(See also Overview of Skin Cancer.)
Squamous cell carcinoma is the 2nd most common type of skin cancer after basal cell carcinoma, with > 1 million cases annually in the United States, and 2500 deaths. It may develop in normal tissue, in a preexisting actinic keratosis, in a patch of oral leukoplakia, or in a burn scar.
The clinical appearance is highly variable, but any nonhealing lesion on a sun-exposed surface should be suspect. The tumor may begin as a red papule or plaque with a scaly or crusted surface and may become nodular or hyperkeratotic, sometimes with a warty surface. In some cases, the bulk of the lesion may lie below the level of the surrounding skin. Eventually the tumor ulcerates and invades the underlying tissue.
Biopsy is essential.
Differential diagnosis varies based on the lesion's appearance.
In general, the prognosis for small lesions removed early and adequately is excellent. Regional and distant metastases of squamous cell carcinomas on sun-exposed skin are uncommon but do occur, particularly with poorly differentiated tumors. Characteristics of more aggressive tumors include
About one third of lingual or mucosal cancers have metastasized before diagnosis (see Oral Squamous Cell Carcinoma).
Late-stage disease, which may require extensive surgery, is far more likely to metastasize. It spreads initially regionally to surrounding skin and lymph nodes and eventually to nearby organs. Cancers that occur near the ears or the vermilion border, in scars, or that have perineural invasion are more likely to metastasize. The overall 5-year survival rate for metastatic disease is 34% despite therapy.
Treatment of squamous cell carcinoma is similar to that for basal cell carcinoma and includes curettage and electrodesiccation, surgical excision, cryosurgery, topical chemotherapy (imiquimod or 5-fluorouracil) and photodynamic therapy, or, occasionally, radiation therapy. Treatment and follow-up must be monitored closely because of the greater risk of metastasis compared with a basal cell carcinoma.
Squamous cell carcinoma on the lip or other mucocutaneous junction should be excised; at times, cure is difficult.
Recurrences and large tumors should be treated aggressively with Mohs microscopically controlled surgery, in which tissue borders are progressively excised until specimens are tumor-free (as determined by microscopic examination during surgery), or by a team approach with surgery and radiation therapy. Because tumors with perineural invasion are aggressive, radiation therapy should be considered after surgery.
Metastatic disease is responsive to radiation therapy if metastases can be identified and are isolated. Widespread metastases do not respond well to chemotherapeutic regimens. For inoperable advanced disease or metastatic disease, programmed death receptor 1 (PD-1) inhibitors (eg, cemiplimab, pembrolizumab) are now an option.
Because squamous cell carcinoma seems to be related to ultraviolet (UV) exposure, a number of measures are recommended to limit exposure.
Sun avoidance: Seeking shade, minimizing outdoor activities between 10 AM and 4 PM (when sun's rays are strongest), and avoiding sunbathing and the use of tanning beds
Use of protective clothing: Long-sleeved shirts, pants, and broad-brimmed hats
Use of sunscreen: At least sun protection factor (SPF) 30 with broad-spectrum UVA/UVB protection, used as directed (ie, reapplied every 2 hours and after swimming or sweating); should not be used to prolong sun exposure
Squamous cell carcinoma, because of its high frequency of occurrence and highly variable appearance, should be considered in any nonhealing lesion in a sun-exposed area.
Metastases are uncommon but are more likely in cancers involving the lingual or mucosal surfaces; that occur near the ears, the vermilion border, or in scars; or that have perineural invasion.
Treatment is usually with locally destructive methods, sometimes also with radiation therapy (eg, for tumors that are large, recurrent, or have perineural invasion).
PD-1 inhibitors such as cemiplimab and pembrolizumab may be useful in patients with advanced or metastatic disease.