Actinic Keratoses and the Incidence of Occult Squamous Cell Carcinoma: A Clinical–Histopathologic Correlation


Address correspondence to: Syd Dromgoole, PhD, Therapeutics Inc., 9025 Balboa Avenue, Suite 100, San Diego, CA 92123, or e-mail:


BACKGROUND The ability to clinically diagnose actinic keratoses (AKs) lesions has been taken for granted for some time. The importance of the malignant potential of these lesions is well known. However, a recent Phase IV, multicenter study assessing the long-term benefit of aminolevulinic acid–based photodynamic therapy provided a unique opportunity to prospectively examine the clinical histopathologic correlation of AKs.

OBJECTIVE The objective was to characterize the histopathology of clinically diagnosed AK lesions in the study population.

METHODS Punch biopsies of 220 clinically diagnosed untreated AKs were performed at baseline plus 51 lesions unresponsive to treatment (total, 271).

RESULTS Clinical diagnosis and histopathologic findings agreed in 91% (246/271) of the lesions biopsied. The balance of the biopsied lesions were: (1) benign changes 4% (11/271) and (2) occult cutaneous malignancy in 5% (14/271) of the cases, 12 squamous cell carcinomas and 2 basal cell carcinomas.

CONCLUSIONS In this study, about 1 in 25 clinically diagnosed AK lesions identified by board-certified dermatologist investigator(s) were occult early-stage squamous cell carcinomas on histologic assessment, a fact surmised by the medical community that until now had not been well quantified. These findings should be considered when clinicians decide how to treat and manage AK patients.