History and exam

Key diagnostic factors

common

growing tumors

Squamous cell carcinomas (SCCs) tend to appear and grow over 3-6 months (as opposed to basal cell carcinomas which usually grow at a slower rate). Keratoacanthomas, in particular, grow rapidly and may spontaneously involute. Keratoacanthoma-like SCCs may not involute and may progress with malignant potential.

Other diagnostic factors

common

previous skin cancer

Evidence demonstrates that a history of previous skin cancer significantly increases the risk of experiencing second primary squamous cell carcinoma (SCC). For melanoma survivors there is a 2.6-fold increase in incidence of SCC.[53]​

bleeding

SCC tumors may be friable and bleed easily.

crusting

The extent of hyperkeratosis varies, and retention of compact keratin layers may result in the formation of a cutaneous horn. SCCs appear as erythematous papules or plaques that often have a scale or hemorrhagic crust.

evidence of sun damage to skin

Solar elastosis, cutaneous furrowing, and wrinkles are also more likely to be present in sun-exposed areas.

tender or itchy nonhealing wound originally caused by trauma

Marjolin ulcer presents in an area of previously traumatized, chronically inflamed or scarred skin.

erythematous papules or plaques

May present as lesions that often have scale or hemorrhagic crust.

thin, flesh-colored or erythematous plaques

In situ tumors (Bowen disease) may present as thin, flesh-colored or erythematous plaques.

dome-shaped nodule

Keratoacanthoma presents as a rapidly growing, dome-shaped nodule with a central keratin-filled crater.

exophytic, fungating, verrucous nodules or plaques

Verrucous carcinoma presents as exophytic, fungating, verrucous nodules, or plaques on skin or mucosa.

uncommon

ulcerated tumors

Invasive SCC may present as ulcerated tumors.

lymphadenopathy

Lymphadenopathy may be present with metastatic disease.

bone pain

Bone pain may be present with metastatic disease.

hepatomegaly

Hepatomegaly may be present with metastatic disease.

neurologic signs

Patients with perineural involvement may present with neurologic signs.

Risk factors

strong

ultraviolet radiation exposure

Ultraviolet (UV) radiation increases risk for squamous cell carcinoma; incidence is higher on sun-exposed skin such as head, neck, extensor arms, and upper torso.[38]

Incidence varies dramatically depending on skin phototype, cumulative sun exposure, and geographic latitude.

UV-B radiation (290-320 nm) is principally responsible, with UV-A radiation (320-400 nm) adding to the risk.[39]

Previous psoralen and UVA light therapy for psoriasis may also increase risk.

solid organ transplant recipient

Solid organ transplant recipients are more likely to develop squamous cell carcinomas.[15][40][41]​ These tumors tend to be more aggressive and are a main cause of death in transplant recipients.[42][43]

immunosuppression

Patients with immunocompromise (other than solid organ transplantation) are at risk for squamous cell carcinoma (SCC).

There is a direct correlation between duration of immunosuppression and skin cancer development. For example, the cutaneous effects of rapidly accelerated fibrosarcoma kinase B (BRAF) inhibitors include the development of SCCs (especially invasive phenotypes), keratoacanthoma, and photosensitivity.[44] In one study, keratoacanthoma and SCCs comprised 22% of lesions in patients with BRAF inhibitor-induced skin lesions.[45]

Fitzpatrick skin phototype

People with Fitzpatrick skin type I and II (white) are at increased risk for the development of skin cancer.[8][9]

Despite people with Fitzpatrick skin type V and VI (brown and black) having more melanin within their melanosomes, which protects the keratinocyte nucleus from UV damage, squamous cell carcinoma is the most common skin cancer for black people, and the second most common for Hispanic and Asian people.[8][16][17]​​​ 

hereditary skin conditions

In people with certain genodermatoses, such as oculocutaneous albinism, squamous cell carcinomas may develop on sun-exposed areas because there is insufficient protective pigment.[46]

In those with xeroderma pigmentosum, UV radiation-induced mutations in DNA cannot be repaired, and as a result multiple skin cancers may develop at an early age.[47]

older age

This imparts a longer history of sun exposure. In addition to increased cumulative UV exposure, older patients have decreased immune surveillance and tumor detection.[48]

male sex

Epidemiologic studies have shown an increased incidence of actinic keratoses and squamous cell carcinoma in males.[10][11]​​​​

exposure to carcinogens

Exposure to carcinogens such as arsenic, soot, or tar predisposes people to squamous cell carcinoma development.[21][49][50]​ 

Arsenical keratoses occur in people chronically exposed to arsenic, and are less common now than historically.

Exposure is usually through drinking water that is obtained from contaminated wells, but may occur in occupational or therapeutic settings.[49]

Affected patients typically have palmoplantar keratotic papules and pits.

actinic keratosis

The rate of transformation of actinic keratoses to invasive squamous cell carcinoma (SCC) is not completely clear, although estimates range from 0.025% to 16% per lesion per year.[51] The vast majority of SCCs arise within or close to actinic keratoses. There is evidence to suggest that patients with Olsen grade 3 actinic keratosis are at the highest risk of developing invasive SCC.[52]

previous skin cancer

Increases the likelihood of developing an squamous cell carcinoma.[53]

weak

exposure to ionizing radiation

Studies on the relative risk of squamous cell carcinoma (SCC) in patients receiving ionizing radiation have been conflicting; however, they may have an increased incidence of SCC, particularly those with sun-sensitive skin.[54]

human papillomavirus

Human papillomavirus is involved in the development of skin cancers, particularly in immunosuppressed individuals.[22]​​​[55][56][57][58]​​​​

However, clinical and experimental data suggest that viral infection alone is not often sufficient to induce malignant progression of infected cells, and that additional alterations in host cells may be required for skin cancer formation.

tobacco smoking

Smoking increases the risk of squamous cell carcinoma, particularly in women.[59][60]

thiazide diuretics and cardiac drugs

Thiazide diuretics and cardiac drugs may predispose to a higher risk for actinic keratoses.[61][62][63]​​​​

tattoos

Tattooing introduces exogenous pigments to the dermis, such that metallic salts and organic dyes remain in the skin permanently. Squamous cell carcinoma (SSC) and keratoacanthoma have been reported on tattoos.[64] SCC arising only in the red inked areas within a multicolored tattoo has been described, suggesting that red tattoo ink in the skin may be an infrequent risk factor for developing SCC.[23] Nonetheless, the number of skin cancers arising in tattoos appears to be low, and coincidental occurrence cannot be excluded.

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