eMedicine Specialties > Hematology > Stem Cells and Disorders

Lymphoma, Diffuse Mixed: Differential Diagnoses & Workup

Author: Clifford H Pemberton, MD, Instructor in Medicine, Jefferson Medical College; Medical Director, Jefferson Hospice and Palliative Care Program; Consulting Staff, Department of Medicine, Division of Hematology/Oncology, Lankenau Hospital
Coauthor(s): Asher A Chanan-Khan, MD, Assistant Professor, Department of Medicine, Division of Lymphoma and Bone Marrow Transplantation, Roswell Park Cancer Institute, State University of New York at Buffalo
Contributor Information and Disclosures

Updated: Dec 18, 2008

Differential Diagnoses

Lymphoma, Mantle Cell
Lymphoma, Non-Hodgkin
Sarcoidosis
Tuberculosis

Workup

Laboratory Studies

  • Complete blood cell (CBC) count: Involvement of the bone marrow may result in anemia, thrombocytopenia, and/or leukopenia.
  • Serum electrolyte levels: Electrolyte abnormalities may occur from renal involvement with lymphoma. Abnormal renal function may require a chemotherapy dose adjustment.
  • LDH level: An elevated level of LDH corresponds with the tumor burden and the extent of disease. The LDH value is part of the IPI and a useful indicator of the response to treatment; it can be used as an early nonspecific indicator of disease relapse.1
  • Uric acid level: An elevated level signifies a high tumor burden and an increased likelihood of tumor lysis syndrome with chemotherapy.
  • Flow cytometry: Expression of different immunophenotypes helps in determining a clonal cell population and in differentiating between B- or T-cell origins.
  • Cytogenetic or fluorescent in situ hybridization (FISH) studies may reveal common chromosomal translocations:
    • t(3q27) (bcl-6) – Occurs in 35% of patients
    • t(14;18)(q32;q21) (bcl-2) – Occurs in 15-20% of patients
    • t(8;14)(q24;q32) – Occurs in fewer than 5% of patients
  • Hepatitis B testing for combination chemoimmunotherapy with rituximab (risk of activation
  • Gene expression profiling may be able to distinguish 2 separate subtypes of diffuse large B-cell lymphomas (diffuse mixed lymphomas) with different prognoses (normal germinal center B-cell pattern vs activated B-cell–like).
  • Results from gene rearrangement studies can be used to establish clonality.

Imaging Studies

  • Computed tomography (CT) scans (neck, chest, abdomen, pelvis)
    • These studies are used to help identify the degree of lymphadenopathy, the presence or absence of extranodal disease, and/or the presence of visceral involvement. CT scans are also part of the complete staging workup for diffuse large B-cell lymphoma (diffuse mixed lymphoma).
    • Baseline CT scan findings aid in disease follow-up care after chemotherapy to assess the degree of response to therapy, as well as aid in planning consolidating radiation therapy, if used.
  • Findings from gallium scans provide an estimate of the extent of disease and are sometimes used as a means of assessing sites of relapse.
  • Findings from positron emission tomography (PET) scanning for glucose uptake can indicate areas of increased metabolic activity and can be useful to help determine whether residual masses represent scars or persistent lymphoma, in addition to their frequent use in initial disease staging. PET scan findings are being investigated as prognostic indicators during treatment (after 2-4 cycles), but the clinical utility of this is still unclear.

Other Tests

  • Findings from multiple gated acquisition (MUGA) scans are used to evaluate the patient's ejection fraction before chemotherapy, because anthracyclines have a potential cardiotoxic effect.

Procedures

  • Perform bone marrow aspiration and biopsy as part of the staging process to help rule out involvement with lymphoma.
  • Lymph node biopsy is required to establish a definitive diagnosis of non-Hodgkin lymphoma. This should be an excisional biopsy rather than a needle biopsy, because nodal architecture is often difficult to assess when small amounts of tissue are used.

Staging

Diffuse large B-cell lymphomas (diffuse mixed lymphomas) are staged according to the commonly used Ann Arbor staging system.

