Abstract
Histological diagnosis of differentiated vulvar intraepithelial neoplasia (dVIN), the precursor of human papillomavirus (HPV)-independent vulvar squamous cell carcinoma (VSCC), can be challenging, as features of dVIN may mimic those of non-dysplastic dermatoses. To aid the diagnosis, p53-immunohistochemistry (IHC) is commonly used, and mutant expression patterns are used to support a histological diagnosis of dVIN. However, a proportion of dVIN can show wild-type p53-expression, which is characteristic of non-dysplastic dermatoses. Furthermore, recent research has identified a novel precursor of HPV-independent VSCC—the p53-wild-type differentiated exophytic vulvar intraepithelial lesion (de-VIL). Currently, there are no established diagnostic IHC-markers for p53-wild-type dVIN or de-VIL. We evaluated IHC-markers, cytokeratin 17 (CK17), and SRY-box 2 (SOX2), as diagnostic adjuncts for dVIN. For this, IHC-expression of CK17, SOX2, and p53 was studied in dVIN (n = 56), de-VIL (n = 8), and non-dysplastic vulvar tissues (n = 46). For CK17 and SOX2, the percentage of cells showing expression, and the intensity and distribution of expression were recorded. We also performed next generation targeted sequencing (NGTS) on a subset of dVIN (n = 8) and de-VIL (n = 8). With p53-IHC, 74% of dVIN showed mutant patterns and 26% showed wild-type expression. Median percentage of cells expressing CK17 or SOX2 was significantly higher in dVIN (p53-mutant or p53-wild-type) and de-VIL than in non-dysplastic tissues (p < 0.01). Diffuse, moderate-to-strong, full epithelial expression of CK17 or SOX2 was highly specific for dVIN and de-VIL. With NGTS, TP53 mutations were detected in both dVIN and de-VIL. We infer that immunohistochemical markers CK17 and SOX2, when used along with p53, may help support the histological diagnosis of dVIN.
Highlights
Vulvar squamous cell carcinoma (VSCC) is classified etiologically into human papilloma virus (HPV)-related, and human papillomavirus (HPV)-independent subtypes [1,2,3,4]
Studies report that Differentiated vulvar intraepithelial neoplasia (dVIN) can progress rapidly to vulvar squamous cell carcinoma (VSCC) [5,6]; lesions diagnosed on histology as dVIN are surgically excised [7,8]
A total of 137 lesions were included after histology review, comprising dVIN (n = 56), differentiated exophytic vulvar intraepithelial lesion (de-VIL) (n = 8), high grade squamous intraepithelial lesion (HSIL) (n = 27), and non-dysplastic vulvar tissue (n = 46)
Summary
Vulvar squamous cell carcinoma (VSCC) is classified etiologically into human papilloma virus (HPV)-related, and HPV-independent subtypes [1,2,3,4]. Pharmaceuticals 2021, 14, 324 is the more prevalent subtype [3] that typically arises in the setting of chronic dermatoses. Differentiated vulvar intraepithelial neoplasia (dVIN) is the most well-characterized precursor lesion of HPV-independent VSCC [1,2,3,4]. Studies report that dVIN can progress rapidly to VSCC [5,6]; lesions diagnosed on histology as dVIN are surgically excised [7,8]. The difficulty in diagnosing dVIN stems largely from its subtle histological appearance, which may mimic that of reactive/non-dysplastic dermatoses [11,12,13,14]. Mutant patterns of p53-expression are used to support a histological diagnosis of dVIN, as these have been reported to reflect
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