Evaluation of intra- and interobserver agreement and its clinical significance for scoring bcl-2 immunohistochemical
Vinicius Freitas Borlot1, Irene Biasoli, Rony Schaffel
1Hematology and Pathology Services, University Hospital, Federal University of Rio de Janeiro, Brazil.
Insights
Immunohistochemistry (IHC) scoring for bcl-2 expression in diffuse large B-cell lymphomas shows good intra-observer agreement. While variations exist, consensus can be reached, supporting its diagnostic use.
Area of Science:
- Hematology
- Oncology
- Pathology
Background:
- Immunohistochemistry (IHC) is crucial for lymphoma diagnosis and research.
- Heterogeneity in IHC expression rates and cut-offs causes diagnostic uncertainty.
- Standardization is needed for prognostic application of IHC in lymphomas.
Purpose of the Study:
- To evaluate the agreement among pathologists when scoring bcl-2 expression using IHC.
- To assess the reliability of IHC for bcl-2 expression in diffuse large B-cell lymphomas.
Main Methods:
- Analysis of 81 diffuse large B-cell lymphoma cases by four pathologists.
- Independent, blinded scoring of bcl-2 expression twice by each pathologist, at least one month apart.
- Calculation of intra- and interobserver agreement using kappa statistics.
Main Results:
- Intra-observer concordance ranged from 88-93% (kappa = 0.71-0.83).
- Complete agreement among all observers was 72-79%.
- Observer experience did not impact intra-observer concordance; consensus was reached on discordant cases.
Conclusions:
- Observed variation in bcl-2 scoring is acceptable for lymphoma diagnosis and classification.
- Standardization and consensus review are necessary for using IHC in clinical treatment decisions.
- Further prospective trials are required to validate prognostic applications.
Abstract:
Immunohistochemistry (IHC) has become an essential part of diagnosis and clinical research in lymphomas. There is considerable heterogeneity, however, in IHC findings regarding expression rate and positivity cut-offs, which creates a degree of uncertainty that has prevented its incorporation for prognostic purposes. The purpose of the present study was to assess intra- and interobserver agreement in scoring bcl-2 expression on IHC. The study materials were 81 diffuse large B-cell lymphomas. Slides were processed in the same laboratory, and were analyzed independently and in a blinded manner by four pathologists twice, at least 1 month apart. The positivity rates ranged from 31% to 41% in the first evaluation, and from 30% to 43% in the second evaluation. The two analyses by the same pathologist gave concordant results in 88-93% of cases (kappa = 0.71-0.83). Complete agreement among all observers varied from 72% to 79%. The experience of the observer did not influence intra-observer concordance. Cooperative analysis of discordant slides led to consensus in all cases. The variation observed in scoring bcl-2 expression is acceptable for use in lymphoma diagnosis and classification. The use of IHC stratification, however, for clinical decisions regarding treatment will require standardization and centralized consensus review, and must await the results of ongoing prospective trials.

