ABSTRACT
The Lower Anogenital Squamous Terminology project and subsequent publication have grouped preinvasive human papillomavirus-associated squamous intraepithelial lesions of the lower genital tract and adjacent skin as a single entity. We are concerned that as a result of this grouping, some of the clinically relevant differences may not be taken into consideration. We describe differences between high-grade squamous intraepithelial lesion of the vulva and cervix (vulvar intraepithelial neoplasia and cervical intraepithelial neoplasia), in embryology (arising from ectoderm vs mesoderm), clinical presentations (symptoms or signs due to many vulvar lesions vs abnormal cytology), examination techniques and diagnosis (clinical examination of potentially widely involved areas vs colposcopy of the transformation zone), natural history, management, and follow-up requirements (long-term clinical assessment vs cytology and human papillomavirus testing). We believe that failure to understand these important differences will lead to errors in management.
Subject(s)
Squamous Intraepithelial Lesions/pathology , Uterine Cervical Dysplasia/pathology , Uterine Cervical Neoplasms/pathology , Vulvar Neoplasms/pathology , Adult , Cervix Uteri/pathology , Colposcopy , Female , Humans , Middle Aged , Squamous Intraepithelial Lesions/surgery , Terminology as Topic , Uterine Cervical Neoplasms/surgery , Vulvar Neoplasms/surgery , Young Adult , Uterine Cervical Dysplasia/surgeryABSTRACT
Importance: Extramammary Paget disease (EMPD) is a rare, highly recurrent cutaneous malignant neoplasm of unclear origin. EMPD arises most commonly on the vulvar and penoscrotal skin. It is not presently known how anatomic subtype of EMPD affects disease presentation and management. Objective: To compare demographic and tumor characteristics and treatment approaches for different EMPD subtypes. Recommendations for diagnosis and treatment are presented. Data Sources: MEDLINE, Embase, Web of Science Core Collection, and Cochrane Reviews CENTRAL from December 1, 1990, to October 24, 2022. Study Selection: Articles were excluded if they were not in English, reported fewer than 3 patients, did not specify information by anatomic subtype, or contained no case-level data. Metastatic cases on presentation were also excluded. Data Extraction and Synthesis: Abstracts of 1295 eligible articles were independently reviewed by 5 coauthors, and 135 articles retained. Reporting was in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. The analysis was cunducted in August 2019 and updated in November 2022. Findings: Most vulvar EMPD cases were asymptomatic, and diagnosis was relatively delayed (mean, 25.1 months). Although most vulvar EMPD cases were intraepidermal (1247/1773 [70.3%]), radical surgeries were still performed in almost one-third of cases. Despite this aggressive surgical approach, 481 of 1423 (34%) recurred, commonly confined to the skin and mucosa (177/198 [89.4%]). By contrast, 152 of 1101 penoscrotal EMPD cases (14%) recurred, but more than one-third of these recurrences were regional or associated with distant metastases (54 of 152 [35.5%]). Perianal EMPD cases recurred in one-third of cases (74/218 [33.9%]), with one-third of these recurrences being regional or associated with distant metastasis (20 of 74 [27.0%]). Perianal EMPD also had the highest rate of invasive disease (50% of cases). Conclusions and Relevance: The diagnosis and treatment of EMPD should differ based on anatomic subtypes. Considerations for updated practice may include less morbid treatments for vulvar EMPD, which is primarily epidermal, and close surveillance for local recurrence in vulvar EMPD and metastatic recurrence in perianal EMPD. Recurrences in penoscrotal subtype were less common, and selective surveillance in this subtype may be considered. Limitations of this study include the lack of replication cohorts and the exclusion of studies that did not stratify outcomes by anatomic subtype.
