101 Burkitt Lymphoma Flashcards
Three distinct forms of Burkitt lymphoma (BL)
- Endemic (African)
- Sporadic
- Immunodeficiency-associated
The most common pediatric tumor in sub-Saharan Africa and other regions of the world where malaria is endemic
Endemic form (eBL)
It typically presents in the jaw or maxilla and is associated with Epstein-Barr virus (EBV) infection at an early age.
BL found to occur in older individuals, typically presenting in the abdomen rather than the orofacial region, and were infrequently associated with EBV
Sporadic BL
Recurrent chromosomal translocations involved in BL
t(8:14)
MYC
Infection by EBV is found in nearly ____of patients with eBL, and higher titers are linked to increased risk of eBL
100%
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.
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
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.
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
The unifying feature of all three types of BL
Activation of the MYC gene via an Ig translocation
Molecular genetics
What are the features that distinguish BL from DLBCLs and other high-grade NHLs
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
Among “molecular BL” (mBL), 3% lacked MYC translocation. These cases shared interstitial gains and telomeric losses of chromosome ___________
Chromosome 11q
WHO Classification: “Burkitt-like lymphoma with 11q aberration”
TRUE OR FALSE
HIV-Associated BL occurrence does not directly correlate with CD4+ T-cell status
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
The endemic (African) form often presents as
Jaw or facial bone tumor
It may spread to extranodal sites, especially to the marrow and meninges.
Nonendemic or American form presents as
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.
Patients with more than _____% marrow involvement with malignant cells often are referred to as having Burkitt cell leukemia
25%
Immunodeficiency-related cases often involve the________and are associated with EBV in _______% of the cases.
Lymph nodes
30%
Staging system modified for childhood BL is used rather than the Ann Arbor system
BL is largely an extranodal lymphoma
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%)
Characteristic pathologic features of BL on smear preparation
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
Burkitt cell leukemia variant was previously classified as ________________, according to the former French-American-British [FAB] classification
Acute lymphocytic leukemia–L3
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,”
“Tingible body macrophages”
Histopathologic key feature in the distinction of BL from DLBCL:
BL nuclear contours are round to oval without cleaves or folds
Immunophenotype of BL
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
EBV can be detected by
Fluorescence In situ hybridization for EBER
EBV positivity
- eBL: 98%
- Sporadic: 20%
- HIV-associated: 30%
The EBV receptor expressed in EBV-positive endemic cases
CD21
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.
TRUE
In contrast to primary effusion lymphomas and DLBCL, EBV-positive, HIV-associated BL does not express latent membrane protein 1 (LMP1) or EBNA2.
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:
- 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
The translocations involving MYC can be detected by
Fluorescence in situ hybridization
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).
Double-hit lymphoma (DHL)
“High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements.”
Distinctive features of B-cell lymphoblastic lymphoma from BL
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.
TRUE OR FALSE
CNS prophylaxis therapy, either intrathecal or systemic, is given in almost all patients with BL.
TRUE
CNS prophylaxis therapy, either intrathecal or systemic, is given in almost all patients with BL.
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.
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.
TRUE OR FALSE
In general, shorter durations of chemotherapy (ie, 6 months) are as good as longer (18-month) periods of treatment.
TRUE
In general, shorter durations of chemotherapy (ie, 6 months) are as good as longer (18-month) periods of treatment.
TRUE OR FALSE
BL has a high proliferative rate, so subsequent chemotherapy cycles should be started as soon as hematologic recovery occurs.
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.
HIV-positive patients with BL should be treated similarly to nonimmunocompromised patients, and this regimen is an excellent option for these patients:
Dose-adjusted R-EPOCH regimen
Regimens for treatment of BL
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.
Regimen that was associated with higher risk of CNS recurrence
Dose-adjusted R-EPOCH
For patients with relapsed or refractory disease, this is best reserved for patients inadequately treated initially, as a consolidation procedure.
ASCT