  • Stage I – Involvement of a single lymph node region or lymphoid structure (ie, spleen, thymus, Waldeyer ring) or involvement of a single extralymphatic site (IE)
  • Stage II – Involvement of 2 or more lymph node regions on the same side of the diaphragm; localized contiguous involvement of only 1 extranodal site and 1 lymph node region on the same side of the diaphragm
  • Stage III – Involvement of lymph node regions on both sides of the diaphragm
  • Stage IV – Diffuse or disseminated involvement of 1 or more extranodal organs or tissues, with or without associated lymph node involvement.

More on Lymphoma, Diffuse Mixed

Overview: Lymphoma, Diffuse Mixed
Differential Diagnoses & Workup: Lymphoma, Diffuse Mixed
Treatment & Medication: Lymphoma, Diffuse Mixed
Follow-up: Lymphoma, Diffuse Mixed
Multimedia: Lymphoma, Diffuse Mixed
References
Further Reading
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References

  1. Sweetenham JW. Diffuse large B-cell lymphoma: risk stratification and management of relapsed disease. Hematology Am Soc Hematol Educ Program. 2005;252-9. [Medline]. [Full Text].

  2. International Non-Hodgkin's Lymphoma Prognostic Factors Project. A predictive model for aggressive non-Hodgkin's lymphoma. N Engl J Med. Sep 30 1993;329(14):987-94. [Medline]. [Full Text].

  3. Vose JM, Link BK, Grossbard ML, et al. Phase II study of rituximab in combination with CHOP chemotherapy in patients with previously untreated, aggressive non-Hodgkin's lymphoma. J Clin Oncol. Jan 15 2001;19(2):389-97. [Medline]. [Full Text].

  4. Pfreundschuh M, Truemper L, Gill D, et al. First analysis of the completed Mabthera International (Mint) Trial in young patients with low-risk diffuse large B-cell lymphoma (DLBCL): addition of rituximab to a CHOP-like regimen significantly improves outcome of all patients with the identification of a very favorable subgroup with IPI=O and no bulky disease [abstract 157]. Blood. 2004;104:48a:[Full Text].

  5. Sehn LH, Donaldson J, Chhanabhai M, et al. Introduction of combined CHOP plus rituximab therapy dramatically improved outcome of diffuse large B-cell lymphoma in British Columbia. J Clin Oncol. Aug 1 2005;23(22):5027-33. [Medline]. [Full Text].

  6. Philip T, Chauvin F, Armitage J, et al. Parma international protocol: pilot study of DHAP followed by involved-field radiotherapy and BEAC with autologous bone marrow transplantation. Blood. Apr 1 1991;77(7):1587-92. [Medline]. [Full Text].

  7. Glass B, Kloess M, Bentz M, et al. Dose-escalated CHOP plus etoposide (MegaCHOEP) followed by repeated stem cell transplantation for primary treatment of aggressive high-risk non-Hodgkin lymphoma. Blood. Apr 15 2006;107(8):3058-64. [Medline]. [Full Text].

  8. Leonard JP, Furman RR, Cheung YKK, et al. Phase I/II trial of bortezomib + CHOP-rituximab in diffuse large B cell (DLBCL) and mantle cell lymphoma (MCL): phase I results [abstract]. Blood. 2005;106:491a:[Full Text].

  9. Fillet G, Bonnet C, Mounier N, et al. No role for chemoradiotherapy when compared with chemotherapy alone in elderly patients with localized low risk aggressive lymphoma: final results of the LNH93-4 GELA study [abstract 15]. Blood. 2005;106:9a:[Full Text].

  10. Kunkel L, Wong A, Maneatis T, et al. Optimizing the use of rituximab for treatment of B-cell non-Hodgkin's lymphoma: a benefit-risk update. Semin Oncol. Dec 2000;27(6 suppl 12):53-61. [Medline].

  11. Link MP, Donaldson SS, Berard CW, Shuster JJ, Murphy SB. Results of treatment of childhood localized non-Hodgkin's lymphoma with combination chemotherapy with or without radiotherapy. N Engl J Med. Apr 26 1990;322(17):1169-74. [Medline].

  12. Martin-Subero JI, Kreuz M, Bibikova M, et al. New insights into the biology and origin of mature aggressive B-cell lymphomas by combined epigenomic, genomic and transcriptional profiling. Blood. Dec 15 2008;epub ahead of print. [Medline].

