You are in: eMedicine Specialties > Plastic Surgery > SKIN Skin Malignancies, Squamous Cell CarcinomaArticle Last Updated: Jan 8, 2008AUTHOR AND EDITOR INFORMATIONSection 1 of 11
  Author: Noah S Scheinfeld, MD, JD, FAAD, Assistant Clinical Professor, Department of Dermatology, Columbia University; Consulting Staff, Department of Dermatology, New York Medical College-Metropolitan Hospital; Private Practice Noah S Scheinfeld is a member of the following medical societies: American Academy of Dermatology Coauthor(s): Candace Thornton Spann, MD, Staff Physician, Department of Dermatology, St Luke's - Roosevelt Hospital Center; Marvin Spann, MD, Staff Physician, Department of General Surgery, New York Hospital Queens; Mia Talmor, MD, Assistant Professor, Department of Surgery, Weill Medical College of Cornell University; Murad Alam, MD, Assistant Professor of Dermatology and Otolaryngology, Chief, Section of Cutaneous and Aesthetic Surgery, Department of Dermatology, Northwestern University; Director, Mohs Micrographic Surgery, Northwestern Memorial Hospital; Marc S Zimbler, MD, FACS, Director of Facial Plastic and Reconstructive Surgery, Director of Residency Education, Department of Otolaryngology, Head and Neck Surgery, Beth Israel Medical Center Editors: Shahin Javaheri, MD, Chief, Department of Plastic Surgery, Martinez Veterans Affairs Outpatient Clinic; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Wayne Stadelmann, MD, Stadelmann Plastic Surgery, PC; Nicolas (Nick) G Slenkovich, MD, Practice Director, Colorado Plastic Surgery Center at Swedish Medical Center; Jorge I de la Torre, MD, FACS, Professor of Surgery and Physical Medicine and Rehabilitation, Residency Program Director, Division of Plastic Surgery, University of Alabama at Birmingham; Director, Center for Advanced Surgical Aesthetics Author and Editor Disclosure Synonyms and related keywords: actinic keratosis, AK, skin cancer, Bowen's disease, Bowen disease, verrucous carcinoma, squamous cell carcinoma in situ, SCC, SCCA, cutaneous SCC, non-melanoma skin cancer, nonmelanoma skin cancer, leukoplakia, mouth cancer, radiation keratosis, radiation dermatitis, scan transformation, chronic ulcers, chronic sinusitis, sun burn, sunburn, sun exposure, over exposure, overexposure, UV exposure, UV light exposure, ultraviolet exposure, ultraviolet light exposure, Mohs surgery, Mohs micrographic surgery, Mohs' micrographic surgery, Mohs' surgery, sun protection factor, SPF INTRODUCTIONSection 2 of 11
  Background Squamous cell carcinoma (SCC) is currently the second most common type of nonmelanoma skin cancer. Basal cell carcinoma (BCC) is the most common. Unlike most BCCs, SCCs of the skin are associated with a risk of metastasis. For excellent patient education resources, visit eMedicine's Cancer and Tumors Center and Skin, Hair, and Nails Center. Also, see eMedicine's patient education articles Skin Cancer and Sunburn. Pathophysiology SCC arises from the malignant transformation and proliferation of keratinocytes in the epidermis. SCC can arise from actinic keratosis, leukoplakia, radiation keratosis or dermatitis, scars, chronic ulcers, or chronic sinusitis. People with actinic keratosis have atypical squamous cells in a third to a half of the epidermis. Those with Bowen disease, or SCC in situ, have atypical keratinocytes in the entire epidermis. Invasive SCC involves the epidermis and invades the dermis. The tumors initially appear as skin patches, plaques, and nodules that enlarge and develop central areas of inflammation, induration, and, subsequently, necrosis and oozing. SCCs metastasize by direct, lymphatic, and hematogenous extension. Frequency
The impact of new molecular techniques on plastic surgery of skin cancers Roman has noted that gene therapy might have a role in plastic and reconstructive surgery.1 Rea noted that PCR current impacts modern plastic surgery practice, specifically in area involving normal and abnormal wound healing, the diagnosis of craniofacial anomalies, the diagnosis and treatment of cancer including melanoma and squamous cell carcinoma of the head and neck, and burns.2 CLINICALSection 3 of 11
