Please select Print from the file menu or right mouse click and choose print from the menu to print this page.

[1077] The Frequency of Specific Chromosomal Abnormalities in Primary Central Nervous System Lymphoma (PCNSL) Differs from Systemic Diffuse Large B-Cell Lymphoma (DLBL), Suggesting a Distinct Pathogenesis

FM Cady, ME Law, AB Porter-Umphrey, BP O'Neill, C Giannini, ED Remstein, A Dogan. Mayo Clinic, Rochester, MN

Background: The molecular pathogenesis of PCNSL is largely unknown. Small preliminary studies have suggested immunoglobulin heavy chain (IGH) gene translocations may play a role, particularly those involving BCL6. The aim of this study is to determine the incidence of IGH, BCL6, and MYC gene rearrangements in PCNSL affecting immunocompetent patients.
Design: Forty-four cases of PCNSL affecting patients without clinical evidence of immunosuppression (including HIV infection) who were diagnosed and treated at Mayo Clinic between 1992 and 2006 were studied. All cases were classified as DLBL according to the World Health Organization classification and were confined to the CNS. Interphase fluorescence in-situ hybridization (FISH) was performed using a two-color IGH-BCL6 dual-fusion probe and a two-color MYC breakapart (BAP) probe on thin sections of paraffin-embedded tumor samples. Two-color BCL6 or IGH BAP FISH probes were also used in cases showing extra FISH signals without fusion using the IGH-BCL6 probe.
Results: Sufficient tumor cells for FISH analysis using the IGH-BCL6 and MYC probes were available in 43 and 39 cases, respectively. IGH-BCL6 fusion was present in 6 (14%) cases, one of which also had a separated MYC signal. Three (7%) cases showed three intact BCL6 signals using both the IGH-BCL6 and BCL6 BAP probes, indicating trisomy 3. One (2%) showed three intact IGH signals using both the IGH-BCL6 and IGH BAP probes, indicating trisomy 14. The remaining 33 (77%) cases lacked abnormalities involving IGH, BCL6, or MYC.
Conclusions: In this study, IGH-BCL6 fusion was present in 14% of cases, one of which also had a translocation involving MYC and an unknown partner gene. All other cases lacked translocations involving IGH, BCL6, and MYC. The frequency of IGH-BCL6 translocations in PCNSL is less than that seen in systemic DLBCL. However, other translocations involving IGH that are described in systemic DLBCL, such as IGH-BCL2 and IGH-MYC, are rare to absent in PCNSL. These data suggest that PCNSL has a distinct pathogenesis from systemic DLBCL.
Category: Hematopathology

Monday, March 26, 2007 9:00 AM

Platform Session: Section B, Monday Morning