BCL2, BCL6 and MYC Gene Rearrangements and Cell-of-Origin Classification in Primary Testicular Diffuse Large B Cell Lymphoma
King L Tan, Susana Ben-Neriah, David Telio, Kerry J Savage, Tawny Hung, Joseph M Connors, David W Scott, Graham W Slack, Christian Steidl, Randy D Gascoyne. British Columbia Cancer Agency, Vancouver, Canada
Background: Primary testicular lymphoma is uncommon and accounts for <5% of testicular malignancies and 1-2% of all non-Hodgkin's lymphomas. Most cases represent diffuse large B cell lymphomas (DLBCL). It has a poor prognosis with a median overall survival of 4-5 years and a continuous risk of relapse, especially in the contralateral testis and central nervous system. We report the frequency of BCL2, BCL6, and MYC gene rearrangements, cell-of-origin classification and correlation with outcome in 85 primary testicular DLBCL.
Design: A tissue microarray was constructed using duplicate 1.0mm cores from diagnostic paraffin blocks of 85 patients with primary testicular DLBCL. For survival analysis, patients not treated with curative intent or were HIV-positive were excluded, leaving 66 patients; 35 treated with R-CHOP and 31 with CHOP-like chemotherapy. IHC for CD10, BCL6, MUM1, GCET1, FOXP1 and LMO2 was performed. Cases were assigned to GCB or non-GCB subtypes using the Hans, Choi and Tally algorithms. FISH was performed using commercial probes for BCL2, BCL6 and MYC. IHC and FISH were scored by 2 independent observers. Survival analysis was determined by Kaplan-Meier method with differences evaluated by log-rank test.
Results: Most primary testicular DLBCL were classified as non-GCB subtype (Table1). There was complete agreement for all three algorithms in 54/85 cases (64%; 6 GCB and 48 non-GCB). BCL2 break-apart was seen in 5/78 cases (6%), BCL6 break-apart was seen in 17/78 (22%), and MYC break-apart was seen in 6/76 (8%). One case showed both BCL2 and MYC break-apart, and 1 case showed both BCL6 and MYC break-apart. No triple-hit cases were seen. There was no significant association for BCL2, BCL6, or MYC break-apart with GCB or non-GCB subtype using any of the algorithms. In the subgroup for survival analysis, 5/57 cases showed MYC break-apart. On univariate analysis with both R-CHOP and CHOP-like chemotherapy together as a single group, MYC break-apart was significantly associated with inferior overall survival (p=0.029) and a trend towards inferior progression free survival (p=0.084). There was no significant association with outcome for GCB vs non-GCB subtypes, BCL2 or BCL6 break-apart.
|Hans||35/85 (41%)||50/85 (59%)|
|Choi||28/85 (33%)||57/85 (67%)|
|Tally||6/85 (7%)||79/85 (93%)|