Subject(s)
Paget Disease, Extramammary , Female , Humans , Paget Disease, Extramammary/diagnosis , Paget Disease, Extramammary/surgery , Paget Disease, Extramammary/pathology , Perineum/pathology , Vulva/pathologyABSTRACT
IMPORTANCE: Extramammary Paget disease (EMPD) is a frequently recurring malignant neoplasm with metastatic potential that presents in older adults on the genital, perianal, and axillary skin. Extramammary Paget disease can precede or occur along with internal malignant neoplasms. OBJECTIVE: To develop recommendations for the care of adults with EMPD. EVIDENCE REVIEW: A systematic review of the literature on EMPD from January 1990 to September 18, 2019, was conducted using MEDLINE, Embase, Web of Science Core Collection, and Cochrane Libraries. Analysis included 483 studies. A multidisciplinary expert panel evaluation of the findings led to the development of clinical care recommendations for EMPD. FINDINGS: The key findings were as follows: (1) Multiple skin biopsies, including those of any nodular areas, are critical for diagnosis. (2) Malignant neoplasm screening appropriate for age and anatomical site should be performed at baseline to distinguish between primary and secondary EMPD. (3) Routine use of sentinel lymph node biopsy or lymph node dissection is not recommended. (4) For intraepidermal EMPD, surgical and nonsurgical treatments may be used depending on patient and tumor characteristics, although cure rates may be superior with surgical approaches. For invasive EMPD, surgical resection with curative intent is preferred. (5) Patients with unresectable intraepidermal EMPD or patients who are medically unable to undergo surgery may receive nonsurgical treatments, including radiotherapy, imiquimod, photodynamic therapy, carbon dioxide laser therapy, or other modalities. (6) Distant metastatic disease may be treated with chemotherapy or individualized targeted approaches. (7) Close follow-up to monitor for recurrence is recommended for at least the first 5 years. CONCLUSIONS AND RELEVANCE: Clinical practice guidelines for EMPD provide guidance regarding recommended diagnostic approaches, differentiation between invasive and noninvasive disease, and use of surgical vs nonsurgical treatments. Prospective registries may further improve our understanding of the natural history of the disease in primary vs secondary EMPD, clarify features of high-risk tumors, and identify superior management approaches.
Subject(s)
Paget Disease, Extramammary , Skin Neoplasms , Aged , Humans , Imiquimod/therapeutic use , Paget Disease, Extramammary/diagnosis , Paget Disease, Extramammary/pathology , Paget Disease, Extramammary/therapy , Prospective Studies , Sentinel Lymph Node Biopsy , Skin Neoplasms/diagnosis , Skin Neoplasms/pathology , Skin Neoplasms/therapyABSTRACT
AIMS: Loss of retinoblastoma protein expression and overexpression of cyclin D1 have been implicated in the development and progression of some cancers. Paget's disease of the vulva (PDV) and Paget's disease of the breast (PDB) are uncommon conditions and the pathogenesis of these diseases is still unclear. The aim was to examine the expression of the retinoblastoma and cyclin D1 proteins in PDV and PDB and to correlate any differences between PDV and PDB, and in the presence or absence of an underlying carcinoma. METHODS AND RESULTS: Seventy-two archival cases of PDV including 10 with invasive disease and 36 cases of PDB were evaluated immunohistochemically for the expression of cyclin D1 and retinoblastoma protein. Forty-four percent (32/72) of cases of PDV showed loss of expression of the retinoblastoma protein, compared with 67% (24/36) of PDB cases. Fifty-nine percent (41/69) of PDV overexpressed cyclin D1. In PDB, 8% (3/34) overexpressed cyclin D1. There were no significant differences in the expression of retinoblastoma and cyclin D1 in PDV cases with or without underlying invasive disease. There were significant differences between the expression of retinoblastoma (P = 0.03) and cyclin D1 (P < 0.001) in PDV compared with PDB. CONCLUSIONS: The differences in the expression of cyclin D1 and retinoblastoma may indicate the differences in the pathogenesis of PDV and PDB.
Subject(s)
Breast Neoplasms/metabolism , Cyclin D1/metabolism , Paget Disease, Extramammary/metabolism , Paget's Disease, Mammary/metabolism , Retinoblastoma Protein/metabolism , Vulvar Neoplasms/metabolism , Chi-Square Distribution , Female , Humans , ImmunohistochemistryABSTRACT
Vulvar cancer continues to rise in incidence. In the absence of screening, attempts to reduce this cancer must focus on recognizing precursor lesions, namely, lichen sclerosus and vulvar intraepithelial neoplasia (VIN). The steep rise in human papillomavirus-repeated VIN will fall after the introduction of vaccination against human papillomavirus; in the meantime, those patients with VIN must be treated and then reviewed carefully and frequently. Lichen sclerosus has a 3% to 5% risk of progressing to vulvar cancer. Recommendations about which patients require referral to and follow-up by specialists/specialist clinics are given.
