Genomics of T-Cell Lymphomas With CD30/CD15 Co-Expression: Comparison With Anaplastic Large-Cell Lymphoma, ALK-Negative.

Abstract

The proper categorization of mature T-cell neoplasms with coexpression of CD30/CD15 is unresolved. Prior studies suggested an overlap with ALK-negative anaplastic large cell lymphoma (ALCL). We evaluated the morphologic, immunophenotypic, and molecular features of 28 T-cell lymphomas coexpressing CD30/CD15, and performed a comparison with 8 ALK/CD15-negative ALCL and published data. Clinical information was retrieved from the submitting physician. Immunohistochemistry, TRG and IG gene rearrangement, DNA and RNA targeted next-generation sequencing, and fluorescence in situ hybridization for DUSP22 rearrangement were performed. Cases were classified as conforming to 3 histologic variants: ALCL-like, Hodgkin-like, and PTCL-NOS-like. Median age was 62 years (range: 33 to 87). Male:female ratio was 3:1. Twenty-four cases presented with lymphadenopathy (24/28, 85.7%). Six cases had skin involvement (6/28, 21.4%), including 4 primary cutaneous cases (4/28, 14.3%). Ten cases were designated as ALCL-like, 12 as Hodgkin-like, and 2 as PTCL-NOS-like. There was frequent loss of T-cell markers, with expression of CD3 in 7/27 cases (25.9%), CD2 in 15/23 (65.2%), and expression of at least one cytotoxic marker in 13/24 (54.2%). DUSP22 was rearranged in 4 cases (4/16, 25%). The JAK-STAT pathway was frequently altered due to mutations in JAK1 (6/28, 21.4%), STAT3 (5/28, 17.8%), and JAK2 fusions (2/28, 7.1%). PI3K-AKT-mTOR pathway alterations due to PIK3R1 mutations (5/28, 17.8%) were also frequent and mutually exclusive with JAK-STAT pathway activation. In summary, most T-cell neoplasms with CD30/CD15 coexpression share clinical, morphologic, immunophenotypic, and molecular features with ALK -negative ALCL but do not segregate as a homogeneous entity as defined by histologic or genetic features.