PTCL-GATA3 and PTCL-TBX21 subtypes were found in ∼85% of cases defined by IHC and GEP. PTCL-GATA3 was associated with monomorphic patterns (histologic patterns 1 and 2), whereas PTCL-TBX21 was associated with polymorphic patterns (histologic patterns 3 and 4). Monomorphic patterns (patterns 1 and 2) were morphologically characterized by a monotonous tumor cell morphology with a minimal inflammatory TME. CD4⁺ T-cell rich, polymorphic patterns (patterns 3 and 4) were characterized by polymorphic neoplastic cells interspersed in a mixed inflammatory TME (pattern 3) or in the classic TME of lympho-histiocytic (Lennert) lymphoma (pattern 4). In the polymorphic patterns, the inflamed TME was CD4⁺ and CD8⁺ T-cell rich and contained eosinophils, plasma cells, and histiocytes. The PTCL-GATA3 subtype was associated with PI3K-mTOR activation, whereas PTCL-TBX21 showed NF-κB activation. Therefore, PTCL-GATA3 subtype patients may benefit from PI3K inhibitors, whereas PTCL-TBX21 subtype patients may benefit from NF-κB inhibitors and TME modulators. Significant differences in overall survival were observed between the PTCL-GATA3 and PTCL-TBX21 subtypes derived by IHC and GEP classification (not shown). CD4⁺ T cell CD8⁺ T cell eosinophil plasma cell histiocyte. The figure has been adapted from Figure 5 in the article by Amador et al that begins on page 2159.