High proportion of nuclear phenotype identifies aggressive cutaneous squamous cell carcinoma

OBJECTIVE: To develop a quantitative histopathology algorithm to predict which patients with cutaneous squamous cell carcinoma (cSCC) were likely to experience recurrence or metastases. STUDY DESIGN: This retrospective study of cSCC lesions compared patients with aggressive disease (n=40) and those with nonaggressive disease (n=35). Based on a previous study using nuclear karyometry, we determined that aggressive lesions had a high proportion of a specific nuclear phenotype. The proportion of those nuclei was used to derive an aggressiveness score for each lesion. The mean age of patients was similar in both groups, as were the locations of index lesions. RESULTS: The mean aggressiveness score for cases with aggressive lesions was 0.60 ± 0.21 and was 0.28±0.35 for those with nonaggressive lesions. The overall accuracy in properly characterizing lesions was 72%. The area under the receiver operating characteristic curve was 0.80±0.05. In general, the aggressive nuclear phenotype is represented by elevated levels of chromatin clumps and short linear segments of dark chromatin/intense pixels. CONCLUSION: These data suggest that discriminant functions may be utilized to distinguish between aggressive and nonaggressive lesions at the time of diagnosis.