scholarly journals Evaluation of Immunohistochemical Markers, CK17 and SOX2, as Adjuncts to p53 for the Diagnosis of Differentiated Vulvar Intraepithelial Neoplasia (dVIN)

2021 ◽  
Vol 14 (4) ◽  
pp. 324
Author(s):  
Shatavisha Dasgupta ◽  
Senada Koljenović ◽  
Thierry P. P. van den Bosch ◽  
Sigrid M. A. Swagemakers ◽  
Nick M. A. van der Hoeven ◽  
...  
Keyword(s):  
Expression Patterns ◽  
Intraepithelial Neoplasia ◽  
Histological Diagnosis ◽  
Vulvar Intraepithelial Neoplasia ◽  
Wild Type ◽  
Median Percentage ◽  
P53 Expression ◽  
Immunohistochemical Markers ◽  
Intraepithelial Lesion ◽  
Ihc Markers

Histological diagnosis of differentiated vulvar intraepithelial neoplasia (dVIN), the precursor of human papillomavirus (HPV)-independent vulvar squamous cell carcinoma (VSCC), can be challenging, as features of dVIN may mimic those of non-dysplastic dermatoses. To aid the diagnosis, p53-immunohistochemistry (IHC) is commonly used, and mutant expression patterns are used to support a histological diagnosis of dVIN. However, a proportion of dVIN can show wild-type p53-expression, which is characteristic of non-dysplastic dermatoses. Furthermore, recent research has identified a novel precursor of HPV-independent VSCC—the p53-wild-type differentiated exophytic vulvar intraepithelial lesion (de-VIL). Currently, there are no established diagnostic IHC-markers for p53-wild-type dVIN or de-VIL. We evaluated IHC-markers, cytokeratin 17 (CK17), and SRY-box 2 (SOX2), as diagnostic adjuncts for dVIN. For this, IHC-expression of CK17, SOX2, and p53 was studied in dVIN (n = 56), de-VIL (n = 8), and non-dysplastic vulvar tissues (n = 46). For CK17 and SOX2, the percentage of cells showing expression, and the intensity and distribution of expression were recorded. We also performed next generation targeted sequencing (NGTS) on a subset of dVIN (n = 8) and de-VIL (n = 8). With p53-IHC, 74% of dVIN showed mutant patterns and 26% showed wild-type expression. Median percentage of cells expressing CK17 or SOX2 was significantly higher in dVIN (p53-mutant or p53-wild-type) and de-VIL than in non-dysplastic tissues (p < 0.01). Diffuse, moderate-to-strong, full epithelial expression of CK17 or SOX2 was highly specific for dVIN and de-VIL. With NGTS, TP53 mutations were detected in both dVIN and de-VIL. We infer that immunohistochemical markers CK17 and SOX2, when used along with p53, may help support the histological diagnosis of dVIN.

The main differences between vulvar intraepithelial neoplasia and vulvar intraepithelial lesion

2020 ◽  
Vol 11 (5) ◽  
Author(s):  
Vivian de Oliveira Rodrigues Brum ◽  
Denise Gasparetti Drumond ◽  
Neila Maria de Góis Speck ◽  
Gabriel Duque Pannain ◽  
Giovana Moreira Bordim
Keyword(s):  
Vulvar Cancer ◽  
Gynecological Cancer ◽  
Squamous Carcinoma ◽  
Intraepithelial Neoplasia ◽  
Final Diagnosis ◽  
Hpv Infection ◽  
Vulvar Intraepithelial Neoplasia ◽  
Low Grade ◽  
Intraepithelial Lesion ◽  
The Difference

Vulvar cancer is a recurrent subject in gynecological cancer. Vulvar Intraepithelial Neoplasia is known for being a precursor lesion of vulvar cancer and can be divided in three different subtypes: Low-grade Vulvar Intraepithelial Lesion (vulvar LSI), High-grade Vulvar Intraepithelial Lesion (vulvar HSIL) and Differentiated Vulvar Intraepithelial Neoplasia (dVIN). These subtypes differ in several aspects, and this article aims to present those differences in order to facilitate its treatment and the final diagnosis. The HSIL is the most associated with cronic Human Papilloma Virus (HPV) infection and can be related to other environment factors. As for dVIN, it’s more frequent in post-menopausal women with sclerosis lichen and it has a higher rate of progression to vulvar squamous carcinoma. The difference must be made in order to choose what is the best treatment, once there are various modalities, such as simple excision, CO2 ablation and topical application of imiquimod or fluoracil. This differences is also important for the development of measures that seek specific prevention, such as HPV vaccine for the HSIL and the proper treatment of vulvar conditions for the dVIN.

