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.

Background/Objectives: Actinic keratosis (AK) is a precancerous lesion that may progress into cutaneous cancer. However, the progression potential of individual lesions remains unpredictable. The histological basal proliferation pattern of AKs may serve as a risk marker for progression, yet it cannot be assessed clinically. The objective was to evaluate whether Olsen grading (hyperkeratosis of AKs) and pain as clinical markers correlate with the histological basal proliferation (PRO) and different histological aspects. Methods: In this retrospective two-center study, 380 clinically diagnosed AKs were graded according to the clinical Olsen classification (I–III) and assessed for pain upon palpation. Histologically, they were classified based on their basal- (PRO I–III) and upward-directed (AK I–III) growth patterns, and additional histopathological features, such as acantholysis, were documented. Results: Olsen grading showed weak correlation with the PRO classification (Spearman’s rho = 0.136, p = 0.008), with exact agreement of 36.3% (κ = 0.07). Pain was significantly associated with higher PRO grades (p = 0.005) and acantholysis (p = 0.023) but not with Olsen grades or upward-directed growth (AK I–III). Conclusions: Olsen grading does not allow reliable prediction of basal proliferation patterns in AKs. Its use as a clinical severity scale may suggest progression relevance; however, no substantiated association with histological indicators of transformation could be demonstrated in this study. The presence of pain, however, correlated with high PRO grades and the presence of acantholysis.

Background: Actinic keratoses (AKs) are considered early in situ forms of cutaneous squamous cell carcinoma (cSCC). However reliable histopathological or molecular markers for predicting the risk of progression are still lacking. The aim of this study was to investigate the relationship between immunohistochemical markers and basal proliferation patterns of AKs in order to identify histopathological associations that may be relevant for malignant transformation. Methods: A total of 97 AK samples from facial and scalp areas were retrospectively analyzed and classified according to their basal proliferation pattern (Pro I: non-proliferative and Pro III: proliferative). Immunohistochemical staining was performed for Ki-67, p53, p16 and podoplanin. In addition, histopathological parameters such as Röwert-Huber grade, inflammatory infiltrate, parakeratosis, elastosis and the presence of acantholysis were evaluated. Results: Pro III lesions were significantly more frequently associated with higher Röwert-Huber grades (AK III: 47.9% vs. 14.3%; p = 0.0004) and with acantholysis (p = 0.0004). No significant differences between the groups were found for Ki-67, p53 and p16. Podoplanin expression, however, was significantly higher in Pro III lesions (93.7% vs. 57.1%, p < 0.0001) and was predominantly localized basally. The combination of a PRO III pattern and podoplanin positivity identified a distinct histopathological subgroup associated with features linked to progression. Conclusions: Podoplanin expression, especially in combination with PRO III pattern and acantholysis, characterizes a histologically and biologically distinct AK subgroup. In contrast, Ki-67, p53 and p16 showed no additional discriminative value in this cohort. Podoplanin could therefore be a useful addition to existing classification systems and in the future support risk-adapted treatment decision. However, prospective longitudinal studies are required to determine its prognostic value.