Karyometry of nuclei from actinic keratosis and squamous cell cancer of the skin

OBJECTIVE: To use karyometric analysis methods to compare actinic keratoses (AKs) to squamous cell carcinomas (SCCs) to determine if SCCs showed a logical progression beyond that seen in AKs and to explore variability within and between lesion types to better understand distinctions between the 2. STUDY DESIGN: Biopsies from 31 subjects with AKs were obtained from upper inner arm skin, forearm skin and AK lesions. Biopsies from 23 different subjects in a related subproject provided SCC biopsies for comparison. RESULTS: Karyometric measures of nuclear abnormality and sun damage were derived. Mean actinic damage levels progressed logically from inner arm to sun-exposed skin, to AK, to SCC. Considerable heterogeneity existed at the case level. Unsupervised learning methods revealed 2 distinct clusters of progressed lesions with different nuclear signatures, reflecting differing levels of actinic damage. Number of AKs and SCCs and invasiveness and differentiation of SCCs were distributed across both clusters in roughly equivalent proportions. CONCLUSION: Karyometric methods, shown previously to be capable of sensitively detecting subtle nuclear changes, revealed the possibility of 2 progression pathways, each containing AKs and SCCs. This finding may have prognostic implications.