Head and Neck Cutaneous Squamous Cell Carcinoma Treatment & Management

Most squamous cell carcinomas (SCCs) are readily treated in the physician's office by surgical or destructive methods, with a high expectation of cure. The treatment of these tumors must take into account multiple patient- and lesion-specific factors. Because SCC is a lesion that can recur, metastasize, and cause death, and, because recurrent disease carries a worse prognosis, every opportunity should be taken to effect complete tumor extirpation at first presentation.

Factors that influence choice and type of treatment are the site and stage of the primary tumor. The “tumor, node, metastasis” (TNM) staging system used for head and neck cancers is a clinical staging system that allows physicians to compare results across patients, assess prognosis, and design appropriate treatment regimens. The same system is employed for laryngeal tumors. The basic premise of these systems is that smaller cancers with no nodal disease have a better prognosis than a larger lesion with positive neck nodes.

Depth of infiltration is predictive of prognosis. With increasing depth of invasion of the primary tumor, the risk of nodal metastasis increases and survival decreases.

See SCC Staging and Classification under Clinical Presentation.

See the following for more information:

• Sentinel Lymph Node Biopsy for Squamous Cell Carcinoma
• Urogenital Squamous Cell Carcinoma
• Imaging of Nasopharyngeal and Laryngeal Squamous Cell Carcinoma
• Cell Biology of Head and Neck Squamous Cell Carcinoma
• Targeted Molecular Therapy in Head and Neck Squamous Cell Carcinoma.
• Mohs Micrographic Surgery
• Mohs Surgery

High-risk SCC

The use of electrodessication and curettage (ED&C) in the treatment of high-risk SCC (see Electrodessication and Curettage), particularly in immunocompromised individuals, is best avoided, because histologic margin status cannot be evaluated. Clear margins must be obtained for optimal outcomes.

Ensuring clear surgical margins wherever possible is highly recommended. A systematic review of available data for high-risk SCC compared cases with clear surgical margins versus those in which margins were not specified and demonstrated statistically better outcomes in cases in which clear margins were documented, with risks of local recurrence, regional metastasis, distant metastasis, and disease-specific death of 5%, 5%, 1%, and 1%, respectively, in clear-margin cases, compared with 8%, 14%, 7%, and 7% in cases with undocumented margins.^[97]

A prospective study identified several risk factors for incomplete excision of SCC, namely, ear lesions, invasive lesions, and previously incompletely excised lesions referred for reexcision. The study also recommended more care with tumor markings, taking margins of at least 5 mm, deeper margins, and referring such lesions to centers with personnel who have more experience.^[98]

No controlled comparative studies of Mohs micrographic surgery versus excision in high-risk SCC have been performed, but case series data suggest that Mohs is superior to excision for these tumors.^[99]

No comparative studies of surgery versus surgery plus adjuvant radiotherapy for high-risk SCC have been performed. With no clear evidence of benefit and the potential of significant morbidity, clinical judgment is required in deciding which patients should receive adjuvant radiation. One systematic review of available outcome data suggests that adjuvant radiation be considered in patients with uncertain or positive surgical margins or advanced nerve involvement (eg, involvement of named nerves, nerves 0.1 mm or larger in diameter, or with clinical or radiologic evidence of nerve invasion).^[97] Adjuvant medication may also be considered in select highest-risk cases. Options include oral 5-fluorouracil (5-FU) (Xeloda) and epidermal growth factor receptor (EGFR) inhibitors via oncology treatment centers. Although survival data are lacking, these medications are generally well tolerated with few adverse effects.

The results of one study found that the use of 5-FU 1% is effective as an adjuvant to surgical excision in treating patients with localized ocular surface squamous neoplasia (OSSN). Although frequent short-term complications were noted, a low rate of local recurrence was found; a full course is usually tolerated, and serious complications were uncommon.^[100]

See Overview of Nonsurgical Management.

Nonsurgical options for the treatment of cutaneous squamous cell carcinoma (SCC) include the following:

• Topical chemotherapy
• Topical immune response modifiers
• Photodynamic therapy (PDT)
• Radiotherapy
• Systemic chemotherapy
• Reduction in immunosuppression
• Cryotherapy

Low-grade SCCs and well-differentiated lesions, such as actinic keratosis, keratoacanthoma, and Bowen disease (SCC in situ [SCCIS]), may be managed with medical therapies. No topical treatment is available for treatment of SCC; the use of topical therapy and PDT is generally limited to premalignant (ie, actinic keratoses) and in situ lesions.

Radiation therapy is a primary treatment option for patients in whom surgery is not feasible and is an adjuvant therapy for those with metastatic or high-risk cutaneous SCC. In current practice, systemic chemotherapy is used exclusively for patients with metastatic disease. However, newer, more targeted drugs, such as epidermal growth factor receptor (EGFR) antagonists (eg, cetuximab), have favorable adverse effect profiles and await trials to determine if they are beneficial in high-risk SCC.

Precancerous Lesions

Several effective treatment modalities exist for precancerous skin lesions, including carcinoma in situ (CIS) and actinic keratosis. Most of these treatments are easily performed in an outpatient setting. Topical application of 5-fluorouracil (5-FU) (Efudex) or imiquimod is effective in treating precancerous lesions of the head and neck. Similarly, the application of liquid nitrogen cryotherapy or electrocautery and curettage is used, with cure rates reported at greater than 95%. Although efficacious in the treatment of CIS and actinic keratoses, these methods should not be used on confirmed or suspected invasive cutaneous SCC, because they fail to provide a diagnostic tissue sample or a way to assess the adequacy of treatment. For confirmed or suspected cutaneous SCC, surgical excision with microscopic assessment of tissue margins is the treatment of choice.

