Combined immunohistochemical profile CD10/LMO2/MYC is a useful tool to screen MYC rearrangements in aggressive large B-cell lymphomas.

Abstract

Aggressive large B-cell lymphomas (LBCL) are a heterogeneous group of lymphomas with variable biological characteristics, for which the identification of MYC rearrangements (MYCr) is a defining and prognostic feature. Both the International Consensus Classification and the 5th edition of the World Health Organization Classification of Hematolymphoid Tumors recommend performing cytogenetic studies in all aggressive LBCL to detect MYCr. Since MYCr incidence is low, cost-effective screening tools are necessary. We asked whether the immunohistochemical combined profile of CD10, LMO2, and MYC could be a useful tool to screen for MYCr. For this purpose, we used two strategies: first, a scoring system assigning 0 points each for CD10 - , LMO2 + , and MYC - and 1 point for CD10 + , LMO2 - , and MYC + , adding the results, and second, an algorithm that selected tumors with CD10 + /LMO2 - profile and/or MYC overexpression. All analyses were performed in a training series including 482 cases from a single center and a validation series of 124 patients from two centers. The resulting system classified cases in scores from 0 to 3. Scores 0 and 1 had low MYCr (0/92 and 7/224, 3%, respectively), being higher for scores 2 (40/98, 41%) and 3 (61/68, 90%) (P < 0.001) in the training cohort. The incidence of MYCr in the validation series was as follows: score 0, 0/29 cases; score 1, 3/64 (5%); score 2, 10/23 (43.5%); score 3, 8/8 (P < 0.001). Sensitivity and negative predictive values were respectively 93.5% and 97.8% for the training and 85.7% and 96.8% for the validation cohorts. The algorithm rescued 2 and 1 MYCr cases included in score 1 from both series. In conclusion, we suggest that both approaches combining the interpretation of CD10/LMO2/MYC by immunohistochemistry are useful to screen for MYCr.