Progression of skin lesions from normal skin to squamous cell carcinoma

Anal Quant Cytol Histol. 2009 Feb;31(1):17-25.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Algorithms
  • Artificial Intelligence
  • Biopsy
  • Carcinoma, Squamous Cell / diagnosis
  • Carcinoma, Squamous Cell / etiology
  • Carcinoma, Squamous Cell / pathology*
  • Cell Nucleus / pathology
  • Cell Nucleus / radiation effects
  • Chromatin / pathology*
  • Chromatin / radiation effects
  • Discriminant Analysis
  • Disease Progression*
  • Humans
  • Image Interpretation, Computer-Assisted / methods
  • Karyometry / methods
  • Keratosis, Actinic / diagnosis
  • Keratosis, Actinic / etiology
  • Keratosis, Actinic / pathology
  • Precancerous Conditions / diagnosis
  • Precancerous Conditions / etiology
  • Precancerous Conditions / pathology*
  • Skin / pathology
  • Skin / radiation effects
  • Skin Neoplasms / diagnosis
  • Skin Neoplasms / etiology
  • Skin Neoplasms / pathology*
  • Statistical Distributions
  • Statistics, Nonparametric
  • Sunlight / adverse effects


  • Chromatin