SMARCB1/INI1-deficient peripheral T-cell lymphoma: two cases expanding the spectrum of an emerging entity and a review of the literature.

SMARCB1/INI1-deficient peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), is a rare entity with limited reported cases. We present two additional cases in young women presenting with aggressive, treatment-refractory PTCL-NOS, and further characterizing their clinicopathologic and molecular features. Both cases demonstrated a monotonous proliferation of medium-sized atypical αβ T cells with clear cytoplasm, dual CD4/CD8 negativity, aberrant CD117 expression, cytotoxic and PTCL-TBX21 phenotype, and loss of SMARCB1/INI1 expression. Molecular analyses revealed copy-neutral loss of heterozygosity and two-copy/homozygous deletion involving the SMARCB1 gene, supporting a heterogeneous genetic basis for SMARCB1 inactivation. Clinically, both patients exhibited rapidly progressive disease with poor response to multi-modality treatment, highlighting the aggressive nature of this tumor. Our findings are consistent with prior reports, suggesting that SMARCB1/INI1-deficient PTCL-NOS preferentially affects children and young adults and demonstrates distinctive morphologic and molecular features that may facilitate recognition. Emerging evidence also indicates that SMARCB1/INI1 loss may confer sensitivity to histone deacetylase inhibitors (HDACi), supporting their potential therapeutic role in this tumor. Given the dismal outcomes associated with this entity, assessment of SMARCB1/INI1 expression should be considered in younger patients with PTCL-NOS displaying these characteristic features. Continued accumulation of cases with integrated molecular profiling, along with prospective evaluation of HDACi-based therapies, will be essential to better define disease biology and establish evidence-based treatment strategies for this aggressive lymphoma.