Basal Proliferation and Acantholysis May Represent Histological High-Risk Factors for Progression into Invasive Squamous Cell Carcinoma: A Comparison Study in Solid Organ Transplant Recipients and Matched Immunocompetent Patients

SIMPLE SUMMARY: AKs restricted to the lower third of the epidermis (AK I), with marked basal growth patterns (PRO III) and acantholysis, are associated with an increased risk of progression to invasive squamous cell carcinoma (iSCC). To confirm that these are high-risk histological features for tumour progression, we compared AKs from solid organ transplant recipients (sOTRs), known to carry an increased risk for progression to iSCC, to a matched immunocompetent control group (ICG). We assessed histological grading (AK I-III), basal growth patterns (PRO I-III) and the presence of acantholysis. The AKs from sOTRs showed significantly more AKs graded as AK I and PRO III compared to the ICG. Acantholysis was significantly more frequent in sOTRs and acantholytic AKs were significantly associated with advanced basal proliferation. Thus, AKs with marked basal proliferation and acantholysis may represent histological high-risk factors for progression into iSCC. ABSTRACT: Histological risk factors of AKs cannot be directly determined. Recent studies indicate that AKs restricted to the lower third of the epidermis (AK I), with marked basal proliferation (PRO III) and acantholysis, are associated with an increased risk of progression to invasive squamous cell carcinoma (iSCC). To confirm the aforementioned histological risk factors, this study compared AKs from solid organ transplant recipients (sOTRs), known to carry an up to 250-fold higher risk for progression into iSCC, to a matched immunocompetent control group (ICG). In total, 111 AKs from 43 sOTRs showed more AKs (n = 54, 48.7%) graded as AK I compared to 35 AKs (31.5%) in the ICG (p = 0.009). In line with these findings, 89 AKs (80.2%) from sOTRs showed pronounced basal proliferation (PRO III) compared to 37 AKs (33.3%) in the ICG (p < 0.0001). Acantholysis was more frequent in sOTRs than the ICG (59.5% vs. 32.4%, p < 0.0001) and more frequently associated with advanced basal proliferation (p < 0.0001). In conclusion, this study showed that acantholytic AKs graded as AK I and PRO III are predominantly found in a population at high risk of iSCC. Thus, AKs with marked basal proliferation and acantholysis should be assumed to be histological high-risk factors for the progression into iSCC.