Perineural invasion (PNI) in vulvar carcinoma: A review of 421 cases

Highlights

• Perineural invasion should be considered a poor prognostic factor in vulvar carcinoma.

• Perineural invasion was associated with higher stage disease.

• Perineural invasion was associated with poorer overall survival.

Abstract

Objectives

To evaluate the prevalence and associated prognostic indicators in patients with vulvar carcinoma with and without evidence of perineural invasion (PNI).

Methods

A retrospective review identified 421 patients with invasive vulvar carcinoma evaluated at a single institution between 1993 and 2011. Medical records were reviewed for demographic data, pathologic information and presence or absence of PNI, treatment type, and recurrence/outcome information. Variables were compared between patients with PNI to those without PNI.

Results

Of the 421 patients included in the study, 32 (7.6%) had tumors with PNI. There were no significant differences in age, race/ethnicity, smoking history, histologic subtype, or grade between the group of patients with PNI and the group without PNI. The group with PNI was more likely to have lichen sclerosus (25.0% vs. 15.4%, p = 0.024), stage III/IV disease (59.4% vs. 36.0%, p = 0.007), lymph node involvement (50.0% vs. 21.6%, p = 0.002), and lymphovascular space invasion (LVSI) (53.1% vs. 15.9%, p < 0.001). A higher proportion of patients in the PNI group underwent primary or adjuvant radiation therapy (68.8% vs. 45.0%, p = 0.016). The median follow-up was 67.1 months (range < 1.0 to 284.3). Patients with PNI had significantly shorter overall survival (OS), median 25.5 vs. 94.3 months (p < 0.001), and progression-free survival (PFS), median 17.5 vs. 29.0 months (p = 0.004). After adjusting for stage, patients with PNI had a greater risk for death and progression (OS: hazard ratio, 2.71; p < 0.001; PFS: hazard ratio, 1.64; p-value = 0.020).

Conclusion

PNI should be considered an independent poor prognostic factor for patients with vulvar carcinoma, and should be included as part of the pathologic analysis.

Introduction

Vulvar cancer is the fourth most common gynecologic cancer in the United States, comprising 5% of all gynecologic malignancies. The American Cancer Society projects about 6190 new cases of invasive vulvar cancer and about 1200 related deaths among women in the United States in 2018 [1]. Risk factors for vulvar cancer include advanced age, cigarette smoking, vulvar dystrophy such as lichen sclerosus, vulvar or cervical intraepithelial neoplasia, high-risk human papillomavirus (HPV) infection, immunocompromised status, and a prior history of cervical cancer [2,3]. Most vulvar cancers are squamous cell carcinomas [4]; other histologies include melanoma, Bartholin gland adenocarcinoma, sarcoma, Paget's disease, verrucous carcinoma and basal cell carcinoma.

Perineural invasion (PNI) is defined as the detection of malignant cells in the perineural space of nerves, regardless of whether the nerve itself is infiltrated by tumor. PNI has been noted to be an important pathologic feature for several malignancies, particularly head and neck cancers where it is associated with poor prognosis and is now a required component of the pathologic analysis [5]. PNI has also been shown to be associated with poor prognosis in prostate, ampullary carcinoma and colorectal cancers [[6], [7], [8]]. The purpose of this study was to evaluate the prevalence and associated prognostic indicators in patients with vulvar carcinoma with and without evidence of perineural invasion (PNI). In addition, we sought to determine the prevalence of PNI in vulvar cancer.