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

in Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc by 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,

TLDR

  • This study looked at two different types of T-cell lymphoma (PTCL) that were not well-defined by other criteria. The researchers used detailed pathologic, immunophenotypic, and gene expression analyses to compare these two types and see if they had different features. They found that the two types had distinct morphological, immunophenotypic, and gene expression profiles, which may have implications for diagnosis and treatment strategies. The study highlights the unique features of these subtypes and their association with overall survival, which may require tailored therapeutic strategies. Future research should focus on validating these findings in larger cohorts and exploring the potential role of these subtypes in response to different treatments.

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 Tbiomarkers) 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 Tmarkers. 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.

Overview

  • The study aims to evaluate the pathologic features of two prognostic subtypes within PTCL-NOS, PTCL-GATA3 and PTCL-TBX21, using detailed pathologic, immunophenotypic, and GEP analyses. The study includes 101 PTCL cases that did not meet specific criteria for well-defined T-cell lymphoma entities. The primary objective is to validate the previously identified differences in the morphology, immunophenotype, and gene expression profiles between these subtypes and their association with overall survival (OS).

Comparative Analysis & Findings

  • The study found a significant association between PTCL-GATA3 and PTCL-TBX21 subtypes and OS. Histopathological assessment showed that 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. 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, while 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 Tmarkers. 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. These findings suggest that the PTCL-GATA3 and PTCL-TBX21 subtypes have distinct morphological, immunophenotypic, and gene expression profiles, which may have implications for diagnosis and treatment strategies.

Implications and Future Directions

  • The study highlights the unique morphologic and phenotypic variations within the newly-identified PTCL subtypes and their association with OS. The findings suggest that the PTCL-GATA3 and PTCL-TBX21 subtypes may have distinct clinical and prognostic implications, which may require tailored therapeutic strategies. Future research should focus on validating these findings in larger cohorts and exploring the potential role of these subtypes in response to different treatments. Additionally, further studies should investigate the potential role of the TME in the pathogenesis and prognosis of these subtypes, as well as the potential for targeted therapies against specific biomarkers associated with these subtypes.
Read Full Article