Many patients with a history of extensive sun exposure and light skin develop epidermal atypia in the form of actinic keratosis and SCCIS over large areas of their skin. Most of these patients also develop multiple invasive SCCs. The management of such patients is highly labor intensive and involves the following steps:

• Surgically remove all tumors that clinically appear to have to have an invasive (dermal) component and confirm clearance of histologic margins.
• Evaluate for underlying immunosuppression, such as from chronic lymphocytic leukemia or an overly impaired immune system from immunosuppressive or immunomodulatory therapy. If this is suspected, discuss with the patient’s other doctors whether the immunosuppression can be safely remedied or lessened.
• Perform field treatment of the areas of epidermal atypia. Treatment options include topical chemotherapy with 5-FU or PDT. Imiquimod has limited utility in diffuse disease because adverse effects increase when applied to large surface areas. If 5-FU therapy is planned, remove any hyperkeratotic lesions with a curette just before beginning therapy to enhance penetration of the medication to the basal layer. A full course of 5-FU therapy is twice-daily administration for 4 weeks. Patients who cannot tolerate this duration may try shorter courses and then resume treatment after a healing phase. Subsequent treatments become more tolerable as the epidermal damage is corrected.
• Follow the patient closely for recurrence of actinic keratosis/SCCIS and for new invasive SCCs. Field treatment may need to be repeated every 6-12 months to keep precursor actinic keratosis and SCCIS lesions to a minimum.
• Oral retinoids in the form of low-dose acitretin can decrease new cancer formation, but they do not generally alter the course of existing tumors.^[101] Although most patients do not require retinoids if the above measures are taken, patients who are still developing multiple cancers 6-12 months after beginning an intensive program to clear disease may benefit from retinoid therapy. Once the desired effect is achieved, considering a dose reduction of long-term maintenance therapy rather than discontinuing therapy is better, because the latter typically leads to a rebound of multiple SCC formation.

Conjunctival intraepithelial neoplasia

Topical cytotoxic therapy (ie, 5-fluorouracil [5-FU], mitomycin C [MMC]) has been used to treat conjunctival intraepithelial neoplasia and to debulk large carcinomas before surgical excision. Orbital invasion may be observed despite topical therapy, however, and careful monitoring of patients on these agents is warranted.^{[102, 103]}

Despite its significant potential deleterious effects on limbal stem cells, mitomycin C 0.04% is effective as a neoadjuvant agent or postoperative agent in the treatment of CIN and primary acquired melanosis. Its utility is less well proven for truly invasive tumors such as melanoma and carcinoma.^[104]

Topical formulations of 5-fluorouracil (5-FU) are available for the treatment of actinic keratoses and superficial basal cell carcinomas (BCCs). Successful treatment of in situ squamous cell carcinoma (SCCIS) has also been reported.^[105] Invasive SCC should not be treated with topical chemotherapy.

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. However, 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.

An oral form of a 5-FU prodrug (capecitabine), which is approved by the US Food and Drug Administration (FDA) for other forms of cancer, may be considered in patients with diffuse SCCIS over large skin areas, on which topical 5-FU is difficult to apply. However, studies of efficacy have not yet been performed.

Topical diclofenac sodium gel has 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 SCCIS lesions.

Imiquimod is an imidazoquinoline that enhances cell-mediated immune responses via the induction of proinflammatory cytokines; that is, it up-regulates interferon and other cytokines. This agent is approved by the US Food and Drug Administration (FDA) for the treatment of genital warts (ie, condylomata acuminata), actinic keratoses, and superficial basal cell carcinoma (BCC).

Imiquimod cream has also shown effectiveness in the treatment of Bowen disease as monotherapy and in combination with topical 5-fluorouracil (5-FU).^[106] However, systemic flulike symptoms and other adverse effects can occur when applied to large surface areas; therefore, using this agent in patients with diffuse in situ squamous cell carcinoma is difficult.^{[107, 108]}

Case reports document success in the treatment of squamous cell carcinoma in situ (SCCIS) of the glans penis and perianal region. This modality seems particularly reasonable for genital SCC, because of the association of SCC in this area with human papillomavirus (HPV) infection, against which imiquimod is known to have therapeutic activity. Imiquimod treatment 3 times per week for 4-6 weeks appears to be effective in the treatment of actinic cheilitis. Local adverse reactions during treatment include increased erythema, induration, and erosions or ulcerations.

Studies continue to confirm the effectiveness of imiquimod for clearing actinic keratoses. Overall, imiquimod may be most effective for treating actinic keratoses and borderline SCCIS 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.

Treatment with photodynamic therapy (PDT) uses a photosensitizing drug, light, and oxygen to induce targeted cell death of neoplastic or abnormal tissue. Specifically, sensitization of the target tissue is selective and occurs through the topically or systemically administered photosensitizing agent. The resulting photochemical reaction causes inflammation and destruction of the targeted lesion(s) via highly reactive oxygen intermediates and free radicals. PDT is used primarily to treat large numbers of actinic keratoses in a single session. Squamous cell carcinoma in situ (SCCIS) is also amenable to PDT, although a wide range of recurrence rates (0-52%) have been reported.

A study of organ transplant recipients with multiple actinic keratoses and field actinic damage showed PDT to be superior to topical 5-fluorouracil (5-FU).^[109] A 2009 noncomparative study showed repeated cycles of PDT to be associated with significant reduction in SCC formation in organ transplant recipients.^[110] At this time, PDT is not recommended for treatment of invasive disease due to poor long-term cure rates.^[111]

The introduction of a new photosensitizing prodrug, 5-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. This agent can also be used for patients with discrete eyelid lesions who are unable or unwilling to undergo an extensive surgical excision of the lesion.^{[13, 112]}

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 to 630 nm and light doses and dose rates ranging from 10 to 540 J/cm² and 10 to 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.

In 2007, Brewster et al reported the results of a randomized trial of adjuvant 13-cis -retinoic acid (13-CRA) and interferon-alpha for patients with aggressive skin SCC.^[113] Their results did not show a benefit from this treatment.