History Typical SCC manifests as a painless skin lesion on a sun-exposed region of the body (eg, extremities, head, neck. It may also arise in regions with prior skin insult or trauma (eg, scars from old burns or vaccinations). Although persons with SCC are often asymptomatic, features such as ulceration, bleeding, pain, and tenderness may be present. The typical patient is of northern European descent and presents with a family history of skin cancer, a personal history of prior skin cancer, and/or an extensive history of sun exposure. Cutaneous SCCs can be experimentally produced with UV light exposure, almost to the exclusion of other types of cancer. Physical causes As previously noted, SCCs may develop in burns or old scars. They may also develop in sites of previous radiation therapy. Likewise, patients previously treated with psoralen and UV-A phototherapy are at increased risk for SCC. Risk factors UV radiation exposure is the most important factor associated with SCC of the skin. Individual risk factors may also be involved. These include exposure to ionizing radiation, arsenic, and certain other chemicals. Host risk factors Most SCCs appear on sun-exposed regions of the body. Persons who engage in outdoor activities are at higher risk of skin cancer than those who spend most of the time indoors. Persons with fair complexions and light-colored hair and those who burn easily when exposed to the sun are at higher risk for cutaneous SCC than those with other physical characteristics. Individuals who have genetic disorders involving decreased melanin production or impaired DNA repair are also at higher risk for skin cancer. DIFFERENTIAL DIAGNOSISSection 4 of 11
Basal Cell Carcinoma of the Skin Desmoplastic melanoma (see Skin Malignancies, Melanoma) Proliferating epidermoid cyst (see Skin, Benign Skin Lesions) Pseudoepitheliomatous hyperplasia WORKUPSection 5 of 11
While no specific laboratory analysis is required to confirm a diagnosis of SCC, history and physical examination findings help determine specific laboratory and imaging needs. Any history of bleeding abnormalities, impaired healing, allergic reactions (eg, anesthetics, other medications), and significant cardiac or other systemic medical problems must be elicited. Depending on the lesion, the physician may elect to obtain additional studies, such as CT scans to evaluate bony involvement or MRIs to delineate the extent of deeply invasive tumors. The patient is also examined for regional adenopathy. To improve accuracy and assess metastatic risk, a sentinel node biopsy for some head and neck cancers has recently been advocated, though this is not yet the standard of care. Procedures Biopsy samples, generally obtained with the patient under local anesthesia in the physician's office, are diagnostic. Punch, shave, incisional, or excisional biopsies may be performed and must extend to the level of the mid dermis in order to establish the level of invasion. Histologic findings SCCs manifest histologically as irregular masses or nests of epidermal cells consisting of varying proportions of normal squamous cells and anaplastic squamous cells. The more poorly differentiated the cells and the deeper the extension, the worse the prognosis. Well-differentiated tumors are marked by the presence of horn pearls, structures composed of concentric layers of squamous cells with increasing keratinization toward the center. Poorly differentiated tumors lack horn pearls and may be difficult to distinguish from mesenchymal tumors, melanoma, or lymphoma. Another variant, spindle cell SCC, may contain intercellular bridges and incipient keratinization. In other cases, spindle cells are intermingled with collagen and may be arranged in whorls. In such cases, special stains for cellular markers can be used to distinguish SCC from other cancers. For example, an S100 stain returns negative results for SCC and positive results for melanoma. Specifically, synaptophysin, CD99, leukocyte common antigen, nonspecific esterase, S100, homatropine methylbromide, and neurofilament stains return negative findings for SCCs, while cytokeratin, vimentin, and epithelial membrane antigen stains return positive findings. Staging Staging is based on the TNM classification table.
