Burkitt Lymphoma and Burkitt-like Lymphoma Workup
- Author: Ali H Kanbar, MD; Chief Editor: Emmanuel C Besa, MD more...
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.
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:
In contrast, Tdt, CD5, CD23, and CD34 are negative.
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).
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.
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.
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.
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.
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.
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). 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]
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. 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. Expression of CD21 (Epstein-Barr virus [EBV]-C3d receptor) is present only in EBV-positive patients (endemic BL).
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).
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).
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