Braathen et al have set forth guidelines for the use of PDT to treat SCCIS.^[114]

Radiation therapy as a primary form of treatment is typically reserved for patients who are unable to undergo surgical excision. More frequently, radiation therapy is used as an adjuvant to surgery for improved locoregional control. Postoperative radiotherapy is considered for tumors that exhibit perineural invasion or other high-risk features and for those that involve regional metastasis.

Primary radiation therapy as a treatment option for squamous cell carcinoma (SCC) offers the potential advantage of avoiding the deformity and trauma of a surgical procedure.^[115] Cure rates for T1 lesions range from 85% to 95%. However, a number of disadvantages are associated with radiation therapy. For example, radiation therapy is expensive and requires a significant time commitment, because treatments are usually given 3-5 times per week for 4-8 weeks (eg, over 15-20 sessions, so-called fractionations of total dosages). Most patients experience significant irritation at the radiation site, and they frequently develop erythema, erosions, alopecia, and pain, which may require narcotic-level analgesia.

In addition, although the initial cosmetic result following radiation is usually good, the long-term outcome is often poor, owing to the development of cutaneous atrophy, dyspigmentation, and telangiectasia in the radiation field. Patients treated with radiation also have a slightly increased risk of developing cutaneous carcinoma (most commonly SCC, 15-20 years after the initial treatment) or sarcoma later in life.

Radiation therapy does not involve histologic margin control and has a lower cure rate compared with surgery. For these reasons, as well as those discussed above, radiation as a primary therapy is usually confined to a small subset of tumors in which the cosmetic or functional outcome would be superior to that of surgery^[116] or in elderly patients with inoperable SCC.

In contrast, radiation is routinely used as an adjunct to surgical treatment in cases of nodal metastasis, and the reported 5-year cure rate is 73% for combined surgical and radiation therapy to involved nodal basins.^[62] Nearly all patients with advanced disease require adjuvant radiotherapy, preoperatively or postoperatively. Preoperative radiotherapy has the risk of increased complications of surgery. Radiation dosage in excess of 6000 cGy is recommended with a boost to areas of high risk.

Indications for radiotherapy include a bulky tumor with significant risk of recurrence (T3 and T4), histologically positive margins, and perineural or perivascular invasion of tumor. SCCs with advanced perineural invasion have an elevated risk of recurrence, even when surgical margins are thought to be clear.^{[60, 63, 73]} Thus, adjuvant radiation may be considered, particularly in cases involving larger nerves, although its utility has yet to be proven.

Until recently, the nasopharynx was regarded as an unapproachable surgical area, and therapy consisted of irradiation alone. In each case, treatment is individualized, and chemotherapy is occasionally used in addition to irradiation. The response to irradiation and, therefore, the prognosis of patients with nasopharyngeal carcinoma is strongly related to the category. Keratinizing SCC responds poorly to irradiation, and the overall 5-year survival rate is approximately 15%. The 5-year survival rate for nonkeratinizing carcinoma of the nasopharynx, which responds to irradiation therapy, is approximately 60%. Approaching this tumor by surgical means has been a topic of recent interest.

For the neck, indications for radiotherapy include elective treatment of the N0 neck not treated surgically where risk of micrometastasis is high, gross residual tumor in the neck following neck dissection, multiple positive lymph nodes, and extranodal extension of tumor.

A systematic review analyzing all reports related to outcomes of high-risk SCC treated with surgical monotherapy compared with those treated with surgery plus adjuvant radiation was unable to show an advantage of adjuvant radiation in the treatment of squamous cell carcinoma with perineural invasion.^[97] However, the available studies were uncontrolled for tumor stage and more advanced tumors with a worse baseline prognosis likely received radiation.

In summary, the additional benefit of adjuvant radiotherapy is uncertain, especially when clear surgical margins are obtained. However, it may be considered in patients with multiple high-risk factors, those with significant nerve involvement (particularly named nerves or nerves >0.1 mm in diameter), those with uncertain surgical margins (eg, poorly differentiated, infiltrative, or multiply recurrent tumors), or as salvage therapy for in-transit metastasis or other tumors which cannot be cleared surgically. A lower threshold for adjuvant radiation should be used in immunocompromised patients with high-risk SCC.^[97]

A variety of different chemotherapeutic agents have been used to treat metastatic cutaneous squamous cell carcinoma (SCC). Adaptation of traditional chemotherapeutics to local and regional administration techniques in treating head and neck cancers is being actively pursued to provide higher local concentrations of otherwise systemically toxic drugs. Bleomycin with or without electroporation has been used.

Cisplatin is another chemotherapeutic drug of choice for head and neck cancers. Although this agent is one of the most successful in the treatment of cancer, it produces major toxicities to normal cells and organs at the concentrations necessary for effective treatment of malignancies.

Combination chemoradiotherapy with cisplatin and concurrent radiation therapy has improved locoregional control in locally advanced SCC. Chemoradiotherapy is now considered the standard of care in locally advanced disease following surgical resection and in unresectable disease. Cisplatin-based combination chemotherapy with 5-fluorouracil (5-FU), methotrexate, bleomycin, and doxorubicin have all been used to treat advanced SCC with variable outcomes.

A combination of cisplatin with interstitial laser therapy has also been reported. Hyperthermia produced by the laser is known to augment the cytotoxic effects of both radiation therapy and some chemotherapy drugs. Temperatures above 38°C enhance cisplatin therapy.

The oral 5-FU prodrug, capecitabine (Xeloda), has been designed to be metabolized to 5-FU selectively within tumor tissues, thus producing less systemic toxicity. Used either alone or in combination with interferon alfa, it has shown some efficacy in the treatment of advanced cutaneous SCC.^[117]

Cetuximab, a chimeric immunoglobulin G1 monoclonal antibody that inhibits epidermal growth factor receptor (EGFR), has had reported as successful in several case reports.^{[118, 119, 120]} In the head and neck literature, phase I and II trials of capecitabine, used with cisplatin or paclitaxel^{[121, 122]} or in combination with radiation therapy^[123] also showed favorable outcomes. EGFR inhibitors are well tolerated with relatively low risks, so they may be considered in cases not amenable to surgery or radiation or as an adjuvant in cases considered to have a high risk of death. Current recommendations are to use cetuximab as an alternative to chemotherapy in patients who cannot tolerate chemotherapy.^[124]

See Targeted therapy under Future Directions in the Treatment of SCC.

