B-cell lymphoblastic lymphoma following intravenous BNT162b2 mRNA booster in a BALB/c mouse: A case report

Sander Eens; Manon Van Hecke; Kasper Favere; Thomas Tousseyn; Pieter-Jan Guns; Tania Roskams; Hein Heidbuchel

doi:10.3389/fonc.2023.1158124

B-cell lymphoblastic lymphoma following intravenous BNT162b2 mRNA booster in a BALB/c mouse: A case report

Front Oncol. 2023 May 1:13:1158124. doi: 10.3389/fonc.2023.1158124. eCollection 2023.

Authors

Sander Eens^{1

2}, Manon Van Hecke³, Kasper Favere^{1

2

4

5}, Thomas Tousseyn³, Pieter-Jan Guns¹, Tania Roskams³, Hein Heidbuchel^{2

4}

Affiliations

¹ Laboratory of Physiopharmacology, Genetics, Pharmacology and Physiopathology of Heart, Blood Vessels and Skeleton (GENCOR), University of Antwerp, Antwerp, Belgium.
² Research Group Cardiovascular Diseases, Genetics, Pharmacology and Physiopathology of Heart, Blood Vessels and Skeleton (GENCOR), University of Antwerp, Antwerp, Belgium.
³ Laboratory of Translational Cell and Tissue Research, Department of Imaging and Pathology, University of Leuven, Leuven, Belgium.
⁴ Department of Cardiology, Antwerp University Hospital, Antwerp, Belgium.
⁵ Department of Internal Medicine, Ghent University, Ghent, Belgium.

Abstract

Unprecedented immunization campaigns have been rolled out worldwide in an attempt to contain the ongoing COVID-19 pandemic. Multiple vaccines were brought to the market, among two utilizing novel messenger ribonucleic acid technology. Despite their undisputed success in decreasing COVID-19-associated hospitalizations and mortality, various adverse events have been reported. The emergence of malignant lymphoma is one of such rare adverse events that has raised concern, although an understanding of the mechanisms potentially involved remains lacking. Herein, we present the first case of B-cell lymphoblastic lymphoma following intravenous high-dose mRNA COVID-19 vaccination (BNT162b2) in a BALB/c mouse. Two days following booster vaccination (i.e., 16 days after prime), at only 14 weeks of age, our animal suffered spontaneous death with marked organomegaly and diffuse malignant infiltration of multiple extranodal organs (heart, lung, liver, kidney, spleen) by lymphoid neoplasm. Immunohistochemical examination revealed organ sections positive for CD19, terminal deoxynucleotidyl transferase, and c-MYC, compatible with a B-cell lymphoblastic lymphoma immunophenotype. Our murine case adds to previous clinical reports on malignant lymphoma development following novel mRNA COVID-19 vaccination, although a demonstration of direct causality remains difficult. Extra vigilance is required, with conscientious reporting of similar cases and a further investigation of the mechanisms of action explaining the aforementioned association.

Keywords: B-cell; BALB/c; BNT162b2; COVID-19; lymphoblastic; lymphoma; mRNA vaccine; mouse.

Publication types

Case Reports

Grants and funding

SE is a predoctoral researcher funded by a Research Foundation Flanders (FWO) TBM project (Master@Heart OZ7552). KF is a predoctoral research fellow of the Research Foundation Flanders (FWO) (grant no. 11C6321N). This work is further supported by a Research Foundation Flanders (FWO) project grant (G099222N, to HH, TR and P-JG).