Recent developments in vulvovaginal pathology

Department of Pathology, Royal Group of Hospitals Trust, Belfast, UK.
Histopathology (Impact Factor: 3.45). 01/2009; 54(2):156-73. DOI: 10.1111/j.1365-2559.2008.03098.x
Source: PubMed


This review discusses recent developments in vulvovaginal pathology. A variety of morphologically bland mesenchymal lesions occur at this site with considerable histological and immunohistochemical overlap. Aggressive angiomyxoma exhibits HMGA2 immunoreactivity in approximately 50% of cases, and this nuclear transcription factor is emerging as a useful and relatively specific marker for aggressive angiomyxoma, although occasional vulvovaginal smooth muscle neoplasms are positive. HMGA2 is useful in the diagnosis of aggressive angiomyxoma and its distinction from mimics, in the evaluation of resection margins and in the assessment of the presence or absence of residual disease in re-excisions. Aggressive angiomyxoma is almost invariably positive with oestrogen and progesterone receptors, and there have been several reports of a dramatic reduction in size following gonadotropin releasing hormone agonist therapy. Recent series of the relatively newly described entities cellular angiofibroma and superficial myofibroblastoma of the lower female genital tract have expanded upon the morphological spectrum of these neoplasms. Recently described mesenchymal lesions at this site include massive oedema and prepubertal vulval fibroma. Gastrointestinal stromal tumours have been described as primary neoplasms in the vagina, and rectovaginal septum and extragastrointestinal stromal tumour should be added to the differential diagnosis of a vulvovaginal mesenchymal lesion. Many mesenchymal lesions in the vulvovaginal region exhibit immunoreactivity with both CD34 and desmin, a somewhat unusual immunophenotype in mesenchymal lesions at other sites. It is now established that there are two distinct types of vulval intraepithelial neoplasia (VIN), most commonly termed classic and differentiated VIN, the former associated with human papillomavirus (HPV) infection. There are two corresponding types of vulval squamous carcinoma with HPV-associated and non-HPV-associated variants, the latter often arising in a vulval dystrophy and associated with p53 mutation. However, in some cases there is clinicopathological overlap between HPV-associated and non-HPV-associated squamous carcinomas, and immunohistochemistry with p16 is more reliable than morphology in predicting the presence of HPV. There have been new developments regarding Paget's disease of the vulva with the identification of markers that are useful in diagnosis and evidence that the neoplastic cells represent a proliferation of adnexal stem cells residing in sebaceous units. The newly described entity vaginal tubulo-squamous polyp typically exhibits immunopositivity with prostatic markers, possibly indicating derivation from displaced periurethral Skene's glands.

