Burkitt Lymphoma

Epidemiology:

• Children >> adults
• EBV (some)
• Endemic BL:
• Equatorial Africa
• Papua, New Guinea
• EBV (majority)
• Immunodeficiency associated:
• HIV (most)
• Often initial manifestation of AIDS
• EBV (25-40%)
• Sporadic
• EBV negative

Common sites:

• Extranodal sites often
• Jaw / facial bones (50% of endemic)
• acute leukemia often
• immunodeficiency-associated:
• nodal (frequent)
• bone marrow

Gross features:

Histologic features:

• starry-sky pattern
• tingeable body macrophages are the stars
• monomorphic cell population (aside from macrophages)
• intermediate size (nucleus about same size as histiocytes)
• uniform, round nuclear margins
• 3-5 nucleoli
• basophilic cytoplasm
• cytoplasmic vacuoles often
• cytoplasm squaring off
• may be difficult to differentiate from DLBCL
• >85% Ki-67 staining required (usually >95%)
• BL with plasmacytoid differentiation
• Some tumoru cells with eccentric basophilic cytoplasm
• Often single central nucleolus
• Monotypic intracytoplasmic immunoglobulin
• More pleomorphism than classical BL
• More common in immunodeficiency states
• atypical Burkitt:
• larger nuclear size
• 1-3 nucleoli

Immunophenotype & Special Stains:

Marker:	Sensitivity:	Specificity:
Surface IgM
Bcl-6
CD5 (neg)
Bcl-2 (neg) May be weak Never strong
CD23 (neg)
CD21 (neg)	Some positive
Ki-67 (>85% staining) *REQUIRED* Homogenous, not heterogenous pattern
CD10 (strong)	Usually
Pan B (CD19, 20, 22, 79a)
CD34 (neg)
TdT (neg)
EBER	15-20% in sporadic 95% in endemic 30-40% in HIV

Molecular features:

• IgH and IgL genes rearranged
• Simple karyotype
• A complex karyotype indicates progression
• rearrangement of c-MYC (90% by FISH) (5% of otherwise classical BL lack a detectable MYC rearrangement)
• if negative, needs to be otherwise completely typical to make a diagnosis of BL
• t(8;14) (75-85%)
• activation of MYC on der(14)
• breakpoint centromeric of MYC
• t(2;8) or t(8;22) (15-25%)
• activation of MYC on der(8)
• breakpoint telomeric of MYC
• not specific; also seen in :
• CLL
• Mantle cell
• FL
• DLBCL
• Breakpoints can be up to almost 1 Mb centromeric of MYC in t(8;14) and telomeric of MYC in t(8;22) and t(2;8)
• This is because the IGH enhancer can act on a distance of several hundred kb
• Breakpoints at both MYC and IGH differ for endemic and sporadic Burkitt
• Note that this variability in breakpoints can lead to false negatives by FISH
• Lack of BCL2 or BCL6 translocation
• Secondary changes (60%) (first 3 are mutually exclusive):
• Structural rearrangements of chromosome 1
• dup(1)(q) (30-50%)
• +7
• +12
• 13q3 rearrangement (15%)
• Complex karyotypes indicate disease progression
• May consider a different diagnosis ex. DLBCL / dual hit
• MYC mutations
• Somatic mutation in part driven by VH mutation machinery after juxtaposition next to IGH
• Other genetic and epigenetic alterations involving:
• p16
• TP53
• p73
• BAX
• P130/RB2
• BCL6
• Consistent gene expression signature distinct from DLBCL
• Intermediate cases also exist

Other features:

• aggressive
• curable
• associated with HIV
• high uric acid and LDH with bulky tumours

References:

• WHO Tumours of Haematopoietic and Lymphoid Tissues (2002, 2008)
• Heim & Mitelman. Cancer Cytogenetics (2009)