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Squamous Cell Carcinoma

By Gregory L. Wells, MD, Dartmouth Medical School and Dartmouth-Hitchcock Medical Center

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Squamous cell carcinoma is a malignant tumor of epidermal keratinocytes that invades the dermis; this cancer usually occurs in sun-exposed areas. Local destruction may be extensive, and metastases occur in advanced stages. Diagnosis is by biopsy. Treatment depends on the tumor’s characteristics and may involve curettage and electrodesiccation, surgical excision, cryosurgery, or, occasionally, radiation therapy.

Squamous cell carcinoma is the 2nd most common type of skin cancer after basal cell carcinoma, with about 700,000 cases annually in the US, and 2,500 deaths. It may develop in normal tissue, in a preexisting actinic keratosis, in a patch of oral leukoplakia, or in a burn scar.

Symptoms and Signs

The clinical appearance is highly variable, but any nonhealing lesion on sun-exposed surfaces should be suspect. The tumor may begin as a red papule or plaque with a scaly or crusted surface and may become nodular, 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

Biopsy is essential.

Differential diagnosis

Differential diagnosis varies based on the lesion's appearance.

Nonhealing ulcers should be differentiated from pyoderma gangrenosum and venous stasis ulcers.

Nodular lesions should be differentiated from keratoacanthomas (probably squamous cell carcinomas themselves) and verruca vulgaris.

Scaling plaques should be differentiated from basal cell carcinoma, actinic keratosis, verruca vulgaris, seborrheic keratosis, psoriasis, and nummular dermatitis (nummular eczema).


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. However, 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, in scars, or that have perineural invasion are more likely to metastasize. The overall 5-yr survival rate for metastatic disease is 34% despite therapy.


  • Usually locally destructive techniques

Treatment of squamous cell carcinoma is similar to that for basal cell carcinoma treatment 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.

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, 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.


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 h and after swimming or sweating); should not be used to prolong sun exposure

Key Points

  • 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, 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).

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