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    • "We were interested by usual vulvar intraepithelial neoplasia (VIN) lesions which are HPV-related and commonly resemble persistent anogenital warts that are often multifocal pigmented papular lesions. Usual VIN is characterized by the presence of poorly differentiated or undifferentiated basal cells and highly atypical squamous epithelial cells [3]. The involvement of the entire thickness of the epithelium defines its grade 3 (VIN3), in which high-risk HPV (HR-HPV) types, essentially HPV16, play a direct role in up to 91% of the cases [4]. "
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    ABSTRACT: T-cell responses (proliferation, intracellular cytokine synthesis and IFNγ ELISPOT) against human papillomavirus 16 (HPV16) E2 peptides were tested during 18 months in a longitudinal study in eight women presenting with HPV16-related usual vulvar intraepithelial neoplasia (VIN) and their healthy male partners. In six women, anti-E2 proliferative responses and cytokine production (single IFNγ and/or dual IFNγ/IL2 and/or single IL2) by CD4+ T lymphocytes became detectable after treating and healing of the usual VIN. In the women presenting with persistent lesions despite therapy, no proliferation was observed. Anti-E2 proliferative responses were also observed with dual IFNγ/IL2 production by CD4+ T-cells in six male partners who did not exhibit any genital HPV-related diseases. Ex vivo IFNγ ELISPOT showed numerous effector T-cells producing IFNγ after stimulation by a dominant E2 peptide in all men and women. Since the E2 protein is absent from the viral particles but is required for viral DNA replication, these results suggest a recent infection with replicative HPV16 in male partners. The presence of polyfunctional anti-E2 T-cell responses in the blood of asymptomatic men unambiguously establishes HPV infection even without detectable lesions. These results, despite the small size of the studied group, provide an argument in favor of prophylactic HPV vaccination of young men in order to prevent HPV16 infection and viral transmission from men to women.
    PLoS ONE 05/2012; 7(5):e36651. DOI:10.1371/journal.pone.0036651 · 3.23 Impact Factor
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    • "The recent reclassification of VIN terminology by the International Society for the Study of Vulvovaginal Diseases [9] replaced the previous three subclassifications of VIN 1 to 3 and introduced the subdivision of VIN into the (a) usual type, comprising the high-grade lesions 2 and 3 occurring mainly in younger women, and the (b) differentiated type, encompassing the previous type of differentiated VIN 3. It is of interest that this reclassification has greatly facilitated the matching of the two putative discrete pathogenetic pathways leading to the development of VSCC; the usual type requiring the presence of HPV infection, mediated by oncogenic subtypes such as 16, 18, 31, and 33, whereas the differentiated type, mostly developing in older women on a background of lichen sclerosis or squamous cell hyperplasia, does not [10]. Thus, the two resulting pathogenetic types of VSCC, which can be considered to arise from the two corresponding pathways, are the basaloid or warty type, derived from the usual VIN pathway through a long transition period, occurring in younger women and associated with HPV [11], and the keratinizing type, originating through the differentiated VIN pathway [6] through a rapid progression , occurring in older women not linked with HPV infection [3]. "
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    ABSTRACT: The molecular mechanisms of vulvar squamous cell carcinoma (VSCC) remain obscure. To this end, we investigated systematically for the first time the expression profile of VSCC using the microarray technology, in a total of 11 snap-frozen samples, from five VSCC patients covering early and advanced stages of VSCC undergoing radical surgery and from six matched healthy controls. All experiments were performed using Affymetrix Human Genome U133A 2.0 oligonucleotide arrays, covering 22,277 probe sets. Genes were filtered and analyzed using analysis of variance, t test, fold-change calculations, and unsupervised hierarchical cluster analysis. Further processing included functional analysis and overrepresentation calculations based on Gene Ontology, Database for Annotation, Visualization, and Integrated Discovery, and Ingenuity Pathway Analysis. The molecular phenotypes of VSCC patients exhibited significant and discrete transcriptional differences from the healthy controls, whereas principal component analysis documented that this separation is mediated by a consistent set of gene expression differences. We detected 1077 genes (306 upregulated and 771 downregulated) that were differentially expressed between VSCC patients and healthy controls by at least twofold (P < .01), whereas a novel subset of patients was revealed displaying a distinct pattern of 125 upregulated genes involved in multiple cellular processes. Functional analysis of the 1077 genes documented their involvement in more than 50 signaling pathways, such as PTEN, oncostatin M, and extracellular signal-regulated kinase signaling, affecting extracellular matrix remodeling and invasion. Comparison of our data set with those of the single VIN study revealed that the two entities share a limited number of genes and display unique features.
    Translational oncology 10/2011; 4(5):301-13. DOI:10.1593/tlo.11148 · 2.88 Impact Factor
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    • "A recent review of vulval intraepithelial neoplasia histopathology recommended 75 replacement of the vulval intraepithelial neoplasia 1/2/3 subdivisions with two 76 categories reflecting the putative aetiology of the disease: usual vulval intraepithelial 77 neoplasia (HPV-associated); and differentiated vulval intraepithelial neoplasia 78 (associated with lichen sclerosis) [Sideri et al., 2005]. However, the existence of 79 differentiated vulval intraepithelial neoplasia is disputed, and in practice this diagnosis 80 is rarely made [McCluggage, 2009]. "
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    ABSTRACT: Vulval intraepithelial neoplasia is a precursor of vulval carcinoma, and is frequently associated with human papillomavirus (HPV) infection. Estimates of HPV prevalence in vulval intraepithelial neoplasia vary widely in the UK. The objective of this study was to assess HPV infection in a sample of women with vulval intraepithelial neoplasia, confirmed histologically, and determine the proportion of disease associated with HPV types targeted by prophylactic HPV vaccines. HPV infection was assessed in biopsies from 59 patients using the Greiner Bio-One PapilloCheck® DNA chip assay. Valid results were obtained for 54 cases. HPV infection was present in 43 of the 54 cases (79.6%: 95% CI 67.1-88.2%). The most common HPV types were HPV 16 (33/54: 61.1%), HPV 33 (8/54: 14.8%), HPV 6 (5/54: 9.3%), and HPV 42 (3/54: 5.6%). The mean age of HPV positive women was significantly less than the mean age of HPV negative women. This is the largest UK series of vulval intraepithelial neoplasia in which HPV type has been investigated, and 34/54 (63.0%, 95% CI: 49.6-78.6%) cases were associated with HPV 16/18, which are targeted by current prophylactic HPV vaccines.
    Journal of Medical Virology 08/2011; 83(8):1358-61. DOI:10.1002/jmv.22107 · 2.35 Impact Factor
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