Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Evaluation, staging, and response assessment of non-Hodgkin lymphoma

Arnold S Freedman, MD
Jonathan W Friedberg, MD
Section Editor
Andrew Lister, MD, FRCP, FRCPath, FRCR
Deputy Editor
Alan G Rosmarin, MD


The initial evaluation of the patient with newly diagnosed non-Hodgkin lymphoma (NHL) must establish the precise histologic subtype, the extent and sites of disease (localized or advanced; nodal or extranodal), and the general health status of the patient. These studies help to determine the appropriate therapy and the patient's prognosis.

A general review of the initial laboratory studies, imaging studies, staging, and prognosis of NHL will be presented here. Of note, the appropriate pretreatment evaluation differs by histologic subtype. As such, details regarding the pretreatment evaluation of many NHL histologies are presented separately as part of the discussion of their initial treatment. The clinical presentation and basic diagnostic tests are presented separately as well. (See "Clinical presentation and diagnosis of non-Hodgkin lymphoma" and "Classification of the hematopoietic neoplasms".)


Overview — After the initial tissue biopsy provides a diagnosis of NHL, the following baseline laboratory tests are appropriate for most histologies:

Complete blood count, white blood cell differential, platelet count, and examination of the peripheral smear for the presence of atypical cells, suggesting peripheral blood and bone marrow involvement

Biochemical tests including blood urea nitrogen (BUN), creatinine, alkaline phosphatase, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and albumin

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Nov 2017. | This topic last updated: Jul 17, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Bloomfield CD, McKenna RW, Brunning RD. Significance of haematological parameters in the non-Hodgkin's malignant lymphomas. Br J Haematol 1976; 32:41.
  2. Conlan MG, Armitage JO, Bast M, Weisenburger DD. Clinical significance of hematologic parameters in non-Hodgkin's lymphoma at diagnosis. Cancer 1991; 67:1389.
  3. McKenna RW, Bloomfield CD, Brunning RD. Nodular lymphoma: bone marrow and blood manifestations. Cancer 1975; 36:428.
  4. Conlan MG, Bast M, Armitage JO, Weisenburger DD. Bone marrow involvement by non-Hodgkin's lymphoma: the clinical significance of morphologic discordance between the lymph node and bone marrow. Nebraska Lymphoma Study Group. J Clin Oncol 1990; 8:1163.
  5. Foucar K, McKenna RW, Frizzera G, Brunning RD. Bone marrow and blood involvement by lymphoma in relationship to the Lukes--Collins classification. Cancer 1982; 49:888.
  6. Cheson BD, Fisher RI, Barrington SF, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol 2014; 32:3059.
  7. Adams HJ, Kwee TC, de Keizer B, et al. FDG PET/CT for the detection of bone marrow involvement in diffuse large B-cell lymphoma: systematic review and meta-analysis. Eur J Nucl Med Mol Imaging 2014; 41:565.
  8. Brunning RD, Bloomfield CD, McKenna RW, Peterson LA. Bilateral trephine bone marrow biopsies in lymphoma and other neoplastic diseases. Ann Intern Med 1975; 82:365.
  9. Juneja SK, Wolf MM, Cooper IA. Value of bilateral bone marrow biopsy specimens in non-Hodgkin's lymphoma. J Clin Pathol 1990; 43:630.
  10. Menon NC, Buchanan JG. Bilateral trephine bone marrow biopsies in Hodgkin's and non-Hodgkin's lymphoma. Pathology 1979; 11:53.
  11. 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.
  12. Luoni M, Declich P, De Paoli Af1p4, et al. Bone marrow biopsy for the staging of non-Hodgkin's lymphoma: bilateral or unilateral trephine biopsy? Tumori 1995; 81:410.
  13. Dumontet C, Drai J, Bienvenu J, et al. Profiles and prognostic values of LDH isoenzymes in patients with non-Hodgkin's lymphoma. Leukemia 1999; 13:811.
  14. Hegde U, Filie A, Little RF, et al. High incidence of occult leptomeningeal disease detected by flow cytometry in newly diagnosed aggressive B-cell lymphomas at risk for central nervous system involvement: the role of flow cytometry versus cytology. Blood 2005; 105:496.
