Simon F Roy

DEVIL, VAAD and vLSC constitute a spectrum of HPV‐independent, p53‐independent intra‐epithelial neoplasia of the vulva

AimsWe aimed to characterise a large cohort of non‐invasive, human papillomavirus (HPV) and p53‐independent verruciform lesions, such as ‘vulvar acanthosis with altered differentiation’ (VAAD), ‘differentiated exophytic vulvar intra‐epithelial lesion’ (DEVIL) and ‘verruciform lichen simplex chronicus’ (vLSC).Methods and resultsFrom January 2008 to December 2020 we retrospectively identified 36 eligible patients with verruciform non‐invasive lesions (n = 36) and collected clinical, histological and follow‐up parameters. Verruciform non‐invasive lesions occurred at a median age of 71 years, with a median follow‐up of 33.5 months. Clinically, pruritus was only reported in patients with VAAD (n = 3, 21%). Lesion colour was significantly different across categories (P = 0.028). Apart from the histopathological criteria already known to distinguish these entities (hypogranulosis, epithelial pallor and low‐magnification architecture), no other significant criteria were discovered and significant overlap was observed, particularly between VAAD and DEVIL. Patients with vLSC trended towards longer survival without recurrence compared to VAAD and DEVIL (P = 0.082), but showed comparable invasion‐free survival interval (P = 0.782). Squamous cell carcinomas (SCC) associated with either VAAD, DEVIL or vLSC displayed similar clinical, histopathological and biological parameters. In non‐invasive precursor lesions, stromal oedema was associated with invasion (P = 0.015) and remained so upon Cox regression analysis (P = 0.009).ConclusionOur study of HPV and p53 independent non‐invasive verruciform lesions of the vulva highlights significant clinical, histopathological and biological overlap between VAAD, DEVIL and vLSC, suggesting that these pre‐invasive lesions should be viewed as a spectrum. We also show that stromal features such as oedema might play an import role in progression to invasion.

Vulvar Cutaneous Myxoma in a Patient With Carney Complex: Avoiding Pitfalls of Myxoid Lesions of the Vulva

We present the case of a 31-year-old woman who underwent surgical excision for a polypoid, vulvar lesion. Histopathological analysis showed a diffuse myxoid stroma admixed with scant collagen fibrils. Thin-walled and branching blood vessels were prominent, with a mild perivascular lymphocytic infiltrate. Cytologically bland spindle cells with inconspicuous nucleoli were immersed in a loose myxoid stroma. This combination of histopathological features along with multinodularity in the subcutaneous fat raised concern for deep angiomyxoma, a locally destructive neoplasm. Among our differential of myxoid lesions of the vulva, we ultimately favored the diagnosis of vulvar cutaneous myxoma. Upon further investigation, we learned that our patient was indeed known for the Carney complex. We highlight that vulvar cutaneous myxomas arising in the context of the Carney complex pose a significant diagnostic challenge for pathologists and should not be overdiagnosed as aggressive lesions such as deep angiomyxoma or other malignant stromal neoplasms.

Tumour necrosis is a valuable histopathological prognostic parameter in melanomas of the vulva and vagina

Vulvar and vaginal melanomas (VVMs) are rare and aggressive malignancies with limited prognostic models available and there is no standard reporting protocol. VVMs were selected from six tertiary Canadian hospitals from 2000-2021, resected from patients aged ≥18 years, with 6 months or longer follow-up data, and confirmation of melanocytic differentiation by at least two immunohistochemical markers. Cases were reviewed by pathologists to identify histological biomarkers. Survival outcomes were tested with Kaplan-Meier log-rank, univariate Cox, and multivariate Cox regression. There were 79 VVMs with median follow-up at 26 months. Univariate analysis revealed that tumour necrosis, tumour ulceration, positive lymph nodes, and metastasis at diagnosis were significantly associated with disease-specific mortality, progression, and metastasis. Multivariate analysis identified tumour necrosis as an independent prognostic factor for disease-specific mortality (HR 4.803, 95% CI 1.954-11.803, p<0.001), progression (HR 2.676, 95% CI 1.403-5.102, p=0.003), and time-to-metastasis for non-metastatic patients at diagnosis (HR 3.761, 95%CI 1.678-8.431, p=0.001). Kaplan-Meier survival analyses demonstrated that tumour necrosis was a poor prognostic factor for disease-specific, progression-free, and metastasis-free survival (p<0.001 for all comparisons). Vaginal melanomas displayed decreased survival compared to vulvar or clitoral melanomas. This study identifies tumour necrosis as an independent prognostic factor for VVMs. Vaginal melanomas specifically showed worse survival outcomes compared to vulvar or clitoral melanomas, consistent with previously reported findings in the literature, emphasising the importance of differentiating between these primary tumour epicentres for prognostication and treatment planning in the care of genital melanoma patients.