attempts at keratinization are often no longer evident. this is a clear-cell squamous-cell carcinoma. the dysplastic cells infiltrated cords through the dermis. poorly differentiated cscc has greatly enlarged pleomorphic nuclei showing a high degree of atypia and frequent mitoses. poorly differentiated clear-cell squamous-cell carcinoma. for this type of cscc, immunostains will likely be required to classify it unless other areas of the tumor show obvious squamous-cell features such as seen here (arrow). 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. a 2016 review of sunscreen for preventing cutaneous squamous-cell carcinoma found insufficient evidence to demonstrate whether it was effective. management most cutaneous 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 cscc. there is little evidence comparing the effectiveness of different treatments for non-metastatic cscc. 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. 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. radiation or radiotherapy can also be a standalone option in treating cscc. as a non-invasive option brachytherapy serves a painless possibility to treat in particular but not only difficult to operate areas like the earlobes or genitals. an example of this kind of therapy is the high-dose brachytherapy rhenium-sct which makes use of the beta rays emitting property of rhenium-188. the radiation source is enclosed in a compound which is applied to a thin protection foile directly over the lesion. this way the radiation source can be applied to complex locations and minimize radiation to healthy tissue. after removal of the cancer, closure of the skin for patients with a decreased amount of skin laxity involves a split-thickness skin graft. a donor site is chosen and enough skin is removed so that the donor site can heal on its own. only the epidermis and a partial amount of dermis is taken from the donor site which allows the donor site to heal. skin can be harvested using either a mechanical dermatome or humby knife. electrodessication and curettage (edc) can be done on selected squamous-cell carcinoma of the skin. in areas where cscc is known to be non-aggressive, and where the patient is not immunosuppressed, edc can be performed with good to adequate cure rate. treatment options for cscc in situ (bowen's disease) include photodynamic therapy with 5-aminolevulinic acid, cryotherapy, topical 5-fluorouracil or imiquimod, and excision. a meta-analysis showed evidence that pdt is more effective than cryotherapy and has better cosmetic outcomes. there is generally a lack of evidence comparing the effectiveness of all treatment options. high-risk squamous-cell carcinoma, as defined by that occurring around the eye, ear, or nose, is of large size, is poorly differentiated, and grows rapidly, requires more aggressive, multidisciplinary management. nodal spread: 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. radiotherapy adjuvant therapy may be considered in those with high-risk cscc even in the absence of evidence for local metastasis. 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. frequent skin exams with a dermatologist is recommended after treatment. prognosis the long-term outcome of squamous-cell carcinoma is dependent upon several factors: the sub-type of the carcinoma, available treatments, location 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. when it does metastasize, the most common involved organs are the lungs, brain, bone and other skin locations. 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%, 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. epidemiology age-standardized death from melanoma and other skin cancers per 100,000 inhabitants in 2004. 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 cutaneous squamous-cell carcinoma continues to rise around the world. a recent study estimated that there are between 180,000 and 400,000 cases of cscc in the united states in 2013. risk factors for cscc varies with age, gender, race, geography, and genetics. the incidence of cscc increases with age and the peak incidence is usually around 60 years old. males are affected with cscc at a ratio of 2:1 in comparison to females. caucasians are more likely to be affected, especially those with fair skin or those chronically exposed to uv radiation. squamous-cell carcinoma of the skin can be found on all areas of the body but is most common on frequently sun-exposed areas, such as the face, legs and arms. solid organ transplant recipients (heart, lung, liver, pancreas, among others) are also at a heightened risk of developing aggressive, high-risk cscc. 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 cscc. additional images biopsy-proven cutaneous squamous-cell carcinoma squamous-cell carcinoma of the dorsum of the hand cscc in situ (bowen's disease) cscc of the right upper cheek; lesion outlined in blue with a dashed line prior to biopsy