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

Bradly M Bauman; Batsukh Dorjbal; Stefania Pittaluga; Yu Zhang; Julie E Niemela; Jennifer L Stoddard; Sergio D Rosenzweig; Ronald Anderson; Gregory M T Guilcher; Iwona Auer; Renee Perrier; Martin Campbell; Samarjeet K Bhandal; Camille Alba; Gauthaman Sukumar; Clifton L Dalgard; Magdalena Schelotto; Nicola A M Wright; Helen C Su; Andrew L Snow

doi:10.1016/j.clim.2023.109732

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

Clin Immunol. 2023 Oct:255:109732. doi: 10.1016/j.clim.2023.109732. Epub 2023 Aug 9.

Authors

Bradly M Bauman¹, Batsukh Dorjbal¹, Stefania Pittaluga², Yu Zhang³, Julie E Niemela⁴, Jennifer L Stoddard⁴, Sergio D Rosenzweig⁴, Ronald Anderson⁵, Gregory M T Guilcher⁵, Iwona Auer⁶, Renee Perrier⁷, Martin Campbell⁸, Samarjeet K Bhandal⁹, Camille Alba¹⁰, Gauthaman Sukumar¹⁰, Clifton L Dalgard¹⁰, Magdalena Schelotto¹¹, Nicola A M Wright⁵, Helen C Su³, Andrew L Snow¹²

Affiliations

¹ Department of Pharmacology & Molecular Therapeutics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
² Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
³ Laboratory of Clinical Immunology & Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA; NIAID Clinical Genomics Program, National Institutes of Health, Bethesda, MD, USA.
⁴ Immunology Service, Department of Laboratory Medicine, National Institutes of Health Clinical Center, Bethesda, MD, USA.
⁵ Department of Pediatrics, Alberta Children's Hospital, University of Calgary, Calgary, AB, Canada.
⁶ Alberta Precision Laboratories, University of Calgary, Calgary, AB, Canada.
⁷ Department of Medical Genetics, University of Calgary, Calgary, AB, Canada.
⁸ Royal Children's Hospital, Melbourne, Australia.
⁹ Department of Radiology, Alberta Children's Hospital, Calgary, AB, Canada.
¹⁰ The American Genome Center, Precision Medicine Initiative for Military Medical Education and Research (PRIMER), Uniformed Services University of the Health Sciences, Bethesda, MD, USA; Department of Anatomy, Physiology & Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
¹¹ Department of Pediatric Hematology and Oncology, Fundación Pérez Scremini, Hospital Pereira Rossell, Montevideo, Uruguay.
¹² Department of Pharmacology & Molecular Therapeutics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA. Electronic address: andrew.snow@usuhs.edu.

PMID: 37562721
PMCID: PMC10551883 (available on 2024-10-01)
DOI: 10.1016/j.clim.2023.109732

Abstract

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.

Keywords: B cell lymphocytosis; BENTA; CARD11; Lobular panniculitis; SPTCL.

Published by Elsevier Inc.

Publication types

Case Reports
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

MeSH terms

CD8-Positive T-Lymphocytes / pathology
Child, Preschool
Humans
Immunologic Deficiency Syndromes*
Lymphocytosis*
Lymphoma, T-Cell* / genetics
Lymphoma, T-Cell* / therapy
Male
Panniculitis* / genetics
Panniculitis* / pathology
Panniculitis* / therapy

Supplementary concepts

Subcutaneous panniculitis-like T-cell lymphoma

Grants and funding

Z01 AI001059/ImNIH/Intramural NIH HHS/United States