Diagnostic Considerations

Burkitt lymphoma (BL) must be distinguished from other primary abdominal tumors in childhood, including Wilms tumor, neuroblastoma, and peripheral neuroectodermal tumor. In the bone marrow, BL must be differentiated from B and T precursor and myeloid leukemias. Among peripheral B-cell lymphomas, the major difficulty is to differentiate BL from diffuse large B-cell lymphoma (DLBCL), lymphoblastic lymphoma, and blastic mantle cell lymphoma (MCL).

DLBCL

DLBCL typically has larger cells, but some Burkitt lymphoma (BL) cases might have centroblast-like (large) cells intermixed with the more common medium-sized monoclonal lymphocytes, resulting in some degree of a diagnostic dilemma, especially when considering that up to 15% of DLBCL cases might test positive for the c-myc translocation. Those borderline cases are categorized under Burkitt-like lymphoma (BLL). In the 2008 World Health Organization (WHO) classification system, these are referred to as "B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma."^{[2, 46]}(See Histologic Features.)

Features that rule out the diagnosis of Burkitt lymphoma (BL) include bcl-6 gene rearrangement (independent from bcl-6 nuclear staining), bcl-2 positivity, presence of t(14;18), and a Ki67 staining of less than 95%.^{[47, 48]}

Researchers have been able to define a specific genetic signature for Burkitt lymphoma (BL). Two different studies explored gene-expression profiling by microarray technology as a tool to accurately diagnose Burkitt lymphoma (BL) and differentiate it from DLBCL due to the significant difference in prognosis and treatment approaches for these diseases.^{[49, 50]}Results showed that 17-34% of DLBCL cases diagnosed by expert pathologists had the typical Burkitt lymphoma (BL) genetic signature; likewise up to 4% of cases signed out as classic or atypical BL lacked the typical genetic signature.

In both studies, rare cases with the Burkitt signature were c-myc negative.^{[49, 50]}Moreover, patients with a Burkitt lymphoma (BL) signature who were treated with CHOP-like (cyclophosphamide, hydroxydaunorubicin hydrochloride [doxorubicin hydrochloride], vincristine and prednisone) regimens had a worse prognosis than those patients who were treated with more intense chemotherapy regimens.^{[49, 50]}Unfortunately, microarray analysis is not readily available in most clinical settings and remains a research tool.

Lymphoblastic and mantle cell lymphomas

Lymphoblastic lymphoma may be histologically similar to Burkitt lymphoma (BL), however, it is a T-cell lymphoma that expresses T-cell markers in addition to TdT, which are usually negative in BL cases. Similarly, mantle cell lymphoma cases can be easily distinguished from Burkitt lymphoma (BL) by immunohistochemistry and flow cytometry as they typically stain strongly for CD5 and cyclin D1, unlike BL.

Differential Diagnoses

Workup

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Media Gallery

Computed tomography scan in a patient with a large, left-sided axillary mass from which a biopsy was obtained. Biopsy findings were consistent with small noncleaved cell non-Hodgkin lymphoma.
Postchemotherapy computed tomography scan in a patient diagnosed with small noncleaved cell lymphoma (SNCCL) (same patient as in previous image). This image shows regression of a left axillary mass.
Coronal magnetic resonance imaging (MRI) section in a patient with large neck mass (same patient as in previous image). Biopsy findings showed Burkitt-like non-Hodgkin lymphoma (NHL). MRI was performed to assess for cord involvement.
Sagittal magnetic resonance imaging (MRI) section of the neck area showing a large mass invading the cervical spine with epidural encroachment (same patient as in the previous image). MRI was performed to rule out cord compression. The first image shows the gallium scan of this patient that correlates with the site of the tumor.
Right-sided pleural effusion in a patient with small noncleaved cell lymphoma (SNCCL) non-Hodgkin lymphoma.
Hematoxylin and eosin (H&E) stain. Sheets of monotonous-appearing lymphoid cells with one or more prominent nucleoli and an area of pale staining resulting from the presence of benign macrophages reveal a starry sky pattern.
The 2-dimensional flow cytometry demonstrates the highlighted cells to be CD5 negative and CD23 negative as well as lambda negative. Small noncleaved cell lymphoma (SNCCL) cells are typically CD19+, CD20+, CD22+, and CD10+.

of 7

Author

Ali H Kanbar, MD Medical Oncologist/Hematologist, Dayton Cancer Center

Ali H Kanbar, MD is a member of the following medical societies: American College of Physicians, American Society of Hematology, American Society of Clinical Oncology

Disclosure: Nothing to disclose.

