Premalignant keratoses and precursors
2026-08-06 Paola Dal Cin, PhD , Stefano Sioletic, MD Affiliation1.Brigham and Women\'s Hospital , Harvard Medical School, Boston , MA (USA)
2.San Camillo-Forlanin Hospital Rome (Italy)
Keywords
actinic keratosis ,sun-exposed skinClassification
Definition
This subgroup includes several intraepidermal squamous dysplastic lesions with premalignant potential. Among these entities, actinic keratosis (AK) is the most common and typically develops in chronically sun-exposed skin showing cumulative photodamage. The risk of progression of AK to invasive cutaneous squamous cell carcinoma (cSCC) varies across studies to range between 5% and 10% in immunocompetent individuals, with significantly increased risk in immunosuppressed patients.1
| Carcinoma precursors and benign simulants | ||
|---|---|---|
| Premalignant keratoses and precursors | Genetic events | |
| Actinic keratosis | Actinic keratosis (AK) is the most prevalent intraepidermal squamous precursor, arising in chronically sun-exposed skin as a consequence of cumulative UV-induced DNA damage. Histological features include atypical basal keratinocytes, parakeratosis, and underlying dermal solar elastosis. The risk of progression to invasive cutaneous squamous cell carcinoma is low for an individual lesion, but increases in patients with multiple lesions and is substantially higher in immunosuppressed individual. 1 | |
| Whole-exome sequencing studies have confirmed that actinic keratosis and cutaneous squamous ccell carcinoma (ccSCC} share a high mutational burden, copy number alterations, and patterns of driver gene mutations.Key molecular alterations, among others include TP53, NOTCH1, NOTCH2, FAT1 , PIK3CA, HMCN1,ABI3BP and IMPA1; loss of 9p21.2 CDKN2A, chromosome 13 and 5q and TGFβ dysregulation signaling .2 | ||
| Arsenical keratosis | Arsenical keratosis develops following chronic arsenic exposure, most commonly via contaminated drinking water or prolonged occupational contact. Lesions are multifocal, hyperkeratotic, and preferentially distributed on the palms and soles | |
| PUVA keratosis | PUVA keratosis develops following prolonged Psoralen-UltraViolet A photochemotherapy, usually in patients treated for psoriasis or other chronic inflammatory dermatoses. The lesions resemble actinic keratosis but are associated with a characteristic PUVA-induced mutational profile, with frequent TP53 alterations, distinct from that induced by solar ultraviolet radiation, as well as HRAS mutation . 3 The risk of progression to invasive cutaneous squamous cell carcinoma correlates with cumulative PUVA exposure and is highest in heavily treated patients. 4 | |
| Squamous cell carcinoma in situ (Bowen disease) | Squamous cell carcinoma in situ (Bowen disease) is a slow growing, precancerous dermatosis that, if left untreated, may progress to invasive cutaneous squamous cell carcinoma (SCC). 5 Key molecular alterations include TP53, RB1,CDKN2A, and NOTCH1 mutations.6 By proteomic analysis a numerous protein expression levels were significantly changed in the lesions between cutaneous SCC and Bowen disease. 7 |
Article Bibliography
| Reference Number | Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|---|
| 1 | 23647091 | 2013 | The natural history of actinic keratosis: a systematic review. | Werner RN et al |
| 2 | 33482222 | 2021 | The Genomic Landscape of Actinic Keratosis. | Thomson J et al |
| 3 | 14962108 | 2004 | The ultraviolet fingerprint dominates the mutational spectrum of the p53 and Ha-ras genes in psoralen + ultraviolet A keratoses from psoriasis patients. | Wolf P et al |
| 4 | 37884686 | 2023 | Effects of psoriasis and psoralen exposure on the somatic mutation landscape of the skin. | Olafsson S et al |
| 5 | 37845077 | 2023 | S3 guideline "actinic keratosis and cutaneous squamous cell carcinoma"- update 2023, part 1: treatment of actinic keratosis, actinic cheilitis, cutaneous squamous cell carcinoma in situ (Bowen's disease), occupational disease and structures of care. | Heppt MV et al |
| 6 | 32461624 | 2020 | Invasive squamous cell carcinomas and precursor lesions on UV-exposed epithelia demonstrate concordant genomic complexity in driver genes. | Lazo de la Vega L et al |
| 7 | 36085041 | 2022 | From Bowen disease to cutaneous squamous cell carcinoma: eight markers were verified from transcriptomic and proteomic analyses. | Biao T et al |
Citation
Paola Dal Cin, PhD ; Stefano Sioletic, MD
Premalignant keratoses and precursors
Atlas Genet Cytogenet Oncol Haematol. 2026-08-06
Online version: http://atlasgeneticsoncology.org/solid-tumor/209382
