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Burkitt Lymphoma and Burkitt-like Lymphoma Workup

  • Author: Ali H Kanbar, MD; Chief Editor: Emmanuel C Besa, MD  more...
 
Updated: Apr 08, 2016
 

Approach Considerations

The least invasive procedure should be used to establish the diagnosis, which usually involves pathologic evaluation of the involved tissue biopsy. The staging workup must be expedited, because Burkitt tumor grows rapidly, causing life-threatening complications.

A diagnosis can sometimes be made by bone marrow aspiration and biopsy if the marrow is involved. If the marrow is not involved, diagnosis will require sampling lymph nodes or the involved extranodal site.

The detection of the classic reciprocal c-myc translocations as well as is not always feasible on routine cytogenetics studies; the use of fluorescence in situ hybridization (FISH) and polymerase chain reaction (PCR) can be very helpful in detecting the presence of c-myc translocations in those cases.[49]

Flow cytometry of biopsied tissue or bone marrow may reveal expression of surface immunoglobulin M (IgM) (most common), as well as other mature B-cell markers, such as the following:

  • CD19
  • CD20
  • CD22
  • CD79a
  • CD10

In contrast, Tdt, CD5, CD23, and CD34 are negative.

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Diagnostic Studies

General laboratory studies should include complete blood cell (CBC) count with differentials; a platelet count; serum levels of electrolytes, uric acid, lactate dehydrogenase (LDH), and creatinine; and liver function tests. All patients should also be checked for human immunodeficiency virus (HIV) and hepatitis B (HBV) infection.

CBC count and coagulation studies

CBC counts may reveal pancytopenia (anemia, thrombocytopenia, and/or leukopenia) due to the involvement of the bone marrow. Coagulation studies (prothrombin time [PT], partial thromboplastin time [PTT], and fibrinogen) should be performed to evaluate the presence of disseminated intravascular coagulopathy (DIC).

Serum chemistries

Electrolyte imbalances occur as a result of renal infiltration with lymphoma. The rapid turnover of the Burkitt lymphoma (BL) cells may cause primary tumor lysis, which is characterized by hyperkalemia, hyperphosphatemia, hyperuricemia, and hypocalcemia—with resultant uric acid nephropathy and oliguric renal failure.

Serum lactate dehydrogenase (LDH) levels are almost always elevated, often to extreme levels. The diagnosis of Burkitt lymphoma (BL) should be considered in any patient with a marked elevation of LDH. This test is also a useful indicator of the patient's response to treatment and can be used as an early nonspecific indicator of disease relapse.

Liver function test results, if abnormal, may be indicative of visceral involvement with lymphoma.

Serum uric acid levels are often high and reflect the high-grade nature of the disease and correlate with the probability of tumor lysis syndrome with initiation of cytotoxic therapy.

Beta2 microglobulin is a predictor of the extent of disease and is used as a surrogate marker for early relapse.

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Radiologic Studies

Imaging studies help assess tumor burden and measurement of tumor masses before therapy. Head or spinal computed tomography (CT) scanning or magnetic resonance imaging (MRI) is indicated if neurologic signs and symptoms are present (see the following images), whereas bone scanning and plain bone radiography are needed for patients with symptoms of bone involvement. These imaging studies are helpful in evaluating the extent of disease and used in assessing sites of relapse. Although complete staging is helpful in assessing the patient, treatment should not be delayed while extensive tests are performed.

Computed tomography scan in a patient with a large 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 pat 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 i 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 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 sma Right-sided pleural effusion in a patient with small noncleaved cell lymphoma (SNCCL) non-Hodgkin lymphoma.

Obtain a CT scan of the chest, abdomen, and pelvis with intravenous contrast. If the patient has evidence of renal insufficiency due to hyperuricemia, obstruction, or renal infiltration, then intravenous (IV) contrast medium should be omitted.

Positron emission tomography (PET) scanning has been reported to be very useful in staging non-Hodgkin lymphomas (NHL) and monitoring treatment response, but this modality is unlikely to alter management in Burkitt lymphoma (BL), therefore, it is reserved for use in clinical trials.

Cardiac imaging studies

Echocardiography (ECG) is indicated for possible arrhythmia resulting from cardiac involvement.

Multiple-gate acquisition (MUGA) scanning is used to evaluate the ejection fraction before chemotherapy treatment, especially if anthracyclines will be used, as these agents have a potential cardiotoxic effect.

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Diagnostic Procedures and Associated Studies

The diagnosis of Burkitt lymphoma (BL) or Burkitt-like lymphoma (BLL) is made by obtaining a biopsy of the tumor mass for histopathology, immunochemistry, and flow cytometry (see the following image). Cytogenetic studies to identify c-myc mutation will aid in the diagnosis. The most suggestive lymph nodes should be selected for excisional biopsy. Frozen sections and needle biopsies are discouraged. Aspiration of bone marrow or effusions may provide the diagnosis and avoid lymph node biopsy.

