Vulva & vagina

• Old: simplex 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%)

• Background of chronic inflammatory dermatoses, lichen sclerosus, lichen simplex chronicus (J Low Genit Tract Dis 2016;20:180)

• Unifocal, gray-white papules or plaques

• Difficult to diagnose in punch biopsies alone; overlapping histological features with other common vulvar lesions, especially lichen simplex

• More likely to progress to invasive carcinoma (32%) than usual vulvar intraepithelial neoplasia; shorter latency to become invasive (Eur J Cancer 2009;45:851, Int J Gynecol Cancer 2009;19:741)
• VAAD may be a possible precursor of verrucous carcinoma

• Conservative excision, careful follow up (Best Pract Res Clin Obstet Gynaecol 2014;28:1051)

Contributed by Matthias Choschzick, M.D.

• p53
  • Mutation type pattern in dVIN: basal overexpression, diffuse overexpression, absent (null) or cytoplasmic (Mod Pathol 2020;33:1595, Mod Pathol 2023;36:100145)
  • Wild type in DEVIL and VAAD
  • Interpretation may be difficult in small biopsies
• Ki67 confined to basal cell layers
• Retained CK17 expression (Int J Gynecol Pathol 2017;36:273)

• Loss of GATA3 expression (Mod Pathol 2018;31:1131)
• p16 negative or patchy (Histopathology 2005;46:718)
• HPV

• HPV ISH negative
• Mutations in TP53 (Mod Pathol 2010;23:404)

• Condyloma:
  • Mild nuclear atypia, most commonly superficially
  • HPV related
• Lichen sclerosus:
  • Lacks basal atypia
  • May be concurrent
• Lichen simplex chronicus:
  • Lacks basal atypia
  • p53 wild type
• Hypertrophic lichen planus:
  • Band-like chronic inflammation
  • Lacks basal atypia

• Clement: Atlas of Gynecologic Surgical Pathology, 4th Edition, 2019, Surg Pathol Clin 2019;12:249

The image 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. EGFR
3. HRAS
4. PIK3CA
5. TP53

E. TP53 is most frequently mutated and probably most relevant for pathogenesis. Answer A is incorrect because it is not mutated. Answer B is incorrect because it is infrequently amplified. Answer C is incorrect because it is frequently mutated but probably not the most relevant. Answer D is incorrect because it is frequently mutated but mostly in HPV associated lesions.

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Reference: HPV independent VIN-vulva

Which immunohistochemical stain shows an aberrant pattern in differentiated vulvar intraepithelial neoplasia?

1. CK18
2. Ki67
3. p16
4. p53
5. SOX10

D. p53 frequently shows a mutation type aberrant staining pattern. Answer A is incorrect because CK18 is not overexpressed in differentiated vulvar intraepithelial neoplasia (dVIN), differentiated exophytic vulvar intraepithelial lesion (DEVIL) or vulvar acanthosis with altered differentiation (VAAD). Answer B is incorrect because Ki67 shows only a variable growth fraction as in many other lesions. Answer C is incorrect because p16 is overexpressed in HPV associated VIN. Answer E is incorrect because it is not aberrantly expressed in dVIN.

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Reference: HPV independent VIN-vulva