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

Area of Science:

• Hematology
• Oncology
• Pathology

Background:

• Peripheral T-cell lymphoma (PTCL) is a heterogeneous cancer, often classified as PTCL-not otherwise specified (PTCL-NOS).
• Gene expression profiling (GEP) identified two prognostic PTCL-NOS subtypes: PTCL-GATA3 and PTCL-TBX21, with distinct transcriptomes and prognoses.

Purpose of the Study:

• To investigate the distinct pathologic, immunophenotypic, and GEP features of PTCL-NOS subtypes.
• To differentiate PTCL-NOS into PTCL-GATA3, PTCL-TBX21, and PTCL-T follicular helper (T_FH) categories for better classification.

Main Methods:

• Analysis of 101 PTCL cases using histopathology, immunophenotyping (including T_FH biomarkers), and GEP.
• Categorization into PTCL-NOS (n=63) and PTCL-TFH (n=38), with PTCL-NOS further divided into PTCL-GATA3 (n=22) and PTCL-TBX21 (n=41).

Main Results:

• PTCL-GATA3 cases showed monotonous cells with minimal tumor microenvironment (TME), predominantly CD4+CD8-, and higher LEF1, MYC, CD30 expression.
• PTCL-TBX21 cases presented with pleomorphic cells in a polymorphous TME, with diverse phenotypes including cytotoxic markers or T_FH markers.
• PTCL-TFH cases correlated with angioimmunoblastic T-cell lymphoma signatures and had more Epstein-Barr virus-positive cells.

Conclusions:

• This study highlights unique morphologic and phenotypic variations within PTCL subtypes.
• The findings support more precise diagnosis and the development of tailored therapeutic strategies for PTCL.