A comparison of the frequency of common lymphoma-
associated gene rearrangements among B-Post transplant
lymphoproliferative disorders (B-PTLD), B-cell HIV-
lymphomas and diffuse large B-cell lymphoma in immune
competent patients (iDLBCL).
Hazem AH Ibrahim, Michael J Neat, Mufaddal Moonim, Amen Furrat, Lia Menasce, Sabine Pomplun,
Margaret Burke, Donald Macdonald, Ed Kanfer, Mark Bower, Paul Fields, Nicola Foot, Alistair Reid and Kikkeri N
Department of Histopathology & Cytopathology,
• Early lesions
• Polymorphic PTLD
• Monomorphic PTLD
• Classical Hodgkin lymphoma-type PTLD
• B-cell neoplasms
Plasmacytoma / plasma cell myeloma
• T-cell neoplasms (~15%)
Peripheral T-cell lymphoma, NOS
Hepatosplenic T-cell lymphoma
• Burkitt lymphoma.
• Diffuse large B-cell lymphoma (DLBCL).
• Primary effusion lymphoma (PEL).
• Plasmablastic lymphoma.
• HHV-8-associated LPDs in patients of MCD.
• Polymorphic lymphoid proliferations resembling
• Genetic changes (translocation, Mutation,......)
• Antigen stimulation
§ 20-40% of iDLBCL and HIV-related DLBCLs
harbour BCL6 rearrangement that are very rarely
seen in PTLDs.
§ Post-transplant Burkitt lymphomas (PT-BL),
similar to HIV-BL and iBL, display chromosomal
breaks at 8q24 involving the c-MYC oncogene.
§ Very few reports investigated chromosomal
translocations among PTLDs
Do common lymphoma-associated gene
rearrangements differ among B-PTLDs, B-cell HIV-
lymphomas and iDLBCL?
Materials & Methods
• 64 B-PTLD TMA
• 41 HIV-BCL
• 139 iDLBCL IHC
BCL2, BCL3, BCL6, c-MYC, PAX5, MALT1 and IGH
Percentage involvement of rearrangements of
different genes among DLBCLs in different settings
Double hit 5%
None, 53% IGH only, 2% BCL3 2%
iDLBCL (139 cases)
8% c-MYC ,
None double hits
PTLD-DLBCL(24 cases) HIV-DLBCL(39cases)
•BCL2 and BCL6 rearrangements were
predominantly restricted to GC and AGC/non-GC
•8% PT-DLBCLs and 30% HIV-DLBCLs showed c-
•PT-DLBCLs and HIV-DLBCLs lacked BCL2 and
•Seven iDLBCLs (5%) and 2 HIV-DLBCLs (8%)
had rearrangements of two oncogenes.
•Among Burkitt lymphoma (BL), 2/2 PT-BL
and 12/13 (92%) HIV-BL had c-MYC
•Among plasmablastic lymphoma (PL), 2/6
(33%) PT-PL and 1/2 HIV-PL had c-MYC
Rearrangements of different genes among iDLBCL subsets
•EBV-association was noted in 6%, 67% and 54% of
iDLBCLs, PT-DLBCLs and HIV-DLBCLs
•100% PT-BL and 63% HIV-BL had EBV-
•83% PT-PL and 100% HIV-PL had EBV-association.
Correlation of rearrangements of c-MYC, BCL2
and BCL6 genes among the EBV-positive cases
•None of the cases with either BCL2 or BCL6
rearrangement showed EBV-association (p=0.031
& p<0.001 respectively).
• No significant correlation between EBV-
association and c-MYC or IGH rearrangement.
Dual-colour break-apart probes
Monomorphic PTLD, plasmablastic lymphoma
Summary and Conclusion
1- Gene rearrangements
• Gene rearrangement, apart from c-MYC-IGH
(characteristically seen in BL and PL), appear
to be very rare among both HIV-BCL and B-
• HIV-DLBCL is more frequently associated
with c-MYC rearrangement than iDLBCL.
• BCL6 rearrangement is frequently seen in
iDLBCL of AGC and non-GC subtypes.
• None of the cases with either BCL2 or BCL6
rearrangement showed EBV-association.
2- Alternate pathogenetic pathways in immune
• Other (cyto)genetic abnormalities that are that
are not conventionally associated primary
abnormalities in lymphomas
• Aberrant somatic hypermutation of critical
• Aberrant hypermethylation of critical genes.
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The Egyptian Government
• Prof. Kikkeri Naresh
• Prof. Gordon Stamp.
• Dr Roberto Dina
• Mahrokh Nohdani.
• Donna Homcastle, Pritesh Trivedi, Tyler Lloyd & Kay
• William Mathieson
• John Brennan and David Peston.
• Prof. Letizia Foroni, Alistair Raid, and Jamshid Sorouri.
All members of the Department of
Histopathology, of Hammersmith Hospital.