In organ transplant recipients, a reduction in the magnitude of immunosuppression may be an effective adjuvant therapeutic strategy in the treatment of aggressive squamous cell carcinoma (SCC). Because a decrease in immunosuppression may increase the risk for rejection of the transplanted organ, this strategy should only be considered in selected high-risk patients and under the careful management of the transplantation physician, who must closely monitor the patient for signs and symptoms of organ rejection.^[125]

Newer immunosuppressive agents (eg, sirolimus) are associated with a lower incidence of SCC when compared with more traditional agents (eg, calcineurin inhibitors), without compromise in graft function.^{[126, 127]} Patients on sirolimus also produce thinner, less vascularized tumors,^[128] likely due to the drug’s antiangiogenic and antitumor properties. In a study of 182 organ transplant recipients, the mean cumulative doses of prednisone, cyclosporine, azathioprine, and mycophenolate were significantly higher in those with skin cancer. Conversely, the cumulative doses of sirolimus and tacrolimus were significantly lower in those with skin cancer, suggesting that these drugs may be protective.

Cryotherapy uses liquid nitrogen to cool small squamous cell carcinomas (SCCs) to tumoricidal temperatures. This is a safe and low-cost procedure for the ablation of selected in situ squamous cell carcinomas (SCCISs), and it is judged especially useful in patients with bleeding disorders and in those who refuse surgery, are poor surgical candidates, or for whom surgery is contraindicated.

The 5-year cure rate for (SCC) can be 95% or greater with proper tumor selection and technique. 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.^[129] Recurrences generally become evident within 2 years.

In the United States, cryosurgery is routinely used for in situ disease and actinic keratoses. It is not often used for invasive SCC, because deeper portions of the tumor may not be eradicated by this technique and because the development of scar tissue at the site of cryotherapy might obscure a recurrence.

The risks associated with cryotherapy include transient pain, edema, and blistering. Hypopigmentation and alopecia are also common and may be permanent, so treatment of hair-bearing areas and in darkly pigmented individuals is generally not recommended.^[130]

Surgical resection remains the criterion standard for treatment of head and neck cancer. Management of all but the earliest confirmed neck metastases is best achieved with surgical removal. The literature reports radiation therapy for patients with N0 or N1 necks and concludes that radiation or surgery can treat them equally well. Because patients with cancers of the head and neck often have had previous radiation therapy, flaps must have an adequate blood supply.

Guidelines of care have been developed for the management of cutaneous squamous cell carcinoma (SCC). Surgical approaches include the following:

• Electrodessication and curettage (ED&C)/curettage and electrosurgery – This procedure is deemed less effective for recurrent lesions or those that invade the subcutis.
• Excision, described as useful in both primary and recurrent tumors, the margins of which can be verified by pathology
• Mohs micrographic surgery, for recurrent tumors and primary lesions displaying 1 or more factors associated with biologic aggressiveness
• Laser surgery, which may be used for excision or destruction and may have the added benefit of ensuring hemostasis

Surgery is the preferred method of treatment for the following tumors, including select SCC variants:

• Conjunctival SCC - Unfortunately, recurrence rates as high as 50% are common for incompletely excised tumors.
• Secondary orbital invasion - Orbital exenteration is preferred.^[67]
• Spindle cell carcinoma, where anatomically feasible - Despite its odd appearance, the behavior of this tumor is about the same as that of conventional SCC of the same stage.
• Verrucous carcinoma - Interest in chemotherapy and radiotherapy to treat this lesion increases from time to time.
• Basaloid SCCs – Unfortunately, the 2-year mortality rate is still 30-40%.
• Papillary SCC, with free margins - This is true for both the in situ and the invasive types.
• All 3 grades of mucoepidermoid tumors – See below.

Low- and intermediate-grade mucoepidermoid lesions are initially treated more conservatively than are high-grade mucoepidermoid tumors, but margins are still made wide enough to ensure reasonable success in complete resection. Neck dissection is not necessary if the lesion is low or intermediate grade, unless clinical or pathologic findings are highly suggestive of metastases to the regional nodes. On respective review, this situation includes fixed, firm, and enlarged neck nodes or unequivocal lymphatic invasion by the main tumor. Many advocate postoperative radiation therapy, particularly for intermediate- or high-grade tumors.

High-grade mucoepidermoid tumors are initially treated with surgery; however, wide resection usually includes margins that are more generous than those obtained with lower-grade lesions, because these tumors frequently extend deeper than what their clinical appearance might suggest, even when observed during surgical examination under anesthesia. Therefore, removal of the facial nerve is likely necessary with high-grade parotid-based lesions. In addition, because of the increased rate of metastatic disease with high-grade mucoepidermoid tumors, neck dissections are frequently included in the surgical procedure. Finally, postoperative radiation is usually given to the tumor bed in cases of high-grade mucoepidermoid tumors.

Until recently, the nasopharynx was regarded as an unapproachable surgical area, and therapy consisted of irradiation alone. However, using a surgical approach has been a topic of recent interest.

Conjunctival SCC

Excisional biopsy is the treatment of choice for conjunctival SCC. For extremely large lesions, incisional biopsy may be performed; however, strict notation of the biopsy site and minimal handling of the surrounding tissues is imperative to prevent seeding of the tumor. Surgical excision is best performed under the operating microscope.^[131]

Removal of a cuff of normal conjunctival tissue surrounding the lesion is prudent, and an episclerectomy at the base of the lesion is also advisable if it is adherent to the sclera in order to remove any superficial cells infiltrating the sclera.

Involved corneal tissues may be best removed following treatment with 100% ethanol. The tissues superficial to the Bowman layer are removed easily in a single sheet and sent to the laboratory for analysis. Care should be taken not to incise into the Bowman membrane.