  13. Philip T, Guglielmi C, Hagenbeek A, et al. Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin's lymphoma. N Engl J Med. Dec 7 1995;333(23):1540-5. [Medline]. [Full Text].

  14. Rodriguez MA, Cabanillas FC, Velasquez W, et al. Results of a salvage treatment program for relapsing lymphoma: MINE consolidated with ESHAP. J Clin Oncol. Jul 1995;13(7):1734-41. [Medline].

  15. Tondini C, Zanini M, Lombardi F, et al. Combined modality treatment with primary CHOP chemotherapy followed by locoregional irradiation in stage I or II histologically aggressive non-Hodgkin's lymphomas. J Clin Oncol. Apr 1993;11(4):720-5. [Medline].

  16. Vose JM, Zhang MJ, Rowlings PA, et al. Autologous transplantation for diffuse aggressive non-Hodgkin's lymphoma in patients never achieving remission: a report from the Autologous Blood and Marrow Transplant Registry. J Clin Oncol. Jan 15 2001;19(2):406-13. [Medline]. [Full Text].

  17. Zainuddin N, Berglund M, Wanders A, et al. TP53 mutations predict for poor survival in de novo diffuse large B-cell lymphoma of germinal center subtype. Leuk Res. Jan 2009;33(1):60-6. [Medline].

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Further Reading

Related eMedicine Topics

Suggested Reading

  • Griffin TC, Weitzman S, Weinstein H, et al, and the Children's Oncology Group. A study of rituximab and ifosfamide, carboplatin, and etoposide chemotherapy in children with recurrent/refractory B-cell (CD20+) non-Hodgkin lymphoma and mature B-cell acute lymphoblastic leukemia: A report from the Children's Oncology Group. Pediatr Blood Cancer. 2009 Feb;52(2):177-81. [Medline].

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Keywords

diffuse mixed lymphoma, diffuse mixed-cell lymphoma, diffuse mixed small and large cell lymphoma, diffuse undifferentiated lymphoma, intermediate grade lymphoma, diffuse small and large cell lymphoma, malignant lymphoma, diffuse mixed type, intermediate-grade lymphoma, mixed histiocytic-lymphocytic malignant lymphoma, mixed small and large cell lymphoma, diffuse mixed lymphomas, cancer, malignant histiocytes, malignant lymphocytes, lymphatic sarcoma, mixed lymphocytic-histiocytic

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Contributor Information and Disclosures

Author

Clifford H Pemberton, MD, Instructor in Medicine, Jefferson Medical College; Medical Director, Jefferson Hospice and Palliative Care Program; Consulting Staff, Department of Medicine, Division of Hematology/Oncology, Lankenau Hospital
Clifford H Pemberton, MD is a member of the following medical societies: American Academy of Hospice and Palliative Medicine, American College of Physicians, American Medical Association, American Society of Hematology, and Pennsylvania Medical Society
Disclosure: Nothing to disclose.

Coauthor(s)

Asher A Chanan-Khan, MD, Assistant Professor, Department of Medicine, Division of Lymphoma and Bone Marrow Transplantation, Roswell Park Cancer Institute, State University of New York at Buffalo
Asher A Chanan-Khan, MD is a member of the following medical societies: American College of Physicians, American Medical Association, and American Society of Hematology
Disclosure: Nothing to disclose.

Medical Editor

Michael Paul Kosty, MD, Associate Director, Associate Professor, Department of Internal Medicine, Divisions of Supportive Care Services and Hematology and Oncology, Ida M and Cecil H Green Cancer Center, Scripps Clinic
Michael Paul Kosty, MD is a member of the following medical societies: American College of Physicians, American Society of Hematology, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Wendy Hu, MD, Consulting Staff, Department of Hematology/Oncology and Bone Marrow Transplantation, Huntington Memorial Medical Center
Wendy Hu, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Blood and Marrow Transplantation, American Society of Hematology, and Physicians for Social Responsibility
Disclosure: Nothing to disclose.

CME Editor

Rajalaxmi McKenna, MD, FACP, Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems
Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis
Disclosure: Nothing to disclose.

Chief Editor

Emmanuel C Besa, MD, Professor, Department of Medicine, Division of Hematologic Malignancies, Kimmel Cancer Center, Thomas Jefferson University
Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, and New York Academy of Sciences
Disclosure: Nothing to disclose.

 
 
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