101 Burkitt Lymphoma

Question 1

Three distinct forms of Burkitt lymphoma (BL)

Answer 1

Endemic (African)
Sporadic
Immunodeficiency-associated

Question 2

The most common pediatric tumor in sub-Saharan Africa and other regions of the world where malaria is endemic

Answer 2

Endemic form (eBL)

It typically presents in the jaw or maxilla and is associated with Epstein-Barr virus (EBV) infection at an early age.

Question 3

BL found to occur in older individuals, typically presenting in the abdomen rather than the orofacial region, and were infrequently associated with EBV

Answer 3

Sporadic BL

Question 4

Recurrent chromosomal translocations involved in BL

Answer 4

t(8:14)

MYC

Question 5

Infection by EBV is found in nearly ______of patients with eBL, and higher titers are linked to increased risk of eBL

Answer 5

100%

Question 6

TRUE OR FALSE

The endemic form of BL is found in equatorial Africa (as well as Brazil, Papua New Guinea, and other malaria-endemic regions), with a peak age incidence at 40 to 70 years, and is nearly twice as frequent in women as in men.

Answer 6

FALSE

The endemic form of BL is found in equatorial Africa (as well as Brazil, Papua New Guinea, and other malaria-endemic regions), with a peak age incidence at 4 to 7 years, and is nearly twice as frequent in boys as in girls.

There is an epidemiologic association with infection by Plasmodium falciparum but not other forms of malaria

Question 7

TRUE OR FALSE

Sporadic BL, defined as cases outside endemic African regions, accounts for 1% to 2% of NHL, is higher in males than in females, and has a median age of 30 years.

Answer 7

TRUE

Sporadic BL, defined as cases outside endemic African regions, accounts for 1% to 2% of NHL, is higher in males than in females, and has a median age of 30 years.

In the United States, BL exhibits primarily a bimodal age distribution, with at least two incidence peaks of approximately 10 and 75 years of age

Question 8

The unifying feature of all three types of BL

Answer 8

Activation of the MYC gene via an Ig translocation

Question 9

Molecular genetics

What are the features that distinguish BL from DLBCLs and other high-grade NHLs

Answer 9

Lower cytogenetic complexity (including near-total absence of translocations involving BCL6 and/or IGH-BCL2)

The presence of MYC translocations involving Ig genes rather than non-Ig partners

Question 10

Among “molecular BL” (mBL), 3% lacked MYC translocation. These cases shared interstitial gains and telomeric losses of chromosome ___________

Answer 10

Chromosome 11q

WHO Classification: “Burkitt-like lymphoma with 11q aberration”

Question 11

TRUE OR FALSE

HIV-Associated BL occurrence does not directly correlate with CD4+ T-cell status

Answer 11

TRUE

HIV-Associated BL occurrence does not directly correlate with CD4+ T-cell status

BL is different from other EBV-associated lymphoproliferative disorders that occur with advanced HIV yet is otherwise comparable to EBV-positive posttransplantation lymphoproliferative disorders (PTLDs) that arise in severely immunosuppressed solid-organ allograft recipients.

The clinical course and pathogenesis of immunodeficiency-associated BL more closely parallels that of sporadic BL in the immunologically intact patient

Question 12

The endemic (African) form often presents as

Answer 12

Jaw or facial bone tumor

Question 13

Nonendemic or American form presents as

Answer 13

Abdominal mass

Approximately 65% of cases, often with ascites.

Involvement of the marrow and CNS is much more common in the nonendemic form.

Only 15% of the nonendemic cases are EBV positive.

Question 14

Patients with more than _____% marrow involvement with malignant cells often are referred to as having Burkitt cell leukemia

Answer 14

25%

Question 15

Immunodeficiency-related cases often involve the________and are associated with EBV in _______% of the cases.

Answer 15

Lymph nodes

30%

Question 16

Staging system modified for childhood BL is used rather than the Ann Arbor system

BL is largely an extranodal lymphoma

Answer 16

Murphy staging system

• Stage I: single nodal or extranodal site excluding the mediastinum or abdomen
• Stage II: single extranodal tumor with regional nodal involvement
  Two extranodal tumors on one side of the diaphragm
  Primary gastrointestinal tumor with or without associated mesenteric nodes
  Two or more nodal areas on one side of the diaphragm
• Stage IIR: completely resected intraabdominal disease
• Stage III: two single extranodal tumors on opposite sides of the diaphragm
  All primary intrathoracic tumors
  All paraspinal or epidural tumors
  All extensive primary intraabdominal disease
  Two or more nodal areas on opposite sides of diaphragm
• Stage IIIA: localized, nonresectable abdominal disease
• Stage IIIB: widespread multiorgan abdominal disease
• Stage IV: initial CNS or marrow involvement (<25%)