Cryotherapy is performed, in a double freeze-thaw manner, to the edges of the uninvolved conjunctiva and Tenon capsule. It also can be applied to the involved limbal area. The exposed sclera occasionally is treated with 100% ethanol to devitalize any remaining tumor cells. All excised tissues are submitted for histopathologic analysis.

Reconstruction is performed with direct closure, local flaps, or free conjunctival grafts. Extensive lesions with orbital involvement require exenteration.

Radiation therapy may be used as adjunctive therapy in cases of extensive lesions with poorly defined margins and as palliative therapy in cases where the patient cannot tolerate extensive surgery.

Invasive SCC

Primary surgical excision and Mohs micrographic surgery are the 2 primary treatment options for invasive cutaneous SCC. With appropriate patient selection, these techniques have comparable cure rates. Mohs surgery was developed by Frederic E. Mohs in the 1930s and is a method of tumor excision in which the surgeon first excises the visible tumor with a small margin of normal tissue. Horizontal frozen sections are then prepared, and the entire margin is evaluated under the microscope. Areas that demonstrate residual microscopic tumor involvement are reexcised, and the margins are reexamined. This cycle is completed until no further tumor is visualized.

This technique has a high reported cure rate for early stage cutaneous SCC and is considered ideal for removing small lesions on the face. However, Mohs surgery is time consuming and highly dependent on technique. Mohs surgery is ill suited for large, aggressive, or recurrent cutaneous SCC, in which the risk of recurrence or regional metastasis is high (see image below). In these cases, en bloc surgical excision is the standard method of treatment.

Unlike melanoma, no large randomized studies have addressed the issue of appropriate margin size in cutaneous SCC. Margins of 4 mm and 6 mm have been suggested for lesions less than and greater than 2 cm, respectively, providing a clearance rate of 95% or greater. However, these should be taken only as rough guidelines with the understanding that large, aggressive lesions frequently have substantial extension beyond the apparent superficial boundary. Therefore, surgeon experience and judgment in planning surgical margins is paramount to the successful treatment of cutaneous SCC.

For patients at risk for metastatic spread to lymph nodes, the standard treatment is surgical excision of the primary lesion along with the involved lymph node basins. Skin cancers located in the periauricular region, frontotemporal scalp, and mid face often drain via lymph nodes in the parotid gland. Consequently, the parotid is the most frequently involved site of metastatic spread. In cases that involve parotid involvement, a parotidectomy with or without a simultaneous neck dissection is the procedure of choice.

Electrodessication and curettage (ED&C) is a simple technique that can be used to treat low-risk squamous cell carcinoma (SCC) on the trunk and extremities. This procedure destroys 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.

The tumor indications are similar to those of cryotherapy (see Cryotherapy). In addition, ED&C can be used to treat superficially invasive SCCs without high-risk characteristics. However, the thick scars that often occur after ED&C can delay the diagnosis of cancer recurrence. Subsequently, ED&C should be used with caution in invasive SCC. It is not appropriate for certain anatomic locations (ie, eyelids, genitalia, lips, ears).

The technique is based on the delineation of tumor margins with a curette, because tumor tissue is generally more friable than the surrounding normal tissue. ED&C is known to be very technique dependent, and cure rates improve with a practitioner's experience. The main disadvantage of ED&C is that no specimen is available for margin evaluation, and most dermatologic surgeons believe the actual long-term cure rate for invasive SCC is much lower than that quoted in the literature. Nevertheless, the 5-year cure rates for small primary SCC may be as high as 96%. Cure rates for high-risk tumors are much lower, although no well-controlled prospective studies have been performed.

Tumor recurrence may result from failure of ED&C treatment to eradicate atypical cells residing deep in the hair follicles or in the dermis. Studies of subjects with Bowen disease treated with only curettage reveal a 10-40% rate of recurrence. Nonetheless, the procedure is fast, minimally invasive, well tolerated, and effective for properly selected lesions.

Standard excision with conventional permanent (ie, paraffin-embedded) tissue sections is an excellent, highly effective, and well-tolerated therapy for primary squamous cell carcinomas (SCCs) that lack high-risk features and are located in areas where tissue sparing is not critical. Surgical excision offers the advantages of histologic verification of tumor margins, rapid healing, and improved cosmesis. Cure rates following simple excision of well-defined T1 lesions may be as high as 95-99%. The generally accepted 5-year cure rate for primary tumors treated with standard excision is 92%; this rate drops to 77% for recurrent SCC.

A 4-mm margin of healthy tissue is recommended for lower-risk lesions (< 2 cm, well-differentiated, without subcutaneous fat invasion) on the trunk and extremities. For lesions larger than 2 cm, invasive to fat, and in high-risk locations (ie, central face, ears, scalp, genitalia, hands, feet), a 6-mm margin of healthy tissue is recommended. Given the cosmetic and functional impact of these wider margins, tumors in this latter category are often removed via Mohs surgery to achieve high cure rates while sparing normal tissue. The depth of an excision should always include a portion of the subcutaneous fat.

Disadvantages of excision include the risks of hematoma, seroma, infection, and wound dehiscence. One pitfall of standard excision is that histologic margins can be reported to be negative when they are, in fact, positive (false negative), because the traditional bread-loaf method of tissue sectioning typically results in evaluation of less than 1% of the specimen’s margins. For this reason, cure rates for SCC following excision do not significantly differ from cure rates following electrodessication and curettage (ED&C). Moreover, excision may even be somewhat less efficacious, with aggregate 5-year cure rates of only 92% for primary SCC.

More commonly, a greater amount of healthy tissue is removed than is necessary for complete tumor extirpation. 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. Therefore, simple excision is most valuable in the treatment of small primary SCCs on the trunk, extremities, or neck, where tissue sparing is less essential.^[132] 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%.

Lymphatic metastasis is the most important mechanism in the spread of head and neck SCCs. The rate of metastasis probably reflects the aggressiveness of the primary tumor and is an important prognostic indicator. Regardless of the site of the primary tumor, the presence of a single lymph node in either the ipsilateral or contralateral side of the neck reduces the 5-year survival rate by 50%.

