Progression of skin lesions from normal skin to squamous cell carcinoma

Abstract

Objective: To assess the changes in the nuclear chromatin pattern concomitant with progressive sun damage in skin biopsies ranging from sun-exposed, normal-appearing skin to squamous cell carcinoma (SCC).

Study design: Biopsies were taken from 140 cases with sun-exposed but histopathologically normal skin, from 20 cases visually assessed as pre-actinic keratosis (pre-AK) or early AK, from 30 cases of AK, and from 21 cases of SCC. A total of 21,094 nuclei were recorded from these biopsies. High-resolution digital imagery was recorded, and features descriptive of the nuclear chromatin pattern were computed. Both supervised learning and unsupervised learning algorithms were employed to derive progression plots.

Results: With increased sun exposure, the proportion of nuclei exhibiting changes in the nuclear chromatin pattern rises notably. Using karyometry, no significant differences could be substantiated between nuclei collected from early AK sites and AK lesions. Cases of SCC fell into 2 distinct groups. A larger group (approximately 66.7% of cases) had characteristics similar to AK. A smaller group (approximately 33.3% of cases) represented much more progressed lesions.

Conclusion: Karyometric assessment can provide a numeric measure of progression for sun damage and of the deviation from normal in both AK and SCC lesions.

Figure 1

Distribution of discriminant function scores DF I,1: sun-exposed normal skin versus nuclei from squamous cell carcinoma (SCC)

Figure 2

Distributions of nuclear abnormality from sun-exposed normal-appearing skin, early actinic keratosis (AK), AK and squamous cell carcinoma (SCC)

Figure 3

Nuclear signatures for sun-exposed normal-appearing skin, early actinic keratosis (AK), AK and squamous cell carcinoma (SCC)

Figure 4

Bivariate plot of DF I,1 score versus nuclear abnormality, showing the overlap between early actinic keratosis (early AK) and AK

Figure 5

Bivariate plot of relative nuclear area versus number of lightly stained pixels, for the subpopulations in squamous cell carcinoma (SCC) revealed by the unsupervised learning algorithm P-index

Figure 6

Nuclear signatures for nuclei from actinic kearatosis (AK) and the two subpopulations of squamous cell carcinoma (SCC)

Figure 7

Representative fields from cases included as actinic keratosis (AK) and squamous cell carcinoma subgroups SCC 1 and SCC 2

Figure 8

Distributions of case mean values for normal-appearing, sun damaged skin, actinic keratosis (AK), and squamous cell carcinoma (SCC) subgroups SCC 1 and SCC 2

Figure 9

Distributions for total optical density for squamous cell carcinoma (SCC) subgroups SCC 1 and SCC 2

Figure 10

Progression curve for actinic damage, from minimally exposed skin from the upper inner arm, to normal-appearing sun- exposed skin, to early actinic keratosis (early AK) and AK, to squamous cell carcinoma (SCC) subgroups SCC 1 and SCC 2