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. 2025 Jul 3.
doi: 10.1097/PAS.0000000000002447. Online ahead of print.

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

Joao V Alves de Castro  1 , Jung Kim, Manoj Tyagi, Liqiang Xi, Valerie Zgonc, Svetlana D Pack, Theresa Davies-Hill, Stefania Pittaluga, Mark Raffeld, Elaine S Jaffe
Affiliations

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

Joao V Alves de Castro et al. Am J Surg Pathol. .

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.

Keywords: anaplastic large cell lymphoma; genomic sequencing; peripheral T-cell lymphoma.

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Conflict of interest statement

Conflicts of Interest and Source of Funding: This work was supported by funding from the Center for Cancer Research, National Cancer Institute, Reference number ZIA SC 000550. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.

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