LYMPHOMA AND COMMON VARIABLE IMMUNODEFICIENCY (CVID)-LIKE PHENOTYPE IN 46 ADULT PATIENTS: CHALLENGING THE USUAL EXCLUSION CRITERIA FOR CVID DIAGNOSIS
- Vincent Allain, France
Abstract
Background and Aims
About 5% of patients with CVID develop lymphoma during follow-up. We hypothesized that lymphoma could be the revealing symptom of PID, challenging the current exclusion criteria for CVID diagnosis.
Methods
This French unicentric retrospective study analyzed adult patients presenting both a CVID-like phenotype and a lymphoma. For patients without a previous genetic diagnosis or extensive genetic investigation, a targeted Next Generation Sequencing of 301 PID-associated genes was performed.
Results
Fifty-two lymphomas developed in 46 patients: non-Hodgkin B-cell lymphoma (65%), Hodgkin lymphoma (27%), and T-cell lymphoma (8%). EBV association was found in 15/33. In 25 patients, lymphoma developed before or within 6 months of the diagnosis of hypogammaglobulinemia. Compared to the 21 patients in whom lymphoma occurred during the follow-up of PID, Hodgkin lymphoma was overrepresented (48% versus 10%) whereas MALT lymphoma was absent (0 versus 33%). However, both groups presented with similar clinical and immunological characteristics, including age at hypogammaglobulinemia diagnosis (33.1 versus 31.4 years), consanguinity rate (20% versus 14%) or severe T-cell defect (LOCID, 44% versus 57%). Genetic analyses identified a probable molecular diagnosis in 9 patients, without peculiar gene recurrence. Possibly damaging variants of uncertain imputability were found in 10 additional patients.
Conclusions
Overall, a genetic cause for PID was identified in 20% of patients. Patients with lymphoma before or at diagnosis of hypogammaglobulinemia had similar characteristics than patients who developed lymphoma after a CVID diagnosis, and a high molecular diagnosis yield in the LOCID subgroup. Thus, a diagnosis of CVID-like PID should not be systematically ruled out in those patients.