Randal S. Weber, MD, is Hubert L. and Olive Stringer Distinguished Professor of Cancer Research and Chairman of the Department of Head and Neck Surgery at the University of Texas M. D. Anderson Cancer Center in Houston.
Non-melanoma skin cancer is the most common malignancy afflicting humans, and is a major public health problem in the United States. The majority occur in the head and neck region due to the significant amount of actinic exposure received through recreational and work-related activities. Fortunately, the less aggressive basal cell carcinoma of the skin occurs at four times the incidence of cutaneous squamous carcinoma. Males predominate for both histologic types, likely because of the increased sun exposure they receive. Although mortality for non-melanoma skin cancer is low, morbidity is significant because of the cosmetic and functional sequelae that may occur following surgical resection and reconstruction in the treatment of aggressive lesions. It is estimated that 2000 deaths annually are attributable to non-melanoma skin cancer, but this figure is only an estimate, as incidence and mortality of non-melanoma skin cancer are no longer tracked in the national cancer databases.
Compared to squamous cell carcinoma of the skin, basal cell carcinomas tend to remain localized and rarely metastasize to regional lymph nodes. Tumor spread along regional nerves (perineural invasion) in the head and neck occurs in both squamous and basal cell carcinoma in approximately 15% and 0.1% of cases, respectively, but is associated with a high rate of local recurrence and regional and distant spread. Most basal cell carcinomas tend to remain localized; however, the infiltrative type previously referred to as morphea is more aggressive and has a higher recurrence rate. In contrast, squamous carcinoma of the skin is more biologically aggressive and has a propensity to spread along nerves and metastasize to regional lymph nodes in approximately 15% of patients. Clayman et al.1 demonstrated in a prospective clinical pathologic study that patients with squamous carcinomas of the skin that are greater than 4 cm in diameter, invade into the underlying subcutaneous tissue and bone, or exhibit perineural invasion are associated with a 40% two-year mortality rate. Non-melanoma skin cancers with any of these features are defined as aggressive non-melanoma skin cancer.
Inadequate treatment or an underestimation of the lethality of aggressive cutaneous squamous cell carcinoma increases the patient’s risk of local recurrence and mortality. Because of their aggressiveness, multidisciplinary management will afford the patient the best chance for cure. Unfortunately, patients may not receive multimodal care that is often indicated to cure their cutaneous malignancies.
Traditional Treatment of Non-Melanoma Skin Cancer
Patients with skin cancer are often managed by head and neck surgeons, Mohs surgeons, or plastic and reconstructive surgeons. Ideally, these disciplines should work collaboratively to provide the patient with optimum cancer management. Unfortunately, this is not always the reality. Standard treatment for aggressive non-melanoma skin cancer is surgical excision with histologically negative margins. The overarching surgical principle is complete surgical resection with tumor-free margins as determined by careful pathologic review of the margins, either by frozen section or delayed review of fixed tissue sections.
The conventional surgical approach is en bloc resection. The surgeon is guided by tactile and visual cues and high resolution imaging to estimate the volume of tumor and the surrounding tissue necessary for complete resection. This approach is analogous to en bloc resection of an upper aerodigestive tract squamous cell carcinoma, and similar principles apply. Take, for example, an invasive squamous cell carcinoma of the lateral oral tongue. The tried-and-true therapeutic approach is partial glossectomy with a generous margin of surrounding normal mucosa and muscle. With the knowledge of the propensity for these tumors to exhibit perineural spread, tracking along muscle bundles and displaying lymphovascular invasion, few would advocated a conservative excision with maximum preservation of the adjacent tongue.
Studies have shown that wide resection with tumor-free margins provides the patient with the best opportunity for local control. Why, then, should we consider cutaneous squamous cell carcinoma to be inherently different from an oral tongue cancer? Their clinical and biologic behavior is not dissimilar. The extent of resection of normal tissue margin should be determined by the biologic behavior of the primary tumor. Squamous cell carcinomas of the skin are inherently different from basal cell carcinomas in the proclivity of the former to infiltrate deeply, exhibit lymphovascular invasion, and propagate along motor and sensory nerves. For cutaneous squamous cell carcinomas, failure of the surgeon to recognize their biologic behavior and aggressively resect the tumor with generous margins will significantly increase the patient’s risk for recurrence.
Differences in Approach
Significant philosophical differences exist in the surgical management. The head and neck surgeon resects aggressive cutaneous squamous cell carcinoma in an en bloc fashion with wide margins. In contrast, the Mohs surgeon may take a fundamentally different approach. While complete surgical resection with histologically clear margins is the goal of Mohs surgery, tissue conservation is a stated priority. The head and neck surgeon relies on the surgical pathologist to microscopically assess the margin status. The Mohs surgeon serves as both the pathologist and surgeon, and advocates this approach because of the precise nature it affords for tumor mapping, the ability to immediately assess the margins, and conservation of normal adjacent tissue. The Mohs surgeon advocates immediate reconstruction, given the confidence that the margins are free of tumor. However, the assessment of the margins and the presence of perineural invasion on frozen section are, at times, difficult even for an experienced dermatopathologist who has training in surgical pathology and has completed a subspecialty fellowship. Studies have demonstrated the variability among experienced pathologists when interpreting frozen sections following excision of cutaneous neoplasms.