Foremost among the factors influencing metastatic risk are the size and location of the tumor and, to a lesser extent, a rapid growth rate. Large lesions (>2 cm in diameter) metastasize at a rate of 30%, which is 3 times that of smaller lesions. Lesions deeper than 4 mm behave similarly. Palme et al have argued that the staging system for SCC of the head and neck is too simple and should account for the many variables involved in a metastatic SCC of the head and neck to be useful in informing treatment.3 Primary SCCs on the trunk and limbs have been associated with a metastatic rate of 4.9% in a series that may be biased toward larger lesions. SCCs that arise in injured or chronically diseased skin are associated with a risk of metastasis that approaches 40%. MEDICAL TREATMENTSection 6 of 11
Low-grade SCCs and well-differentiated lesions, such as actinic keratosis, keratoacanthoma, and Bowen disease (SCC in situ), may be managed with medical therapies. No topical treatment is available for treatment of SCC; topical treatments are for actinic keratoses. Drug therapies Actinic keratoses can be treated with various modalities, in addition to the routine approach of liquid nitrogen cryotherapy for spot treatment. A month-long course of daily topical 5-fluorouracil (5-FU) can successfully improve skin areas with severe diffuse actinic damage and clusters of actinic keratoses. Even if newer, low-concentration 5-FU cream is used (0.5% vs previously available 5% concentration), significant discomfort and irritation are inevitable and residual erythema at the site of application may persist for months. Topical diclofenac sodium gel has recently been approved for the treatment of actinic keratoses. Twice-daily applications for 60-90 days may similarly clear actinic damage, with the longer course potentially offset by a lesser degree of cutaneous irritation. Success is difficult to measure when treatment of actinic damage is attempted with topical medications because biopsies are rarely performed before and after treatment (ie, to compare results). Instead, improved skin appearance is used as a gauge for apparent resolution of early in situ SCC lesions. Imiquimod 5% cream, a topical immune response modifier that acts by up-regulating interferon and other cytokines involved in the cell-mediated immune response, has become increasingly popular for the treatment of superficial BCC and, more recently, for the treatment of SCC in situ. This has been borne out in studies.4 Studies continue to confirm the effectiveness of imiquimod for clearing actinic keratoses. Overall, imiquimod may be most effective for treating actinic keratoses and borderline SCC in situ rather than invasive SCC. Some practitioners are concerned that the ease of use of this therapy may result in enthusiastic overprescription for lesions that are not clearly superficial; the result may be inadequate treatment of primary invasive SCC, which may lead to the preventable morbidities of recurrence or metastasis. Photodynamic therapy Photodynamic therapy (PDT) is frequently reported in the literature. Braathen et al have set forth guidelines for the use of PDT to treat SCC in situ.5 The introduction of a new photosensitizing prodrug, aminolevulinic acid (ALA), is a novel approach for the induction of photosensitization because ALA penetrates the stratum corneum to reach the deep stroma of skin tumors, where it is transformed into the highly photoactive endogenous protoporphyrin IX. One of the most successful indications for ALA-PDT in dermatology is the treatment of actinic keratosis. A number of studies report response rates of 71-100% for facial actinic keratoses after a single treatment. Various noncoherent and coherent light sources have been used, with wavelengths ranging from 417-630 nm and light doses and dose rates ranging from 10-540 J/cm2 and 10-300 mW/cm2, respectively. Most studies of ALA-PDT for actinic keratosis are limited by a lack of histologic confirmation, and they have short follow-up periods (3-20 mo). Nonfacial hyperkeratotic lesions respond poorly to ALA-based PDT and have weighted clearance rates of 44%, compared with 91% clearance rates for facial lesions. Response rates to ALA-PDT appear to be comparable to those associated with topical 5-FU and cryotherapy. Lesions not completely resolved after PDT may be treated a second time after 8 weeks. Patients should avoid excessive sun exposure before, during, and after treatment. Thus far, the procedural complexity and posttreatment photosensitivity associated with PDT have limited its popularity among physicians and patients. Indeed, although recent medical literature is replete with reports and trials of PDT used for the treatment of actinic keratosis and Bowen disease, the inevitable bias in favor of new technology should not obscure the fact that this treatment is currently used for only a very small minority of patients. SURGICAL TREATMENTSection 7 of 11
