Burkitt Lymphoma

1. Epidemiology of Burkitt lymphoma:
--almost always associated with a c-myc translocation/deregulation (chromosome 8)
--in all groups there is a 3 or 4:1 male predominance
a. endemic form: most commonly seen in equatorial Africa, associated with EBV infection.  Tumors primarily present as bony masses in the jaw/facial bones and then spreads to extranodal sites.  Associated with c-myc translocation t(8;14).  Incidence is 50x higher than in U.S.
b. sporadic form: occurs most commonly in the U.S. and Western Europe.  Usually found in children and young adults (<35 yrs). Accounts for 1/3 of all pediatric lymphomas.Often has an intra-abdominal presentation and can present as a large abd mass, with complications including bowel strangulation, GI bleeding etc.
c. HIV/immunodeficiency related: usually involves lymph nodes, can present with hematologic involvement as well.  Unlike many other AIDS-related malignancies/infxns, Burkitt lymphoma is NOT more common in patients with a low CD4 ct, and being on HAART therapy does not reduce risk of acquiring the disease (ie. not related to degree of immunosuppression).  

2. Diagnosis/pathology in Burkitt lymphoma:
--FNA or core bx is NOT SUFFICIENT in diagnostic workup of lymphoma.  When at all possible, you need an excisional biopsy, to ascertain the architecture of the node (which is critical in correctly classifying the lymphoma)
--time is of the essence in obtaining these biopsies, when suspicion is high, as they are rapidly growing and very chemosensitive
--Pathologic B-Cell subset of normal germinal center B-cells; express B-cell surface markers, including CD10, CD19, CD-20 and CD77.Endemic variants express CD21 but sporadic do not (acts as an EBV receptor)
--Histology shows monomorphic, medium-sized cells with round nuclei, multiple nucleoli, and basophilic cytoplasm.  A "starry-sky" pattern is often present, which is due to numerous macrophages which ingest the tumor cells--ie. "a tingible body"
--staining for Ki-67, which accounts for the mitotic index, is very high, approaching 100%

3. Evaluation/treatment in Burkitt lymphoma:
--initial evaluation should include an LP for eval of CNS disease (up to 20% of cases have CNS involvement), BM bx (30-40% have BM involvement), CT chest/abd/pelvis for staging (or PET CT).  All pts should receive CNS prophylaxis with intrathecal chemotx regardless of CNS disease, although the dosing frequency of the IT chemotx is affected. 
--the chemo regimen is complicated and aggressive for Burkitt's (not conventional CHOP); recently Rituximab has been added to the regimen, although there are too few cases to know how this may change long-term survival rates
--monitoring and prevention of TUMOR LYSIS SYNDROME is essential in Burkitt's.  The highly aggressive nature of this lymphoma predisposes to TLS both prior to and especially after initiating chemotherapy.  Checking uric acid, phosphorus and calcium (as well as BMP) as often as every 6 hrs is critical while initiating therapy. Prophylactic use of allopurinol +/- rasburicase is recommended, as well as aggressive IVF hydration.  There is marginal data for urinary alkanalization, and this can precipitate calcium-phosphate deposition, leading to kidney stones/obstruction.
--preservation of fertility is an important issue in the pediatric and young adult populations; given the need to initiate therapy quickly in Burkitt's lymphoma, and the use of a highly toxic chemotx (specifically cyclophosphamide), ovarian stimulation and cryopreservation of eggs is not possible.  Alternate therapies include ovarian cryopreservation (the only option for prepupertal girls) or testes (in boys).  Ovarian suppression with GNRH analogues (ie. Lupron) to suppress ovulation and theoretically, protect the ovarian follicles from the effects of chemotx (which is what they did for this patient). 

(Victoria Kelly MD, 6/29/10)