Lymphocytic Variant Hypereosinophilic Syndrome: Case Series From a Tertiary Referral Center in Canada

Background

Lymphocytic variant hypereosinophilic syndrome (L-HES) is a rare disorder characterized by persistent eosinophilia driven by aberrant T-cell populations. Diagnosis remains challenging due to the lack of standardized diagnostic criteria.

Methods

We retrospectively analyzed 18 patients diagnosed with L-HES between 2016 and 2023. Comprehensive flow cytometry was performed on peripheral blood samples.

Results

Nine patients demonstrated the classic sCD3⁻CD4⁺CD5⁺CD2⁺CD45RO⁺CD45RA⁻ immunophenotype, ranging from 0.6% to 70% of total lymphocytes. Two patients showed variant sCD3⁻CD4⁺ phenotypes, five had expanded (> 10%) sCD3⁺CD4⁺CD7⁻ T-cells, and two displayed aberrant CD8⁺ T-LGL populations. Clonality was established in all patients with nonclassic phenotypes by molecular TCR testing or based on uniform TRBC1. We assessed a serial gating strategy to quantify the classic L-HES phenotype and found this to be highly sensitive and specific with an estimated limit of detection of 0.06% of lymphocytes. Using this strategy, we identified decreased but detectable abnormal T-cells in all classic phenotype patients reassessed posttreatment, down to as low as 0.3% of lymphocytes. The identification of T-LGL phenotypes with eosinophilia is a novel finding.

Conclusion

Our study highlights the diverse immunophenotypic spectrum of L-HES, emphasizing the importance of comprehensive flow cytometry analysis for accurate diagnosis.