BI29 Mycosis fungoides presenting in a patient with NFKB1 haploinsufficiency-associated common variable immunodeficiency

A 52-year-old man with a history of common variable immunodeficiency (CVID) secondary to NFKB1 haploinsufficiency was referred to the dermatology clinic. He had a worsening rash on his arms and legs with a background of a longstanding rash on his trunk for the last 2 years and his groin area for the preceding 12 years. He was diagnosed with CVID in 2009 and was receiving three-weekly intravenous immunoglobulin infusions. He had a history of childhood eczema and his son also had a history of eczema. On examination, the patient had erythematous infiltrated impetiginized plaques on his upper abdomen, buttocks and thighs and more subtle patches on his right chest consistent with a diagnosis of mycosis fungoides. His modified Severity-Weighted Assessment Score was 27.6 (patch 3.4%, plaque 12.1%). His staging investigations identified a weak clonal T-cell population in his bone marrow biopsy [B0b (L) lymphopenia]; a fludeoxyglucose F18 (FDG) avid lymph node in the region of his rash (likely dermatographic) and a discordant B-cell lymphoproliferation in biopsies of his FDG avid lung lesions. Lymphoma occurs in an estimated 2–8% of patients with CVID, the majority of which are non-Hodgkin lymphoma. To our knowledge, this is the first reported case of mycosis fungoides, the most common form of cutaneous T-cell lymphoma (CTCL) arising in a patient with NFKB1 haploinsufficiency. A recent report by Spangenberg et al. (Spangenberg MN, Grille S, Simoes C et al. Case report: mycosis fungoides as an exclusive manifestation of common variable immunodeficiency in a family with a NFKB2 gene mutation. Front Oncol 2023; 13: 1248964) described a family with two brothers who presented with mycosis fungoides as an exclusive symptom of a CVID, where whole-exome sequencing of the index patient revealed a pathogenic variant of the NFKB2 gene. High constitutive nuclear factor (NF)-κB activity in CTCL is responsible for increased malignant cell survival and proliferation and induction of NF-κB-dependent proinflammatory and anti-inflammatory cytokines. The role of NF-κB in CTCL lymphomagenesis warrants further investigation. Our case highlights that not only does a gain in NF-κB activity appear to confer an increased risk of developing mycosis fungoides, but a loss of such activity can also appear to confer an increased risk.