Utilization of Cell Blocks in the Diagnostic and Prognostic Work-up of Large B-cell Lymphomas

Summary: Introduction: Recommended panels for large B-cell lymphoma work-up comprise several immunohistochemical (IHC) and in situ hybridization (ISH) studies for accurate lymphoma classification and prognostication. Definitive diagnosis based on small volume biopsies, such as cell blocks, would avoid unnecessary additional sampling, and align with the WHO goal of providing actionable lymphoma diagnoses on cytologic specimens. This study investigated whether BCL-2, BCL-6, and C-MYC IHC, and EBV-ISH evaluated on cell block sections correlated with surgical specimens in patients with large B-cell lymphomas. Materials and Methods: Cytology cases with cell blocks and available surgical specimens were included. BCL-2, BCL-6, and C-MYC IHC were visually assessed by pathologists. Percentage thresholds of 50%, 30%, and 40% for BCL-2, BCL-6, and C-MYC, respectively, were employed to dichotomize IHC status as positive or negative. EBV-ISH results were evaluated using a 10% threshold. Results: The overall concordance rates between cytologic and surgical specimens for BCL-2, BCL-6, and C-MYC were 62.2%, 53.5%, and 68.3%, respectively (p=0.064, p=0.929, and p=0.034, respectively) (Table). Linear regression model for C-MYC IHC percentages showed a statistically significant correlation between cytologic and surgical specimens (R²=0.33, p<0.0001) (Figure). EBER-ISH showed 100% concordance between cell block and surgical specimens (1 positive and 37 negative cases). Conclusions: Our study suggests that EBV-ISH can be safely performed on cell block sections in patients with large B-cell lymphoma, although only 1 case with EBV-ISH positivity was present in the cohort. C-MYC IHC shows significant correlation between cytologic and surgical specimens, however, validation studies are needed. BCL-2 and BCL-6 IHC show poor correlation between cell block and surgical specimen sections. Further studies are needed to validate the findings of this study and to standardize the IHC methods for these markers in cytologic specimens.