefPubMedGoogle Scholar
  2. 2.
    Buchmann I, Moog F, Schirrmeister H, Reske SN. Positron emission tomography for detection and staging of malignant lymphoma. Recent Results Cancer Res 2000;156:78–89.PubMedGoogle Scholar
  3. 3.
    Kostakoglu L, Coleman M, Leonard JP, Kuji I, Zoe H, Goldsmith SJ. PET predicts prognosis after 1 cycle of chemotherapy in aggressive lymphoma and Hodgkin’s disease. J Nucl Med 2002;43:1018–27.PubMedGoogle Scholar
  4. 4.
    Juweid ME, Stroobants S, Hoekstra OS, Mottaghy FM, Dietlein M, Guermazi A, et al. Use of positron emission tomography for response assessment of lymphoma: consensus of the Imaging Subcommittee of International Harmonization Project in Lymphoma. J Clin Oncol 2007;25:571–8. doi: 10.1200/JCO.2006.08.2305.CrossRefPubMedGoogle Scholar
  5. 5.
    Seam P, Juweid ME, Cheson BD. The role of FDG-PET scans in patients with lymphoma. Blood 2007;110:3507–16. doi: 10.1182/blood-2007-06-097238.CrossRefPubMedGoogle Scholar
  6. 6.
    Juweid ME. Utility of positron emission tomography (PET) scanning in managing patients with Hodgkin lymphoma. Hematology Am Soc Hematol Educ Program 2006;259–65:510–1.Google Scholar
  7. 7.
    Carr R, Barrington SF, Madan B, O’Doherty MJ, Saunders CA, van der Walt J, et al. Detection of lymphoma in bone marrow by whole-body positron emission tomography. Blood 1998;91:3340–6.PubMedGoogle Scholar
  8. 8.
    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.PubMedGoogle Scholar
  9. 9.
    Pakos EE, Fotopoulos AD, Ioannidis JP. 18F-FDG PET for evaluation of bone marrow infiltration in staging of lymphoma: a meta-analysis. J Nucl Med 2005;46:958–63.PubMedGoogle Scholar
  10. 10.
    Rutherford SC, Andemariam B, Philips SM, Elstrom RL, Chadburn A, Furman RR, et al. FDG-PET in prediction of splenectomy findings in patients with known or suspected lymphoma. Leuk Lymphoma 2008;49:719–26. doi: 10.1080/10428190801927387.CrossRefPubMedGoogle Scholar
  11. 11.
    Sugawara Y, Fisher SJ, Zasadny KR, Kison PV, Baker LH, Wahl RL. Preclinical and clinical studies of bone marrow uptake of fluorine-1-fluorodeoxyglucose with or without granulocyte colony-stimulating factor during chemotherapy. J Clin Oncol 1998;16:173–80.PubMedGoogle Scholar
  12. 12.
    Brunning RD, Bloomfield CD, McKenna RW, Peterson L. Bilateral trephine bone marrow biopsies in lymphoma and other neoplastic disease. Ann Intern Med 1975;82:365–6.PubMedGoogle Scholar
  13. 13.
    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.PubMedGoogle Scholar
  14. 14.
    Haddy TB, Parker RI, Magrath IT. Bone marrow involvement in young patients with non-Hodgkin’s lymphoma: the importance of multiple bone marrow samples for accurate staging. Med Pediatr Oncol 1989;17:418–23.PubMedCrossRefGoogle Scholar
  15. 15.
    Barrington SF, Carr R. Staging of Burkitt’s lymphoma and response to treatment monitored by PET scanning. Clin Oncol (R Coll Radiol) 1995;7:334–5. doi: 10.1016/S0936-6555(05)80549-7.Google Scholar
  16. 16.
    Okada J, Yoshikawa K, Imazeki K, Minoshima S, Uno K, Itami J, et al. The use of FDG-PET in the detection and management of malignant lymphoma: correlation of uptake with prognosis. J Nucl Med 1991;32:686–91.PubMedGoogle Scholar
  17. 17.
