Aggressive cutaneous squamous cell carcinomas of the upper extremities in solid-organ transplant recipients

Abstract Solid organ transplant recipients (SOTRs) have a significantly higher incidence of cutaneous squamous cell carcinoma (SCC), which often exhibit a more aggressive clinical course. Besides immunosuppression, a key risk factor for aggressive SCC is anatomical location—particularly tumors arising in the head and neck region. Recently, we observed an increasing number of SOTRs presenting with aggressive SCCs in the upper extremities—a site traditionally considered low risk. This study aimed to explore the clinical, pathological, and outcome features of these tumors. A retrospective search of the electronic files of a tertiary medical center was conducted (2016-2024) to identify SOTRs diagnosed with upper-extremity SCC with an aggressive course. Data on patient demographics, tumor characteristics, treatment, and outcomes were extracted. The cohort included 7 kidney transplant recipients who developed aggressive SCC in the upper extremities at a median of 31 years after transplantation. Treatments consisted of radical surgeries, radiotherapy, and chemotherapy. Six patients received immune checkpoint inhibitors, 3 of whom achieved a durable complete response. Two patients died of disease-related complications. Aggressive SCCs in the upper extremities are rare in SOTRs but may exhibit a highly malignant course. This series highlights the importance of heightened vigilance in SOTRs, particularly those with prolonged immunosuppression, even for SCCs arising in traditionally low-risk sites. The results also underscore the critical role of dedicated transplant dermatology clinics and the importance of multidisciplinary management in this complex population. Early identification and timely initiation of immunotherapy should be considered to improve outcomes.