Presentation is loading. Please wait.

Presentation is loading. Please wait.

A comparison of the frequency of common lymphoma- associated gene rearrangements among B-Post transplant lymphoproliferative disorders (B-PTLD), B-cell.

Similar presentations


Presentation on theme: "A comparison of the frequency of common lymphoma- associated gene rearrangements among B-Post transplant lymphoproliferative disorders (B-PTLD), B-cell."— Presentation transcript:

1 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 Naresh. Department of Histopathology & Cytopathology, Hammersmith Hospital Imperial College London

2 Background

3 Post-transplant lymphoproliferative disorders (PTLD) Early lesions Polymorphic PTLD Monomorphic PTLD Classical Hodgkin lymphoma-type PTLD

4 Monomorphic PTLD B-cell neoplasms DLBCL Burkitt lymphoma Plasmacytoma / plasma cell myeloma Plasmacytoma-like Others T-cell neoplasms (~15%) Peripheral T-cell lymphoma, NOS Hepatosplenic T-cell lymphoma Others

5 HIV-LPDs 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 PTLDs.

6 Aetiology Viruses: 1) EBV 2) HHV-8 Genetic changes (translocation, Mutation,......) Antigen stimulation

7  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

8 Question ?

9 Do common lymphoma-associated gene rearrangements differ among B-PTLDs, B-cell HIV- lymphomas and iDLBCL?

10 Materials & Methods

11 H&E ISH Serial sections TMA FISH IHC Tissue microarray 64 B-PTLD 41 HIV-BCL 139 iDLBCL Cases collected BCL2, BCL3, BCL6, c-MYC, PAX5, MALT1 and IGH Genes investigated

12 Results

13 Percentage involvement of rearrangements of different genes among DLBCLs in different settings HIV-DLBCL(39cases) PTLD-DLBCL(24 cases) iDLBCL (139 cases)

14 BCL2 and BCL6 rearrangements were predominantly restricted to GC and AGC/non-GC subtypes respectively. 8% PT-DLBCLs and 30% HIV-DLBCLs showed c- MYC rearrangement. PT-DLBCLs and HIV-DLBCLs lacked BCL2 and BCL6 rearrangements. Seven iDLBCLs (5%) and 2 HIV-DLBCLs (8%) had rearrangements of two oncogenes.

15 Among Burkitt lymphoma (BL), 2/2 PT-BL and 12/13 (92%) HIV-BL had c-MYC rearrangement. Among plasmablastic lymphoma (PL), 2/6 (33%) PT-PL and 1/2 HIV-PL had c-MYC rearrangement.

16 Rearrangements of different genes among iDLBCL subsets

17 EBV-association was noted in 6%, 67% and 54% of iDLBCLs, PT-DLBCLs and HIV-DLBCLs respectively. 100% PT-BL and 63% HIV-BL had EBV-association. 83% PT-PL and 100% HIV-PL had EBV-association. EBV association

18 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. Correlation of rearrangements of c-MYC, BCL2 and BCL6 genes among the EBV-positive cases

19 Dual-colour break-apart probes EBER IGH C-MYC Monomorphic PTLD, plasmablastic lymphoma

20 Summary and Conclusion

21 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- PTLD. 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.

22 2- Alternate pathogenetic pathways in immune deficiency LPDs Other (cyto)genetic abnormalities that are that are not conventionally associated primary abnormalities in lymphomas Aberrant somatic hypermutation of critical genes. Aberrant hypermethylation of critical genes.

23 1. Jaffe ES, Harris NL, Stein H et al: World Health Organization Classification of Tumour: Pathology and Genetics, Tumours of Haematopoietic and Lymphoid Tissues. IARC Press: Lyon, Vega F, Medeiros LJ: Chromosomal translocations involved in non-Hodgkin lymphomas. Arch Pathol Lab Med 127: , Tibiletti MG, Martin V, Bernasconi B et al: BCL2, BCL6, MYC, MALT 1, and BCL10 rearrangements in nodal diffuse large B-cell lymphomas: a multicenter evaluation of a new set of fluorescent in situ hybridization probes and correlation with clinical outcome. Hum Pathol 40: , Vakiani E, Nandula SV, Subramaniyam S et al: Cytogenetic analysis of B-cell posttransplant lymphoproliferations validates the World Health Organization classification and suggests inclusion of florid follicular hyperplasia as a precursor lesion. Hum Pathol 38: , Gaidano G, Lo CF, Ye BH et al: Rearrangements of the BCL-6 gene in acquired immunodeficiency syndrome-associated non-Hodgkin's lymphoma: association with diffuse large-cell subtype. Blood 84: , Windebank K, Walwyn T, Kirk R et al: Post cardiac transplantation lymphoproliferative disorder presenting as t(8;14) Burkitt leukaemia/lymphoma treated with low intensity chemotherapy and rituximab. Pediatr Blood Cancer 53: , Capello D, Rossi D, Gaidano G: Post-transplant lymphoproliferative disorders: molecular basis of disease histogenesis and pathogenesis. Hematol Oncol 23:61-67, 2005 References

24 Acknowledgements Prof. Kikkeri Naresh Prof. Gordon Stamp. Dr Roberto Dina Mahrokh Nohdani. Donna Homcastle, Pritesh Trivedi, Tyler Lloyd & Kay Elderfield. William Mathieson John Brennan and David Peston. Prof. Letizia Foroni, Alistair Raid, and Jamshid Sorouri. The Egyptian Government All members of the Department of Histopathology, of Hammersmith Hospital.

25 Thank you


Download ppt "A comparison of the frequency of common lymphoma- associated gene rearrangements among B-Post transplant lymphoproliferative disorders (B-PTLD), B-cell."

Similar presentations


Ads by Google