Volume 79, Issue 6 pp. 975-988

Original Article

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

Simon F Roy,

Simon F Roy

orcid.org/0000-0002-5444-0349

Département de Pathologie, Centre hospitalier de l’Université de Montréal, University of Montréal, Montréal, Canada

Département de Pathologie et de Biologie Cellulaire, Université de Montréal, Montréal, Canada

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Jahg Wong,

Jahg Wong

Département de Pathologie, Centre hospitalier de l’Université de Montréal, University of Montréal, Montréal, Canada

Département de Pathologie et de Biologie Cellulaire, Université de Montréal, Montréal, Canada

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Cécile Le Page,

Cécile Le Page

orcid.org/0000-0002-8020-1544

Département de Pathologie, Centre hospitalier de l’Université de Montréal, University of Montréal, Montréal, Canada

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Danh Tran-Thanh,

Danh Tran-Thanh

Département de Pathologie, Centre hospitalier de l’Université de Montréal, University of Montréal, Montréal, Canada

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Maroie Barkati,

Maroie Barkati

Département de Radio-oncologie, Centre hospitalier de l’Université de Montréal, Montréal, Canada

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Annick Pina,

Annick Pina

Département d’Obstétrique et Gynécologie, Centre hospitalier de l’Université de Montréal, Montréal, Canada

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Vincent Quoc-Huy Trinh,

Vincent Quoc-Huy Trinh

orcid.org/0000-0002-3267-2843

Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA

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Kurosh Rahimi,

Corresponding Author

Kurosh Rahimi

[email protected]

Département de Pathologie, Centre hospitalier de l’Université de Montréal, University of Montréal, Montréal, Canada

Département de Pathologie et de Biologie Cellulaire, Université de Montréal, Montréal, Canada

Address for correspondence: K Rahimi, Gynecological Pathology, University of Montreal, Centre hospitalier de l’université de Montréal (CHUM), 1050 Rue Sanguinet, Montréal, H2X 0C1, Québec, Canada. e-mail: [email protected]

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Simon F Roy,

Simon F Roy

orcid.org/0000-0002-5444-0349

Département de Pathologie, Centre hospitalier de l’Université de Montréal, University of Montréal, Montréal, Canada

Département de Pathologie et de Biologie Cellulaire, Université de Montréal, Montréal, Canada

Search for more papers by this author

Jahg Wong,

Jahg Wong

Département de Pathologie, Centre hospitalier de l’Université de Montréal, University of Montréal, Montréal, Canada

Département de Pathologie et de Biologie Cellulaire, Université de Montréal, Montréal, Canada

Search for more papers by this author

Cécile Le Page,

Cécile Le Page

orcid.org/0000-0002-8020-1544

Département de Pathologie, Centre hospitalier de l’Université de Montréal, University of Montréal, Montréal, Canada

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Danh Tran-Thanh,

Danh Tran-Thanh

Département de Pathologie, Centre hospitalier de l’Université de Montréal, University of Montréal, Montréal, Canada

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Maroie Barkati,

Maroie Barkati

Département de Radio-oncologie, Centre hospitalier de l’Université de Montréal, Montréal, Canada

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Annick Pina,

Annick Pina

Département d’Obstétrique et Gynécologie, Centre hospitalier de l’Université de Montréal, Montréal, Canada

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Vincent Quoc-Huy Trinh,

Vincent Quoc-Huy Trinh

orcid.org/0000-0002-3267-2843

Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA

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Kurosh Rahimi,

Corresponding Author

Kurosh Rahimi

[email protected]

Département de Pathologie, Centre hospitalier de l’Université de Montréal, University of Montréal, Montréal, Canada

Département de Pathologie et de Biologie Cellulaire, Université de Montréal, Montréal, Canada

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First published: 15 July 2021

https://doi.org/10.1111/his.14451

Citations: 10

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Abstract

Aims

We 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 results

From 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).

Conclusion

Our 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.

Graphical Abstract

Conflicts of interest

The authors declare no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Supporting Information

Filename	Description
his14451-sup-0001-FigS1A.tifTIFF image, 2.6 MB	Figure S1A. Vulvar verruciform lesions of the vulva (VAAD, DEVIL and vLSC) could be present in either a majority pattern, constituting most of the surface area of the lesion, or as a focal finding in another lesion. For example, this case demonstrates the abrupt transition that could be found from vLSC (left until middle) to VAAD (middle until right), showing how hypergranulosis becomes hypogranulosis, and orthohyperkeratosis becomes parakeratosis. (1A: HE, original magnification ×40).
his14451-sup-0002-FigS1B.tifTIFF image, 4.6 MB	Figure S1B.
his14451-sup-0003-FigS2A.tifTIFF image, 2.3 MB	Figure S2A. Stromal lymphohistiocytic inflammation was observed at the epithelial-stromal interface underneath verruciform lesions of the vulva and its presence was associated with the absence of squamous cell carcinoma during the study period (P = 0.018). Stromal inflammation could be band-like in pattern, such as within these cases diagnosed as VAAD (2A, HPS, original magnification ×40 and 2B: HPS, original magnification ×100).
his14451-sup-0004-FigS2B.tifTIFF image, 2.2 MB	Figure S2B.
his14451-sup-0005-TableS1.docxWord document, 17 KB	Table S1. Pathological factors of VVLs associated with SCC at any time.
his14451-sup-0006-Supinfo.docxWord document, 13.6 KB	Data S1. Histopathological features- definitions.

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

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Citing Literature

Volume79, Issue6

December 2021

Pages 975-988