Vulva, vagina & female urethra

Squamous carcinoma and precursor lesions

HPV independent SIL

Editorial Board Member: Jennifer A. Bennett, M.D.
Editor-in-Chief: Debra L. Zynger, M.D.
Matthias Choschzick, M.D.

Last author update: 6 January 2021
Last staff update: 6 January 2021

Copyright: 2003-2022,, Inc.

PubMed Search: dVIN

Matthias Choschzick, M.D.
Page views in 2021: 9,382
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Cite this page: Choschzick M. HPV independent SIL. website. Accessed August 13th, 2022.
Definition / general
  • Differentiated vulvar intraepithelial neoplasia (dVIN) is the putative precursor lesion of HPV independent vulvar squamous cell carcinoma
    • Subtypes: differentiated exophytic vulvar intraepithelial lesion (DEVIL) and vulvar acanthosis with altered differentiation (VAAD) with currently unknown prognosis but potential to develop carcinoma
Essential features
  • Highly differentiated with overlapping histological features to benign vulvar lesions
  • Currently, there are no reliable immunohistochemical or molecular markers to establish the diagnosis
  • Differentiated vulvar intraepithelial neoplasia is an aggressive lesion with higher potential to become invasive than HPV associated vulvar intraepithelial neoplasia (usual type)
  • Old: simplex vulvar intraepithelial neoplasia
ICD coding
  • ICD-10: D07.1 - carcinoma in situ of vulva
  • ICD-O: 8071/2 - differentiated type vulvar intraepithelial neoplasia
  • Postmenopausal women, sixth to eighth decade, 2 - 29% of all vulvar intraepithelial neoplasia (Pathology 2016;48:291)
  • Labia minora, commonly found adjacent to invasive squamous cell carcinoma (70%)
Clinical features
  • Unifocal gray-white papules or plaques
  • Difficult to diagnose in punch biopsies alone; overlapping histological features with other common vulvar lesions, especially lichen simplex
Prognostic factors
Case reports
Microscopic (histologic) description
  • Mild to moderate atypical cells in basal and parabasal layers with hyperchromatic nuclei, lacks full thickness atypia
  • Enlarged squamous cells with eosinophilic cytoplasm, vesicular nuclei and prominent nucleoli, prominent intercellular bridges
  • Acanthosis, parakeratosis, elongation and anastomosis of rete ridges (Histopathology 2020;76:128)
  • Rare basaloid differentiation with atypical cells in upper cell layers (Am J Surg Pathol 2009;33:1659)
  • DEVIL: exophytic verruciform lesion with acanthosis; no basal atypia, no koilocytosis (Mod Pathol 2017;30:448)
  • VAAD: verruciform acanthosis, parakeratosis, absence of nuclear atypia, cytoplasmaic pallor cells in upper layers (Am J Surg Pathol 2004;28:638)
Microscopic (histologic) images

Contributed by Matthias Choschzick, M.D.

Differentiated VIN


Positive stains
Negative stains
Molecular / cytogenetics description
Sample pathology report
  • Labium majora, biopsy:
    • Differentiated vulvar intraepithelial neoplasia (see comment)
    • Comment: p16 is negative and p53 is overexpressed (aberrant pattern).
Differential diagnosis
Board review style question #1

The picture above shows an example of HPV independent squamous cell carcinoma of the vulva in association with differentiated vulvar intraepithelial neoplasia. Which gene is most relevant for the pathogenesis of this subgroup of vulvar cancer?

  1. BRCA1
  2. CDKN2A
  3. HRAS
  4. PIK3CA
  5. TP53
Board review style answer #1
Board review style question #2
Which immunohistochemical stain shows an aberrant (mutated) pattern in differentiated vulvar intraepithelial neoplasia?

  1. CK17
  2. Ki67
  3. p16
  4. p53
  5. SOX2
Board review style answer #2
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