  15. D'Addario G, Dieterle A, Torhorst J, et al. HIV-testing and newly-diagnosed malignant lymphomas. The SAKK 96/90 registration study. Leuk Lymphoma 2003; 44:133.
  16. National Comprehensive Cancer Network (NCCN). NCCN Clinical practice guidelines in oncology. http://www.nccn.org/professionals/physician_gls/f_guidelines.asp (Accessed on February 27, 2016).
  17. Viswanatha DS, Dogan A. Hepatitis C virus and lymphoma. J Clin Pathol 2007; 60:1378.
  18. Spinelli JJ, Lai AS, Krajden M, et al. Hepatitis C virus and risk of non-Hodgkin lymphoma in British Columbia, Canada. Int J Cancer 2008; 122:630.
  19. Schöllkopf C, Smedby KE, Hjalgrim H, et al. Hepatitis C infection and risk of malignant lymphoma. Int J Cancer 2008; 122:1885.
  20. Engels EA, Cho ER, Jee SH. Hepatitis B virus infection and risk of non-Hodgkin lymphoma in South Korea: a cohort study. Lancet Oncol 2010; 11:827.
  21. Yeo W, Chan TC, Leung NW, et al. Hepatitis B virus reactivation in lymphoma patients with prior resolved hepatitis B undergoing anticancer therapy with or without rituximab. J Clin Oncol 2009; 27:605.
  22. Hsu C, Hsiung CA, Su IJ, et al. A revisit of prophylactic lamivudine for chemotherapy-associated hepatitis B reactivation in non-Hodgkin's lymphoma: a randomized trial. Hepatology 2008; 47:844.
  23. Yağci M, Acar K, Sucak GT, et al. A prospective study on chemotherapy-induced hepatitis B virus reactivation in chronic HBs Ag carriers with hematologic malignancies and pre-emptive therapy with nucleoside analogues. Leuk Lymphoma 2006; 47:1608.
  24. Besson C, Canioni D, Lepage E, et al. Characteristics and outcome of diffuse large B-cell lymphoma in hepatitis C virus-positive patients in LNH 93 and LNH 98 Groupe d'Etude des Lymphomes de l'Adulte programs. J Clin Oncol 2006; 24:953.
  25. Lau GK, Lee CK, Liang R. Hepatitis B virus infection and bone marrow transplantation. Crit Rev Oncol Hematol 1999; 31:71.
  26. Takai S, Tsurumi H, Ando K, et al. Prevalence of hepatitis B and C virus infection in haematological malignancies and liver injury following chemotherapy. Eur J Haematol 2005; 74:158.
  27. Lalazar G, Rund D, Shouval D. Screening, prevention and treatment of viral hepatitis B reactivation in patients with haematological malignancies. Br J Haematol 2007; 136:699.
  28. Aksoy S, Harputluoglu H, Kilickap S, et al. Rituximab-related viral infections in lymphoma patients. Leuk Lymphoma 2007; 48:1307.
  29. Artz AS, Somerfield MR, Feld JJ, et al. American Society of Clinical Oncology provisional clinical opinion: chronic hepatitis B virus infection screening in patients receiving cytotoxic chemotherapy for treatment of malignant diseases. J Clin Oncol 2010; 28:3199.
  30. Terrault NA, Bzowej NH, Chang KM, et al. AASLD guidelines for treatment of chronic hepatitis B. Hepatology 2016; 63:261.
  31. Barrington SF, Mikhaeel NG, Kostakoglu L, et al. Role of imaging in the staging and response assessment of lymphoma: consensus of the International Conference on Malignant Lymphomas Imaging Working Group. J Clin Oncol 2014; 32:3048.
  32. Karam M, Novak L, Cyriac J, et al. Role of fluorine-18 fluoro-deoxyglucose positron emission tomography scan in the evaluation and follow-up of patients with low-grade lymphomas. Cancer 2006; 107:175.
  33. Allen-Auerbach M, Quon A, Weber WA, et al. Comparison between 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography and positron emission tomography/computed tomography hardware fusion for staging of patients with lymphoma. Mol Imaging Biol 2004; 6:411.
  34. Schaefer NG, Hany TF, Taverna C, et al. Non-Hodgkin lymphoma and Hodgkin disease: coregistered FDG PET and CT at staging and restaging--do we need contrast-enhanced CT? Radiology 2004; 232:823.
