Differentiated VIN (dVIN) is a precursor of vulval cancer in which significant atypia is confined to the basal layers of the epithelium. It was first described as an intraepithelial carcinoma in 1961 [1] and later termed ‘differentiated’ as the upper epithelium continues to differentiate in an orderly manner. As discussed previously, it is recognised that there are two distinct pathways in the development of vulval squamous cell carcinoma (SCC) [2, 3]. The precursor lesion in the HPV‐independent pathway is predominantly dVIN, and it carries a higher risk of invasive malignancy than the HPV‐associated type. It is the type that is seen on a background of a chronic inflammatory dermatosis such as lichen sclerosus (LS) and is associated with keratinising SCC. It remains a separate category in the updated ISSVD terminology for squamous intraepithelial lesions [4].

Epidemiology

It usually occurs in older women between 60 and 80 years of age but has been reported in younger women. In a series of 21 women under the age of 40, 3 of 21 had dVIN [5].

Pathophysiology

The pathophysiology of the pathway to vulval cancer by HPV‐independent means is not well worked out. The scarring and trauma to the epithelium in LS may be involved, and if genetic mutations start to progress, malignancy develops [6]. In addition to the changes in p53 (see below), mutations in NOTCH1 [7] HRAS, CDKN2A, and PIK3CA have been found [8]. Mutations in NOTCH1 result in loss of tumour suppression function, and HRAS is an oncogene regulating cell proliferation.

Histological features

Unlike the HPV‐related high‐grade squamous intraepithelial lesion (HSIL), differentiated VIN shows well‐differentiated squamous cells with atypia confined to the basal layers and only a slight disturbance of maturation above this. The diagnostic criteria for dVIN were put initially put forward in 2000 [9]. The main features are parakeratosis, a thickened epidermis, elongated rete ridges, abnormal keratinocytes, and cytological atypia in the basal layer (Figure 41.1). Keratin pearl formation in the rete ridges is sometimes seen. Involvement of the appendages is rare. The epidermis above the basal layers usually shows normal differentiation, and this can be difficult to distinguish from the reactive and reparative basal changes seen in inflammatory disease. There are usually prominent slender elongations of the rete pegs resembling pseudo‐epitheliomatous hyperplasia, but the elongations may be bulbous or absent, with minimal simple acanthosis. There is usually a dense chronic inflammatory cell infiltrate in the adjacent dermis or stroma, sometimes containing eosinophils [9].

The basal nuclear atypia must be present to make the diagnosis of dVIN. There are enlarged hyperchromatic and irregular nuclei and prominent nucleoli. This nuclear atypia may just be seen in the basal layers. Mitotic figures are present but are usually confined to the basal layer or adjacent abnormal keratinocytes, and they may be atypical. The premature maturation of the epithelium exhibits marked cytoplasmic eosinophilia. Differentiated VIN may be non‐keratinising or keratinising, and sub‐types are described [10].

The histological changes can be subtle and so it is not difficult to overlook them, especially if the diagnosis is not suggested by the clinician. When biopsies previously diagnosed as LS in patients who had gone on to develop an SCC were reviewed, 42% were found to show features of dVIN [11].

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