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

Nieuwenhof, H.P. van de; Bulten, Johan; Hollema, Harrie; Dommerholt, Rianne G; Massuger, Leon F.A.G.; Zee, Ate G.J. van der; Hullu, Joanne A. de; Kempen, Léon C van

doi:10.1038/modpathol.2010.192

Cited by 141 publications

(98 citation statements)

References 28 publications

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“…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.…”

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confidence: 99%

“…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.…”

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

et al. 2013

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No published data concerning intraobserver and interobserver variability in the histopathological diagnosis of differentiated vulvar intraepithelial neoplasia (DVIN) are available, although it is widely accepted to be a subtle and difficult histopathological diagnosis. In this study, the reproducibility of the histopathological diagnosis of DVIN is evaluated. Furthermore, we investigated the possible improvement of the reproducibility after providing guidelines with histological characteristics and tried to identify histological characteristics that are most important in the recognition of DVIN. A total number of 34 hematoxylin and eosin-stained slides were included in this study and were analyzed by six pathologists each with a different level of education. Slides were reviewed before and after studying a guideline with histological characteristics of DVIN. Kappa statistics were used to compare the interobserver variability. Pathologists with a substantial agreement were asked to rank items by usefulness in the recognition of DVIN. The interobserver agreement during the first session varied between 0.08 and 0.54, which slightly increased during the second session toward an agreement between À 0.01 and 0.75. Pathologists specialized in gynecopathology reached a substantial agreement (kappa 0.75). The top five of criteria indicated to be the most useful in the diagnosis of DVIN included: atypical mitosis in the basal layer, basal cellular atypia, dyskeratosis, prominent nucleoli and elongation and anastomosis of rete ridges. In conclusion, the histopathological diagnosis of DVIN is difficult, which is expressed by low interobserver agreement. Only in experienced pathologists with training in gynecopathology, kappa values reached a substantial agreement after providing strict guidelines. Therefore, it should be considered that specimens with an unclear diagnosis and/or clinical suspicion for DVIN should be revised by a pathologist specialized in gynecopathology. When adhering to suggested criteria the diagnosis of DVIN can be made easier.

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

et al. 2013

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“…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.…”

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confidence: 99%

“…[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.…”

Section: P-s6 In Nondysplastic Vulvar Epithelial Lesionsmentioning

confidence: 98%

“…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.…”

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Phosphorylated S6 as an immunohistochemical biomarker of vulvar intraepithelial neoplasia

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As life expectancy lengthens, cases of non-viral-associated vulvar squamous cell carcinoma and its precursor lesion, so-called differentiated vulvar intraepithelial neoplasia (VIN), continue to increase in frequency. Differentiated VIN often is difficult to recognize and failure to detect it before invasion results in morbidity and mortality. Thus, identification of a reliable biomarker for this type of lesion would be of great clinical benefit. Our recent studies have identified activation (ser235/236 phosphorylation) of ribosomal protein S6 (p-S6) in basal epithelial cells as an event that precedes and accompanies laminin c 2 overexpression in most preinvasive oral dysplasias. To test this as a potential biomarker of vulvar dysplasia, we immunostained seven differentiated VINs and nine papillomavirusrelated 'classic' VINs, most of which were associated with carcinoma, for p-S6. All carcinomas, all differentiated VINs, and most classic VINs contained regions of p-S6 staining in the basal layer, whereas basal and parabasal cells of normal vulvar epithelium and hyperplastic and inflamed lesions lacking cellular atypia were p-S6 negative. Laminin c 2 was expressed in a subset of VINs, always occurring within basal p-S6 positive regions, as we had found previously for oral dysplasias. Lichen sclerosus is considered a potential precursor of vulvar carcinoma. Two lichen sclerosus lesions of patients with a concurrent carcinoma and one of six lichen sclerosus lesions without atypia or known concurrent carcinoma were basal p-S6 positive. In summary, there is a distinct difference in p-S6 basal cell layer staining between benign and neoplastic vulvar squamous epithelium, with consistent staining of differentiated VIN and of some lichen sclerosus lesions. These results support further studies to assess the potential of p-S6 as a biomarker to identify vulvar lesions at risk of progressing to invasive cancer.

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Vulvar Dermatoses as a Cause of Dyspareunia

Burrows

Goldstein²,

Moawad

et al. 2020

Female Sexual Pain Disorders

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

Cited by 141 publications

References 28 publications

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

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

Phosphorylated S6 as an immunohistochemical biomarker of vulvar intraepithelial neoplasia

Vulvar Dermatoses as a Cause of Dyspareunia

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