Severe lympho-depletion, abrogated thymopoiesis and systemic EBV positive T-cell lymphoma of childhood, a case

Abstract

Epstein-Barr virus (EBV) associated T-cell and NK-cell lymphoproliferative diseases are lethal and extremely rare in Caucasians. We expand on the clinical, immunological and histogenetic characteristics associated with this second European case (19 years old, previously healthy, Caucasian boy) of systemic EBV positive T-cell lymphoma of childhood. We report, as novel findings, severe lympho-depletion and abrogation of thymopoiesis secondary to severe EBV activation and excessive immune activation. Similar to the first European case, we also detected a somatic missense variant in the proto-oncogene FYN. In the first European patient however, the FYN variant allele frequency (VAF) was 10% and the patient only experienced moderate leukopenia, whereas in our case, the VAF was 48% and the patient experienced severe leukopenia and lymphopenia. This could suggest a pathogenic role of these FYN variants in driving excessive T cell activation. If confirmed, FYN might become target in future treatments of this fatal disorder.

Keywords:

• Systemic EBV positive T-cell lymphoma of childhood
• sjTRECs
• lympho-depletion
• immune activation
• somatic FYN variants

Acknowledgements

This work is dedicated to our patient, his brother and his parents.

Author contributions

KA and AA conceived the case, collected data and wrote the initial version of the manuscript. LQF and MBM were responsible for histologic characterization. ML and CF performed whole genome sequencing characterization of the proband and his parents. MBH was responsible for sjTRECS analysis. MBJ and KRJ attended the patient and collected data. KR was responsible for diagnostic imaging. MBB conducted flow-cytometric analyses of T cells. All authors agreed to the final version of the manuscript.

Ethics

Written informed consent was obtained from the patient’s parents. Publishing permission was obtained from the chairman of the Regional Committee on Health Research Ethics for Southern Denmark (S-20192000-48).

Disclosure statement of interests

none

Funding

none

Data availability statement

Data are available on request (by e-mail) to corresponding author: Kristian Assing