Subject(s)
Carcinoma/pathology , Vulvar Neoplasms/pathology , Carcinoma/therapy , Carcinoma/virology , Female , Humans , Papillomavirus Infections/pathology , Vulvar Lichen Sclerosus/pathology , Vulvar Neoplasms/therapy , Vulvar Neoplasms/virologyABSTRACT
The growth and metastasis of many cancers is due in part to loss of cell-cell adhesion. E-cadherin, plakoglobin and beta-catenin are important in cell adhesion. Our aim was to examine the presence of these molecules in Paget's disease of the vulva and Paget's disease of the breast, and to correlate any differences in their expression with the presence of invasive disease or an underlying carcinoma. Sixty-three archival cases of Paget's disease of the vulva, including eight associated with invasive disease, and 23 archival cases of Paget's disease of breast, which included 10 cases with ductal carcinoma in situ alone, four cases with both ductal carcinoma in situ and invasive carcinoma, and five cases with underlying invasive carcinoma alone, were analysed immunohistochemically for expression of E-cadherin, plakoglobin and beta-catenin proteins. The respective mRNAs were also detected by in situ hybridisation using digoxigenin-labelled cRNA probes. Seventy-six percent (41/54) of Paget's disease of vulva cases had >50% of Paget cells expressing the E-cadherin protein, compared with 28 % (2/7) of Paget's disease vulva with invasive disease. This result was significant, with a P-value of 0.039. Twenty-five percent (14/55) of the intraepidermal Paget's disease of the vulva cases had >50% of Paget cells expressing the plakoglobin protein, compared with 12% (1/8) of cases of Paget's disease of vulva with invasive disease, and for beta-catenin, 9% (5/55) of the non-invasive Paget's disease of the vulva had >50% of Paget cells expressing beta-catenin, compared with 12% (1/8) of Paget's disease of the vulva cases with invasive disease. Sixty-five percent (15/23) of the Paget's disease of the breast had >50% of Paget cells expressing E-cadherin, and for plakoglobin and beta-catenin it was 17% (4/23) and 28% (6/21), respectively. The results were not significant. The results suggest that reduced expression of E-cadherin may have a role to play in the pathogenesis of invasive Paget's disease of the vulva. Abnormal plakoglobin expression may be involved in the formation of some cases of Paget's of the vulva and the breast.
Subject(s)
Biomarkers, Tumor/metabolism , Breast Neoplasms/metabolism , Cadherins/metabolism , Paget Disease, Extramammary/metabolism , Paget's Disease, Mammary/metabolism , Vulvar Neoplasms/metabolism , Breast Neoplasms/pathology , Cadherins/genetics , Cell Count , DNA, Neoplasm/analysis , Desmoplakins/metabolism , Disease Progression , Female , Gene Expression Regulation, Neoplastic , Humans , Immunoenzyme Techniques , In Situ Hybridization , Paget Disease, Extramammary/pathology , Paget's Disease, Mammary/pathology , RNA, Messenger/metabolism , Vulvar Neoplasms/pathology , beta Catenin/metabolism , gamma CateninABSTRACT
It is recommended that women with vulvar lichen sclerosus be followed in specialist clinics where difficulty exists with symptom control or where there is clinical evidence of localized skin thickening. Follow-up is also recommended for women who have previously been treated for squamous cell carcinoma of the vulva (arising in lichen sclerosus or vulvar intraepithelial neoplasia) or where the pathologist expresses concern and is unable to make a definitive diagnosis of differentiated vulvar intraepithelial neoplasia.
Subject(s)
Vulvar Lichen Sclerosus/complications , Vulvar Lichen Sclerosus/therapy , Ambulatory Care , Carcinoma, Squamous Cell/epidemiology , Comorbidity , Continuity of Patient Care , Disease Progression , Female , Gynecology/methods , Humans , Vulvar Lichen Sclerosus/diagnosis , Vulvar Lichen Sclerosus/epidemiology , Vulvar Lichen Sclerosus/pathology , Vulvar Neoplasms/epidemiologyABSTRACT
OBJECTIVE: To perform a pilot study to investigate the relationship between localized, provoked vulvodynia of the vestibule and inflammatory cytokine expression. STUDY DESIGN: Women with a diagnosis of localized, provoked vulvodynia had tissue samples taken for vulvar expression of Interleukin 1alpha and 1beta and tumor necrosis factor alpha and compared to those of a control group. RESULTS: The study group did not show a significant increase in expression of inflammatory markers. CONCLUSION: There was no evidence in this study that localized, provoked vulvodynia is an inflammatory condition, as previously thought. This may be helpful in explaining why some women are resistant to medical or antiinflammatory treatment and may allow treatment to be prescribed more effectively.
