Evolution of histology of new cutaneous squamous cell carcinomas over time in solid organ transplant recipients

Solid organ transplant recipients (SOTRs) develop a greater number and aggressive cutaneous squamous cell carcinomas (cSCC). Additionally, poor histological differentiation has been associated with worse clinical outcomes. Here, we examined the evolution of histological differentiation of new cSCCs post-transplant, seeking to determine whether development of poorly differentiated tumors is random or a stepwise event. We performed a retrospective cohort study at Columbia University Irving Medical Center examining 48 patients (22 SOTRs; 26 non-SOTRs) with 228 tumors (157 SOTRs; 71 non-SOTRs). On average, SOTRs developed a greater number of cSCCs compared to non-SOTRs (7.14 vs. 2.73, p = 0.007). There was a difference in distribution of the histologic differentiation in the final cSCC between groups with SOTRs exhibiting a higher proportion of poorly differentiated tumors (p = 0.009). A greater proportion of patients with sequential loss of tumor differentiation from the first tumor to last tumor was found in SOTRs versus non-SOTRs (41% vs. 4%; p = 0.002). In SOTRs, death was more likely related to cSCC (32% vs. 4.5%, p = 0.03). cSCC differentiation was associated with cSCC-related death for both SOTRs (rho=-0.699, p < 0.001) and non-SOTRs (rho=-0.549, p = 0.008). In SOTRs, new cSCCs undergo an evolution over time, with gradual loss of histological differentiation post-transplant. In SOTRs, the change in histologic differentiation of cSCCs towards less differentiated tumors is a signal of adverse futures outcomes. This highlights the importance of considering alternative surveillance strategies, earlier introduction of changes to immunosuppression regimens, and more aggressive therapeutic options as patients begin to develop less differentiated tumors.