50% versus 70%: is there a difference between these BCL2 cut-offs in immunohistochemistry for diffuse large B-cell lymphomas (DLBCL)?

Abstract

Abstract Introduction The World Health Organization’s (WHO) update of 2017 defines the cut-off for BCL2 in immunohistochemistry (IHC) in 50% of stained cells in diffuse large B-cell lymphomas (DLBCL). The WHO’s 2017 classification, however, has no standardized value. This study analyzes associations between immunohistochemistry results for BCL2 in relation to the detection of translocations of MYC, BCL2, and BCL6 in DLBCL. Method Sixty-seven patients with DLBCL were evaluated using IHC, with CD20, CD10, BCL6, BCL2, MUM1, TDT and MYC, and fluorescence in situ hybridization (FISH) for translocations involving the BCL2, BCL6, and MYC. Two cut-offs for BCL2 in IHC were used (50 and 70%), with the calculation of sensitivity (S), specificity (E), positive predictive value (PPV), negative predictive value (NPV), accuracy and concordance test, with a significance level of 5%. Results Using a 70% cut-off, there is a good relationship between S (88.9%, IC95% = 68.4–109.4) and E (67.2, 95% CI = 55.2–79.3), with a high NPV (97.5, 95% CI = 92.7–102.3) and statistically significant agreement (K = 0.30, p = 0.02). Using a 50% cut-off, S and NPV increase to 100%, with a specificity of 39.7% (95% CI = 27.1–52.2) and a statistically significant concordance (K = 0.15, p = 0.017). Conclusion Reduction in the percentage of immunostaining increases the detection of DLBCL with a “double-expressor” immunophenotype. The lower criterion amplifies the S and the NPV of IHC to detect translocations involving the BCL2 gene, with an impact on the diagnosis of DLBCL “double expressor”, an unfavorable prognostic group.

Keywords

• Lymphoma
• Non-Hodgkin lymphoma
• Immunohistochemistry
• In situ hybridization, fluorescence
• Genes, BCL2
• Genes, MYC