Subject(s)
Cytokines/metabolism , Vulvar Diseases/metabolism , Case-Control Studies , Female , Humans , Immunohistochemistry , Interleukin-1alpha/metabolism , Interleukin-1beta/metabolism , Pain , Pilot Projects , Tumor Necrosis Factor-alpha/metabolism , Vulvar Diseases/pathologyABSTRACT
The incidence of vulval cancer is rising, both in older women and those under 50 years of age. Vulval cancer has at least two types, one arising in association with lichen sclerosus (LS) and the other with vulval intraepithelial neoplasia (VIN). Recent pathological and aetiological descriptions are included, along with the latest description of VIN terminology. Prevention of and screening for vulval cancer will require greater understanding of why some women with LS and VIN are at greater risk: recent studies of molecular change might contribute to this. The use of vulval cytology and toluidine blue staining is described. Patient or vulval awareness may help but clinical features are non-specific. Prophylactic vaccination against HPV and campaigns against smoking may contribute in the future.
Subject(s)
Mass Screening/methods , Vulvar Neoplasms/diagnosis , Vulvar Neoplasms/prevention & control , Carcinoma in Situ/classification , Disease Progression , Female , Humans , Lichen Planus/pathology , Patient Education as Topic/methods , Precancerous Conditions/pathology , Terminology as Topic , Vulvar Lichen Sclerosus/pathology , Vulvar Neoplasms/classificationABSTRACT
BACKGROUND: Paget's disease of the vulva and the breast are uncommon conditions. The pathogenesis underlying these diseases is still unclear. Vascular endothelial growth factor-A (VEGF-A), a potent angiogenic factor, has been demonstrated in a variety of tumour cell types and is thought to be involved in tumour expansion. Platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP) has also been shown to stimulate angiogenesis. MATERIALS AND METHODS: Fifty-four cases of Paget's disease of the vulva, including 10 with an associated invasive adenocarcinoma, and 38 cases of Paget's disease of the breast, including 26 with available associated ductal carcinoma in situ (DCIS) and/or invasive carcinoma of the breast, were evaluated immunohistochemically for the expression of VEGF-A and PD-ECGF/TP. RESULTS: VEGF-A was not expressed in Paget's disease of the vulva or breast. PD-ECGF/TP was expressed in 22 out of 54 (41%) cases of Paget's disease of the vulva. Four of the cases associated with invasive disease (40%) expressed PD-ECGF/TP. Twenty-one out of 38 (55%) cases of Paget's disease of the breast were positive for PD-ECGF/TP. CONCLUSION: Our data suggest that PD-ECGF/TP may have a role to play in the pathogenesis of Paget's disease of the vulva and the breast. The role of VEGF-A in Paget's disease of the vulva and the breast remains to be fully elucidated.
Subject(s)
Breast Neoplasms/metabolism , Endothelial Growth Factors/biosynthesis , Paget Disease, Extramammary/metabolism , Paget's Disease, Mammary/metabolism , Thymidine Phosphorylase/biosynthesis , Vulvar Neoplasms/metabolism , Breast Neoplasms/enzymology , Breast Neoplasms/pathology , Female , Humans , Neoplasm Invasiveness , Paget Disease, Extramammary/enzymology , Paget Disease, Extramammary/pathology , Paget's Disease, Mammary/enzymology , Paget's Disease, Mammary/pathology , Prognosis , Vascular Endothelial Growth Factor A , Vulvar Neoplasms/enzymology , Vulvar Neoplasms/pathologyABSTRACT
Our understanding of the pathogenesis of Paget's disease of the vulva and the breast remains limited. Current evidence supports the fact that angiogenesis plays an important role in the pathogenesis of several diseases. Therefore, we sought to define its role, as correlated with microvessel density, in Paget's disease of the vulva and the breast. Microvessels were analysed using anti-von Willebrand factor antibody in 105 cases of Paget's disease of the vulva and the breast comprising 71 cases of Paget's disease of the vulva, including 8 cases with invasive disease, and 34 cases of Paget's disease of the breast. The latter included 12 cases with DCIS, 5 cases with both DCIS and invasive carcinoma, and 6 with carcinoma alone. Eleven cases had no underlying tumour identified. Increased microvessel density was demonstrated in Paget's disease of the breast with DCIS and with carcinoma alone compared to Paget's disease of the breast alone, P < 0.08 and P < 0.013, respectively. There were no significant differences in microvessel density in the vulval cases. Neovascularisation is an important process in the development of Paget's disease of the breast. Other biological and molecular processes are more involved in the pathogenesis of Paget's disease of the vulva.
