Clinical Investigation
Perineural Infiltration of Cutaneous Squamous Cell Carcinoma and Basal Cell Carcinoma Without Clinical Features

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Purpose

To review the factors that influence outcome and patterns of relapse in patients with cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) with perineural infiltration (PNI) without clinical or radiologic features, treated with surgery and radiotherapy.

Methods and Materials

Between 1991 and 2004, 222 patients with SCC or BCC with PNI on pathologic examination but without clinical or radiologic PNI features were identified. Charts were reviewed retrospectively and relevant data collected. All patients were treated with curative intent; all had radiotherapy, and most had surgery. The primary endpoint was 5-year relapse-free survival from the time of diagnosis.

Results

Patients with SCC did significantly worse than those with BCC (5-year relapse-free survival, 78% vs. 91%; p < 0.01). Squamous cell carcinoma with PNI at recurrence did significantly worse than de novo in terms of 5-year local failure (40% vs. 19%; p < 0.01) and regional relapse (29% vs. 5%; p < 0.01). Depth of invasion was also a significant factor. Of the PNI-specific factors for SCC, focal PNI did significantly better than more-extensive PNI, but involved nerve diameter or presence of PNI at the periphery of the tumor were not significant factors.

Conclusions

Radiotherapy in conjunction with surgery offers an acceptable outcome for cutaneous SCC and BCC with PNI. This study suggests that focal PNI is not an adverse feature.

Introduction

Nearly 2% of the Australian population, or 374,000 people, are treated for nonmelanomatous skin cancer every year (1). Perineural infiltration (PNI) can occur in skin cancer, with the reported incidence of PNI on pathologic examination ranging between 0.18% and 10% for basal cell carcinoma (BCC) (2) and between 2.5% and 14% for squamous cell carcinoma (SCC) 3, 4.

Perineural infiltration is a phenomenon whereby tumor extends along the perineurium of a nerve, detected histologically. Sometimes the PNI can involve large nerves, which can be associated with clinical symptoms or signs of dysthesia or hypoesthesia, and sometimes when large nerves are involved, PNI can be detected on MRI. Perineural infiltration has been classified into two groups: that in which it is detected just on microscopic examination and there are no clinical or radiologic abnormalities from the PNI; and a second group in which there are also clinical and/or radiologic findings of PNI 5, 6. The PNI group in which there are clinical features has a worse prognosis than the group in which PNI is just an incidental finding on histology 7, 8. Perineural infiltration is being increasingly recognized and reported by pathologists, and it is regarded as an adverse prognostic feature, but how significant is uncertain.

The aim of this study was to assess the factors that affect outcome of patients with cutaneous SCC and BCC who have PNI detected on histology without clinical features of PNI. All patients had radiotherapy (RT) and most (216 of 222) had surgery.

Section snippets

Methods and Materials

Between 1991 and 2004, patients with cutaneous SCC or BCC with PNI on histologic examination and treated with RT were identified from the oncology database, Royal Brisbane and Women’s Hospital. Patients with clinical or radiologic features of PNI were not included. Patients were excluded from the analysis if the intent of treatment was palliative or they did not receive the full prescribed dose of RT. Melanoma, Merkel cell carcinoma, and skin appendage tumors were excluded from the study. A

Results

Of the 222 patients, 89 had BCC and 133 had SCC. Patient characteristics, tumor factors, and treatment are listed in Table 1. Twenty-two patients had a predisposing medical condition, such as renal impairment or Chronic Lymphocytic Leukemia or other lymphoproliferative disease that may cause immunosuppression.

Discussion

There have been several published series of PNI in nonmelanomatous skin cancers of the head and neck without clinical and/or radiologic features that have examined the outcome after RT (Table 7) 5, 7, 9, 10. The University of Florida studies analyzed the combined outcome for both BCC and SCC and reported 5-year local control rates ranging from 78% to 87% 7, 10. Both series included patients dating back to 1965. The present study is larger and more recent, with patients presenting from 1991, so

Conclusions

In our series the main factors that influenced outcome were those related to the tumor itself, including histology (particularly SCC), PNI at recurrence rather than de novo, and depth of invasion. The only significant PNI-specific factor was the degree of PNI, and this study suggests that focal PNI is not an adverse feature.

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