LabMed

Burkitt Lymphoma/Leukemia (BL)

At a Glance

Burkitt Lymphoma (BL) is a fast growing malignancy of B cell origin typically associated with a rapid onset and progression of symptoms. The clinical presentation varies according to the site of origin and the presence of metastatic disease. Primary sites may involve extranodal (more common in children) and/or nodal tissue (more common in adults). Common sites of origin include the gastrointestinal tract (particularly the ileocecal region) and the head and neck. Other primary sites have been described in the bone, liver, kidney, breast, gonads, pancreas, mediastinum, and retroperitoneum.

Abdominal BL may present with a palpable mass, abdominal pain, nausea and vomiting, constipation, melena, weight loss, and/or jaundice. BL can also serve as the lead point for an intussusception and can mimic appendicitis. Common metastatic sites include the spinal fluid, bone, and bone marrow. Because of the rapid cellular growth and turnover, patients may present with tumor lysis syndrome.

When the bone marrow contains more than 25% malignant Burkitt cells, the definition of Burkitt leukemia is met, which can occur with or without lymphomatous involvement. Burkitt leukemia typically presents with similar signs and symptoms as other types of acute leukemia and may include pallor, bruising, fatigue, fevers, bone pain, night sweats, and weight loss.

BL has 3 recognized clinical variants: endemic, sporadic, and immunodeficiency-associated.

Endemic BL is the most common malignancy found in children living in equatorial Africa and compromises approximately 50% of all childhood malignancies. The mandible, maxilla and orbital bones, in addition to the abdomen are frequently encountered sites of disease. Endemic cases are more likely to have central nervous system spread and less likely to have bone marrow involvement when compared to sporadic cases. A strong association exists with Epstein Barr Virus (EBV) infection and to a lesser extent, malaria.

Sporadic BL is the most common type (30-40%) of childhood non-Hodgkin lymphoma. The abdomen (particularly the ileocecal area) is the most frequent site of origin. Jaw involvement is rare. EBV is only found in 15-20% of cases.

Immunodeficiency-associated BL has been described in numerous clinical settings of immunosuppression. BL should be suspected when a new mass is detected in an immunodeficiency patient. Syndromes found to greatly increase the relative risk of developing BL include but are not limited to; congenital immunodeficiency syndromes (e.g., X-linked hypogammaglobulinemia, Wiskott-Aldrich syndrome, Bloom syndrome, ataxia telangiectasia), acquired immunodeficiency (e.g., human immunodeficiency virus, HIV), post-transplantation and chronic immunosuppressant therapy.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

Radiographic imaging of suspected primary and potential metastatic sites is recommended. Ultrasound can be a useful initial screening tool when the diagnosis is uncertain or when other technologies are not readily available. Commuted tomography (CT) scans of the chest, abdomen and pelvis are commonly utilized to evaluate newly suspected patients. Positron emission tomography (PET) scans can be useful in identifying areas of metastatic disease and, potentially, as a marker for response to treatment.

Ultimately, a biopsy of the mass is required to confirm diagnosis. Institutional preferences and guidelines, as well as the patient's clinical condition, influence the technique utilized for obtaining the specimen. An adequate fresh tissue sample (~1 cm3) helps ensure an accurate diagnosis. The pathologist, typically, divides the fresh tissue for flow cytometry, cytogenetics, and formalin fixation. The remainder is frozen. If core biopsies are performed, they usually take a minimum of 3-4 cores to obtain enough tissue to perform all of the recommended testing. If Burkitt leukemia is suspected, perform a bone marrow biopsy and place cores in transport medium.(Table 1)

Table 1.

Test Results Indicitive of the Disorder
CT scan Flow Cytometry Cytogenetics
Lobulated, hypodense, hypoattenuated mass; cavitation can be seen with bowel lumen communication Postive: CD10, 19, 20, 22, 43, 79a, Bcl-6 and monotype surface IgM Translocation involving the c-myc gene (8q24)
Negative: CD 5, 23, 138, Bcl-2, TdT t(8;14)(q24;q32)
Proliferative fraction = 95-100% t(2;8)(p12;q24)
t(8;22)(q24;q11)

Morphologic Description

Classic BL consists of sheets of monotonous, non-cleaved, medium-sized, vacuolated lymphoid cells with fine nuclear chromatin, small amounts of basophilic cytoplasm, 2-5 nucleoli per cell, and high proliferative and apoptotic activity. Squared-off edges are often observed between neighboring cells. A "starry sky" appearance is seen under low power because of scattered macrophages containing apoptotic tumor cells.

Some BL tumors possess many but not all of the classic histologic or cytogenetic features. Historically, they were classified as atypical BL or Burkitt-like lymphoma. In the current 2008 World Health Organization (WHO) classification scheme, cases with atypical morphology but otherwise classic immunophenotyping and cytogenetic changes are to be classified as BL. Similarly, cases with classic morphology and immunophenotyping but lacking classic cytogenetic changes are classified as BL.

Variant Morphologies

In addition to classic BL, two variant histologies have been described historically which are no longer in use. Those variant histologies were referred to as BL with plasmacytoid differentiation and atypical Burkitt/Burkitt-like lymphoma. The classic histology was described in most endemic and sporadic cases, but in a minority of immunodeficiency-associated cases. The variant histologies possessed greater nuclear pleomorphism and fewer, more prominent nucleoli than the classic variant.

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications - OTC drugs or Herbals - that might affect the lab results?

Pretreatment with corticosteroids may decrease the viability and interpretability of the pathologic specimen. Specimens not processed immediately are at significant risk for reduced viability.

What Lab Results Are Absolutely Confirmatory?

The combination of morphologic appearance with immunophenotype and cytogenetics is confirmatory.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

Because of rapid cellular turnover, patients are at risk for tumor lysis syndrome. For the evaluation of metastatic disease, prechemotherapy status, and overall health assessment, the following tests are typically ordered for new patients:

  • bone marrow aspirate +/- biopsy (bilateral for nonmarrow primary)

  • complete blood count (CBC) with differential and platelet count

  • electrolytes including calcium and phosphorus

  • alkaline phosphatase

  • urea (BUN)

  • creatinine

  • uric acid

  • lactate dehydrogenase (LDH)

  • liver transaminases (AST/ALT)

  • bilirubin

  • lumbar puncture (cell count with differential and cytology)

  • possible HIV testing

Based on the patient's clinical condition, consider CT or magnetic resonance imaging (MRI) of the brain, bone scan, and testicular ultrasound.

Echocardiogram should be ordered prior to chemotherapy with anthracycline.

Differential diagnosis

Some cases of diffuse large B-cell lymphoma (DLBCL) may have significant overlapping pathologic features with BL. Differentiating between DLBCL, BL and atypical BL in these cases can be very difficult. Moreover, the distinction has significant treatment implications. DLBCL is favored with lower proliferative indices, greater heterogeneity, bcl-2 or bcl-6 gene rearrangement, and lower c-myc protein expression. DLBCL is rare in pediatrics. Gene expression studies may be helpful in the future for differentiating between these entities. For cases in which significant overlap is seen, the 2008 WHO classification scheme has created the diagnostic category: B-cell neoplasms, unclassifiable, with features intermediate between DLBCL and BL.

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications - OTC drugs or Herbals - that might affect the lab results?

Pretreatment with corticosteroids may decrease the viability and interpretability of the pathologic specimen.

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