Squamous precursor lesions of the vulva: current classification and diagnostic challenges

Abstract

Summary Growing evidence has established two major types of vulvar intraepithelial neoplasia (VIN), which correspond to two distinct oncogenic pathways to vulvar squamous cell carcinoma (VSCC). While the incidence of VSCC has remained relatively stable over the last three decades, the incidence of VIN has increased. VIN of usual type (uVIN) is human papillomavirus (HPV)-driven, affects younger women and is a multicentric disease. In contrast, VIN of differentiated type (dVIN) occurs in post-menopausal women and develops independent of HPV infection. dVIN often arises in a background of lichen sclerosus and chronic inflammatory dermatoses. Although isolated dVIN is significantly less common than uVIN, dVIN bears a greater risk for malignant transformation to VSCC and progresses over a shorter time interval. On histological examination, uVIN displays conspicuous architectural and cytological abnormalities, while the morphological features that characterise dVIN are much more subtle and raise a wide differential diagnosis. On the molecular level, dVIN is characterised by a higher number of somatic mutations, particularly in TP53. Here we review the classification, epidemiology, clinical features, histomorphology, ancillary markers and molecular genetics of both types of VIN, and discuss the morphological challenges faced by pathologists in interpreting these lesions.

Clinical and molecular classification of vulvar squamous pre-cancers

“…Up to 40% of vulvar squamous cell carcinoma may arise via this HPV-dependent route. HPV16 is the most prevalent sub-type in these tumors, followed by HPV18 and HPV33 7. HPV-associated vulvar squamous cancer typically affects younger women, aged <65 years, and its incidence is increasing owing to the rising incidence of HSIL in young women and the increasing prevalence of infection with high-risk HPV strains 20.…”

“…The introduction of an HPV vaccination program in many countries is expected to result in a marked decline in the incidence of HSIL 6. In contrast, a relative increase in dVIN is expected due to an aging population and the predicted decrease in HSIL 7. Furthermore, the risk of progression from dVIN to invasive disease increases with advancing age 8.…”

Superficially invasive stage IA vulvar squamous cell carcinoma—therapy and prognosis

“…Figure 1 displays the current theory regarding vulvar tumorigenesis 7. Although isolated dVIN is significantly less common than uVIN, it bears a greater risk for malignant transformation to VSCC8 (32.9% vs 5.7%) over a shortened time-frame (22.8 vs 41.4 months) than uVIN 9. dVIN (5% of PVL) usually develops in older women, and is often accompanied by atrophical or chronic inflammatory skin diseases such as LS as a major risk factor (4–5-fold) 8 10.…”

“…dVIN is not linked to HPV but p53 inactivation and/or a higher number of somatic mutations (molecular TP53, EGFR, CDK2NA, HRAS/KRAS, PIK3CA/PTEN/PPP2R1A, microsatellite instability) (Figure 1). 8 …”

Optical coherence tomography in gynecology: a narrative review

“…42 Although cervical tissue is mucosa, while vulvar tissue is skin, due to similar morphologic structure of cervical tissue and vulvar tissue represented by an epidermal layer with an underlying connective tissue layer, the approaches for employment OCT in evaluation of vulva pathologies are similar to that employed for cervix. In the pioneering paper in OCT inspection of vulva, 35 the OCT images of vulva with Paget's disease were reported and compared with corresponding histology images.…”