Recurrent SWI/SNF Deficiency Defines a Subset of Peripheral T-Cell Lymphoma With Distinct Clinicopathologic Features

Peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS) rarely occurs in pediatric and young adult populations, where little is known about its clinicopathologic and molecular features. We characterized 16 cases of PTCL, NOS diagnosed in patients ≤21 years old. Seven (44%) cases demonstrated SMARCB1/INI1 loss by immunohistochemistry and SMARCB1/INI1 alterations by next-generation sequencing, including biallelic SMARCB1/INI1 deletion (n = 4), stop codon variant with 1-copy deletion (n = 1) or copy-neutral loss-of-heterozygosity (n = 1), and frameshift variant (n = 1). One case demonstrated biallelic SMARCE1 alterations (a nonsense variant and copy-neutral loss-of-heterozygosity), which, to our knowledge, has not been previously described in a hematopoietic neoplasm. The SWI/SNF-intact group harbored pathogenic TET2, PTEN, EZH2, or TP53 variants. CDKN2A deletions were present in 3 of 7 SWI/SNF-deficient and 0 of 4 SWI/SNF-intact cases. Chromosome 22q11.2 alterations were present on karyotype in 2 of 3 SMARCB1/INI1-deficient cases. SWI/SNF deficiency was associated with intermediate-to-large cell cytomorphology, frequent mitotic (88%; P = .041) and apoptotic (88%) activity, Reed-Sternberg-like cells (63%), necrosis (50%), and fibrosis (50%). All cases expressed CD45 and CD43 at initial diagnosis. SWI/SNF-deficient cases predominantly demonstrated a CD4⁺/CD8^-, TCRab, and PTCL-GATA3 phenotype, whereas SWI/SNF-intact cases predominantly demonstrated a CD8⁺/CD4^-, TCRgd, and PTCL-TBX21 phenotype. A PTCL-TBX21 phenotype was more common in SWI/SNF-intact than in SWI/SNF-deficient cases (P = .041). Cytotoxic markers were expressed in 71% of SWI/SNF-deficient and 88% of SWI/SNF-intact cases. Decreased or absent CD3 expression characterized 88% of SWI/SNF-deficient and 13% of SWI/SNF-intact cases (P = .01). Moreover, 63% of SWI/SNF-deficient cases demonstrated decreased or absent expression of ≥3 pan-T-cell antigens, compared with 13% of SWI/SNF-intact cases. Treatment was heterogeneous. Primary treatment failure or relapse occurred in 4 of 8 SWI/SNF-deficient and 4 of 7 SWI/SNF-intact cases. The median overall survival and event-free survival were 48.7 and 47.5 months for the SWI/SNF-deficient group, and 16.4 and 8.9 months for the SWI/SNF-intact group (P = nonsignificant). Death due to disease or therapy-related complications occurred in 4 of 8 (50%) cases in the SWI/SNF-deficient group and 6 of 7 (86%) of cases in the SWI/SNF-intact group. Our findings expand the knowledge of the clinicopathologic and molecular features of pediatric PTCL and highlight SWI/SNF-deficient T-cell lymphoma as a biologically distinct type of PTCL that is associated with characteristic clinicopathologic features.