Transplantation from a donor with malignancy could produce a valuable increase in organs with a reasonable value of safety 4,5. The reported risk of transmission varied from 0.01 to 0.05% 4–6. Despite of a low risk, it has been intermittently reported, resulting in fatal consequences 1–3, 7,8. This was the first reported synovial sarcoma transmission through a multiorgan procedure from 1 donor to 3 recipients.
The identification of synovial sarcoma remained a challenge due to histological overlap with other tumor types, mainly based upon a combination of traditional morphology, identification of the chromosomal t(X;18) translocation and a panel of immunohistochemical markers 9. Due to the limitation of diagnostic capacity or emergency of donation, misdiagnosis of malignancy before organ procurement might directly result in the use of malignant donor organs. In this study, synovial sarcoma was unidentified at the time of donation, leading to the subsequent unanticipated donor-derived transmission, that indicated the importance of systemic donor assessment. Due to the unrecognizability of some uncommon tumors or malignant potential, whether to use organs from a donor with initial diagnosis of benign tumor needs to be cautious. A list of benign tumors with malignant potential or other factors related to organ transplantation was summarized in Table 1. Donors with these tumors were recommended to receive a more detailed assessment to exclude malignant potential, otherwise, these donors should be discarded.
It remained speculative regarding the donor-derived transmission of malignancy from the donor without any signs of metastasis. Micro-metastasis of malignancy was considered as one hypothesis. Previous study demonstrated a greater risk for metastases of larger synovial sarcoma 10. Given the tumor size of donor in this study, micro-metastasis was considered to be existing before organ procurement procedure. Another hypothesis was that changes of immune system in cancer surveillance might promote development of malignancy, due to the use of immunosuppressant 11–13. On this account, the synovial sarcoma grew faster after organ transplantation.
In this study, all recipients eventually developed synovial sarcoma, revealing a high transmission rate. Previous study suggested that timely removal of allograft might be beneficial to prevent the development of metastasis 2. In order to prevent transmission, it should be considered in all recipients after notification of cancer transmission in one recipient from a multiorgan donor. In this study, if the donor-derived transmission was recognized and warned earlier, we might prevent the transmission events by earlier removing the allograft.
Synovial sarcoma was considered an aggressive sarcoma, noted for its propensity of local recurrence and metastasis, with a poor prognosis owing to its resistance to radiation and chemotherapy. The treatment of allograft synovial sarcoma was rarely reported. However, several therapeutic options for allograft renal mass were listed, including partial nephrectomy, transplant nephrectomy, radiofrequency ablation and cryoablation, followed by altered or withdraw of immunosuppression 14. Numbers of transplant surgeons and urologists faced with dilemma that required maximizing preservation of renal function while ensuring adequate cancer control. This study suggested that compared with local therapy, allograft nephrectomy followed by withdrawal of immunosuppression might be the best therapeutic option and more beneficial to local recurrence, which was supported by previous study 3. Nevertheless, it did not prevent the development of metastasis, probably owing to the above-mentioned delayed treatment. Anlotinib was a new oral tyrosine kinase inhibitor, designed to primarily inhibit multi-targets in vasculogenesis and angiogenesis, which exhibited direct anti-tumor activity towards synovial sarcoma 15. In this study, Anlotinib was proved to be effective towards synovial sarcoma by the elimination of metastases and prolonged progression-free survival of two kidney transplant recipients. Further observation of efficacy, drug resistance and safety were needed.
Donor-derived transmission of malignancy is not merely case report, but a notable public problem, which is considered to be underestimated, deserving much attention. Since 2005, Organ Procurement and Transplantation Network (OPTN) policy has required reporting of all unanticipated potential donor-derived transmission events in support of efforts to track, understand and learn from donor-derived disease transmission events in the United States 16. China has made efforts to established several official transplant registry systems for post-transplant surveillance, nonetheless separated from each other that lack of systemic surveillance for donor-derived transmission events. Given the importance of timely notification to all risky recipients, it is necessary and urgency to establish a systemic surveillance system specially for donor-derived cancer transmission events in the current era of deceased donor organ transplantation.
This report highlights the importance of detailed donor assessment for preventing donor-derived malignancy, as well as the need for establishing a post-transplant surveillance system specially for donor-derived transmission events in the current era of deceased donor organ transplantation. Whether to use organs from a donor with initial diagnosis of benign tumor needs to be cautious. Malignant potential of tumors needs to be excluded before transplantation, otherwise, the organs should be discarded. Timely removal of allograft is the best option to prevent and cure donor-derived cancer transmission that should be considered in all recipients after notification of transmission in one recipient from a multiorgan donor. Besides, Anlotinib is proved to be effective towards synovial sarcoma.