  35. Hernandez-Maraver D, Hernandez-Navarro F, Gomez-Leon N, et al. Positron emission tomography/computed tomography: diagnostic accuracy in lymphoma. Br J Haematol 2006; 135:293.
  36. Kwee TC, Kwee RM, Nievelstein RA. Imaging in staging of malignant lymphoma: a systematic review. Blood 2008; 111:504.
  37. Freudenberg LS, Antoch G, Schütt P, et al. FDG-PET/CT in re-staging of patients with lymphoma. Eur J Nucl Med Mol Imaging 2004; 31:325.
  38. Juweid ME, Stroobants S, Hoekstra OS, 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.
  39. Barrington SF, Qian W, Somer EJ, et al. Concordance between four European centres of PET reporting criteria designed for use in multicentre trials in Hodgkin lymphoma. Eur J Nucl Med Mol Imaging 2010; 37:1824.
  40. Isasi CR, Lu P, Blaufox MD. A metaanalysis of 18F-2-deoxy-2-fluoro-D-glucose positron emission tomography in the staging and restaging of patients with lymphoma. Cancer 2005; 104:1066.
  41. de Jong PA, van Ufford HM, Baarslag HJ, et al. CT and 18F-FDG PET for noninvasive detection of splenic involvement in patients with malignant lymphoma. AJR Am J Roentgenol 2009; 192:745.
  42. Carr R, Barrington SF, Madan B, et al. Detection of lymphoma in bone marrow by whole-body positron emission tomography. Blood 1998; 91:3340.
  43. Elstrom R, Guan L, Baker G, et al. Utility of FDG-PET scanning in lymphoma by WHO classification. Blood 2003; 101:3875.
  44. Itti E, Meignan M, Berriolo-Riedinger A, et al. An international confirmatory study of the prognostic value of early PET/CT in diffuse large B-cell lymphoma: comparison between Deauville criteria and ΔSUVmax. Eur J Nucl Med Mol Imaging 2013; 40:1312.
  45. Seam P, Juweid ME, Cheson BD. The role of FDG-PET scans in patients with lymphoma. Blood 2007; 110:3507.
  46. Kostakoglu L, Leonard JP, Kuji I, et al. Comparison of fluorine-18 fluorodeoxyglucose positron emission tomography and Ga-67 scintigraphy in evaluation of lymphoma. Cancer 2002; 94:879.
  47. Wirth A, Seymour JF, Hicks RJ, et al. Fluorine-18 fluorodeoxyglucose positron emission tomography, gallium-67 scintigraphy, and conventional staging for Hodgkin's disease and non-Hodgkin's lymphoma. Am J Med 2002; 112:262.
  48. Zijlstra JM, Hoekstra OS, Raijmakers PG, et al. 18FDG positron emission tomography versus 67Ga scintigraphy as prognostic test during chemotherapy for non-Hodgkin's lymphoma. Br J Haematol 2003; 123:454.
  49. Tsukamoto N, Kojima M, Hasegawa M, et al. The usefulness of (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG-PET) and a comparison of (18)F-FDG-pet with (67)gallium scintigraphy in the evaluation of lymphoma: relation to histologic subtypes based on the World Health Organization classification. Cancer 2007; 110:652.
  50. Feeney J, Horwitz S, Gönen M, Schöder H. Characterization of T-cell lymphomas by FDG PET/CT. AJR Am J Roentgenol 2010; 195:333.
  51. Weiler-Sagie M, Bushelev O, Epelbaum R, et al. (18)F-FDG avidity in lymphoma readdressed: a study of 766 patients. J Nucl Med 2010; 51:25.
  52. Schot BW, Zijlstra JM, Sluiter WJ, et al. Early FDG-PET assessment in combination with clinical risk scores determines prognosis in recurring lymphoma. Blood 2007; 109:486.
  53. Juweid ME, Cheson BD. Role of positron emission tomography in lymphoma. J Clin Oncol 2005; 23:4577.
  54. Liedtke M, Hamlin PA, Moskowitz CH, Zelenetz AD. Surveillance imaging during remission identifies a group of patients with more favorable aggressive NHL at time of relapse: a retrospective analysis of a uniformly-treated patient population. Ann Oncol 2006; 17:909.