    Hoh CK, Glaspy J, Rosen P, Dahlbom M, Lee SJ, Kunkel L, et al. Whole-body FDG-PET imaging for staging of Hodgkin’s disease and lymphoma. J Nucl Med 1997;38:343–8.PubMedGoogle Scholar
  18. 18.
    Schaefer NG, Strobel K, Taverna C, Hany TF. Bone involvement in patients with lymphoma: the role of FDG-PET/CT. Eur J Nucl Med Mol Imaging 2007;34:60–7. doi: 10.1007/s00259-006-0238-8.CrossRefPubMedGoogle Scholar
  19. 19.
    Menon NC, Buchanan JG. Bilateral trephine bone marrow biopsies in Hodgkin’s and non-Hodgkin’s lymphoma. Pathology 1979;11:53–7. doi: 10.3109/00313027909063538.CrossRefPubMedGoogle Scholar
  20. 20.
    Juneja SK, Wolf MM, Cooper IA. Value of bilateral bone marrow biopsy specimens in non-Hodgkin’s lymphoma. J Clin Pathol 1990;43:630–2. doi: 10.1136/jcp.43.8.630.CrossRefPubMedGoogle Scholar
  21. 21.
    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.PubMedGoogle Scholar
  22. 22.
    Wang J, Weiss LM, Chang KL, Slovak ML, Gaal K, Forman SJ, et al. Diagnostic utility of bilateral bone marrow examination: significance of morphologic and ancillary technique study in malignancy. Cancer 2002;94:1522–31. doi: 10.1002/cncr.10364.CrossRefPubMedGoogle Scholar
  23. 23.
    Ribrag V, Vanel D, Leboulleux S, Lumbroso J, Couanet D, Bonniaud G, et al. Prospective study of bone marrow infiltration in aggressive lymphoma by three independent methods: whole-body MRI, PET/CT and bone marrow biopsy. Eur J Radiol 2008;66:325–31. doi: 10.1016/j.ejrad.2007.06.014.CrossRefPubMedGoogle Scholar
  24. 24.
    Newman JS, Francis IR, Kaminski MS, Wahl RL. Imaging of lymphoma with PET with 2-[F-18]-fluoro-2-deoxy-D-glucose: correlation with CT. Radiology 1994;190:111–6.PubMedGoogle Scholar
  25. 25.
    Hasenclever D, Diehl V. A prognostic score for advanced Hodgkin’s disease. International Prognostic Factors Project on Advanced Hodgkin’s Disease. N Engl J Med 1998;339:1506–14. doi: 10.1056/NEJM199811193392104.CrossRefPubMedGoogle Scholar
  26. 26.
    Zielinski CC, Preis P, Aiginger P, Eibl MM. Acute-phase-proteins and parameters of humoral immunity in patients with advanced Hodgkin’s disease. J Cancer Res Clin Oncol 1985;110:65–70. doi: 10.1007/BF00402504.CrossRefPubMedGoogle Scholar
  27. 27.
    Axdorph U, Sjöberg J, Grimfors G, Landgren O, Porwit-MacDonald A, Björkholm M. Biological markers may add to prediction of outcome achieved by the International Prognostic Score in Hodgkin’s disease. Ann Oncol 2000;11:1405–11. doi: 10.1023/A:1026551727795.CrossRefPubMedGoogle Scholar
  28. 28.
    Núñez R, Rini JN, Tronco GG, Tomas MB, Nichols K, Palestro CJ. Correlation of hematologic parameters with bone marrow and spleen uptake in FDG PET [in Spanish]. Rev Esp Med Nucl 2005;24:107–12. doi: 10.1157/13071686.CrossRefPubMedGoogle Scholar
  29. 29.
