Vulvar Cancer

The strongest expression in dVIN-associated VSCC highlights a possible link between aggressive tumor behavior and PRAME. dVIN-associated lesions may therefore represent promising candidates for PRAME-targeted therapy.

P2, N=798, Active, not recruiting, National Cancer Institute (NCI) | Trial primary completion date: May 2027 --> May 2026

P2, N=80, Recruiting, MacroGenics | N=60 --> 80 | Trial completion date: Aug 2027 --> Dec 2027 | Trial primary completion date: Feb 2027 --> Jul 2027

P=N/A, N=112, Active, not recruiting, Wake Forest University Health Sciences | Trial completion date: Mar 2027 --> Oct 2026 | Trial primary completion date: Aug 2026 --> Mar 2026

HLS shows neither the classic morphology of LS nor dVIN but can be p53 aberrant/mutant. Because of its CK17/D2-40 immunophenotype, it should be considered as atypical LS.

Vulvar aberrant maturation (VAM) encompasses HPVi lesions of uncertain neoplastic potential arising in lichen sclerosus that raise concern for but are not diagnostic of HPVi VIN. Collaboration between clinicians and pathologists is essential to achieve accurate diagnosis, optimal individualized treatment, and consistent application of this terminology in practice and research.

Expression patterns varied by lesion type, suggesting potential differences in the local immune microenvironment. Taken together, these findings support differences in clinical presentation and immune features of LS by menopausal status, warranting further investigation in larger cohorts.

We discuss the recent literature describing the added diagnostic value of immunohistochemical biomarkers p53, CK17, CK13, SOX2, GATA3, GLUT1 and others, which may be particularly helpful when morphology is inconclusive. It is anticipated that with improved VSCC classification and precursor recognition, avenues for more tailored therapeutic strategies and earlier therapeutic intervention can be achieved.

We propose a practical diagnostic framework that separates incidental marker expression from clinically meaningful neuroendocrine differentiation and links this distinction to reporting, prognosis and treatment. The central diagnostic question is not whether neuroendocrine markers are expressed but whether their expression defines a morphologically, biologically and clinically meaningful tumor category.

ICI demonstrated modest activity in recurrent VVC, with durable responses observed in a small subset of patients. Although survival outcomes were limited overall, ICI therapy may provide meaningful benefit for select patients.

HPV testing was negative. These findings support the hypothesis of stepwise tumor progression from a squamous precursor with RB1 and TP53 alterations, suggesting a mechanism for neuroendocrine transdifferentiation.

This review highlights the key changes in the evolution of VSCC care, with particular emphasis on the expanding responsibilities of pathologists in tumor subtyping [by human papillomavirus (HPV) and p53 status], biomarker-based prognostication, margin evaluation, recognition of precursors and alignment of precursor terminology (particularly HPV independent p53 wild-type lesions). By highlighting both progress and limitations, this review aims to inform future strategies that will further optimize patient outcomes and advance the standard of care in VSCC.