ICD-9 : 173.0 • ICD-10 : M8076/2-3
Epidemiology and Etiology
Older than 55 years of age in the United States; in Australia, New Zealand, in Florida, Southwest and Southern California persons in their twenties and thirties.
Continental United States: 12 per 100,000 white males; 7 per 100,000 white females. Hawaii: 62 per 100,000 whites.
Males > females, but SCC can occur more frequently on the legs of females.
Sunlight. Phototherapy, PUVA (oral psoralen + UVA). Excessive photochemotherapy can lead to promotion of SCC, particularly in patients with skin phototypes I and II or in patients with history of previous exposure to ionizing radiation or methotrexate treatment for psoriasis.
Persons with white skin and poor tanning capacity (skin phototypes I and II) (see Section 10). Brown- or black-skinned persons can develop SCC from numerous etiologic agents other than UVR.
Most common in areas that have many days of sunshine annually, i.e., in Australia and southwestern United States.
Persons working outdoors—farmers, sailors, lifeguards, telephone line installers, construction workers, dock workers.
Oncogenic HPV type-16, -18, -31 most commonly, -33, -35, -39, -40, and -51 to -60 are associated with epithelial dysplasia, SCCIS, and invasive SCC. HPV-5, -8, -9 have also been isolated from SCCs.
Solid organ transplant recipients, individuals with chronic immunosuppression of inflammatory disorders, and those with HIV disease are associated with an increased incidence of UVR- and HPV-induced SCCIS and invasive SCCs. SCCs in these individuals are more aggressive than in nonimmunosuppressed individuals.
Chronic cutaneous lupus erythematosus, chronic ulcers, burn scars, chronic radiation dermatitis, lichen planus of oral mucosa.
Pitch, tar, crude paraffin oil, fuel oil, creosote, lubricating oil, nitrosoureas.
Trivalent arsenic had been used in the past in medications such as Asiatic pills, Donovan pills, Fowler solution (used as a treatment for psoriasis). Historically trivalent arsenic was used for treatment of psoriasis. Arsenic is still present in drinking water in some geographic regions (West Bengal and Bangladesh).
Slowly evolving—any isolated keratotic or eroded papule or plaque in a suspect patient that persists for over a month is considered a carcinoma until proved otherwise. Also, a nodule evolving in a plaque that meets the clinical criteria of SCCIS (Bowen disease), a chronically eroded lesion on the lower lip or on the penis, or nodular lesions evolving in or at the margin of a chronic venous ulcer or within chronic radiation dermatitis. Note that SCC is always asymptomatic. Potential carcinogens often can be detected only after detailed interrogation of the patient.
Rapidly evolving—invasive SCC can erupt within a few weeks and is often painful and/or tender.
For didactic reasons, two types can be distinguished:
Highly differentiated SCCs, which practically always show signs of keratinization either within or on the surface (hyperkeratosis) of the tumor. These are firm or hard upon palpation (Figs. 11-6, 11-7, 11-8 and Figs. 11-10, 11-11, 11-12).
Poorly differentiated SCCs, which do not show signs of keratinization and clinically appear fleshy, granulomatous, amd consequently are soft upon palpation (Figs. 11-5 and 11-9).
Squamous cell carcinoma: invasive on the lip, two stages of development A. A large but subtle nodule, which is better felt than seen, on the vermilion border of the lower lip with areas of hyperkeratosis and erosion, arising in the setting of dermatoheliosis of the lip (cheilitis actinica). B. This nodule is larger and can be felt to infiltrate the entire lip.
Squamous cell carcinoma A round nodule, firm and indolent with a central black eschar. Note yellowish color in the periphery of the tumor indicating the presence of keratin. All three SCC shown in Fig. 11-6 and here are hard and occur on the lower lip. SCC hardly occurs on the upper lip because this is shaded from the sun. SCC on the lip is easily distinguished from nodular BCC because BCC does not develop hyperkeratosis or keratosis inside the tumor and does not occur on the vermilion lip.
Squamous cell carcinoma, well differentiated A. A nodule on the lower arm covered with a dome-shaped dark hyperkeratosis. B. A large, round, hard nodule on the nose with central hyperkeratosis. Neither lesion can be distinguished from keratoacanthoma (see Fig. 11-15).
Squamous cell carcinoma, undifferentiated There is a circular, dome-shaped reddish nodule with partly eroded surface on the temple of a 78-year-old male. The lesion shows no hyperkeratoses and is soft and friable. When scraped it bleeds easily.
Squamous cell carcinoma, advanced, well differentiated, on the hand of a 65-year-old farmer The big nodule is smooth, very hard upon palpation, and shows a yellowish color, focally indicating keratin in the body of the nodule. If the lesion were incised in the yellowish areas, a yellowish-white material (keratin) could be expressed.
Squamous cell carcinoma, highly differentiated, on the ear There is a relatively large plaque covered by adherent hard hyperkeratoses. Although SCCs are in general not painful, lesions on the helix or anthelix usually are, as was the case in this 69-year-old man.
Squamous cell carcinoma in the setting of chronic statis dermatitis and long-standing, nonhealing venous ulcer There was a venous ulcer of more than 10 years' duration at the site, which was unsuccessfully treated with topical remedies. Gradually the center of the ulcer became harder and elevated and now represents a firm elevated, easily bleeding mass with yellow necroses. Long-standing ulcers of the leg should always be biopsied to rule out squamous cell carcinoma.