Question 17

Characteristic pathologic features of BL on smear preparation

Answer 17

Intermediate-size cells with round nuclei, multiple nucleoli, strongly basophilic cytoplasm (a consequence of the abundant polyribosomes), and the presence of lipid-filled cytoplasmic vesicles, some of which overlie the nucleus

Question 18

Burkitt cell leukemia variant was previously classified as ________________, according to the former French-American-British [FAB] classification

Answer 18

Acute lymphocytic leukemia–L3

Question 19

A term derived from a description of phagocytized nuclear debris of small lymphocytes by macrophages in germinal centers of normal lymph nodes that are embedded in the solid monomorphic infiltrate of Burkitt cells and give rise to the “starry sky appearance,”

Answer 19

“Tingible body macrophages”

Question 20

Histopathologic key feature in the distinction of BL from DLBCL:

Answer 20

BL nuclear contours are round to oval without cleaves or folds

Question 21

Immunophenotype of BL

Answer 21

Positive:
CD19, CD20, CD22, and CD79a, and have monotypic surface IgM
BCL6, CD10, Tcl1, and CD38

Negative:
CD5 and CD23
Mum-1, CD44, CD138, TdT (terminal deoxynucleotidyl transferase)
Little to no expression of BCL2

Question 22

EBV can be detected by

Answer 22

In situ hybridization for EBER

Question 23

The EBV receptor expressed in EBV-positive endemic cases

Answer 23

CD21

Question 24

TRUE OR FALSE

In contrast to primary effusion lymphomas and DLBCL, EBV-positive, HIVassociated BL does not express latent membrane protein 1 (LMP1) or EBNA2.

Answer 24

TRUE

In contrast to primary effusion lymphomas and DLBCL, EBV-positive, HIV-associated BL does not express latent membrane protein 1 (LMP1) or EBNA2.

Question 25

Virtually all cases of BL have a translocation between the long arm of chromosome 8, the site of the MYC protooncogene (8q24), and one of three translocation partners:

Answer 25

Ig heavy-chain region on chromosome 14
κ light-chain locus on chromosome 2
λ light-chain locus on chromosome 22

A key feature of BL is the relative simplicity of their karyotype; in the majority of cases, the MYC translocation is the sole abnormality

In general, this noncomplex cytogenetic profile for BL distinguishes it from DLBCL

Question 26

The translocations involving MYC can be detected by

Answer 26

Fluorescence in situ hybridization

Question 27

Refers to the subset of aggressive mature B-cell (non-Burkitt) lymphomas harboring translocations of MYC as well as at least one other proto-oncogene (most commonly BCL2 or BCL6).

Answer 27

Double-hit lymphoma (DHL)

“High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements.”

Question 28

Distinctive features of B-cell lymphoblastic lymphoma from BL

Answer 28

Expression of TdT, absence of mature B-cell markers (eg, surface immunoglobulin expression and BCL6), and the distinctive cytologic and flow cytometric features of immature blasts.

Question 29

TRUE OR FALSE

CNS prophylaxis therapy, either intrathecal or systemic, is given in almost all patients with BL.

Answer 29

TRUE

CNS prophylaxis therapy, either intrathecal or systemic, is given in almost all patients with BL.

Question 30

TRUE OR FALSE

Radiation therapy play a role in the treatment of BL, and use of radiation therapy for limited-stage diseases is of additional benefit.

Answer 30

FALSE

Radiation therapy does not play a role in the treatment of BL, and use of radiation therapy for limited-stage diseases is of no additional benefit.

Question 31

TRUE OR FALSE

In general, shorter durations of chemotherapy (ie, 6 months) are as good as longer (18-month) periods of treatment.

Answer 31

TRUE

In general, shorter durations of chemotherapy (ie, 6 months) are as good as longer (18-month) periods of treatment.

Question 32

TRUE OR FALSE

BL has a high proliferative rate, so subsequent chemotherapy cycles should be started as soon as hematologic recovery occurs.

Answer 32

TRUE

BL has a high proliferative rate, so subsequent chemotherapy cycles should be started as soon as hematologic recovery occurs.

Waiting for a fixed period between cycles may lead to regrowth of resistant tumor cells between cycles.

Question 33

HIV-positive patients with BL should be treated similarly to nonimmunocompromised patients, and this regimen is an excellent option for these patients:

Answer 33

Dose-adjusted R-EPOCH regimen

Question 34

Regimens for treatment of BL

Answer 34

CODOXM/ IVAC
Hyper-CVAD,
Dose adjusted R-EPOCH

The three most common therapeutic regimens used (CODOXM/ IVAC, hyper-CVAD, and dose adjusted R-EPOCH) did not yield statistically significant differences in progression-free survival using stratified threeway comparison.

Question 35

Regimen that was associated with higher risk of CNS recurrence

Answer 35

Dose-adjusted R-EPOCH

Question 36

For patients with relapsed or refractory disease, this is best reserved for patients inadequately treated initially, as a consolidation procedure.

Answer 36

ASCT