The Positive Predictive Value of High-Grade Squamous Intraepithelial Lesion on Cytology for the Histological Diagnosis of Cervical Intraepithelial Neoplasia 2 or Higher: A Systematic Review

2019 ◽  
Vol 63 (3) ◽  
pp. 206-214 ◽  
Author(s):  
Nina Karia ◽  
Alison Van Loon ◽  
Cindy Simoens ◽  
Ina Benoy ◽  
Johannes Bogers
Keyword(s):  
Systematic Review ◽  
Cervical Cancer ◽  
Positive Predictive Value ◽  
Cervical Intraepithelial Neoplasia ◽  
Predictive Value ◽  
Intraepithelial Neoplasia ◽  
Histological Diagnosis ◽  
High Grade ◽  
Cervical Lesions ◽  
Intraepithelial Lesion

Cervical cancer is a major worldwide health problem. Therefore, regular cervical screening in order to make an early diagnosis can help to prevent cervical cancer, through identifying and treating preinvasive cervical lesions. The aim of this review is to evaluate the correlation between the cytological screening result and the final gold standard histological outcome in the diagnosis of cervical lesions. More specifically, the correlation between high-grade intraepithelial lesion (HSIL) on cytology and histological cervical intraepithelial neoplasia grade 2 or higher (CIN2+) was intended, by calculating the positive predictive value (PPV). PPV is an important value from a clinical point of view. An electronic search was carried out in the electronic databases MEDLINE (through PubMed) and the Cochrane Library (last searched beginning of December 2017), supplemented with the related article feature in PubMed and snowballing. Article selection (predefined inclusion and exclusion criteria) and data extraction were evaluated by two independent reviewers (N.K. and A.V.L.). After identifying 1,146 articles, 27 articles were finally included in this systematic review, representing 28,783 cytological HSIL diagnoses in total. The PPV of HSIL was 77.5% (range: 45.4–95.2%) for the histological diagnosis of CIN2+ and 55.4% (range: 36.4–67.6%) for the diagnosis of CIN3+. In this systematic review, 77.5% of the HSIL-positive women eventually had a CIN2+ diagnosis. The diagnostic value of a cytological HSIL result (conventional or liquid-based cytology) in the diagnosis of CIN2+ lesions is good, but a combination of tests could raise this value.

scholarly journals A Precursor to HPV-Independent VSCC : Differentiated Exophytic Vulvar Intraepithelial Lesion - A Case Report

2020 ◽  
Author(s):  
Weiping Zheng ◽  
Minhua Li
Keyword(s):  
Malignant Disease ◽  
Intraepithelial Neoplasia ◽  
Hpv Infection ◽  
Vulvar Intraepithelial Neoplasia ◽  
Sufficient Evidence ◽  
Small Lesion ◽  
Precursor Lesions ◽  
Case Presentation ◽  
The Past ◽  
Intraepithelial Lesion

Abstract Background: Vulvar cancer is a relatively rare gynecologic malignant disease. The majority of these tumors are vulvar squamous cell carcinoma (VSCC). There are two distinct aetiopathogenic pathways leading to VSCC: human papillomavirus (HPV)-dependent and HPV-independent. The precursor lesions of HPV-independent VSCC include differentiated vulvar intraepithelial neoplasia(VIN), vulvar acanthosis with altered differentiation(VAAD) and differentiated exophytic vulvar intraepithelial lesion(DE-VIL) . To date, the report of DE-VIL has not been found after this term was proposed in 2017. So it usually has been under-recognised by pathologists in the past owing to the incidence of DE-VIL is relatively small.Case presentation: Here, we report a typical case of DE-VIL, which exhibits the absence of HPV infection and mutations in TP53. Interesting, a small lesion showed similar morphologic feature to HSIL nearby the lesion of DE-VIL.However, it showed same immunochemical patterns with DE-VIL. To date, no other study has reported this phenomenon. Whether it is a rare subtype of DE-VIL or only a accompanying status is still unclear.Conclusions: As the precursor lesions of HPV-independent VSCC, DE-VIL was too difficult to diagnosis due to the lack of sufficient evidence. Therefore, we should pay more and more attention for DE-VIL.

p53 and bcl-2 proteins as prognostic markers in human papillomavirus-associated cervical lesions.

