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

King, Rebecca L. MD*; Dao, Linda N. MD*; McPhail, Ellen D. MD*; Jaffe, Elaine S. MD; Said, Jonathan MD; Swerdlow, Steven H. MD§; Sattler, Christopher A. BS*; Ketterling, Rhett P. MD*; Sidhu, Jagmohan S. MD; Hsi, Eric D. MD; Karikehalli, Shridevi MD#; Jiang, Liuyan MD**; Gibson, Sarah E. MD§; Ondrejka, Sarah L. MD; Nicolae, Alina MD; Macon, William R. MD*; Dasari, Surendra PhD††; Parrilla Castellar, Edgardo MD‡‡; Feldman, Andrew L. MD*

The American Journal of Surgical Pathology: January 2016 - Volume 40 - Issue 1 - p 36–43
doi: 10.1097/PAS.0000000000000500
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Systemic anaplastic large cell lymphomas (ALCLs) are classified into ALK-positive and ALK-negative types. We recently reported that ALK-negative ALCLs are genetically heterogenous. The largest subset, representing 30% of cases, had rearrangements of the DUSP22 locus. These cases had favorable outcomes similar to ALK-positive ALCL, and superior to other ALK-negative ALCLs. Here, we examined the morphologic features of these cases in more detail. First, we conducted blinded review of hematoxylin and eosin slides of 108 ALCLs from our previous study, scoring cases for the presence of 3 histologic patterns and 5 cell types. Cases then were unblinded and re-reviewed to understand these features further. DUSP22-rearranged ALCLs were more likely than other ALK-negative ALCLs to have so-called doughnut cells (23% vs. 5%; P=0.039), less likely to have pleomorphic cells (23% vs. 49%; P=0.042), and nearly always (95%) had areas with sheet-like growth (common pattern). To examine the reproducibility of these findings, we conducted blinded review of hematoxylin and eosin slides of 46 additional ALK-negative ALCLs using a 0 to 3 scoring system to predict likelihood of DUSP22 rearrangement, the results of which correlated strongly with subsequent findings by fluorescence in situ hybridization (P<0.0001). Although all ALCLs share certain morphologic features, ALCLs with DUSP22 rearrangements show significant differences from other ALK-negative ALCLs, typically showing sheets of hallmark cells with doughnut cells and few large pleomorphic cells. These morphologic findings and our previous outcome data suggest that ALK-positive ALCLs and DUSP22-rearranged ALCLs represent prototypical ALCLs, whereas ALCLs lacking rearrangements of both DUSP22 and ALK require further study.

Supplemental Digital Content is available in the text.

*Department of Laboratory Medicine and Pathology

††Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN

Hematopathology Section, Laboratory of Pathology, National Cancer Institute, Bethesda, MD

Department of Pathology, David Geffen School of Medicine, University of California, Los Angeles, CA

§Division of Hematopathology, University of Pittsburgh Medical Center, Pittsburgh, PA

Department of Pathology and Laboratory Medicine, United Health Services Hospitals, Johnson City/Binghamton

#Department of Pathology and Laboratory Medicine, Centrex Clinical Laboratories, Utica, NY

Department of Clinical Pathology, Cleveland Clinic, Cleveland, OH

**Department of Laboratory Medicine and Pathology, Mayo Clinic, Jacksonville, FL

‡‡Department of Pathology, Duke University, Durham, NC

Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website, www.ajsp.com.

Conflicts of Interest and Source of Funding: Supported by Award Numbers R01 CA177734 (A.L.F.) and P50 CA97274 (University of Iowa/Mayo Clinic Lymphoma SPORE) from the National Cancer Institute, by Award Number UL1 TR000135 (Mayo Clinic CTSA) from the National Center for Advancing Translational Science, and by the Predolin Foundation. S.H.S. has accepted a speaker honorarium and meeting travel expenses from Chugai Pharmaceutical Co. E.D.H. has received a speaker honorarium from Seattle Genetics and sponsored research support from Abbvie, Eli Lilly, and Cellerant Therapeutics. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.

Correspondence: Andrew L. Feldman, MD, Department of Laboratory Medicine and Pathology, Hilton Building, Room 8-00F, Mayo Clinic, 200 First St. SW, Rochester, MN 55905 (e-mail: feldman.andrew@mayo.edu).

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