Article

Cutaneous Squamous Cell Carcinoma With Perineural Invasion: A Case Report and Review of the Literature

Cutis. 2014 March;93(3):141-144

References

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Perineural invasion can be further classified as clinical or microscopic (incidental) for prognostic purposes. A study by Garcia-Serra et al¹³ found that patients with clinical PNI had a notably poorer prognosis than those with microscopic (incidental) PNI. The clinical group achieved a local control rate of 55% at 5 years’ follow-up versus 87% in the microscopic group. McCord et al²² found a 5-year local control rate of 78% for microscopic (incidental) PNI versus 50% for clinical PNI; they also found that patients with radiologic evidence of PNI had a worse prognosis, noting that patients with radiologic evidence of PNI were nearly all clinically symptomatic.

Prognosis also is altered by the diameter of the nerve involved. In a study of 48 patients, Ross et al²³found that patients with cutaneous SCC involving small-caliber nerves (diameter, ≤0.1 mm) had a 0% disease-specific death rate versus 32% in those with large-caliber nerves (>0.1 mm). Perineural involvement of small-caliber nerves (<0.1 mm) was a positive prognostic indicator in that it was associated with smaller tumor diameter, more shallow invasion, and increased likelihood to be primary tumors.²³ In a recent study, Jambusaria-Pahlajani et al²⁴ investigated tumor staging for cutaneous SCC and reported that PNI is a statistically independent prognostic risk factor for nodal metastasis (subhazard ratio, 2.2 [95% confidence interval, 0.9-5.1]) and disease-specific death (subhazard ratio, 3.4 [95% confidence interval, 0.9-13.3]). Of interest, this increased risk applied only to PNI in nerves that were greater than 0.1 mm.²⁴

Treatment Options—Management of confirmed cases of cutaneous SCC with PNI is difficult because of the nature of the lesions, including their increased propensity for metastasis, increased frequency of poorly differentiated cell types, highly aggressive nature, and the unique challenge of skip lesions.^4,¹⁶ Skip lesions are found microscopically and show (or appear to show) neoplastic cells invading a nerve in a discontinuous fashion. This phenomenon has been suggested as one explanation for the relatively higher postsurgical recurrence rate of SCC with PNI compared to lesions without PNI.⁷ They are of particular interest when removing cutaneous SCC with PNI using MMS and attempting to define clear margins. Despite this limitation, MMS generally is accepted as the primary mode of excision of cutaneous SCCs with PNI, as it has the highest known cure rate.⁷ Cotte^l4 did not report any cases of local recurrence over 1 to 42 months in 17 patients who were treated with MMS, in contrast to Rowe et al²⁵ who demonstrated that traditional surgical excision had a 47% (34/72) local recurrence rate; however, it bears noting that the varying follow-up periods in the Cotte^l4 study may underestimate recurrence rate. Leibovitch et al⁷ had similar findings in their prospective case series study of 70 patients, which revealed an 8% recurrence rate within 5 years in patients treated with MMS, a rate lower than other non-MMS modalities. In this same study, the authors noted that some researchers believe an additional level should be taken with MMS beyond the appearance of free margins in cases with PNI.⁷

Jambusaria-Pahlajani et al²¹ reported that PNI is one of the most common reasons cited for using adjuvant radiation therapy for cases of cutaneous SCC because of the known propensity of local recurrence; however, in 74 reviewed cases, there was no statistically significant difference in outcomes in cases of surgery alone versus surgery and adjuvant irradiation. Radiation therapy is a possible alternative primary treatment of cutaneous SCC with PNI, especially in cases of perineural involvement that is extensive or affects proximal portions of cranial nerves when surgery is a less viable option.¹⁷ Mendenhall et al¹⁶ suggested that patients with positive margins after excision who display extensive PNI should be treated with adjuvant irradiation locally and along the course of the involved nerve to the skull base.

Conclusion

Physicians should recognize the importance of early detection of PNI in cases of cutaneous SCC. A thorough history with good neurologic examination of the head and neck in patients with cutaneous SCC is imperative so patients can be treated earlier in the course of the lesion, increasing the likelihood of local control, minimizing the risk for future recurrence, and decreasing mortality.