1996 ◽  
Vol 14 (7) ◽  
pp. 2120-2130 ◽  
Author(s):  
K Kurvinen ◽  
K Syrjänen ◽  
S Syrjänen
Keyword(s):  
Human Papillomavirus ◽  
Clinical Course ◽  
Expression Patterns ◽  
Low Grade ◽  
Cervical Lesions ◽  
P53 Expression ◽  
Associated Lesions ◽  
Intraepithelial Lesion ◽  
Epithelial Layers ◽  
High Risk Hpv

PURPOSE The present study was designed to analyze the expression of p53, mdm2, and bcl-2 proteins, with special emphasis on their association with the grade of squamous intraepithelial lesion (SIL), human papillomavirus (HPV) type, and clinical course of the disease. Special attention was focused on the value of individual protein expressions, as well as combined p53/mdm2 and p53/bcl-2 phenotypes, in predicting the clinical course of cervical lesions. MATERIALS AND METHODS The expression of p53, mdm2, and bcl-2 was studied immunohistochemically in a series of 98 HPV lesions of the uterine cervix. RESULTS Frequent expression of p53, mdm2, and bcl-2 proteins was found in the cervical lesions. However, only p53 expression independently provided information for prediction of the clinical course of HPV lesions. High levels of p53 expression were detected in most low-grade SILs (LSILs) (83%) and HPV 6/11/42-associated lesions (86%). In high-grade SILs (HSILs) positive for high-risk HPV types, p53 expression was frequently either totally absent or it only occurred in a few scattered cells. These lesions were closely associated with disease progression. The evaluation of bcl-2 expression alone was not useful for predicting clinical outcome, although abnormal bcl-2 expression in suprabasal layers was more common in HSILs. By contrast, the combined p53/bcl-2 phenotype, which showed a low percentage of p53-positive cells with bcl-2 overexpression in upper epithelial layers, was found to be involved in the progression of HPV lesions. CONCLUSION The present study showed that HPV lesions with a high percentage of cells that express p53 are more likely to regress than those with low or absent p53. p53 thus seems to hold promise as a molecular marker for the risk of the progression of HPV-associated SILs. In addition, the assessment of p53 and bcl-2 expression patterns may be useful to predict the clinical course of cervical HPV lesions.

scholarly journals Histological interpretation of differentiated vulvar intraepithelial neoplasia (dVIN) remains challenging—observations from a bi-national ring-study

2021 ◽  
Author(s):  
Shatavisha Dasgupta ◽  
Elf de Jonge ◽  
Mieke R. Van Bockstal ◽  
Luthy S. M. Wong-Alcala ◽  
Suzanne Wilhelmus ◽  
...  
Keyword(s):  
Expression Patterns ◽  
Intraepithelial Neoplasia ◽  
Observer Agreement ◽  
Vulvar Intraepithelial Neoplasia ◽  
Stained Glass ◽  
Diagnostic Features ◽  
Histological Features ◽  
Pathological Evaluation ◽  
Diagnostic Usefulness ◽  
Cellular Alignment

AbstractDifferentiated vulvar intraepithelial neoplasia (dVIN) is a premalignant lesion that is known to progress rapidly to invasive carcinoma. Accurate histological diagnosis is therefore crucial to allow appropriate treatment. To identify reliable diagnostic features, we evaluated the inter-observer agreement in the histological assessment of dVIN, among a bi-national, multi-institutional group of pathologists. Two investigators from Erasmus MC selected 36 hematoxylin-eosin-stained glass slides of dVIN and no-dysplasia, and prepared a list of 15 histological features of dVIN. Nine participating pathologists (i) diagnosed each slide as dVIN or no-dysplasia, (ii) indicated which features they used for the diagnosis, and (iii) rated these features in terms of their diagnostic usefulness. Diagnoses rendered by > 50% participants were taken as the consensus (gold standard). p53-immunohistochemistry (IHC) was performed for all cases, and the expression patterns were correlated with the consensus diagnoses. Kappa (ĸ)-statistics were computed to measure inter-observer agreements, and concordance of the p53-IHC patterns with the consensus diagnoses. For the diagnosis of dVIN, overall agreement was moderate (ĸ = 0.42), and pair-wise agreements ranged from slight (ĸ = 0.10) to substantial (ĸ = 0.73). Based on the levels of agreement and ratings of usefulness, the most helpful diagnostic features were parakeratosis, cobblestone appearance, chromatin abnormality, angulated nuclei, atypia discernable under × 100, and altered cellular alignment. p53-IHC patterns showed substantial concordance (ĸ = 0.67) with the consensus diagnoses. Histological interpretation of dVIN remains challenging with suboptimal inter-observer agreement. We identified the histological features that may facilitate the diagnosis of dVIN. For cases with a histological suspicion of dVIN, consensus-based pathological evaluation may improve the reliability of the diagnosis.

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