Chapter 65: Burkitt Lymphoma

INTRODUCTION

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

• Evidence for involvement of the c-MYC gene came from studies on the recurrent translocations in BL involving the long arm of chromosome 8, which involved the c-MYC locus.

EPIDEMIOLOGY

• The endemic form is found in eastern equatorial Africa, with a peak age incidence at 4 to 7 years, and 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 percent 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 Burkitt lymphoma 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.

• A distinctive feature of BL is the translocations involving the long arm of chromosome 8 and chromosomes 14, 2, or 22. 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.

• The incidence of Epstein-Barr virus (EBV) positivity in the various forms of BL: it is found in essentially all patients with African BL, 30 to 40 percent of patients with immunosuppression associated BL, and in 20 percent 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 percent 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 ...