eMedicine Specialties > Hematology > Stem Cells and Disorders

Lymphoma, High-Grade Malignant Immunoblastic

Author: Beata Holkova, MD, Oncology Fellow, NIH/NCI, National Cancer Institute
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 16, 2009

Introduction

Background

Immunoblastic lymphoma (IBL), also known as diffuse histiocytic lymphoma, is a malignant disorder of the B cell. (See image below.)

Lymph node biopsy (hematoxylin and eosin stain) s...

Lymph node biopsy (hematoxylin and eosin stain) showing diffuse involvement with loss of architecture in a patient with immunoblastic non-Hodgkin lymphoma (NHL).

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Lymph node biopsy (hematoxylin and eosin stain) s...

Lymph node biopsy (hematoxylin and eosin stain) showing diffuse involvement with loss of architecture in a patient with immunoblastic non-Hodgkin lymphoma (NHL).


Earlier classifications subdivided diffuse large B-cell lymphomas (DLBCLs) either by morphology or by the biological behavior.
  • Kiel's classification subdivides large B-cell lymphoma into immunoblastic and centroblastic lymphomas.
  • In the Working Formulation, IBL is classified with lymphoblastic and small noncleaved-cell lymphoma as a high-grade non-Hodgkin lymphoma (NHL).
  • The International Lymphoma Study group uses all available information, morphology, immunophenotype, genetic features, and clinical features, to define a disease entity.

The World Health Organization (WHO) consensus classification should replace all existing classifications. The WHO classification of hematologic malignancies uses an updated version of the Revised European-American Lymphoma (REAL) classification for lymphoid neoplasms.

Although initially IBL was considered a more aggressive variety of lymphoma with a poor prognosis when compared with diffuse large-cell NHL (DLCL), newer combination chemotherapeutic approaches now associate IBL with a similar overall survival rate when compared with DLCL.

IBL is a fatal disease if untreated and is potentially curable with intensive chemotherapy. The success of treatment depends on the extent of disease at the time of presentation, associated B symptoms, initial therapeutic choice, and response to therapy.

Pathophysiology

IBL can originally derive from B or T cells. The Working Formulation differentiates subtypes of IBL by cell of origin. The subtypes include plasmacytoid, clear cell, polymorphous, and epithelial cell component. From a clinical point of view, this subclassification has little value; B- or T-cell origin cannot be predicted based on morphology.

In the REAL classification, except in morphologic descriptions, the schema includes immunologic, cytogenetic, and molecular information in order to define distinct lymphoma entities. The DLBCLs are considered in the REAL classification as the classic DLCL of B-cell origin defined by the Working Formulation.

Frequency

United States

The frequency rate in the United States is approximately 9% of all NHLs. Of these, 70% are of B-cell origin and 25% are of T-cell origin.

Mortality/Morbidity

  • The International Prognostic Index is now commonly used to assess the prognosis of aggressive NHL.1,2 Based on these pretreatment risk factors, the complete remission (CR) rate and 5-year overall survival rate of patients who are at low risk is 87% and 73%, respectively, compared to 44% and 26% in the high-risk group.
  • Patients undergoing combination chemotherapy may experience long-term morbidity primarily associated with the chemotherapeutic agents.

Race

  • No difference exists among races.

Sex

  • No difference exists between the sexes.

Age

  • IBL can appear in persons of any age but appears most commonly in persons who are middle-aged or older.
  • IBL is commonly observed in patients of any age who are immunocompromised.

Clinical

History

Most patients present with advanced disease; only as few as 30% present with limited-stage disease (I or II). Symptoms vary and depend on the site of involvement.

  • Painless lymphadenopathy
    • This is the most common presenting feature.
    • Occasionally, pain might be associated with aggressive tumor growth.
    • Adenopathy is usually marked and may involve any site; often, it is generalized.
  • B symptoms
    • Patients report profuse night sweats.
    • Fever is usually low grade (range 100-101°F).
    • Patients may report unintentional weight loss of more than 10% in 6 months.
  • Fatigue (anemia)
  • Neurologic deficit (CNS involvement)

Physical

  • Lymphadenopathy
  • Pallor (anemia)
  • Hemorrhage: Petechiae, ecchymoses, epistaxis, and bleeding gums may be present.
  • Hepatosplenomegaly: This may be present as a result of organ involvement.
  • Common sites of extranodal IBL
    • Gastrointestinal tract
    • Bone
    • Testis
    • Central nervous system
  • Unilateral or bilateral tonsillar enlargement: This may be present and typically is refractory to antibiotic treatment.
  • Skin lesions: Rarely, patients may present with skin lesions.