Modified neck dissection

Modified neck dissection is designed to preserve the spinal accessory nerve, the great auricular, and the sternocleidomastoid muscle. The jugular vein and submandibular gland also have been preserved. In addition, successful results can be achieved through less than complete lymph node removal, selectively removing only those lymph node levels likely to be involved by metastases. Modified radical neck dissection removes all 5 lymph node levels, preserving one or all of the spinal accessory nerves, jugular vein, and sternocleidomastoid muscle.

Selective dissection removes either levels 1, 2, and 3 (supraomohyoid neck dissection); levels 2, 3, and 4 (anterior neck dissection); or levels 2, 3, 4 and 5 (anterolateral neck dissection). Modified and selective neck dissections clearly have been demonstrated as oncologically equal to the radical neck dissection in treating N0 neck disease. However, when there is one positive node, the likelihood of another positive node in an unexpected location increases significantly. For this reason, selective neck dissection is usually limited to patients without pathologically involved lymph nodes on the side of the dissection.

Classic radical neck dissection

Classic radical neck dissection was described by Crile in 1901 and includes removal of all 5 levels of cervical lymph nodes en bloc down to the deep muscular fascia. This removal includes the sternocleidomastoid muscle, submandibular gland, jugular vein, and spinal accessory nerve. This operation remains the best procedure for definitive control of neck disease. Radical neck dissection can be combined with resection of the primary cancer and postoperative radiation therapy.

Radical neck dissection has significant morbidity because of the resection of the spinal accessory nerve and, in bilateral dissection, the sacrifice of the internal jugular veins. Severing the spinal accessory nerve results in paralysis of the trapezius muscle in approximately 70% of patients. In most patients, the shoulder subsequently loses support, rotates forward, and droops, and the patient has pain and difficulty lifting his or her arm.

Mohs micrographic surgery (MMS) is a specialized technique for removing many forms of skin cancer, including squamous cell carcinoma (SCC). Because of its many advantages, Mohs micrographic surgery is the procedure of choice for SCC in which tissue preservation is needed, for ill-defined SCC, recurrent tumors, and for high-risk SCC.

The main advantage of this procedure over simple excision is the ability to histologically examine nearly 100% of the surgical margins (as compared with < 1% of the margin visualized via standard histologic sectioning) and to carefully map residual foci of invasive carcinoma, making incomplete excision much less likely than with standard pathologic processing. This residual tumor is mapped before removal, removed in a step-wise fashion until clear margins are obtained, and the excised specimens are managed in a way that maintains orientation relative to the operative site. Consequently, Mohs surgery offers both microscopic margin control and tissue sparing, thus facilitating small, minimally disfiguring reconstructions of the resulting defects.

Nail SCC

Mohs micrographic surgery 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. This procedure 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 micrographic surgery.

Extensive or deep SCC

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 micrographic 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, this procedure may be relegated to obtaining clearance of peripheral skin margins, with other surgical techniques used to clear the deep margins.

High-risk SCC

After excision of massive or high-risk cutaneous SCC using Mohs micrographic 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.

Cure rates for Mohs surgery

Mohs micrographic surgery provides the best available cure rates (94-99%) for SCC. This procedure 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 reported a 5-year cure rate of 98.1% in 213 cases of eyelid SCCs that had been treated.^[133] Wide local excision with frozen-section monitoring of margins may be performed when Mohs micrographical excision is not readily available.^[67]

Furthermore, 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.

In a comprehensive historical review, Rowe et al noted that local recurrences are less frequent when SCC is treated with this procedure compared with all non-Mohs modalities.^[3] This local recurrence rate differential in favor of Mohs micrographic surgery was observed in primary SCC of the skin and lip (3.1% vs 10.9%), for locally recurrent SCC (10% vs 23.3%), for poorly differentiated SCC (32.6% vs 53.6%), and for SCC with perineural involvement (0% vs 47%).

This technique offers the added benefit of preserving healthy tissue, thus facilitating reconstruction and optimizing cosmetic and functional outcomes. It is performed on a single operative day in an outpatient setting with local anesthesia and is therefore a safe and cost-effective procedure, even in very elderly patients with multiple morbidities.^{[134, 135]} Mohs micrographic surgery is less expensive than surgical excision with anesthesia in a hospital setting.^{[134, 135]}

As a result of the fellowship training programs in Mohs surgery overseen by the American College of Mohs Surgery and the new Accreditation Council for Graduate Medical Education (ACGME)–accredited Procedural Dermatology Fellowship programs, this technique has become widely available throughout the United States.^{[99, 136]}

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 squamous cell carcinoma (SCC).

This section will discuss experimental therapies such as photosensitizers and interstitial laser therapy and immune, gene, and targeted therapy.

Photosensitizers and interstitial laser therapy

Photosensitizing drugs that concentrate in cancer cells form the basis for photodynamic therapy. Activation of the drug with light results in cancer cell death. Laser photothermal ablation may be an alternative to surgery for the palliative treatment of head and neck cancer because of its tissue-sparing access, the possibility of repeated treatment, and experimental evidence suggesting lower recurrence at tumor margins compared with surgery. The combination of interstitial laser therapy with regional chemotherapy agents that are activated by light or heat is under investigation as a combined therapeutic regimen.

Immune therapy

Recruitment of immune cells and administration of stimulatory immune factors to augment treatment of cancer through the host immune response have been advocated but have had little success to date in treating head and neck cancers. Nonspecific immunoadjuvant systemic treatment with factors, such as levamisole or bacillus Calmette-Guérin (BCG), or targeted treatment with purified or recombinant factors, such as interferons or interleukin-2 (IL-2), have not improved either response rate or duration. Severe toxicities also are associated with the systemic use of these factors.

