Morphologic Features of ALK-negative Anaplastic Large Cell Lymphomas With DUSP22 Rearrangements.

Area of Science:

• Hematopathology
• Oncology
• Molecular Pathology

Background:

• Systemic anaplastic large cell lymphomas (ALCLs) are classified into anaplastic lymphoma kinase (ALK)-positive and ALK-negative subtypes.
• ALK-negative ALCLs are genetically heterogeneous, with a significant subset characterized by DUSP22 locus rearrangements.
• DUSP22-rearranged ALCLs demonstrate favorable outcomes, comparable to ALK-positive ALCL.

Purpose of the Study:

• To investigate the detailed morphologic features of DUSP22-rearranged ALCLs.
• To correlate specific histologic patterns and cell types with DUSP22 rearrangement status.
• To assess the diagnostic utility of morphologic assessment in predicting DUSP22 rearrangement.

Main Methods:

• Blinded review of hematoxylin and eosin stained slides from 108 ALCL cases.
• Scoring of histologic patterns and cell types, including hallmark cells, doughnut cells, and pleomorphic cells.
• Validation using a scoring system on 46 additional ALK-negative ALCLs and fluorescence in situ hybridization (FISH).

Main Results:

• DUSP22-rearranged ALCLs were significantly more likely to display doughnut cells (23% vs. 5%) and less likely to show pleomorphic cells (23% vs. 49%) compared to other ALK-negative ALCLs.
• Sheet-like growth was a common pattern (95%) in DUSP22-rearranged ALCLs.
• Morphologic scoring demonstrated strong correlation with FISH results for DUSP22 rearrangement (P<0.0001).

Conclusions:

• ALCLs with DUSP22 rearrangements exhibit distinct morphologic characteristics, differentiating them from other ALK-negative ALCLs.
• Morphologic assessment, including the presence of doughnut cells and sheet-like growth, can help predict DUSP22 rearrangement.
• ALK-positive and DUSP22-rearranged ALCLs represent prototypical ALCLs, while ALCLs lacking both rearrangements warrant further investigation.