Although the Mohs technique is appropriate for most patients with basal cell carcinomas and nonaggressive squamous cell carcinomas, it does not take into account the biology and mechanisms of spread demonstrated by these aggressive tumors. Rather than an en bloc resection, the Mohs surgeon estimates the tumor extent by initially using a curette to remove all gross tumor. Next, the tumor is resected in levels with careful geometric orientation and mapping of the margins. Each excision is referred to as a level, and multiple levels may be required for complete tumor extirpation. Though very precise and consistent with a philosophy of maximum conservation of normal tissue, distance from the leading edge of the invasive tumor and the surrounding normal tissue may only be a few millimeters or less. This defies the biologic behavior of these aggressive cancers. For instance, the Mohs surgeon may accurately identify perineural invasion, but with a tissue conservation approach may not completely encompass the skip metastasis present in the involved nerve.
Analogous to the surgical management of oral tongue cancer, aggressive squamous cell carcinomas of the skin require careful treatment planning with preoperative imaging and multidisciplinary assessment by a radiation oncologist and, at times, the reconstructive surgeon. Determining the extent of the tumor facilitates complete resection. Pretreatment assessment by the radiation oncologist and reconstructive surgeon allows comprehensive planning for the appropriate use of radiation therapy and a method of reconstruction that will withstand the rigors of postoperative radiotherapy and restore the patient’s form and function.
Presurgical planning is particularly important for periauricular tumors that invade the parotid fascia. With the Mohs technique the facial nerve trunk and branches are approached directly within the depths of the wound and are at greater risk for injury. The more traditional en bloc resection dictates identification of the main trunk of the facial nerve and serial dissection of each branch. The nerve is preserved, provided that a plane of dissection exists between the tumor and the nerve. When encased by tumor, the nerve is resected. En bloc parotidectomy and wide excision provide a safe deep margin while maintaining the integrity of the facial nerve whenever possible.
Multidisciplinary Management Necessary
A multidisciplinary and comprehensive management philosophy will optimize care for these patients. Patients with aggressive cutaneous squamous cell carcinoma frequently require radiation therapy as an adjunct to surgical resection when the margins are either close or microscopically involved, nerve invasion is present, or lymph node metastasis occurs. In addition, the dental oncologist should assess the patient for the need for extractions or dental restorations if radiation therapy is indicated. Our philosophy is also to engage the reconstructive surgeon as a member of the team, so that the oncologic surgeon can resect the tumor unencumbered by the need to perform a reconstruction. The reconstructive surgeon can repair the defect with the confidence that oncologically free margins are obtained and the tumor has been adequately removed. This multidisciplinary approach affords the patient with the optimum opportunity for disease control and for functional and cosmetic restoration.
Follow-up care is also an integral aspect of care. Although lymph node metastasis at the time of presentation is less than 20%, subsequent relapse does occur and if not detected early and aggressively managed, the patient’s chances for disease control and cure are dramatically diminished. These patients require close observation by the multidisciplinary team members, not only by their primary physician or general dermatologist, who may be unfamiliar with signs, symptoms, and patterns of relapse.
In summary, it is not whether Mohs surgery is more or less effective than conventional resection; the key is that the therapeutic approach should be tailored to the biologic behavior of the disease. For patients with cutaneous basal cell carcinoma and nonaggressive squamous carcinoma of the head and neck, Mohs micrographic surgery with careful tumor mapping and complete resection will achieve three desired goals: (1) cost-effective eradication of the tumor in an outpatient setting, (2) conservation of involved tissue, and (3) immediate reconstruction. In contrast, patients with aggressive squamous cell carcinomas require multidisciplinary management with the surgeon following oncologic principles of en bloc resection and wide tumor-free margins as determined by frozen section or analysis of fixed tissue. Appropriate use of adjuvant radiation therapy will enhance local-regional control and may improve survival. An experienced reconstructive surgeon will provide the patient with the optimum repair for restoration of form and function. Careful follow-up by the treatment team will facilitate rehabilitation, detect early recurrences, and permit effective salvage. Providing these patients with the most effective and comprehensive management will in the long run prove to be the most efficacious and cost-effective.
- Clayman GL, Lee JJ, Holsinger FC, et al. Mortality risk from squamous cell skin cancer. J Clin Oncol 2005;23(4):759-65.
©2007 The Triological Society