title: Morphologic Features of ALK-negative Anaplastic Large Cell Lymphomas With DUSP22 Rearrangements.
abstract: 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.
authors.affiliation: *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.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: King
authors.forename: Linda N
authors.initials: LN
authors.lastname: Dao
authors.forename: Ellen D
authors.initials: ED
authors.lastname: McPhail
authors.forename: Elaine S
authors.initials: ES
authors.lastname: Jaffe
authors.forename: Jonathan
authors.initials: J
authors.lastname: Said
authors.forename: Steven H
authors.initials: SH
authors.lastname: Swerdlow
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Sattler
authors.forename: Rhett P
authors.initials: RP
authors.lastname: Ketterling
authors.forename: Jagmohan S
authors.initials: JS
authors.lastname: Sidhu
authors.forename: Eric D
authors.initials: ED
authors.lastname: Hsi
authors.forename: Shridevi
authors.initials: S
authors.lastname: Karikehalli
authors.forename: Liuyan
authors.initials: L
authors.lastname: Jiang
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Gibson
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Ondrejka
authors.forename: Alina
authors.initials: A
authors.lastname: Nicolae
authors.forename: William R
authors.initials: WR
authors.lastname: Macon
authors.forename: Surendra
authors.initials: S
authors.lastname: Dasari
authors.forename: Edgardo
authors.initials: E
authors.lastname: Parrilla Castellar
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Feldman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000077548:Anaplastic Lymphoma Kinase; D014408:Biomarkers, Tumor / Q000235:genetics*; D001706:Biopsy; D002648:Child; D054637:Dual-Specificity Phosphatases / Q000235:genetics*; D005260:Female; D015321:Gene Rearrangement; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D017728:Lymphoma, Large-Cell, Anaplastic / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D054639:Mitogen-Activated Protein Kinase Phosphatases / Q000235:genetics*; D010641:Phenotype; D011237:Predictive Value of Tests; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases; D054639:Mitogen-Activated Protein Kinase Phosphatases; C442824:DUSP22 protein, human; D054637:Dual-Specificity Phosphatases