    Rueffer U, Sieber M, Josting A, Breuer K, Grotenhermen F, Bredenfeld H, et al. Prognostic factors for subdiaphragmatic involvement in clinical stage I-II supradiaphragmatic Hodgkin’s disease: a retrospective analysis of the GHSG. Ann Oncol 1999;10:1343–8. doi: 10.1023/A:1008377629280.CrossRefPubMedGoogle Scholar
  30. 30.
    Trotter MC, Cloud GA, Davis M, Sanford SP, Urist MM, Soong SJ, et al. Predicting the risk of abdominal disease in Hodgkin’s lymphoma. A multifactorial analysis of staging laparotomy results in 255 patients. Ann Surg 1985;201:465–9.CrossRefPubMedGoogle Scholar
  31. 31.
    Tubiana M, Henry-Amar M, Hayat M, Burgers M, Qasim M, Somers R, et al. Prognostic significance of the number of involved areas in the early stages of Hodgkin’s disease. Cancer 1984;54:885–94. doi: 10.1002/1097-0142(19840901)54:5<885::AID-CNCR2820540522>3.0.CO;2-B.CrossRefPubMedGoogle Scholar
  32. 32.
    Rueffer U, Sieber M, Stemberg M, Gossmann A, Josting A, Koch T, et al. Spleen involvement in Hodgkin’s lymphoma: assessment and risk profile. Ann Hematol 2003;82:390–6. doi: 10.1007/s00277-003-0631-3.CrossRefPubMedGoogle Scholar
  33. 33.
    Sandrasegaran K, Robinson PJ, Selby P. Staging of lymphoma in adults. Clin Radiol 1994;49:149–61. doi: 10.1016/S0009-9260(05)81766-0.CrossRefPubMedGoogle Scholar
  34. 34.
    Plat M, Erk JU. Abdominal ultrasound diagnosis of malignant lymphomas [in German]. Gastroenterol J 1990;50:117–23.PubMedGoogle Scholar
  35. 35.
    Munker R, Stengel A, Stäbler A, Hiller E, Brehm G. Diagnostic accuracy of ultrasound and computed tomography in the staging of Hodgkin’s disease. Verification by laparotomy in 100 cases. Cancer 1995;76:1460–6. doi: 10.1002/1097-0142(19951015)76:8<1460::AID-CNCR2820760825>3.0.CO;2-Y.CrossRefPubMedGoogle Scholar
  36. 36.
    Hancock SL, Scidmore NS, Hopkins KL, Cox RS, Bergin CJ. Computed tomography assessment of splenic size as a predictor of splenic weight and disease involvement in laparotomy staged Hodgkin’s disease. Int J Radiat Oncol Biol Phys 1994;28:93–9.PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Pierre Y. Salaun
    • 1
    • 2
  • Thomas Gastinne
    • 3
  • Caroline Bodet-Milin
    • 4
  • Loïc Campion
    • 5
    • 7
  • Pierre Cambefort
    • 1
  • Anne Moreau
    • 6
  • Steven Le Gouill
    • 3
    • 7
  • Christian Berthou
    • 8
  • Philippe Moreau
    • 3
    • 7
  • Françoise Kraeber-Bodéré
    • 2
    • 4
    • 7
  1. 1.Nuclear Medicine DepartmentUniversity Hospital of BrestBrestFrance
  2. 2.Nuclear Medicine DepartmentRené Gauducheau Cancer CenterNantesFrance
  3. 3.Department of HaematologyUniversity Hospital of NantesNantesFrance
  4. 4.Nuclear Medicine DepartmentUniversity Hospital of NantesNantesFrance
  5. 5.Biostatistics UnitRené Gauducheau Cancer CenterNantesFrance
  6. 6.Department of HistopathologyUniversity Hospital of NantesNantesFrance
  7. 7.CRCNAINSERM UMR 892NantesFrance
  8. 8.Department of HaematologyUniversity Hospital of BrestBrestFrance

Personalised recommendations