  55. Moskowitz CH, Schöder H, Teruya-Feldstein J, et al. Risk-adapted dose-dense immunochemotherapy determined by interim FDG-PET in Advanced-stage diffuse large B-Cell lymphoma. J Clin Oncol 2010; 28:1896.
  56. Jerusalem G, Beguin Y, Fassotte MF, et al. Whole-body positron emission tomography using 18F-fluorodeoxyglucose for posttreatment evaluation in Hodgkin's disease and non-Hodgkin's lymphoma has higher diagnostic and prognostic value than classical computed tomography scan imaging. Blood 1999; 94:429.
  57. Naumann R, Vaic A, Beuthien-Baumann B, et al. Prognostic value of positron emission tomography in the evaluation of post-treatment residual mass in patients with Hodgkin's disease and non-Hodgkin's lymphoma. Br J Haematol 2001; 115:793.
  58. Spaepen K, Stroobants S, Dupont P, et al. Early restaging positron emission tomography with ( 18)F-fluorodeoxyglucose predicts outcome in patients with aggressive non-Hodgkin's lymphoma. Ann Oncol 2002; 13:1356.
  59. Friedberg JW, Chengazi V. PET scans in the staging of lymphoma: current status. Oncologist 2003; 8:438.
  60. Zinzani PL, Fanti S, Battista G, et al. Predictive role of positron emission tomography (PET) in the outcome of lymphoma patients. Br J Cancer 2004; 91:850.
  61. Svoboda J, Andreadis C, Elstrom R, et al. Prognostic value of FDG-PET scan imaging in lymphoma patients undergoing autologous stem cell transplantation. Bone Marrow Transplant 2006; 38:211.
  62. Safar V, Dupuis J, Itti E, et al. Interim [18F]fluorodeoxyglucose positron emission tomography scan in diffuse large B-cell lymphoma treated with anthracycline-based chemotherapy plus rituximab. J Clin Oncol 2012; 30:184.
  63. Mato AR, Svoboda J, Feldman T, et al. Post-treatment (not interim) positron emission tomography-computed tomography scan status is highly predictive of outcome in mantle cell lymphoma patients treated with R-HyperCVAD. Cancer 2012; 118:3565.
  64. Haioun C, Itti E, Rahmouni A, et al. [18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in aggressive lymphoma: an early prognostic tool for predicting patient outcome. Blood 2005; 106:1376.
  65. Hutchings M, Loft A, Hansen M, et al. FDG-PET after two cycles of chemotherapy predicts treatment failure and progression-free survival in Hodgkin lymphoma. Blood 2006; 107:52.
  66. Kostakoglu L, Goldsmith SJ, Leonard JP, et al. FDG-PET after 1 cycle of therapy predicts outcome in diffuse large cell lymphoma and classic Hodgkin disease. Cancer 2006; 107:2678.
  67. Hutchings M, Kostakoglu L, Zaucha JM, et al. In vivo treatment sensitivity testing with positron emission tomography/computed tomography after one cycle of chemotherapy for Hodgkin lymphoma. J Clin Oncol 2014; 32:2705.
  68. Pregno P, Chiappella A, Bellò M, et al. Interim 18-FDG-PET/CT failed to predict the outcome in diffuse large B-cell lymphoma patients treated at the diagnosis with rituximab-CHOP. Blood 2012; 119:2066.
  69. Horning SJ, Juweid ME, Schöder H, et al. Interim positron emission tomography scans in diffuse large B-cell lymphoma: an independent expert nuclear medicine evaluation of the Eastern Cooperative Oncology Group E3404 study. Blood 2010; 115:775.
  70. Spaepen K, Stroobants S, Dupont P, et al. Prognostic value of positron emission tomography (PET) with fluorine-18 fluorodeoxyglucose ([18F]FDG) after first-line chemotherapy in non-Hodgkin's lymphoma: is [18F]FDG-PET a valid alternative to conventional diagnostic methods? J Clin Oncol 2001; 19:414.
  71. Gawande RS, Khurana A, Messing S, et al. Differentiation of normal thymus from anterior mediastinal lymphoma and lymphoma recurrence at pediatric PET/CT. Radiology 2012; 262:613.