Indurated papule, plaque, or nodule (Figs. 11-1, 11-6, 11-7, 11-8); adherent thick keratotic scale or hyperkeratosis (Figs. 11-1, 11-6, 11-7, 11-8, 11-11); when eroded or ulcerated, the lesion may have a crust in the center and a firm, hyperkeratotic, elevated margin (Figs. 11-7 and 11-8). Horny material may be expressed from the margin or the center of the lesion (Figs. 11-7, 11-8, and 11-10). Erythematous, yellowish, skin color. Hard. Polygonal, oval, round (Figs. 11-6 and 11-10), or umbilicated and ulcerated.
Usually isolated but may be multiple. Usually exposed areas. Sun-induced keratotic and/or ulcerated lesions especially on the bald scalp (Fig. 11-1), cheeks, nose, lower lips (Fig. 11-6), ears (Fig. 11-11), preauricular area, dorsa of the hands (Fig. 11-10), forearms, trunk, and shins (females) (Fig. 11-12).
Regional lymphadenopathy due to metastases.
In UV-related SCC evidence of dermatoheliosis and solar keratoses. SCCs of the lips develop from leukoplasia or actinic cheilitis; in 90% of cases they are found on the lower lip (Fig. 11-6). In chronic radiodermatitis they arise from radiation-induced keratoses (see Fig. 10-34); in individuals with a history of chronic intake of arsenic, from arsenical keratoses. Differentiated (i.e., hyperkeratotic) SCC due to HPV on genitalia; SCC due to excessive PUVA therapy on lower extremities (pretibial) or on genitalia. SCCs in scars from burns, in chronic stasis ulcers of long duration, and in sites of chronic inflammation are often difficult to identify. Suspicion is indicated when nodular lesions are hard and show signs of keratinization (Figs. 11-8, 11-10, and 11-11).
Special form: carcinoma cuniculatum, usually on the soles, highly differentiated, HPV-related but can also occur in other settings (Fig. 11-13).
Squamous cell carcinoma (carcinoma cuniculatum) in a patient with peripheral neuropathy due to leprosy A large fungating, partially necrotic and hyperkeratotic tumor on the sole of the foot. The lesion had been considered a neuropathic ulcer, ascribed to leprosy, but continued growing and became elevated and ulcerated.
SCCs with various grades of anaplasia and keratinization.
Fleshy, granulating, easily vulnerable, erosive papules and nodules and papillomatous vegetations (Fig. 11-9). Ulceration with a necrotic base and soft, fleshy margin. Bleeds easily, crusting. Red. Soft. Polygonal, irregular, often cauliflower-like.
Isolated but also multiple, particularly on the genitalia, where they arise from erythroplasia (see Fig. 35-24) and on the trunk (Fig. 11-5), lower extremities, or face, where they arise from Bowen disease.
Miscellaneous Other Skin Changes
Lymphadenopathy as evidence of regional metastases is far more common than with differentiated, hyperkeratotic SCCs.
Anaplastic SCC with multiple mitoses and little evidence of differentiation and keratinization.
As stated previously, any persistent nodule, plaque, or ulcer, but especially when these occur in sun-damaged skin, on the lower lips, in areas of radiodermatitis, in old burn scars, or on the genitalia, must be examined for SCC. Keratoacanthoma may be clinically indistinguishable from differentiated SCC (Fig. 11-8A).
Depending on localization and extent of lesion, excision with primary closure, skin flaps, or grafting. Microscopically controlled surgery in difficult sites. Radiotherapy should be performed only if surgery is not feasible.
Recurrence and Metastases
SCC causes local tissue destruction but it has a significant potential for metastases. Metastases are directed to regional lymph nodes and appear 1 to 3 years after initial diagnosis. In-transit metastases occur. In solid organ transplant recipients, can be present when SCC is diagnosed/detected or shortly after. SCC in the skin has an overall metastatic rate of 3–4% and tends to occur with tumors that are large, recurrent, and involve deep structures of cutaneous nerves. High-risk SCCs are defined as having a diameter >2 cm, a level of invasion >4 mm, and Clark levels IV or V*; tumor involvement of bone, muscle, and nerve (so-called neurotropic SCC, occurs frequently on the forehead and scalp); location on ear, lip, and genitalia; tumors arising in a scar or following ionizing radiation are usually highly dedifferentiated tumors. Cancers arising in chronic osteomyelitis sinus tracts, in burn scars, and in sites of radiation dermatitis have a metastatic rate of 31, 20, and 18%, respectively. On the other hand, SCC arising in solar keratoses have the lowest potential for metastasis. A special group of high-risk SCCs are those in patients who are immunosuppressed (Fig. 11-14).
Squamous cell carcinoma in a renal transplant recipient on the base of the scrotum In addition to this ulcerating firm nodule of the base of the scrotum, the patient had smaller, similar lesions elsewhere on the body. Since he had psoriasis and had therefore spent considerable time in the sun, the lesions in the sun-exposed sides were probably due to UVR. The lesion shown here was probably initiated by HPV as he had a similar lesion perianally and on the glans.
SCCs in Immunosuppression
Organ transplant recipients have a markedly increased incidence of NMSCs, primarily SCC, which is 40 to 50 times greater than in the general population. Risk factors include skin type, cumulative sun exposure, age at transplantation, male sex, HPV infections, the degree and length of immunosuppression, and the type of immunosuppressant. Lesions are often multiple, usually in sun-exposed sites but also in the genital, anal, and perigenital regions (Fig. 11-14).
These tumors grow rapidly and are aggressive; in one series of heart-transplant patients from Australia, 27% died of skin cancer.
Patients with AIDS have only a slight increased risk of NMSC. In one series a fourfold increase in their risk of developing lip SCC was noted. However, SCC of the anus is significantly increased in this population (see also Section 21).
*Clark level I, intraepidermal; level II, invades papillary dermis; level III fills papillary dermis; level IV, invades reticular dermis; level V, invades subcutaneous fat.