Guidelines of care have been developed for the management of cutaneous SCC. Surgical approaches include (1) curettage and electrosurgery, which is deemed less effective for recurrent lesions or those that invade the subcutis; (2) cryosurgery, judged especially useful in patients with bleeding disorders and in those for whom surgery is contraindicated; (3) excision, described as useful in both primary and recurrent tumors, the margins of which can be verified by pathology; (4) Mohs micrographic surgery, for recurrent tumors and primary lesions displaying 1 or more factors associated with biologic aggressiveness; (5) laser surgery, which may be used for excision or destruction and may have the added benefit of ensuring hemostasis; and (6) radiation therapy. Curettage and electrosurgery Curettage and electrodesiccation destroy the tumor and a surrounding margin of clinically unaffected tissue via cauterization and scraping of the area with a curette. The process is repeated several times to maximize the probability of complete tumor extirpation. A disadvantage of this modality is that no specimen is available for margin evaluation. Nevertheless, the 5-year cure rates for small primary SCC may be as high as 96%. Cure rates for high-risk tumors treated with curettage and electrodesiccation are much lower, although no well-controlled prospective studies have been performed. Curettage alone as a treatment modality for SCC is not recommended because the extension of cells down hair follicles and eccrine structures may render the intervention ineffective, thus increasing the risk of subsequent metastatic disease. Studies of subjects with Bowen disease treated with only curettage reveal a 10-40% rate of recurrence. Cryosurgery Cryotherapy uses liquid nitrogen to cool small SCCs to tumoricidal temperatures. Patients with bleeding disorders or contraindications for surgery may be candidates for cryotherapy. Graham and Clark reported a cure rate of 97.3% for 563 primary SCCs, the majority of which were 0.5-1.2 cm in diameter. Recurrences generally become evident within 2 years. Excision Low-risk primary tumors can be locally excised. Surgical excision offers the advantages of histologic verification of tumor margins, rapid healing, and improved cosmesis. Disadvantages of excision include the risks of hematoma, seroma, infection, and wound dehiscence. Note that surgical excision uses the traditional bread-loafing method of histopathologic processing, which provides a view of less than 1% of the complete margin of the surgical specimen. For this reason, cure rates for SCC following excision do not significantly differ from cure rates following curettage and electrodesiccation. Moreover, excision may even be somewhat less efficacious, with aggregate 5-year cure rates of only 92% for primary SCC. To achieve a 95% clearance rate, a 4-mm margin around the clinical borders of the lesion has been recommended for well-differentiated tumors smaller than 2 cm in diameter not occurring on the scalp, ears, eyelids, lips, or nose and not involving subcutaneous fat. Recurrence rates after the excision of low-risk lesions range from 5-8%. For tumors in high-risk sites or those larger than 2 cm, a 6-mm margin is recommended. However, individuals with high-risk tumors have an increased risk of recurrence, with tumors larger than 2 cm recurring at a rate of 15.7% after excision and tumors smaller than 2 cm recurring at a rate of 5.8%. Poorly differentiated lesions recur at a rate of 25% after excision, as opposed to well-differentiated lesions, which recur at a rate of 11.8%. Mohs micrographic surgery The treatment with the highest cure rates for high-risk primary and recurrent SCC is Mohs micrographic surgery. Pioneered by Fredrick Mohs, modern Mohs surgery is performed in stages on a single operative day, and the Mohs technique of horizontal frozen sectioning provides a view of 100% of the peripheral and deep margins of each specimen, making incomplete excision much less likely than with standard pathologic processing. Lesions to be removed using Mohs surgery are mapped before removal, and the excised specimens are managed in a way that maintains orientation relative to the operative site. In the event of subtotal removal of the tumor after excision of the first stage, previous mapping permits the surgeon to return to the operative site and remove only the tissue along the margins deemed to remain positive. Consequently, Mohs surgery offers both microscopic margin control and tissue sparing, thus facilitating small, minimally disfiguring reconstructions of the resulting defects. Mohs surgery achieves a 5-year local cure rate of 96.9% for primary cutaneous SCCs at all sites except for the lips and ears, in contrast to a 5-year local cure rate of 92.1% for other modalities. Mohs surgery is associated with 5-year cure rates of 90-93.3% for recurrent SCC, in contrast to recurrence rates of 23.3% for recurrent tumors treated with standard excision. For SCCs associated with perineural invasion, Mohs offers a cure rate of approximately 90%, compared with a rate of only 50% for wide surgical excision. Mohs is the treatment of choice for nail unit SCC because of the technique's tissue-sparing properties and the concurrent need to limit damage to the nail matrix. Mohs may also be appropriate when the visible borders of SCC are indistinct or if they are masked by hypertrophic tissue (as in rhinophyma). Genital SCC, including disease of the penile shaft, is another potential indication for Mohs