Malignancies after vascularized composite allotransplantation.

BACKGROUND: Vascularized composite allotransplantation (VCA) has emerged as a reconstructive option for complex tissue defects, yet its oncologic long-term safety remains poorly characterized. AIMS: This study aims to provide the most comprehensive overview of post-VCA malignancies to date. METHODS AND RESULTS: A systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, searching PubMed/MEDLINE, EMBASE, and Web of Science for malignancies that emerged after VCA. Additionally, registry cases were identified through the Organ Procurement and Transplantation Network (OPTN). Risk of bias and methodological quality of included case reports were assessed using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Case Reports and Case Series. The review protocol is registered on PROSPERO (CRD420261350024). 13 articles met the inclusion criteria, comprising 13 patients with 18 malignancies, reflecting multiple malignancies in individual patients. A total of 15 patients with 22 malignancies, including two additional OPTN registry cases, were analyzed. The most frequently diagnosed malignancies included non-melanoma skin cancer (NMSC; 41%; n=9/22 malignancies) and lymphoproliferative disorders (36%; n=8/22 malignancies). One malignancy was a recurrence in a patient who was transplanted due to squamous cell carcinoma of the mouth. Median time to malignancy was 24 (interquartile range [IQR]: 12-72) months after transplantation, malignancy-associated mortality was 33% (n=5/15 patients) and mean survival time after VCA was 74 ± 58 months in these patients. Notably, no malignancy was identified at the graft site and 23% (n=5/22) of malignancies led to a modification of the immunosuppressive regimen. Two patients self-reported symptoms prior to their scheduled follow-up, including cutaneous morphologic changes and systemic symptoms (night sweats, dyspnea, swelling). CONCLUSION: In our cohort, post-VCA malignancies were associated with a malignancy-associated mortality of 33%, with NMSC (41%) and lymphoproliferative disorders (36%) predominating the spectrum. Notably, two patients self-reported symptoms prior to their scheduled follow-up, suggesting that structured patient education may be warranted. Given the elective nature of VCA, careful patient selection, structured dermatologic screening, and Epstein-Barr virus surveillance may be useful to enable early detection of post-VCA malignancies. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier CRD420261350024.