A unilateral bone marrow aspirate and biopsy should be performed for every patient with Burkitt lymphoma (BL), because the frequent presence of unexpected bone marrow involvement has important implications for treatment planning. If lymphoma cells are present in the aspirate, flow cytometry/immunophenotyping should be ordered to further characterize the disease. Bone marrow is involved in 20% of sporadic cases and 8% of endemic cases of Burkitt lymphoma (eBL).

Lumbar puncture (LP) is considered part of the staging workup to evaluate for cerebrospinal fluid (CSF) involvement. This test should be deferred in the presence of significant thrombocytopenia or coagulation defects. The CSF should be sent for cytology and flow cytometry evaluation in addition to the usual studies. Intrathecal chemotherapy is usually given at the time of the initial lumbar puncture.

Paracentesis or thoracentesis may be needed for cytogenetic studies if ascites or pleural effusion is present.

Years ago, laparotomy was indicated for the initial diagnosis and for resection of the disease; this procedure is not recommended by current guidelines.

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Histologic Features

Burkitt cells are homogeneous in size and shape, with round to oval nuclei and slightly coarse chromatin, with multiple nucleoli, and with intensely basophilic vacuolated cytoplasm that contains neutral fat. Extranodal involvement shows infiltration with monotonous cells of uniform size and shape. The cytoplasm is scanty, and the nucleus is round or slightly irregular with slightly coarse chromatin and several nucleoli.

Burkitt lymphoma

Histologically, Burkitt lymphoma (BL) is characterized by a monoclonal proliferation of medium-sized, noncleaved B-cells that are uniform in appearance and that produce a diffuse pattern of tissue involvement. These cells typically have a scant basophilic cytoplasm characterized by numerous lipid vacuoles, round nuclei with stippled chromatin and multiple small nucleoli.

Under the microscope, the hallmark of Burkitt lymphoma (BL) is the presence of a "starry sky" appearance (also observed in other highly proliferative lymphomas), imparted by scattered macrophages phagocytizing cell debris and apoptotic cells (tingible body macrophages) (see the image below).[3] However, the starry sky pattern is not pathognomonic for Burkitt lymphoma (BL) and may be observed in other highly proliferative lymphomas. Immunophenotype and cytogenetic studies aid in the diagnosis of Burkitt lymphoma (BL).[3, 44]

Hematoxylin and eosin (H&E) stain. Sheets of monot 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.

Burkitt lymphoma (BL) tumor cells are derived from mutated activated germinal center B-lymphocytes based on the fact that they share the same surface markers such as CD10, CD77, and bcl-6 (nuclear staining only) and the presence of somatic mutations in their immunoglobulins gene, similar to normal germinal center B cells.[50] They also express other B-cell antigens like CD10, CD19, CD20, CD22, as well as HLA-DR and surface immunoglobulin M (IgM) (see the image below). Ki67 staining usually approaches 100%. They typically lack CD5, CD23, TdT and are usually bcl-2 negative.[3] Expression of CD21 (Epstein-Barr virus [EBV]-C3d receptor) is present only in EBV-positive patients (endemic BL).[51]

The 2-dimensional flow cytometry demonstrates the 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+.

Burkitt-like lymphoma

Burkitt-like lymphoma (BLL), a subcategory of Burkitt lymphoma (BL) in the World Health Organization (WHO) classification, has greater polymorphism in the nuclear size and shape, and the expression of surface markers is more variable. Morphologically, these tumors have features that are intermediate between diffuse large B-cell lymphoma (DLBCL) and classic Burkitt lymphoma (BL), with some large cells resembling DLBCL and other, smaller cells resembling typical BL cells. They are also characterized by a high proliferation rate, a starry-sky pattern, and an immunophenotype similar to classic Burkitt lymphoma (BL).[52]

The WHO describes cases that are morphologically typical of Burkitt lymphoma (BL) but that have an atypical immunophenotype or genetic features. Around 35-50% of these cases have 8q24/c-myc translocations, and approximately 15% have bcl-2 translocations (double hit lymphoma). Interestingly, not all c-myc translocations in Burkitt-like lymphoma (BLL) patients involve immunoglobulin loci (Non IG-MYC).[44]

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Contributor Information and Disclosures
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, MB, BCh, FRCPC, DTM&H Professor, Internal Medicine and Pathology, Director, Hoxworth Blood Center, University of Cincinnati Academic Health Center

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

Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: GSK Pharmaceuticals,Alexion,Johnson & Johnson Talecris,,Grifols<br/>Received honoraria from all the above companies for speaking and teaching.

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.

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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+.
 
 
 
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