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Cutaneous squamous-cell carcinoma

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Squamous cell skin cancer
Other namesCutaneous squamous cell carcinoma (cSCC), epidermoid carcinoma, squamous cell epithelioma
SCC of the skin tends to arise from pre-malignant lesions, actinic keratoses; surface is usually scaly and often ulcerates (as shown here).
SpecialtyDermatology, plastic surgery, otorhinolaryngology
SymptomsHard lump with a scaly top or ulceration.[1]
Risk factorsUltraviolet radiation, actinic keratosis, lighter skin, arsenic exposure, radiation therapy, poor immune system function, HPV infection[2]
Diagnostic methodTissue biopsy[2][3]
Differential diagnosisKeratoacanthoma, actinic keratosis, melanoma, warts, basal cell cancer[4]
PreventionDecreased UV radiation exposure, sunscreen[5][6]
TreatmentSurgical removal, radiation therapy, chemotherapy[2][7]
PrognosisUsually good[5]
Frequency2.2 million (2015)[8]
Deaths51,900 (2015)[9]

Squamous-cell skin cancer, also known as cutaneous squamous-cell carcinoma (cSCC), is one of the main types of skin cancer along with basal cell cancer, and melanoma.[10] It usually presents as a hard lump with a scaly top but can also form an ulcer.[1] Onset is often over months.[4] Squamous-cell skin cancer is more likely to spread to distant areas than basal cell cancer.[11]

The greatest risk factor is high total exposure to ultraviolet radiation from the Sun.[2] Other risks include prior scars, chronic wounds, actinic keratosis, lighter skin, Bowen's disease, arsenic exposure, radiation therapy, poor immune system function, previous basal cell carcinoma, and HPV infection.[2][12] Risk from UV radiation is related to total exposure, rather than early exposure.[13] Tanning beds are becoming another common source of ultraviolet radiation.[13] It begins from squamous cells found within the skin.[14] Diagnosis is often based on skin examination and confirmed by tissue biopsy.[2][3]

Decreasing exposure to ultraviolet radiation and the use of sunscreen appear to be effective methods of preventing squamous-cell skin cancer.[5][6] Treatment is typically by surgical removal.[2] This can be by simple excision if the cancer is small otherwise Mohs surgery is generally recommended.[2] Other options may include application of cold and radiation therapy.[7] In the cases in which distant spread has occurred chemotherapy or biologic therapy may be used.[7]

As of 2015, about 2.2 million people have cSCC at any given time.[8] It makes up about 20% of all skin cancer cases.[15] About 12% of males and 7% of females in the United States developed cSCC at some point in time.[2] While prognosis is usually good, if distant spread occurs five-year survival is ~34%.[4][5] In 2015 it resulted in about 51,900 deaths globally.[9] The usual age at diagnosis is around 66.[4] Following the successful treatment of one case of cSCC people are at high risk of developing further cases.[2]

Signs and symptoms

Squamous cell carcinoma
Biopsy-proven squamous cell carcinoma

SCC of the skin begins as a small nodule and as it enlarges the center becomes necrotic and sloughs and the nodule turns into an ulcer.

  • The lesion caused by SCC is often asymptomatic
  • Ulcer or reddish skin plaque that is slow growing
  • Intermittent bleeding from the tumor, especially on the lip
  • The clinical appearance is highly variable
  • Usually the tumor presents as an ulcerated lesion with hard, raised edges
  • The tumor may be in the form of a hard plaque or a papule, often with an opalescent quality, with tiny blood vessels
  • The tumor can lie below the level of the surrounding skin, and eventually ulcerates and invades the underlying tissue
  • The tumor commonly presents on sun-exposed areas (e.g. back of the hand, scalp, lip, and superior surface of pinna)
  • On the lip, the tumor forms a small ulcer, which fails to heal and bleeds intermittently
  • Evidence of chronic skin photodamage, such as multiple actinic keratoses (solar keratoses)
  • The tumor grows relatively slowly

Spread

  • Unlike basal-cell carcinoma (BCC), squamous cell carcinoma (SCC) has a substantial risk of metastasis
  • Risk of metastasis is higher in SCC arising in scars, on the lower lips or mucosa, and occurring in immunosuppressed patients.

