eMedicine Specialties > Hematology > Stem Cells and Disorders

Lymphoma, Diffuse Mixed

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

Introduction

Background

In 1956, Rappaport initially described a subset of non-Hodgkin lymphoma (NHL) that was characterized by a mixed population of diffusely infiltrating malignant histiocytes and lymphocytes; he referred to them as mixed histiocytic-lymphocytic malignant lymphomas. These malignant histiocytes were later identified as lymphocytes; thus, the term malignant lymphoma, mixed small and large cell, was adopted. Histologically, these lymphomas contain an equal number of small and large cells (30-70%).

In the Working Formulation classification system proposed by a National Cancer Institute working group in 1982, these lymphomas were classified as an intermediate-grade non-Hodgkin lymphoma, representing 3-11% of all non-Hodgkin lymphomas.

With the development of immunophenotypic and molecular diagnostics, the Revised European-American Lymphoma (REAL) classification was subsequently proposed and then modified by the World Health Organization (WHO) in 2001. Diffuse mixed lymphoma is now classified as diffuse large B-cell lymphoma. Clinically, patients with this type of lymphoma usually present with advanced and, often, extranodal disease.

For excellent patient education resources, visit eMedicine's Blood and Lymphatic System Center. Also, see eMedicine's patient education article Lymphoma.

Related eMedicine topics:
Cutaneous CD30+ (Ki-1) Anaplastic Large-Cell Lymphoma
Lymphoma, Diffuse Large Cell
Malignant Lymphoma

Pathophysiology

Diffuse large B-cell lymphomas (diffuse mixed lymphomas) are more or less composed of equal numbers of small and large cells. The small cells are usually slightly larger than normal lymphocytes, and they have a cleaved or indented nucleus and coarse chromatin. The large cells can be cleaved or noncleaved. The cytoplasm of these cells is pale, and the cells have an irregular, central, indented nucleus with inconspicuous nucleoli. A subset of the large cells has rounded nuclei with one or more nucleoli; these are the noncleaved large cells and are somewhat larger compared with the cleaved cells.

Similar to all other intermediate-grade lymphomas, the mixed small and large cell non-Hodgkin lymphomas most often manifest as primary nodal disease, although involvement of the spleen and other organs is common.

Frequency

International

Diffuse large B-cell lymphomas (diffuse mixed lymphomas) comprise approximately 30% of all non-Hodgkin lymphomas.

Mortality/Morbidity

Based on the International Prognostic Index (IPI), patients with diffuse large B-cell lymphomas (diffuse mixed lymphomas) can be grouped into the prognostic categories of low risk (category 0 or 1), low-intermediate risk (category 2), high-intermediate risk (category 3), and high risk (category 4 or 5).1 The 5 factors rated in the IPI are age, lactate dehydrogenase (LDH) level, stage, performance status, and number of extranodal sites.2

  • For intermediate and aggressive lymphomas, the complete remission (CR) rate for low-risk patients is 87%, and the 5-year overall survival (OS) rate is 73%.
  • The CR rate for high-risk patients is 44%, and the 5-year OS rate is 26%

Sex

Diffuse large B-cell lymphoma (diffuse mixed lymphoma) affects females more often than males.

Age

Most patients with diffuse large B-cell lymphomas (diffuse mixed lymphomas) are diagnosed during the seventh or eighth decade of life, with a median age of 63 years.

Clinical

History

Patients with diffuse large B-cell lymphomas (diffuse mixed lymphomas) usually present with lymphadenopathy, most commonly affecting either the cervical or inguinal region. Other common complaints from the history findings may include the following:

  • B symptoms (eg, fever, night sweats, >10% weight loss)
  • Anorexia
  • Pedal edema (caused by pelvic lymphadenopathy)
  • Fatigue
  • Chest discomfort or shortness of breath (caused by mediastinal lymphadenopathy)

Physical

Common findings upon physical examination are as follows:

  • Lymphadenopathy (ie, cervical, axillary, inguinal)
  • Splenomegaly
  • Low-grade fever
  • Pedal edema, resulting from extensive pelvic lymphadenopathy

Causes

A number of risk factors have been associated with non-Hodgkin lymphomas in general. These include Epstein-Barr virus, HIV, pesticides, hair dyes, primary and transplant-related immunodeficiency, and rheumatoid arthritis and other autoimmune disorders. Occupational factors have a weak or an inconsistent risk.

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

  • 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: Nothing to disclose.

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, Consulting Staff, Department of Medicine, Southwest Medical Consultants, SC, 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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