Skin carcinoma of the head and neck with perineural invasion

Abstract

Purpose

The aim of the study was to update the experience treating cutaneous squamous cell and basal cell carcinomas of the head and neck with incidental or clinical perineural invasion (PNI) with radiotherapy (RT).

Materials and methods

From 1965 to 2007, 216 patients received RT alone or with surgery and/or chemotherapy.

Results

The 5-year overall, cause-specific, and disease-free survivals for incidental and clinical PNIs were 55% vs 54%, 73% vs 64%, and 67% vs 51%. The 5-year local control, local-regional control, and freedom from distant metastases for incidental and clinical PNIs were 80% vs 54%, 70% vs 51%, and 90% vs 94%. On univariate and multivariate (P = .0038 and .0047) analyses, clinical PNI was a poor prognostic factor for local control. The rates of grade 3 or higher complication in the incidental and clinical PNI groups were 16% and 36%, respectively.

Conclusions

Radiotherapy plays a critical role in the treatment of this disease. Clinical PNI should be adequately irradiated to include the involved nerves to the skull base.

Introduction

Skin carcinoma with perineural invasion (PNI) is relatively uncommon, occurring in approximately 2% of cutaneous basal cell carcinomas (BCCs) and 3% of squamous cell carcinomas (SCCs) of the head and neck [1]. The cancer cells surround the nerve sheath and spread proximally down the length of the nerve toward the skull base, although distal spread is also possible [2].

Perineural invasion is grouped into incidental and clinical. Incidental PNI includes asymptomatic patients with evidence of microscopic invasion of the nerve detected only by histopathology. Clinical PNI includes patients with evidence of a cranial neuropathy (most commonly cranial nerve [CN] V or VII) on physical examination and/or radiographic evidence of gross tumor involvement along the tract of a nerve [3]. Magnetic resonance imaging (MRI) is used to detect and define the extent of PNI. Positron emission tomography computed tomography (PET-CT) is unlikely to define the extent of gross PNI as accurately as MRI. Of note, it is rare to observe radiographic evidence of PNI in an asymptomatic patient. Perineural invasion associated with SCC increases the risk of metastases to the regional lymph nodes, which should be evaluated with contrast-enhanced CT.

Patients may experience a subtle feeling of ants crawling underneath the skin (formication), which may progress to pain, numbness, and/or facial weakness over 6 months to 2 years before diagnosis [2]. There is an increased risk of PNI with midface location, male sex, increasing tumor size, recurrence after prior treatment, and poor histologic differentiation [4], [5], [6], [7], [8]. Although PNI is a result of direct extension along a nerve, it may be associated with apparent “skip” lesions along the nerve, which increases the risk of a recurrence after resection even if negative margins are obtained on surgical pathology [9], [10]. Patients with PNI have a poorer prognosis compared with those who do not have PNI [2].

Patients with incidental PNI typically receive a wide local excision of the primary lesion before the diagnosis and are then considered for postoperative radiotherapy (RT). Patients with minimal focal PNI, particularly those with BCC, may be considered for surgery alone depending on the primary site and the reliability of the patient for close follow-up [11]. Patients with completely resectable clinical PNI cancers usually undergo surgery followed by postoperative RT to reduce the risk of local-regional recurrence. Patients with incompletely resectable clinical PNI cancers are treated with definitive RT. The RT clinical target volume includes the involved nerves to the base of skull because the extent of subclinical disease is often difficult to define. Hyperfractionation is preferred to once-daily fractionation to reduce the risk of damage to the visual apparatus when the retina, optic nerve(s), and/or chiasm receive high-dose RT [12], [13]. Extrapolating from patients treated with mucosal head and neck SCCs, concurrent chemotherapy may be considered in the treatment to improve the likelihood of local control for patients with SCC and clinical PNI [14]. However, there is no definitive evidence that the probability of cure is enhanced by the addition of chemotherapy. Clinically negative regional lymph nodes should also be electively treated in patients with SCC because of the 15% to 20% risk of subclinical disease [15], [16]. Patients with CN deficits and/or pain before treatment usually do not experience amelioration of these problems after RT even if the cancer has been eradicated [15].

The purpose of this study is to update the University of Florida experience using RT to treat cutaneous SCCs and BCCs of the head and neck with either incidental or clinical PNI.