Gene therapy

Gene therapy involves various delivery vehicles that can transfer therapeutic genes to target cells. Therapeutic genes may encode a product that induces a biologic response, such as activation of the immune system with transferred interleukin sequences. Head and neck cancers are known to have high levels of TP53 mutations. Normal functions of TP53 are cell growth regulation. Insertion of the TP53 gene into various tumor cell lines in vitro and into animal models in vivo has resulted in suppressed cell growth through cell cycle arrest and apoptosis. Head and neck cancers are accessible to injection therapy and are good candidates for trials of TP53 gene therapy.

Another form of therapeutic gene delivery is the adenovirus vector, which uses a genetically engineered virus that is replication incompetent.^[137]

Prodrug gene therapy, also known as suicide gene therapy, is designed to induce negative selection of cancer cells. By transducing cancer cells with a gene encoding an enzyme that metabolizes a nontoxic prodrug into its toxic form, cancer cells can be selectively killed.

Herpes simplex virus (HSV) is a common human virus that produces a unique thymidine kinase. This viral enzyme preferentially phosphorylates the prodrug ganciclovir, a guanine nucleoside analogue, to produce a metabolite that, after cellular phosphorylation, is incorporated into replicating DNA, inhibiting DNA polymerase and ultimately killing the cell. This therapy is most effective in treating cancer cells growing in tissues where normal cells are not proliferating.

Many phase I and II trials are being pursued, and may ultimately provide nontoxic, tumor-specific, locally and regionally active, and biologically active injectable modalities that add therapeutic advantages to the existing treatment of head and neck cancers.

Roman et al noted that gene therapy might have a role in plastic and reconstructive surgery,^[138] and Rea and O’Sullivan suggested that polymerase chain reaction (PCR) currently 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.^[139]

Targeted therapy

Molecular markers that have prognostic and treatment value are currently under investigation.^[140] Epidermal growth factor receptors (EGFR) and human papillomavirus (HPV) are already being used in this manner, and many new markers are currently under investigation.^[141] These markers will allow the development of new therapies and the individualization of existing treatment options to create personally tailored regimens for each patient.^[124]

More recently, cetuximab, an EGFR inhibitor, has reportedly had success in several case reports.^{[118, 119, 120]} In the head and neck literature, phase I and II trials of capecitabine, used with cisplatin or paclitaxel^{[121, 122]} or in combination with radiation therapy^[123] also showed favorable outcomes.

A primary complication following treatment of squamous cell carcinoma (SCC) is recurrence, which typically occurs within the first year after excision but may occur much later. In intraocular cases, invasion has been demonstrated in 2-8%. Orbital invasion has been reported in 12-16% of cases. Poor conjunctival and/or corneal healing may occur, especially if aggressive keratectomy, sclerectomy, or 100% ethanol application were performed. Symblepharon formation is a common surgical complication following tumor resection and ocular surface reconstruction. Limbal stem cell damage may result from excision of large lesions.

Surgery for SCC may cause bleeding, infection, scar formation, physical deformity, and nerve damage. The removal of deeply invasive lesions may lead to substantial morbidity, including paralysis and pain syndromes.

Malpractice suits are uncommon following the diagnosis and treatment of squamous cell carcinoma (SCC) because, in most cases, both are straightforward and readily accomplished. Nonetheless, SCC is a lesion with the potential to cause substantial morbidity and even mortality, and physicians who diagnose and treat squamous cell carcinoma are held legally accountable for actions that are taken (or not taken) that fall outside the standard of care.

Failure to diagnose SCC

Failure to diagnose SCC may also lead to substantial morbidity and occasionally mortality.

Confusion of SCC with other cancers, such as desmoplastic melanoma (which can mimic SCC), and a failure to treat such cancers properly can be a source of liability. Seeking the services of a skilled dermatopathologist to assess SCC is, therefore, advisable. Large court awards have been set for cases in which failure to diagnose SCC has led to death.

Failure to treat/perceived inadequate treatment

Failure to treat and perceived inadequate treatment are common causes of malpractice claims against physicians. These cases occur most frequently when physicians fail to use an adequately aggressive primary treatment or fail to recognize a high-risk lesion. Some of the newer medical therapies (eg, imiquimod 5% cream, photodynamic therapy) 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.

Recognizing that high-risk SCC may metastasize and lead to death is important. Therefore, appropriately aggressive and prompt treatment is indicated in such cases. However, because defined prognostic criteria and models have not been developed, little information is available to guide clinicians in the most appropriate staging and treatment for individuals with high-risk SCC. Due to a lack of data, care standards regarding nodal staging, radiologic imaging, and postsurgical adjuvant therapy have not been developed. Subsequently, a lack of uniformity exists among experienced physicians in the treatment of high-risk SCC.^[60]

Failure to provide appropriate follow-up

Failure to provide appropriate follow-up is a potential pitfall. The courts hold the physician, not the patient, responsible for appropriate follow-up. Because primary treatment of SCC is not a guarantee of cure, ensuring adequate patient follow-up is essential.

Failure to inform patients of the potential morbidity associated with SCC may lead to the lesion being regarded as trivial and not requiring follow-up. Missed appointments may indicate the patient is worried or angry. Thus, patients with a history of SCC who miss follow-up appointments should be contacted by phone (or when necessary, with a certified letter) to reschedule. All medical staff are advised to document phone calls in writing and to save certified letter documentation.

It is critical for the operating physician to provide the medical record and operative/pathology report to the patient who is moving to another region (eg, out of state/country) and to encourage the patient to continue frequent follow-up with the new physician. The patient also should be assisted in locating a new physician to provide this care.

Failure to explain operative risks and complications

Informed consent should always be obtained and documented before proceeding with any procedure. Failure to explain all possible risks and complications of surgery is a legal pitfall. Explaining all possible risks before surgery is essential (see Complications). Such explanations should ideally be documented in written consent forms signed by the treating physician and the patient. Additionally, the physician should not treat lesions outside the realm of his or her comfort zone. If a surgical complication develops, the physician who performed the primary procedure is held legally responsible, regardless of who handles the complication.

