title: Diagnostic accuracy of a defined immunophenotypic and molecular genetic approach for peripheral T/NK-cell lymphomas. A North American PTCL study group project.
abstract: The diagnosis of peripheral T-cell and NK-cell lymphomas (PTNKCL) is difficult with few standards for required ancillary studies. We evaluated a series of PTNKCLs using a tiered approach to immunohistochemistry and molecular genetic characterization to document diagnostic accuracy and clinical relevance. Seven hematopathologists reviewed 374 cases that included PTNKCL and non-PTNKCL cases to mimic diagnostic practice. Cases received tier 0, 1, and 2 diagnoses by 3 independent pathologists, on the basis of hematoxylin and eosin stains and progressive immunohistochemistry panels. A tier 2b diagnosis was rendered when gene rearrangement data were available, and a final consensus diagnosis was rendered after discussion of each case. Across all 374 cases, consensus agreement was 92.5%. For PTNKCLs, World Health Organization subclassification was possible in 16.5%, 37.1%, 82.8%, and 85.9% of individual reviewer diagnoses at tier 0, 1, 2, and 2b, respectively. Gene rearrangement contributed to a change in diagnosis in 51 of 647 (8%) individual reviews. Following this algorithm may provide prognostic information on the basis of individual marker expression in common PTNKCL types (CD4 in peripheral T-cell lymphoma, not otherwise specified and PD-1 in angioimmunoblastic T-cell lymphoma). This evidence-based approach to the diagnosis of PTNKCL informs practicing pathologists, clinical trial designers, and policy-makers regarding required ancillary studies.
authors.affiliation: *Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH †Department of Pathology, University of California Los Angeles, Los Angeles, CA ‡Department of Anatomic Pathology ¶Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN §Department of Pathology, Brigham and Women's Hospital, Boston, MA ∥British Columbia Cancer Agency, Vancouver, BC, Canada.
authors.forename: Eric D
authors.initials: ED
authors.lastname: Hsi
authors.forename: Jonathan
authors.initials: J
authors.lastname: Said
authors.forename: William R
authors.initials: WR
authors.lastname: Macon
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Rodig
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Ondrejka
authors.forename: Randy D
authors.initials: RD
authors.lastname: Gascoyne
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Morgan
authors.forename: David M
authors.initials: DM
authors.lastname: Dorfman
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Maurer
authors.forename: Ahmet
authors.initials: A
authors.lastname: Dogan
mesh_terms: D000465:Algorithms; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D015321:Gene Rearrangement; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D053208:Kaplan-Meier Estimate; D054391:Lymphoma, Extranodal NK-T-Cell / Q000235:genetics* / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D016411:Lymphoma, T-Cell, Peripheral / Q000235:genetics* / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D025202:Molecular Diagnostic Techniques; D009656:North America; D010641:Phenotype; D011237:Predictive Value of Tests; D011379:Prognosis; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor