Subcutaneous panniculitis-like T-cell lymphoma in two unrelated individuals with BENTA disease

• Published in: Clinical immunology (Orlando, Fla.) Vol. 255; p. 109732
• Main Authors: Bauman, Bradly M., Dorjbal, Batsukh, Pittaluga, Stefania, Zhang, Yu, Niemela, Julie E., Stoddard, Jennifer L., Rosenzweig, Sergio D., Anderson, Ronald, Guilcher, Gregory M.T., Auer, Iwona, Perrier, Renee, Campbell, Martin, Bhandal, Samarjeet K., Alba, Camille, Sukumar, Gauthaman, Dalgard, Clifton L., Schelotto, Magdalena, Wright, Nicola A.M., Su, Helen C., Snow, Andrew L.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-10-2023
• Subjects: B cell lymphocytosis; BENTA; CARD11; CD8-Positive T-Lymphocytes - pathology; Child, Preschool; Humans; Immunologic Deficiency Syndromes; Lobular panniculitis; Lymphocytosis; Lymphoma, T-Cell - genetics; Lymphoma, T-Cell - therapy; Male; Panniculitis - genetics; Panniculitis - pathology; Panniculitis - therapy; SPTCL; TCR; B cell lymphocytosis; OS; HLH; Lobular panniculitis; G-CSF; ALLP; SPTCL; ATL; BENTA; TIM-3; HSCT; CARD11; GOF
• ISSN: 1521-6616; 1521-7035; 1521-7035
• DOI: 10.1016/j.clim.2023.109732

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare primary cutaneous non-Hodgkin lymphoma involving CD8+ T cells, the genetic underpinnings of which remain incompletely understood. Here we report two unrelated patients with B cell Expansion with NF-κB and T cell Anergy (BENTA) disease and a novel presentation of SPTCL. Patient 1 presented early in life with recurrent infections and B cell lymphocytosis, linked to a novel gain-of-function (GOF) CARD11 mutation (p.Lys238del). He developed SPTCL-like lesions and membranoproliferative glomerulonephritis by age 2, treated successfully with cyclosporine. Patient 2 presented at 13 months with splenomegaly, lymphadenopathy, and SPTCL with evidence of hemophagocytic lymphohistiocytosis. Genetic analysis revealed two in cis germline GOF CARD11 variants (p.Glu121Asp/p.Gly126Ser). Autologous bone marrow transplant resulted in SPTCL remission despite persistent B cell lymphocytosis. These cases illuminate an unusual pathological manifestation for BENTA disease, suggesting that CARD11 GOF mutations can manifest in cutaneous CD4+and CD8+ T cell malignancies.
•We describe 2 patients with BENTA disease and a novel presentation of SPTCL/ALLP.•Though unusual, SPTCL noted in BENTA may require aggressive treatment if severe.•CARD11 GOF variants can occur in both CD4+ and CD8+ T cell dyscrasias.