Coauthor(s)

Ronald A Sacher, MD, FRCPC, DTM&H Professor Emeritus of Internal Medicine and Hematology/Oncology, Emeritus Director, Hoxworth Blood Center, University of Cincinnati Academic Health Center

Ronald A Sacher, MD, FRCPC, DTM&H is a member of the following medical societies: American Association for the Advancement of Science, American Association of Blood Banks, American Clinical and Climatological Association, American Society for Clinical Pathology, American Society of Hematology, College of American Pathologists, International Society of Blood Transfusion, International Society on Thrombosis and Haemostasis, Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

Chief Editor

Emmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American Society of Clinical Oncology, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, New York Academy of Sciences

Disclosure: Nothing to disclose.

Acknowledgements

Patturajah Anbumani, MD, MBBS, MS, MCh Associate Medical Director, Best Medical Care; Former Associate Medical Director, Jeanes Hospital, Temple University Health System; Former Adjunct Clinical Assistant Professor, New York College of Osteopathic Medicine; Former Clinical Assistant Professor, Department of Medicine, State University of New York-Downstate

Patturajah Anbumani, MD, MBBS, MS, MCh is a member of the following medical societies: American College of Physicians, American Medical Association, and American Medical Women’s Association

Disclosure: Nothing to disclose.

Samer A Bleibel, MD Staff Physician, Department of Internal Medicine, Wayne State University School of Medicine, St John's Hospital and Medical Centers

Samer A Bleibel, MD is a member of the following medical societies: American College of Physicians

Disclosure: Nothing to disclose.

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.

Hanxian Huang, MD, PhD Staff Physician, Department of Internal Medicine, Leesburg Regional Medical Center, The Villages Regional Hospital

Hanxian Huang, MD, PhD is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine

Disclosure: Nothing to disclose.

Anand B Karnad, MBBS Program Director, Fellowship Programs in Hematology-Oncology, Professor of Medicine, Division of Medical Oncology, Department of Medicine, University of Texas Health Sciences Center, San Antonio

Anand B Karnad, MBBS is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Osler Society, American Society of Hematology, Assocation of Subspecialty Professors, and Massachusetts Medical Society

Disclosure: Nothing to disclose.

Olga Kozyreva, MD Attending Physician, Division of Hematology-Oncology, St Elizabeth's Medical Center; Assistant Professor, Tufts University School of Medicine

Disclosure: Nothing to disclose.

Sarah K May, MD Consulting Staff, Department of Hematology-Oncology, Caritas Carney Hospital, Commonwealth Hematology-Oncology PC

Disclosure: Nothing to disclose.

from Memorial Sloan-Kettering - Philip Schulman, MD Chief, Medical Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center; Clinical Professor, Department of Medicine, New York University School of Medicine

Philip Schulman, MD is a member of the following medical societies: American Association for Cancer Research, American College of Physicians, American Society of Hematology, and Medical Society of the State of New York

Disclosure: Nothing to disclose.

Karen Seiter, MD Professor, Department of Internal Medicine, Division of Oncology/Hematology, New York Medical College

Karen Seiter, MD is a member of the following medical societies: American Association for Cancer Research, American College of Physicians, and American Society of Hematology

Disclosure: Novartis Honoraria Speaking and teaching; Schering Honoraria Speaking and teaching; Cephalon Honoraria Speaking and teaching; Celgene Honoraria Speaking and teaching

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Yubao Wang, MD, PhD Fellow, Division of Hematology/Medical Oncology, University of Texas Health Science Center, San Antonio

Yubao Wang, MD, PhD is a member of the following medical societies: American College of Physicians, American Society of Clinical Oncology, and American Society of Hematology

Disclosure: Nothing to disclose.