Refining Diagnostic Subtypes of Peripheral T-cell Lymphoma Using a Multiparameter Approach

Catalina Amador; Dennis D Weisenburger; Ana Gomez; Alyssa Bouska; Ahmad Alshomrani; Sunandini Sharma; Rauf Shah; Timothy C Greiner; Francisco Vega; Andreas Rosenwald; German Ott; Andrew L Feldman; Elaine S Jaffe; Neval Ozkaya; Sarah L Ondrejka; James R Cook; Philipp W Raess; Kerry J Savage; Graham W Slack; Joo Y Song; David W Scott; Elias Campo; Lisa M Rimsza; Joseph D Khoury; Louis M Staudt; Wing C Chan; Javeed Iqbal; A Leukemia and Lymphoma Molecular Profiling Project (LLMPP) Consortium

doi:10.1016/j.modpat.2024.100646

Refining Diagnostic Subtypes of Peripheral T-cell Lymphoma Using a Multiparameter Approach

Mod Pathol. 2024 Nov 2:100646. doi: 10.1016/j.modpat.2024.100646. Online ahead of print.

Authors

Catalina Amador¹, Dennis D Weisenburger², Ana Gomez³, Alyssa Bouska², Ahmad Alshomrani², Sunandini Sharma², Rauf Shah², Timothy C Greiner², Francisco Vega⁴, Andreas Rosenwald⁵, German Ott⁶, Andrew L Feldman⁷, Elaine S Jaffe⁸, Neval Ozkaya⁸, Sarah L Ondrejka⁹, James R Cook⁹, Philipp W Raess¹⁰, Kerry J Savage¹¹, Graham W Slack¹¹, Joo Y Song¹², David W Scott¹¹, Elias Campo¹³, Lisa M Rimsza¹⁴, Joseph D Khoury², Louis M Staudt¹⁵, Wing C Chan¹², Javeed Iqbal¹⁶; A Leukemia and Lymphoma Molecular Profiling Project (LLMPP) Consortium

Affiliations

¹ Department of Pathology and Laboratory Medicine, University of Miami Miller School of Medicine, Miami, FL. Electronic address: [email protected].
² Department of Pathology, Microbiology and Immunology, University of Nebraska Medical Center, Omaha, NE.
³ Department of Pathology and Laboratory Medicine, University of Miami Miller School of Medicine, Miami, FL.
⁴ Department of Hematopathology, Division of Pathology and Laboratory Medicine, UT MD Anderson Cancer Center.
⁵ Institute of Pathology, University of Würzburg, and Comprehensive Cancer Center Mainfranken, Würzburg, Germany.
⁶ Department of Clinical Pathology, Robert-Bosch Krankenhaus and Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany.
⁷ Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine and Science, Rochester, MN.
⁸ Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, MD.
⁹ Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH.
¹⁰ Department of Pathology and Laboratory Medicine, Oregon Health & Science University, Portland, OR.
¹¹ Center for Lymphoid Cancer, British Columbia Cancer, Vancouver, BC, Canada.
¹² Department of Pathology, City of Hope National Medical Center, Duarte, CA.
¹³ Hematopathology Unit, Hospital Clinic, Barcelona, Spain; Institute of Biomedical Research August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
¹⁴ Department of Laboratory Medicine and Pathology, Mayo Clinic Arizona, Scottsdale, AZ.
¹⁵ Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD.
¹⁶ Department of Pathology, Microbiology and Immunology, University of Nebraska Medical Center, Omaha, NE. Electronic address: [email protected].

PMID: 39491745
DOI: 10.1016/j.modpat.2024.100646

Abstract

Peripheral T-cell lymphoma (PTCL) is a heterogeneous category, and many cases are unclassifiable and designated as PTCL-not otherwise specified (PTCL-NOS). Gene expression profiling (GEP) has delineated two prognostic subtypes within PTCL-NOS, PTCL-TBX21, and PTCL-GATA3, characterized by distinctive transcriptomes and a different prognosis. To further evaluate the pathologic features of these subgroups, 101 PTCL cases that did not meet specific criteria for well-defined T-cell lymphoma entities underwent detailed pathologic, immunophenotypic (including T_FH biomarkers) and GEP analyses, separating them into PTCL-NOS (n=63) and PTCL-TFH (a.k.a. nodal PTCL-TFH, NOS, and TFH lymphoma, NOS) (n=38). PTCL-NOS cases were further categorized into PTCL-GATA3 (n=22; 34%) and PTCL-TBX21 (n=41; 66%), and a significant association (p < 0.02) with overall survival (OS) was reaffirmed. Histopathological assessment showed PTCL-GATA3 cases were characterized by monotonous medium-sized or large transformed cells with a minimal tumor microenvironment (TME) compared to PTCL-TBX21 cases, which consisted of pleomorphic cells in a polymorphous TME (p < 0.05). GEP analysis validated these TME distinctions. Immunophenotypic analysis showed that PTCL-GATA3 cases were predominantly CD4+CD8- and associated with significantly higher LEF1, MYC, and CD30 expression (p < 0.05). PTCL-TBX21 displayed a more diverse biomarker profile with two subgroups: one expressing cytotoxic antigens and enriched in CD8+CD4- or CD8-CD4- phenotype, and another lacking cytotoxic markers but showing a CD4+CD8- phenotype with increased ICOS expression, but devoid of other T_FH markers. The PTCL-TFH cases correlated with an angioimmunoblastic T-cell lymphoma (AITL) gene signature, had more EBER-positive cells than the PTCL-GATA3 and PTCL-TBX21 cases, and a subset had some morphologic features of AITL (p < 0.01). This study highlights the unique morphologic and phenotypic variations within the newly-identified PTCL subtypes and should enable more precise diagnosis and tailored therapeutic strategies in the future.