Causes

Squamous cell carcinoma is the second-most common cancer of the skin (after basal-cell carcinoma but more common than melanoma). It usually occurs in areas exposed to the sun. Sunlight exposure and immunosuppression are risk factors for SCC of the skin, with chronic sun exposure being the strongest environmental risk factor.[16] There is a risk of metastasis starting more than 10 years[citation needed] after diagnosable appearance of squamous cell carcinoma, but the risk is low,[specify] though much[specify] higher than with basal-cell carcinoma. Squamous cell cancers of the lip and ears have high rates of local recurrence and distant metastasis (20–50%).[17] In a recent study, it has also been shown that the deletion or severe down-regulation of a gene titled Tpl2 (tumor progression locus 2) may be involved in the progression of normal keratinocytes into becoming squamous cell carcinoma.[18]

SCCs represent about 20% of the non-melanoma skin cancers, but due to their more obvious nature and growth rates, they represent 90% of all head and neck cancers that are initially presented.[19]

The vast majority of SCCs are those of the skin, and like all skin cancers, are the result of ultraviolet exposure. SCCs usually occur on portions of the body commonly exposed to the Sun; the face, ears, neck, hands, or arm. The main symptom is a growing bump that may have a rough, scaly surface and flat reddish patches. Unlike basal-cell carcinomas, SCCs carry a significant risk of metastasis, often spreading to local nerves or the lymph nodes,[20]

During its earliest stages, it is sometimes known as Bowen's disease.

Squamous cell carcinoma are generally treated by surgical excision, Mohs surgery or electrodessication and curettage. Non-surgical options for the treatment of cutaneous SCC include topical chemotherapy, topical immune response modifiers, photodynamic therapy (PDT), radiotherapy, and systemic chemotherapy. The use of topical therapy, such as Imiquimod cream and PDT is generally limited to premalignant (i.e., actinic keratoses) and in situ lesions. Radiation therapy is a primary treatment option for patients in whom surgery is not feasible and is an adjuvant therapy for those with metastatic or high-risk cutaneous SCC. At this time, systemic chemotherapy is used exclusively for patients with metastatic disease.[citation needed]

Immunosuppression

People who have received solid organ transplants are at a significantly increased risk of developing squamous cell carcinoma due to the use of chronic immunosuppressive medication. While the risk of developing all skin cancers increases with these medications, this effect is particularly severe for SCC, with hazard ratios as high as 250 being reported, versus 40 for basal cell carcinoma.[21] The incidence of SCC development increases with time posttransplant.[22] Heart and lung transplant recipients are at the highest risk of developing SCC due to more intensive immunosuppressive medications used. Squamous cell cancers of the skin in individuals on immunotherapy or suffering from lymphoproliferative disorders (i.e. leukemia) tend to be much more aggressive, regardless of their location.[23] The risk of SCC, and non-melanoma skin cancers generally, varies with the immunosuppressive drug regimen chosen. The risk is greatest with calcineurin inhibitors like cyclosporine and tacrolimus, and least with mTOR inhibitors, such as sirolimus and everolimus. The antimetabolites azathioprine and mycophenolic acid have an intermediate risk profile.[24]

Diagnosis

Diagnosis is confirmed via biopsy of the tissue(s) suspected to be affected by SCC. For the skin, look under skin biopsy.

The pathological appearance of a squamous cell cancer varies with the depth of the biopsy. For that reason, a biopsy including the subcutaneous tissue and basalar epithelium, to the surface is necessary for correct diagnosis. The performance of a shave biopsy (see skin biopsy) might not acquire enough information for a diagnosis. An inadequate biopsy might be read as actinic keratosis with follicular involvement. A deeper biopsy down to the dermis or subcutaneous tissue might reveal the true cancer. An excision biopsy is ideal, but not practical in most cases. An incisional or punch biopsy is preferred. A shave biopsy is least ideal, especially if only the superficial portion is acquired.[citation needed]

Prevention

Appropriate sun-protective clothing, use of broad-spectrum (UVA/UVB) sunscreen with at least SPF 50, and avoidance of intense sun exposure may prevent skin cancer.[25] A 2016 review of sunscreen for preventing squamous cell skin cancer found insufficient evidence to demonstrate whether it was effective.[26]

