Chapter 64: Burkitt Lymphoma

DEFINITION AND EPIDEMIOLOGY

• Burkitt lymphoma (BL) may present in three distinct forms: endemic (African), sporadic, and immunodeficiency-associated.

• The endemic form is found in eastern equatorial Africa, with a peak age incidence at 4 to 7 years, and it is nearly twice as frequent in boys as in girls.

• Sporadic BL, defined as cases outside of endemic African regions, accounts for 1% to 2% of all patients with non-Hodgkin lymphoma (NHL).

• The incidence is higher in males than in females, and the median age of onset is 30 years.

• Immunosuppression-related BL increased in incidence during the AIDS epidemic.

PATHOPHYSIOLOGY

• The unifying feature of all three types of BL is activation of the c-MYC gene, typically resulting from translocations involving the long arm of chromosome 8, which carries c-MYC.

  — Such translocations commonly involve also the long arm of chromosome 14, which carries the immunoglobulin heavy chain gene complex, but might instead involve chromosome 2 or 22, which carries the immunoglobulin kappa or lambda light chain gene complex, respectively.

  — The constitutive activation of c-MYC increases the expression of a number of genes encoding proteins involved in cell proliferation.

• Translocations are thought to occur via double-strand breaks that occur during the normal B-cell class-switch reaction and somatic hypermutation.

• Up to one-third of cases also might have alterations involving the short arm of chromosome 17 at 17p13.1, involving the TP53 gene encoding p53. Loss of p53 function might be selected in BL cells that otherwise would be induced to undergo apoptosis in response to overexpression of c-MYC.

• Next-generation sequencing has found frequently occurring mutations in ID3, TCF3, and CCND3.

• Evidence of Epstein-Barr virus (EBV) is found in essentially all patients with African BL, one-third of patients with immunosuppression associated BL, and in one-fifth of patients with nonendemic form of disease.

CLINICAL FEATURES

• The endemic (African) form often presents as a jaw or facial bone tumor. It may spread to extranodal sites, especially to the marrow and meninges. Almost all cases are EBV positive.

• The nonendemic or American form presents as an abdominal mass in approximately 65% of cases, often with ascites. Extranodal sites, such as the kidneys, gonads, breast, marrow, and central nervous system (CNS) may be involved. Involvement of the marrow and CNS is much more common in the nonendemic form.

• Tumor lysis syndrome is very common following induction chemotherapy but also can occur spontaneously prior to therapy, especially in patients with a high tumor burden. Spontaneous tumor lysis is a poor prognostic indicator.

• The syndrome results in some or all of the following: hyperuricemia and hyperuricosuria, hyperkalemia, hyperphosphatemia, hypocalcemia, metabolic acidosis, and uric acid nephropathy with renal failure as a result of the extraordinary proliferative nature of BL cells.

LABORATORY FEATURES

• Patients with bulky disease may have BL cells in marrow ...