Fatal Cardiac Intimal Sarcoma in a 35-Year-Old Male Following COVID-19 mRNA Vaccination: Plasmid DNA Fragments Encoding the S-Protein Detected in Tumor Tissue
Background: Primary cardiac intimal sarcoma is an exceedingly rare and aggressive malignancy of the heart, characterized by poorly differentiated spindle-shaped cells, frequent MDM2 gene amplification, and a propensity for early metastasis. Residual plasmid DNA from the manufacturing process, carrying a theoretical risk for insertional mutagenesis, has been quantified in mRNA COVID-19 vaccine products at levels far exceeding regulatory thresholds, with direct delivery into human cells by a lipid nanoparticle carrier.
Case Presentation: We present the case of a 35-year-old male with no personal or family history of malignancy and no identified hereditary cancer predisposition who was diagnosed with primary cardiac intimal sarcoma of the left atrium with multifocal cerebral metastases 170 days after his first dose, and 146 days after his second dose, of the Pfizer-BioNTech BNT162b2 mRNA COVID-19 vaccine. The diagnosis was established only at surgical resection. Comprehensive molecular profiling at a CLIA-certified reference laboratory demonstrated MDM2 and KDR (VEGFR2) amplification, consistent with intimal sarcoma. Whole-body FDG PET/CT showed no extracardiac disease besides cerebral metastases, supporting a cardiac primary. In 2025, archived tissue from the resected left atrial tumor underwent two qualitative research-use analyses. Polymerase chain reaction of total tissue DNA detected three codon-optimized vaccine spike (S) protein coding fragments — distinguishable from wild-type SARS-CoV-2 — and the plasmid backbone origin of replication (ORI) sequence; the SV40 enhancer was not detected. A separate analysis of the same material found no viral S protein nor SARS-CoV-2 nucleocapsid protein, ruling out infection as a source of genetic material. Despite multimodal treatment including surgical resection, doxorubicin-based chemotherapy, radiotherapy, gamma knife radiosurgery, and a total of four craniotomies, the patient developed progressive multifocal cerebral metastases, sustained an intratumoral brainstem hemorrhage, and died 675 days after diagnosis. Serial neuroimaging documented a tumor volume doubling time of approximately 10 days. At that rate, growing the 175 cm³ primary from a single transformed cell would have taken 350 to 385 days — and over 900 days at published sarcoma doubling times — yet only 170 days elapsed between vaccination and diagnosis, indicating acceleration of pre-existing occult disease.
Conclusions: This case documents the recovery of vaccine-derived plasmid DNA sequences from tumor tissue in a patient who developed an exceptionally rare and aggressive cardiac malignancy within 170 days of mRNA COVID-19 vaccination, in the absence of any identified oncologic risk factor. mRNA COVID-19 vaccination is a potential determinant of this malignancy. These findings add to converging in vitro, case-level and population-level evidence concerning the oncogenic potential of residual plasmid DNA in mRNA vaccine products and warrant urgent systematic investigation.
https://zenodo.org/records/22677693
https://zenodo.org/records/22677693/files/Fatal%20Cardiac%20Sarcoma%20Following%20COVID-19%20Vaccination.pdf