Track

Clinical Studies

Abstract

Differentiated vulvar intraepithelial neoplasia (dVIN) is an HPV-independent precursor lesion to vulvar squamous cell carcinoma (VSCC), an aggressive gynecological cancer. dVIN is difficult to diagnose, and can rapidly progress to VSCC. There is a need for specific histologic markers of dVIN. 

4 dVIN-associated VSCC, 12 dVIN, and 8 benign vulvar lesions were retrieved from our institution’s surgical pathology archives, using a keyword search over 2022-2023. At least one board-certified dermatopathologist or gynecologic pathologist reviewed each case for 7 histopathological features, all associated with dVIN. Chromosomal microarray analysis was conducted to assess genomic aberrations in all cases. Fisher’s Exact Test was used to analyze which histologic features differentiate dVIN from benign lesions and assess correlations between histology and gene alterations in dVIN.

Among dVINs, the presence of keratin pearls was significantly associated with 8q gain (p < .005), and hypergranulosis was significantly associated with 3q gain (p = 0.01), 9p loss of heterozygosity or loss (p =0.04), and 13q gain (p = 0.04). Importantly, 6 dVIN cases showed 9p loss, one of which had a homozygous focal deletion of CDKN2A, suggesting that CDKN2A is a relevant gene. 

To our knowledge, these associations are novel. Our findings suggest that drugs modulating pathways influenced by genes on chromosomes 8q, 3q, 13q, and 9p could be useful in halting dVIN progression. Additionally, a histopathological and genomic diagnostic approach could clarify cases wherein histology alone does not lead to a clear dVIN diagnosis. This work may lead to more precise diagnoses in the future.