Am J Clin Pathol. 2026 May 5;165(5):aqag030. doi: 10.1093/ajcp/aqag030.
ABSTRACT
OBJECTIVES: Diagnosing adult T-cell leukemia/lymphoma (ATLL) remains challenging due to its clinical and histopathologic heterogeneity. While HTLV-1 serology is a key diagnostic criterion, it is often unavailable at the time of diagnosis and does not confirm viral integration in tumor cells. The HTLV-1-encoded HBZ RNA is a reliable diagnostic biomarker for ATLL. We evaluated the diagnostic performance of RNAscope in situ hybridization (ISH) for HBZ RNA in formalin-fixed, paraffin-embedded (FFPE) tissues to distinguish ATLL from other T-cell lymphomas.
METHODS: HBZ ISH was evaluated in 72 cases, including 52 ATLLs and 20 non-ATLL T-cell lymphomas, to determine diagnostic sensitivity and specificity, interobserver agreement, interlaboratory reproducibility, and comparison with digital gene expression.
RESULTS: This assay demonstrated 86.5% sensitivity and 100% specificity, with sensitivity improving to 97% when excluding bone marrow clot sections and FFPE blocks older than 5 years. Interobserver agreement among 3 pathologists was excellent (κ = 0.92, percent agreement: 94%). Interlaboratory reproducibility of HBZ ISH was high, with 93% to 95% concordance across these Clinical Laboratory Improvement Amendments-certified laboratories. HBZ RNA ISH-positive cases demonstrated significantly higher HBZ gene expression levels by digital gene expression profiling.
CONCLUSIONS: We established HBZ ISH as a reliable tissue-based surrogate for HTLV-1 infection in ATLL. This assay will enhance diagnostic accuracy, expedite definitive diagnosis, and improve patient selection for targeted therapies and clinical trials, particularly in regions with a high prevalence of HTLV-1.
PMID:42106909 | DOI:10.1093/ajcp/aqag030
