Pathogenesis (disease development)
UV radiation, X-rays, and chemical carcinogens cause DNA damage to the skin (signature mutations). These are only partially repaired, so that mutations (changes in genetic material) lead to malignant proliferation (“malignant proliferation”) of keratinocytes (“horn-forming cells”) of the skin or skin appendages. Squamous cell carcinoma (PEC) of the skin usually develops on the basis of precancerous lesions or carcinoma in situ (literally: “cancer in situ”; actinic keratoses (PEC develops from approx. 10% of all actinic keratoses), leukoplakia, Bowen’s disease/erythroplasia queyrate). For further causes see etiology below. In rare cases, it is a de novo tumor (malignant tumor that does not develop via a precursor). Mutations in the tumor suppressor gene p53 are common genetic alterations in squamous cell carcinoma of the skin.
Etiology (Causes)
Biographic causes
- Genetic burden: diseases leading to increased UV sensitivity (dyskeratosis congenita, epidermodysplasia verruciformis, oculocutaneous albinism, or xeroderma pigmentosum).
- Age – older age (from the age of 70).
- Skin type – fair skin type (Fitzpatrick I-II).
- Occupations – occupations with high sun exposure (e.g., agriculture) [lifetime cumulative UV dose].
Behavioral causes
- Stimulants
- Alcohol – dose-dependent association: with each glass of alcohol drunk daily, risk increased by an additional 22%;
- Men: > 20 g alcohol per day significant risk increase (+ 33%).
- Women: 5.0-9.9 g alcohol per day significant risk increase (+ 35%).
bes. carcinogenic seems to be white wine
- Tobacco (smoking) – smokers: especially on the trunk and extremities (+20%).
- Alcohol – dose-dependent association: with each glass of alcohol drunk daily, risk increased by an additional 22%;
- UV light exposure (sun; solarium) [lifetime cumulative UV dose].
- Intensive use of tanning salons increases the risk of squamous cell carcinoma of the skin by approximately 80%.
- In women, the rate of squamous cell carcinoma with tanning salon users was 43% higher when all known associated factors and sun-related UV exposure were considered.
Disease-related causes
- Actinic keratosis – chronic damage to the keratinized epidermis caused by long-term intense exposure to sunlight; considered a facultative precancerous condition (risk of degeneration is less than 30%).
- Chronic degenerative dermatoses (skin diseases).
- Chronic inflammatory dermatoses (chronic discoid lupus erythematosus, erosive lichen ruber mucosae, lymphedema and lower leg ulcers).
- Chronic papillomavirus infection (HPV infection) – HPV triggers malignant transformation.
- Chronic scarring (late effects of radiation dermatitis or burns).
- Skin atrophy
- Hypertriglyceridemia (lipid metabolism disorder with elevation of triglycerides in the blood).
- Lichen sclerosus et atrophicus – chronic inflammatory disease of the connective tissue, which is probably one of the autoimmune diseases.
- Lupus vulgaris (tuberculosis cutis luposa) – chronic skin tuberculosis.
- Bowen’s disease – in situ squamous cell carcinoma of the skin and transitional mucous membranes.
- Recurrent mechanical injuries of the skin
- Tight atrophic scars as in burn scars.
- Sclerosing scars – hardened scars.
- Lower leg ulcers (ulcers of the lower leg)
- Vulvadystrophy – disease of the female reproductive organ, which is associated mainly with itching and burning.
Medication
- Hydrochlorothiazide (HCT) → photosensitivity ↑ → increase in dose-dependent risk of non-melanoma skin cancer (Engl. Non-Melanoma Skin Cancer, NMSC)/basal cell carcinoma (BCC; basal cell carcinoma), lip cancer, and squamous cell carcinoma (PEC) of the skin/spinalioma: for basal cell carcinoma, an odds ratio of 1.29 (95% confidence interval (CI):1.23-1.35), for lip cancer 2. 1 (1.7-2.6) and for squamous cell carcinoma (PEK) of the skin/spinalioma one of 3.98 (3.68-4.31).
- Prolonged immunosuppression (because of organ transplantation, patients with inflammatory bowel disease, or diseases such as rheumatoid arthritis)
- Azathioprine (thiopurine).
- Calcineurin inhibitors
- Ciclosporin (cyclosporin A)
- TNF-alpha inhibitor
Environmental pollution – intoxications (poisonings).
- Chronic exposure to heat
- Occupational contact with carcinogens such as polycyclic aromatic hydrocarbons (PAHs), arsenic, tar, or mineral oils (agricultural or road workers)
- Exposure to ionizing radiation
- UV radiation (chronic UV exposure; group 1 of established carcinogens) – actinic keratosis (precancerous condition; risk factor for squamous cell carcinoma); especially so-called “outdoor-workers” – such as farmers, bricklayers, bridge and track workers, roofers, lifeguards, fishermen and seamen – are affected by this (occupational disease list; BK list) [lifetime cumulative UV dose].
- X-ray irradiation
Other causes
- Long-term therapy with UV or PUVA (= psoralen plus UV-A; synonym: photochemotherapy).
- Long-term complication of chronic immunosuppression: patients receiving immunosuppressants [frequently. aggressive subclinical expansion (ASE)]
- Condition after organ transplantation (due toimmunosuppression) [frequent. aggressive subclinical expansion (ASE); up to 250-fold increased risk of squamous cell carcinoma (PEK) of the skin]
- Papillomaviruses (HPV) associated with UV light promote the development of PEK of the skin.