  72. Spaepen K, Stroobants S, Dupont P, et al. Prognostic value of pretransplantation positron emission tomography using fluorine 18-fluorodeoxyglucose in patients with aggressive lymphoma treated with high-dose chemotherapy and stem cell transplantation. Blood 2003; 102:53.
  73. Schot B, van Imhoff G, Pruim J, et al. Predictive value of early 18F-fluoro-deoxyglucose positron emission tomography in chemosensitive relapsed lymphoma. Br J Haematol 2003; 123:282.
  74. Derenzini E, Musuraca G, Fanti S, et al. Pretransplantation positron emission tomography scan is the main predictor of autologous stem cell transplantation outcome in aggressive B-cell non-Hodgkin lymphoma. Cancer 2008; 113:2496.
  75. Ulaner GA, Goldman DA, Sauter CS, et al. Prognostic Value of FDG PET/CT before Allogeneic and Autologous Stem Cell Transplantation for Aggressive Lymphoma. Radiology 2015; 277:518.
  76. North LB, Libshitz HI, Lorigan JG. Thoracic lymphoma. Radiol Clin North Am 1990; 28:745.
  77. Castellino RA, Hilton S, O'Brien JP, Portlock CS. Non-Hodgkin lymphoma: contribution of chest CT in the initial staging evaluation. Radiology 1996; 199:129.
  78. Shibuya H, Kamiyama R, Watanabe I, et al. Stage I and II Waldeyer's ring and oral-sinonasal non-Hodgkin's lymphoma. Cancer 1987; 59:940.
  79. Saul SH, Kapadia SB. Primary lymphoma of Waldeyer's ring. Clinicopathologic study of 68 cases. Cancer 1985; 56:157.
  80. Dodd GD. Lymphoma of the hollow abdominal viscera. Radiol Clin North Am 1990; 28:771.
  81. Silverman JF, Geisinger KR, Raab SS, Stanley MW. Fine needle aspiration biopsy of the spleen in the evaluation of neoplastic disorders. Acta Cytol 1993; 37:158.
  82. Moriarty AT, Schwenk GR Jr, Chua G. Splenic fine needle aspiration biopsy in the diagnosis of lymphoreticular diseases. A report of four cases. Acta Cytol 1993; 37:191.
  83. Phillips G, Kumari-Subaiya S, Sawitsky A. Ultrasonic evaluation of the scrotum in lymphoproliferative disease. J Ultrasound Med 1987; 6:169.
  84. Mazzu D, Jeffrey RB Jr, Ralls PW. Lymphoma and leukemia involving the testicles: findings on gray-scale and color Doppler sonography. AJR Am J Roentgenol 1995; 164:645.
  85. Charnsangavej C. Lymphoma of the genitourinary tract. Radiol Clin North Am 1990; 28:865.
  86. Rosenberg SA. Validity of the Ann Arbor staging classification for the non-Hodgkin's lymphomas. Cancer Treat Rep 1977; 61:1023.
  87. Moormeier JA, Williams SF, Golomb HM. The staging of non-Hodgkin's lymphomas. Semin Oncol 1990; 17:43.
  88. Anderson T, Chabner BA, Young RC, et al. Malignant lymphoma. 1. The histology and staging of 473 patients at the National Cancer Institute. Cancer 1982; 50:2699.
  89. Younes A, Hilden P, Coiffier B, et al. International Working Group consensus response evaluation criteria in lymphoma (RECIL 2017). Ann Oncol 2017; 28:1436.
  90. Cheson BD, Ansell S, Schwartz L, et al. Refinement of the Lugano Classification lymphoma response criteria in the era of immunomodulatory therapy. Blood 2016; 128:2489.
  91. Lee SM, Ryder WD, Clemons MJ, et al. Treatment outcome and prognostic factors for relapse after high-dose chemotherapy and peripheral blood stem cell rescue for patients with poor risk high grade non-Hodgkin's lymphoma. Bone Marrow Transplant 1999; 24:271.
  92. Shipp MA, Ross KN, Tamayo P, et al. Diffuse large B-cell lymphoma outcome prediction by gene-expression profiling and supervised machine learning. Nat Med 2002; 8:68.
Topic Outline