Was this TURBO cancer in the mice rodent model? Eens et al. reported on 14 mice where B-cell lymphoblastic lymphoma occurred after intravenous Pfizer mRNA booster in a BALB/c mouse

by Paul Alexander

'B-cell lymphoblastic lymphoma following intravenous BNT162b2 mRNA booster in a BALB/c mouse'; a first case of fatal B-cell lymphoblastic lymphoma (B-LBL) mouse model after COVID gene vaccine


‘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…


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.’

Figure 1

Schematic overview of the study design. Intravenous (IV) immunization with the BNT162b2 mRNA COVID-19 vaccine was performed following a two-dose regimen at 12 and 14 weeks of age, with spontaneous death of the animal two days following booster vaccination.

Figure 2

Necropsy examination of organs following spontaneous death. (A) A disproportional enlargement of several of the animal’s major organs was observed at necropsy, including the liver, kidneys, spleen, and intestines (black arrows). (B) Animal with normal phenotype for reference.

‘Following organ dissection, tissues were formalin-fixed and paraffin-embedded, cut into 5 µm sections, and hematoxylin and eosin (HE) stained for histopathological examination (3801540BBE and 3801590BBE by Leica Biosystems, Wetzlar, Germany, see Figure 3A). Cardiac sections showed a normal aspect of the cardiomyocytes, with congestion of the large blood vessels and capillaries in the myocardium. At the epicardial surface, a localized, solid population of medium-sized atypical cells was present. These atypical cells showed large, polygonal nuclei with coarse chromatin, a small nucleolus, and mitotic figures. Many of the atypical cells were apoptotic with abundant presence of foamy macrophages containing debris, creating a ‘starry sky’ appearance. The epicardial focus extended slightly between the cardiomyocytes. In other regions of the epicardium, reactive changes of visceral pericardial cells were observed. The liver showed infiltration by the same population of atypical cells as described above, located in the sinusoids and surrounding the portal blood vessels. Moreover, numerous scattered megakaryocytes were present in the parenchyma, indicating extramedullary hematopoiesis. The renal interstitium was completely overgrown and distended by the same population of atypical cells as described earlier. Only few glomeruli and tubuli were recognizable in the corticomedullary region. Although they appeared intact on microscopy, their normal back-to-back arrangement was distorted due to the interstitial expansion. In the spleen, the amount of white pulp was strongly increased, with only minimal red pulp remaining. Again, the white pulp was completely infiltrated by the same population of atypical cells as described earlier. Similar to the liver, a large number of scattered megakaryocytes were observed in the parenchyma. In the sections of the lungs, only a limited amount of pulmonary parenchyma was recognizable. Most of the parenchyma was overgrown by the same population of atypical cells as described earlier, originating from the perivascular space. The extensor digitorum longus (EDL) muscle was examined to investigate the potential involvement of skeletal muscle. Although the capillaries contained an increased number of inflammatory cells, suggesting systemic leukocytosis, no further histopathological abnormalities were observed. Unfortunately, the intestines, pancreas, and lymph nodes were not dissected during necropsy, nor was blood sampling feasible given that the circulation had already stopped.’