SMARCB1/INI1-deficient peripheral T-cell lymphoma: two cases expanding the spectrum of an emerging entity and a review of the literature.
This report describes two young women with aggressive, treatment-refractory SMARCB1/INI1-deficient PTCL-NOS, documenting characteristic pathology and distinct genetic routes to SMARCB1 inactivation while reviewing the limited literature on this emerging entity.
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This report describes two young women with aggressive, treatment-refractory SMARCB1/INI1-deficient PTCL-NOS, documenting characteristic pathology and distinct genetic routes to SMARCB1 inactivation while reviewing the limited literature on this emerging entity.
Research significance
The cases support SMARCB1/INI1 loss as a diagnostic and biologic feature of this lymphoma; the suggestion that this loss could confer sensitivity to histone deacetylase inhibitors is an inference from emerging prior evidence and was not prospectively tested or shown to produce benefit in the two reported patients.
Source abstract
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.