Management

Most squamous cell carcinomas are removed with surgery. A few selected cases are treated with topical medication. Surgical excision with a free margin of healthy tissue is a frequent treatment modality. Radiotherapy, given as external beam radiotherapy or as brachytherapy (internal radiotherapy), can also be used to treat squamous cell carcinomas. There is little evidence comparing the effectiveness of different treatments for non-metastatic SCC of the skin.[27]

Mohs surgery is frequently utilized; considered the treatment of choice for squamous cell carcinoma of the skin, physicians have also utilized the method for the treatment of squamous cell carcinoma of the mouth, throat, and neck.[28] An equivalent method of the CCPDMA standards can be utilized by a pathologist in the absence of a Mohs-trained physician. Radiation therapy is often used afterward in high risk cancer or patient types.[citation needed]

Electrodessication and curettage or EDC can be done on selected squamous cell carcinoma of the skin. In areas where SCC's are known to be non-aggressive, and where the patient is not immunosuppressed, EDC[clarification needed] can be performed with good to adequate cure rate.

High-risk squamous cell carcinoma, as defined by those occurring around the eye, ear, or nose, is of large size, is poorly differentiated, and grows rapidly, requires more aggressive, multidisciplinary management.

Nodal spread:

  1. Surgical block dissection if palpable nodes or in cases of Marjolin's ulcers but the benefit of prophylactic block lymph node dissection with Marjolin's ulcers is not proven.
  2. Radiotherapy
  3. Adjuvant therapy may be considered in those with high-risk SCC even in the absence of evidence for local mestastasis. Imiquimod (Aldara) has been used with success for squamous cell carcinoma in situ of the skin and the penis, but the morbidity and discomfort of the treatment is severe. An advantage is the cosmetic result: after treatment, the skin resembles normal skin without the usual scarring and morbidity associated with standard excision. Imiquimod is not FDA-approved for any squamous cell carcinoma.

In general, squamous cell carcinomas have a high risk of local recurrence, and up to 50% do recur.[29] Frequent skin exams with a dermatologist is recommended after treatment.

Prognosis

The long-term outcome of squamous cell carcinomas is dependent upon several factors: the sub-type of the carcinoma, available treatments, location(s) and severity, and various patient health-related variables (accompanying diseases, age, etc.). Generally, the long-term outcome is positive, as less than 4% of Squamous cell carcinoma cases are at risk of metastasis.[30][31] Some particular forms of squamous cell carcinomas have a higher mortality rate. One study found squamous cell carcinoma of the penis had a much greater rate of mortality than some other forms of squamous cell carcinoma, that is, about 23%,[32] although this relatively high mortality rate may be associated with possibly latent diagnosis of the disease due to patients avoiding genital exams until the symptoms are debilitating, or refusal to submit to a possibly scarring operation upon the genitalia. Squamous cell carcinoma occurring in the organ transplant population is also associated with a higher risk of mortality.[33]

Epidemiology

Age-standardized death from melanoma and other skin cancers per 100,000 inhabitants in 2004.[34]
  no data
  less than 0.7
  0.7–1.4
  1.4–2.1
  2.1–2.8
  2.8–3.5
  3.5–4.2
  4.2–4.9
  4.9–5.6
  5.6–6.3
  6.3–7
  7–7.7
  more than 7.7

The incidence of squamous cell carcinoma continues to rise around the world. A recent study estimated that there are between 180,000 and 400,000 cases of SCC in the United States in 2013.[35] Risk factors for squamous cell carcinoma varies with age, gender, race, geography, and genetics. The incidence of SCC increases with age and the peak incidence is usually around 60 years old. Males are affected with SCC at a ratio of 2:1 in comparison to females. Caucasians are more likely to be affected, especially those with fair Celtic skin and chronically exposed to UV radiation. Squamous cell carcinoma of the skin is the most common among all sites of the body. Solid organ transplant recipients (heart, lung, liver, pancreas, among others) are also at a heightened risk of developing aggressive, high-risk SCC. There are also a few rare congenital diseases predisposed to cutaneous malignancy. In certain geographic locations, exposure to arsenic in well water or from industrial sources may significantly increase the risk of SCC.[16]

See also

References

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