Anaplastic Large Cell Lymphomas with Equivocal DUSP22 FISH Results: Recommendations for Clinical Reporting and Diagnostic Evaluation

Overview

Journal Hum Pathol

Specialty Pathology

Date 2023 Aug 26

PMID 37633531

Authors

Amr Fadl

Naoki Oishi

Min Shi

Surendra Dasari

Stephen M Ansell

Rhett P Ketterling

Andrew L Feldman

Affiliations

Soon will be listed here.

Abstract

Anaplastic large cell lymphoma (ALCL), one of the most common T-cell lymphomas, shows unifying pathological features but is clinically and genetically heterogeneous. One genetic subgroup, characterized by recurrent DUSP22 rearrangements (R), has distinct morphologic, immunophenotypic, and molecular features and can be identified in routine pathology practice using a breakapart (BAP) fluorescence in situ hybridization (FISH) probe. However, some cases show equivocal BAP-FISH findings (BAP-FISH) and the features of these cases are poorly understood. Here, we sought to characterize DUSP22 BAP-FISH ALCLs further. First, we applied an immunohistochemistry (IHC) algorithm using TIA1, pSTAT3, and LEF1, which can predict DUSP22-R with high accuracy. Among 37 BAP-FISH ALCLs, 18 (49%) were IHC-algorithm positive (IHC), 8 (21%) were IHC-algorithm negative (IHC), and 11 (30%) were IHC. In 32 BAP-FISH cases, we also applied a dual-color, dual-fusion (D-FISH) probe for t(6;7)(p25.3;q32.3), which accounts for 45% of DUSP22-R ALCLs. Among BAP-FISH cases, D-FISH was positive in 10/18 IHC cases (56%), 0/9 IHC cases (0%), and 0/5 IHC cases (0%). Median survival in BAP-FISH ALCLs was 105 months, intermediate between BAP-FISH ALCLs (median survival not reached) and BAP-FISH ALCLs (19 months). Thus, DUSP22 BAP-FISH ALCLs are clinicopathologically heterogeneous, likely due to an admixture of cases with an unbalanced DUSP22-R and cases with focal deletions without rearrangement. For clinical reporting, we recommend that DUSP22 BAP-FISH ALCLs be reported as equivocal, and not be grouped with BAP-FISH ALCLs. Clinical adoption of an IHC algorithm, possibly supplemented by t(6; 7) D-FISH, could facilitate genetic subtyping in about two-thirds of BAP-FISH ALCLs.

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