Differentiated vulvar intraepithelial neoplasia is often found in lesions, previously diagnosed as lichen sclerosus, which have progressed to vulvar squamous cell carcinoma

Abstract

Lichen sclerosus is considered to be the precursor lesion of vulvar squamous cell carcinoma, of which only 2-5% progress to squamous cell carcinoma. Differentiated vulvar intraepithelial neoplasia (VIN) has been proposed to be the direct precursor lesion, but this is a recently recognized, and a difficult to diagnose, entity, which may easily be mistaken for a benign dermatosis. The aim of this study was to test the hypothesis that of all lesions that have been diagnosed as lichen sclerosus in the past, a part might currently be diagnosed as differentiated VIN, and to identify histopathological differences between lichen sclerosus lesions with and without progression to vulvar squamous cell carcinoma. All lichen sclerosus slides were revised by two expert gynecopathologists and histopathological characteristics were documented. After revision of lichen sclerosus biopsies without progression (n ¼ 61), 58 were reclassified as lichen sclerosus. Revision of lichen sclerosus biopsies with progression yielded concordant diagnoses in 18 of 60 cases (30%). Of 60 lesions, 25 (42%) were reclassified as differentiated VIN. The median time from differentiated VIN to vulvar squamous cell carcinoma was shorter (28 months) than that from lichen sclerosus to vulvar squamous cell carcinoma (84 months) (Po0.001). Lichen sclerosus that progressed to squamous cell carcinoma, but did not meet the criteria for differentiated VIN, more often showed parakeratosis (P ¼ 0.004), dyskeratosis (Po0.001), hyperplasia (P ¼ 0.048) and basal cellular atypia (P ¼ 0.009) compared with lichen sclerosus without progression. In conclusion, differentiated VIN diagnosis has been frequently missed and is associated with rapid progression to squamous cell carcinoma. Patients with lichen sclerosus with dyskeratosis and parakeratosis, hyperplasia and/or basal cellular atypia should be kept under close surveillance as these lesions also tend to progress to squamous cell carcinoma.

Interobserver variability and the effect of education in the histopathological diagnosis of differentiated vulvar intraepithelial neoplasia

“…DVIN is often found directly adjacent to squamous cell carcinoma and is characterized by a thickened epithelium that is typically associated with elongation and anastomosis of rete ridges ( Figure 1a). 4 (Figure 1d) may be seen mainly in the lower layers. 4 The most superficial layers show normal maturation without atypical cells, although dyskeratosis may be present above the (para)basal layers with cells that have vesicular nuclei, prominent nucleoli and abundant eosinophilic cytoplasm.…”

“…Differentiated VIN (DVIN), which is an entity that has no relation with HPV, is believed to be the precursor lesion associated with this type of vulvar squamous cell carcinoma. [3][4][5] Until 2003, a three grade system for premalignant VIN (VIN grades 1-3, Table 1) was used. As clinicopathological data did not appear to support the concept of a continuous spectrum of VIN lesions leading to vulvar carcinoma that does exist for cervical intraepithelial neoplasia and cervical carcinoma, [6][7][8] this grading system was abolished.…”

Phosphorylated S6 as an immunohistochemical biomarker of vulvar intraepithelial neoplasia

“…This finding suggests the possibility that p-S6 staining detects premalignant change in lichen sclerosus lesions before the appearance of morphologic atypia. As lichen sclerosus may sometimes precede 11,13,14 and be genetically linked 8 to differentiated VIN, p-S6 may detect premalignant change before the appearance of morphologically detectable VIN.…”

“…[11][12][13][14] In our survey of the 16 VINs described above, we found p-S6-positive basal cells in a region of lichen sclerosus without morphologic atypia adjacent to a differentiated VIN and invasive carcinoma in case 5 (data not shown). This observation prompted us to examine an additional case of lichen sclerosus associated with carcinoma plus a set of 12 vulvar biopsies that had been classified histopathologically as nondysplastic and were not associated with apparent VIN or carcinoma at the time of biopsy.…”

“…Vulvar carcinoma may also arise within nondysplastic or minimally dysplastic lichen sclerosus lesions, so may go unheralded until invasive carcinoma has developed. [11][12][13][14] The incidence of VIN has increased 44-fold since the early 1970s. 15 Whereas classic VIN and its associated carcinoma are expected to decrease substantially in the future as the result of vaccination against high-risk papillomaviruses, 16 the incidence of differentiated VIN and its associated carcinoma is rising, likely owing to the increasing lifespan of our population.…”