Given the central role that ultraviolet (UV) radiation plays in the pathogenesis of cutaneous squamous cell carcinoma (SCC), methods aimed at decreasing such exposure form the cornerstone of disease prevention. Use of sunscreens, wearing protective clothing, and avoiding excessive sun exposure (or artificial sources of UV light [eg, tanning beds]), such as by limiting outdoor activities (especially between 10:00 am and 4:00 pm), should be recommended to all patients, especially fair-skinned elderly patients. Even young patients should be advised to take precautions against excessive sun exposure to reduce risk of developing cutaneous malignancies in future.

Sunscreens

The efficacy of UV protection is measured by its sun protection factor (SPF), which is the ratio of the least amount of UVB radiation that will induce erythema on covered skin to the amount of UVB 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. For patients at risk for SCC, if avoiding sun exposure is not possible, the minimum recommended SPF is 30 or higher. Sunscreen should be reapplied every 30 minutes during acute sun exposure.

Several randomized controlled clinical trials have shown a protective role for the daily application of a broad-spectrum sunscreen in the prevention new actinic keratoses and new cutaneous SCC. All patients should be advised to protect their eyelids from sun exposure. Physical sunblocks with the active ingredients of zinc oxide or titanium oxide provide the most complete protection from UVA and UVB rays.^[142] Alternatively, a combination chemical sunblock of octocrylene, ecamsule, and avobenzone also provides excellent broad-spectrum UV protection.^[143]

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 these are often expensive and restrictive.

Skin screening

Treatment of precancerous actinic keratoses and in situ SCC may prevent the future development of invasive lesions. Current recommendations for screening skin examinations from the American Cancer Society call for a skin examination every 3 years for persons aged 20-39 years and annually after age 40 years. The American Academy of Dermatology recommends annual screening for all patients.

Other preventive measures

The evidence behind other measures to prevent cutaneous SCC is lacking. Large well-controlled studies failed to show a beneficial role for dietary supplements in the prevention of skin cancers, including selenium, beta-carotene, retinal, and isotretinoin.

Chemoprevention with systemic retinoids is effective for reducing the number of new SCCs in both immunocompetent and immunosuppressed patients. Most recent studies have focused on the prophylactic use of oral acitretin, which has a relatively long half-life compared with isotretinoin. Low doses are often sufficient for prophylaxis. However, treatment must be continued indefinitely, because a relapse in tumor development occurs following discontinuation of oral retinoids. Furthermore, systemic retinoids have not been shown to be beneficial in treating existing SCC or at reducing the risk of recurrence after treatment.^[144]

The mechanisms by which retinoids protect against the development of SCC have not been fully elucidated. Data suggest that retinoids induce the expression of proapoptotic and antiproliferative genes, including TP53, caspases, and P73, in keratinocytes. The increase in epidermal Langerhans cells noted in one study suggests that retinoids may also enhance cutaneous immunosurveillance.^{[145, 146]}

Many patients are unable to tolerate the adverse effects associated with systemic retinoid therapy, although lower doses are better tolerated than higher doses. Organ transplant recipients appear to be more sensitive to the adverse effects of systemic retinoids than other patients. Adverse effects of systemic retinoids include mucocutaneous xerosis, dyslipidemia, liver function abnormalities, and teratogenicity.

Most cases of squamous cell carcinoma (SCC) are easily and successfully treated by dermatologists or Mohs surgeons. However, in certain cases, a multidisciplinary approach may be needed, such as in the following cases:

• Large or deep tumors in which excision and reconstruction under local anesthesia is not feasible
• When clear surgical margins are not achieved or are in doubt
• Cases of nodal or distant metastasis

A multidisciplinary approach using Mohs micrographic surgery performed in conjunction with an otolaryngologist and/or a plastic surgeon may aid in completely removing deeply invasive SCC, preserving a vital structure (eg, facial nerve), and facilitating the reconstruction of a large operative defect. For example, Mohs micrographic surgery may be used in cases of SCC of the scalp involving bone to establish peripheral margins to the level of the galea. Mohs micrographic surgery is then followed by resection of the deep margin, including bone, with the patient under general anesthesia, performed by a head and neck or plastic surgeon. Because the peripheral margins are established in advance, the head and neck or plastic surgeon can then focus on the deep margin and reconstruction. The patient is often spared hours of anesthesia time, lowering surgical morbidity.

Metastatic disease also requires aggressive management by a multidisciplinary team. Surgical treatment of metastatic disease may require the expertise of an otolaryngologist, a general surgeon, or a surgical oncologist. Adjuvant or palliative radiotherapy may be administered by a radiation oncologist. A medical oncologist should be consulted if systemic chemotherapy is considered for metastatic disease.

With exposure to risk factors, patients require vigilant follow-up care even after successful treatment, because they continue to be at risk for development of additional cutaneous skin malignancies (eg, basal cell carcinoma [BCC] and squamous cell carcinoma [SCC] of eyelid). The incidence of multiple primaries is 40% in long-term survivors. Therefore, early detection of head and neck cancers and cessation of alcohol and tobacco use is essential to improve prognosis.

Low-risk tumors are usually cured with appropriate surgical therapy; however, patients who develop one SCC have a 40% risk of developing additional SCCs within the next 2 years. This risk is likely even greater as more time elapses. Thus, patients with a history of SCC should be evaluated with a complete skin examination every 6-12 months.

Patients with high-risk tumors require skin and lymph node examinations at 3- to 6-month intervals for at least 2 years after diagnosis. In very high-risk cases, surveillance with computed tomography (CT) scanning or magnetic resonance imaging (MRI) may be considered.

Recurrent lesions should be treated aggressively. For example, occasionally, pyogenic granulomas can occur soon after tumor excision in areas of bare sclera. These lesions typically respond quickly to topical steroid treatment and must be differentiated from recurrent tumor. Success in treating recurrences with topical mitomycin C drops has been reported.

Encourage patients to follow up with the various specialists involved in their care.