surgery. Although Mohs is a definitive procedure, it is a safe intervention for the vast majority of eligible patients, including very elderly patients with multiple morbidities, even though it is typically performed with patients under local anesthesia in an outpatient setting. When used as indicated, Mohs is a cost-effective modality because (1) it markedly reduces recurrence and the need for re-treatment and (2) the outpatient setting minimizes hospital-related overhead costs. In some cases, when tumor is very extensive or very deep, radical surgical procedures may be indicated. Primary or metastatic SCC deriving from chronic osteomyelitis is often amenable to Mohs surgery as a limb-sparing procedure, but certain cases may require limb amputation. Similarly, if SCC lesions invade deep into muscular, glandular, or bony structures or if they involve the viscera, Mohs surgery may be relegated to obtaining clearance of peripheral skin margins, with other surgical techniques used to clear the deep margins. After excision of massive or high-risk cutaneous SCC using Mohs surgery, some practitioners advise adjuvant radiotherapy, but this has not been shown to lengthen survival or decrease morbidity. Indeed, in the absence of any data supporting the efficacy of adjuvant radiotherapy for locally invasive disease, the associated morbidity from such radiotherapy may be in itself a contraindication. Some authorities have recommended sentinel lymphadenectomy in combination with Mohs micrographic surgery for the treatment of high-risk SCCs. As an experimental therapeutic intervention, sentinel lymphadenectomy may help identify regional metastases, which may later be extirpated in a timely manner. Laser surgery Laser surgery may be used for excision or destruction and may have the added benefit of ensuring hemostasis. This modality is most useful for the treatment of superficial skin cancers in sensitive locations. The cure rate is dependent on the depth of the SCC. Radiation therapy Radiation therapy is best used in older patients, who are poor surgical candidates. Its main adverse effect is the induction of skin cancer 15-20 years after the initial treatment. Radiation is usually administered over 15-20 sessions (so-called fractionations of total dosages). It has a high cure rate (~90-95%). Unlike surgical treatments, radiation treatment does not allow for histological evaluation of therapy. PREVENTIONSection 8 of 11
Because exposure to UV radiation is a primary cause of SCC, prevention is possible through education and the use of sunscreens and protective clothing. The efficacy of UV protection is measured by its sun protection factor (SPF), which is the ratio of the least amount of UV-B radiation that will induce erythema on covered skin to the amount of UV-B required to generate the same amount of erythema on uncovered skin. Often, it is described as the amount of additional time a person can spend in the sun with protection versus without protection. Clothing Clothing is the simplest method of protection; however, it is often inadequate. For example, a cotton T-shirt has an SPF of less than 10, which decreases sharply when the cloth is wet. Hats with a wide brim or extra-long bill may offer additional protection. Clothing with a high SPF rating is available but is often expensive and restrictive. Sunscreens Sunscreens offer protection from UV rays and are classified according to their SPF rating. Patients at high risk for SCC should be counseled regarding sun avoidance. For days when sun exposure is inevitable, recommend sunscreens with an SPF rating of 30 or higher. Sunscreens containing zinc oxide or titanium dioxide provide greater protection. Emphasize the need to reapply sunscreen every 30 minutes during acute sun exposure. MEDICOLEGAL PITFALLSSection 9 of 11
Relatively few malpractice cases result from SCCs. A high index of suspicion and effective management in accord with standards of care can prevent much of the associated morbidity and mortality. Therefore, some of the newer medical therapies (eg, imiquimod 5% cream, PDT) may not yield adequate destruction of the tumor and could heighten the morbidity risk. Their use should be limited to actinic keratoses and biopsy-confirmed in situ lesions. A source of liability is confusion with other cancers, such as desmoplastic melanoma, which can mimic SCC, and a failure to treat such cancers properly. Seeking the services of a skilled dermatopathologist to assess SCC is therefore advisable. Even seemingly adequate treatment or excision of SCC can be complicated by recurrence; accordingly, providing appropriate follow-up care is critical. Failure to do so may lead to preventable morbidity and, rarely, death, which may be grounds for a malpractice claim. Informed consent should always be obtained before proceeding with any procedure. All risks and potential complications should be explained to patients, and this should be documented. Bleeding, infection, scar formation, deformity, nerve damage, and recurrence are some potential risks of surgical treatment for SCC. MULTIMEDIASection 10 of 11
REFERENCESSection 11 of 11
Skin Malignancies, Squamous Cell Carcinoma excerpt Article Last Updated: Jan 8, 2008 | |||||||||||||||||||||