ABSTRACT
Polycyclic aromatic hydrocarbons (PAHs) are combustion products of organic materials, mixtures of which contain multiple known and probable human carcinogens. PAHs occur in indoor and outdoor air, as well as in char-broiled meats and fish. Human exposure to PAHs occurs by inhalation, ingestion and topical absorption, and subsequently formed metabolites are either rendered hydrophilic and excreted, or bioactivated and bound to cellular macromolecules. The formation of PAH-DNA adducts (DNA binding products), considered a necessary step in PAH-initiated carcinogenesis, has been widely studied in experimental models and has been documented in human tissues. This review describes immunohistochemistry (IHC) studies, which reveal localization of PAH-DNA adducts in human tissues, and semi-quantify PAH-DNA adduct levels using the Automated Cellular Imaging System (ACIS). These studies have shown that PAH-DNA adducts concentrate in: basal and supra-basal epithelium of the esophagus, cervix and vulva; glandular epithelium of the prostate; and cytotrophoblast cells and syncitiotrophoblast knots of the placenta. The IHC photomicrographs reveal the ubiquitous nature of PAH-DNA adduct formation in human tissues as well as PAH-DNA adduct accumulation in specific, vulnerable, cell types. This semi-quantative method for PAH-DNA adduct measurement could potentially see widespread use in molecular epidemiology studies.
Subject(s)
Carcinogens/analysis , DNA Adducts/analysis , Immunohistochemistry/methods , Polycyclic Aromatic Hydrocarbons/analysis , Carcinogens/metabolism , DNA Adducts/metabolism , Female , Humans , Immunohistochemistry/instrumentation , Male , Polycyclic Aromatic Hydrocarbons/metabolism , Tissue DistributionABSTRACT
The cyclic hormonal changes that regulate the menstrual cycle are a significant biological influence on the female body, one with both physical and emotional ramifications. Menstruation is governed by tightly orchestrated changes in the levels of ovarian estrogen and progesterone, which produce varying responses in diverse tissues and organs. The skin, the largest organ in the body, is replete with estrogen receptors (in both dermis and epidermis) and to a lesser extent, progesterone receptors. Cyclically fluctuating levels of estrogen and progesterone influence numerous characteristics of the epidermis, including skin surface lipid secretion and sebum production, skin thickness, fat deposition, skin hydration, and barrier function. Dermal collagen content, which contributes to skin elasticity and resistance to wrinkling, is also influenced. Interestingly, estrogen levels also influence skin pigmentation and UV susceptibility, as well as resident microflora. In addition, changing hormone levels across the menstrual cycle produce measurable variations in immune function and disease susceptibility. An understanding of the profound influence that fluctuating estrogen and progesterone levels have on the biological responses of the premenopausal adult woman is critical to optimizing the efficacy of medical therapies in this population.
Subject(s)
Estrogens/physiology , Menopause/physiology , Menstrual Cycle/physiology , Pregnancy/physiology , Skin Physiological Phenomena , Female , Humans , Progesterone/physiology , Skin/anatomy & histology , Skin/metabolism , Skin/microbiology , Skin Physiological Phenomena/immunologyABSTRACT
The hormones progesterone and estrogen and, more precisely, their sophisticated interdependent fluctuations over the course of the female human lifespan, have long been known to play a dominant role in the physiological development and homeostasis of the human female. What is only recently coming to light, however, is that the fluctuation of these two hormones also plays a crucial role in neurological and psychological development and function which impacts brain function, cognition, emotional status, sensory processing, appetite, and more. The ability of reproductive hormones to impact psychoneurological processes involves the interplay of several body systems, lending credibility to the view of premenstrual syndrome (PMS) as a disorder founded in real biochemical disturbances. The effects of the menstrual cycle on cognitive, emotional, and sensory function in the female of childbearing age are reviewed. In addition, recent evidence is discussed which confirms the biological basis of PMS as a real disorder of primarily autoimmune origin.
Subject(s)
Menstrual Cycle/psychology , Premenstrual Syndrome/psychology , Cognition/physiology , Emotions/physiology , Female , Humans , Menstrual Cycle/physiology , Premenstrual Syndrome/physiopathology , Sensation/physiologyABSTRACT
OBJECTIVE: The study was undertaken to provide further understanding of the phenomenon of "acetowhite epithelium". METHODS: Solutions of acetic and similar acids were applied to the atypical transformation zone to demonstrate (or not) acetowhite epithelium. RESULTS: Acetowhite epithelium is not unique to acetic acid, but can be mimicked by other water soluble carboxylic acids. CONCLUSIONS: Acetowhite epithelium is probably due to the reflection of light from the superficial layers of epithelium when they become opaque following the rapid penetration of these non-coagulant fixatives and their effect on nucleoprotein.