Causes

  • Environmental - Previous radiation exposure or exposure to pesticides and herbicides
  • Infectious - HIV infection (Patients with AIDS have a higher incidence of IBL.)
  • Autoimmune
    • Sjögren syndrome - Associated with IBL
    • Solid organ transplant or bone marrow transplant - Associated with a higher risk of developing IBL

More on Lymphoma, High-Grade Malignant Immunoblastic

Overview: Lymphoma, High-Grade Malignant Immunoblastic
Differential Diagnoses & Workup: Lymphoma, High-Grade Malignant Immunoblastic
Treatment & Medication: Lymphoma, High-Grade Malignant Immunoblastic
Follow-up: Lymphoma, High-Grade Malignant Immunoblastic
Multimedia: Lymphoma, High-Grade Malignant Immunoblastic
References
Further Reading
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References

  1. Bernd HW, Ziepert M, Thorns C, Klapper W, Wacker HH, Hummel M, et al. Loss of HLA-DR expression and immunoblastic morphology predict adverse outcome in diffuse large B-cell lymphoma - analyses of cases from two prospective randomized clinical trials. Haematologica. Nov 2009;94(11):1569-80. [Medline].

  2. The 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].

  3. Yunis JJ, Mayer MG, Arnesen MA, et al. bcl-2 and other genomic alterations in the prognosis of large-cell lymphoma. N Engl J Med. Apr 20 1989;320(16):1047-54. [Medline].

  4. Ennishi D, Asai H, Maeda Y, et al. Statin-independent prognosis of patients with diffuse large B-cell lymphoma receiving rituximab plus CHOP therapy. Ann Oncol. Nov 2 2009;[Medline].

  5. Seki R, Ohshima K, Fujisaki T, et al. Prognostic significance of S-phase kinase-associated protein 2 and p27kip1 in patients with diffuse large B-cell lymphoma: effects of rituximab. Ann Oncol. Nov 4 2009;[Medline].

  6. Hsiao SC, Ichinohasama R, Lin SH, Liao YL, Chang ST, Cho CY, et al. EBV-associated diffuse large B-cell lymphoma in a psoriatic treated with methotrexate. Pathol Res Pract. 2009;205(1):43-9. [Medline].

  7. Coiffier B, Lepage E, Briere J, et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. Jan 24 2002;346(4):235-42. [Medline].

  8. De Paepe P, Achten R, Verhoef G, et al. Large cleaved and immunoblastic lymphoma may represent two distinct clinicopathologic entities within the group of diffuse large B-cell lymphomas. J Clin Oncol. Oct 1 2005;23(28):7060-8.

  9. Dean RM, Bishop MR. Allogeneic hematopoietic stem cell transplantation for lymphoma. Clin Lymphoma. Mar 2004;4(4):238-49. [Medline].

  10. Harris NL, Jaffe ES, Diebold J, et al. The World Health Organization classification of neoplasms of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting--Airlie House, Virginia, November, 1997. Hematol J. 2000;1(1):53-66.

  11. Harris NL, Jaffe ES, Stein H, et al. A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. Blood. Sep 1 1994;84(5):1361-92. [Medline].

  12. Skarin AT, Dorfman DM. Non-Hodgkin's lymphomas: current classification and management. CA Cancer J Clin. Nov-Dec 1997;47(6):351-72. [Medline].

  13. 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].

  14. 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].

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Further Reading

Clinical guidelines

Rituximab for the treatment of relapsed or refractory stage III or IV follicular non-Hodgkin's lymphoma.
National Institute for Health and Clinical Excellence (NICE) - National Government Agency [Non-U.S.]. 2002 Mar (revised 2008 Feb). 29 pages. NGC:006360

Alemtuzumab in chronic lymphocytic leukemia: a clinical practice guideline.
Program in Evidence-based Care - State/Local Government Agency [Non-U.S.]. 2006 Jun 14. 32 pages. NGC:005097

Clinical trial

Immunotherapy in Peripheral T Cell Lymphoma - the Role of Alemtuzumab in Addition to Dose Dense CHOP

Related eMedicine topics

 Lymphoma, Lymphoblastic

Lymphoma, Non-Hodgkin

Non-Hodgkin Lymphoma

Lymphoma, Diffuse Large Cell

Primary CNS Lymphoma

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Keywords

high-grade malignant immunoblastic lymphoma, lymphoma, non-Hodgkin's lymphoma, non-Hodgkin lymphoma, diffuse large-cell lymphoma, diffuse large B-cell lymphoma, DLBCL, DLCL, high-grade lymphoma, large-cell immunoblastic lymphoma, diffuse histiocytic lymphoma, immunoblastic lymphoma, B-cell disorder, high-grade non-Hodgkin lymphoma

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Contributor Information and Disclosures

Author

Beata Holkova, MD, Oncology Fellow, NIH/NCI, National Cancer Institute
Beata Holkova, MD is a member of the following medical societies: American College of Physicians and American Society of Hematology
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

Paul Schick, MD, Emeritus Professor, Department of Internal Medicine, Thomas Jefferson University Medical College; Research Professor, Department of Internal Medicine, Drexel University College of Medicine; Adjunct Professor of Medicine, Lankenau Hospital, Wynnewood, PA
Paul Schick, MD is a member of the following medical societies: American College of Physicians, American Heart Association, American Society of Hematology, International Society on Thrombosis and Haemostasis, and New York Academy of Sciences
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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