Subject(s)
Acetic Acid , Uterine Cervical Dysplasia/pathology , Uterine Cervical Neoplasms/pathology , Biopsy , Cell Transformation, Neoplastic/pathology , Cervix Uteri/pathology , Epithelial Cells/pathology , Female , HumansABSTRACT
PURPOSE OF REVIEW: An increasing number of patients present with symptoms of vulvar pain, soreness, burning or irritation, which become chronic. Clinicians are often uncertain of the diagnosis. Terminology and an understanding of aetiology and therapy are evolving. RECENT FINDINGS: Previous descriptions of vulvodynia have grouped patients according to whether pain is provoked by coitus (vulvar vestibulitis syndrome) or generalized and neuropathic pain (dysesthetic vulvodynia). Recent terminology debates have questioned whether 'vulvodynia' should be replaced by 'dysesthesia' and the term 'vestibulitis' avoided. Definitions of pain provocation, quality, duration, and distribution vary. Prevalence studies suggest one in six women may experience vulvodynia, although such a figure reflects clinic, patient or author reporting bias. Symptoms are as likely to be found in non-white as in white women. Although infection is often blamed, evidence for its role or that of inflammation is minimal. Immunohistochemistry has shown altered density of nerve endings and oestrogen receptors. There may be overlap with other pain syndromes. Several reviews have examined the many therapies available. Pharmacological alteration of nerve conduction (tricyclic antidepressants, gabapentin, local anaesthetics), biofeedback and sometimes surgery are helpful, but not always. Counselling and an understanding between patient and clinician/therapist are important for long-term results. SUMMARY: Gynaecologists should be aware that they will encounter patients with vulvodynia who will need assessment and management. There are increasing numbers of clinics or clinicians with expertise to whom these patients can be referred.
Subject(s)
Pain/etiology , Vulvar Diseases/complications , Female , Humans , Pain/epidemiology , Pain Management , Vulvar Diseases/diagnosis , Vulvar Diseases/epidemiology , Vulvar Diseases/therapyABSTRACT
OBJECTIVE: A pilot study was performed to investigate the relationship between vulvar vestibulitis syndrome and estrogen receptor expression. STUDY DESIGN: Women with a diagnosis of vulvar vestibulitis syndrome had tissue samples taken for vulvar estrogen receptor-alpha expression and this was compared with a control group. RESULTS: The study group showed a significant decrease in estrogen receptor expression, and 50% of the samples did not exhibit any receptor expression. CONCLUSION: There appears to be a subgroup of women with vulvar vestibulitis syndrome who exhibit abnormal estrogen receptor-alpha expression. This may be helpful in explaining why some women are resistant to medical treatment and may allow treatment to be prescribed more effectively.
Subject(s)
Pain/etiology , Receptors, Estrogen/metabolism , Vulvitis/complications , Vulvitis/metabolism , Adult , Case-Control Studies , Estrogen Receptor alpha , Female , Humans , Immunohistochemistry , SyndromeABSTRACT
OBJECTIVES: We compared microvessel density (MVD) in normal, benign, preneoplastic, and neoplastic (squamous cell carcinoma (SCC)) vulvar disease to ascertain if this parameter could identify cases with lichen sclerosus (LS) and high-grade vulvar intraepithelial neoplasia (VIN3) at risk of developing malignancy. METHODS: Microvessels were immunohistochemically stained in paraffin wax-embedded vulvar tissue sections with anti-von Willebrand factor (vWF) antibody using the streptavidin-biotin-horseradish peroxidase complex technique. Three "hot spots" with the greatest MVD were identified within 200 microm of the subepithelial dermis under low magnification (x 40 and x 100). The highest (HVD) and average (AVD) MVDs were quantified for each sample under high magnification (x 200) using an image analysis system. RESULTS: HVD and AVD showed similar significant differences. SCC had significantly the highest MVD followed by VIN3, normal vulva, and LS. LS had significantly the lowest MVD, even lower than that of normal vulva. Two cases of VIN3 had much higher HVD (9.16 and 9.61) and AVD (6.89 and 7.71) compared with the main cluster of cases. CONCLUSION: In vulvar LS, MVD, as assessed by HVD/AVD, is not a useful parameter in determining potential malignant progression, while in VIN3 this parameter could be valuable in identifying cases at greatest risk of progression to invasive disease.