聚焦超声治疗外阴上皮内非瘤样病变的近远期疗效及其影响因素

目的 探讨聚焦超声治疗外阴上皮内非瘤样病变的近远期疗效及并发症,并初步分析其预后影响因素。方法 选择经病理检查证实为外阴上皮内非瘤样病变患者共76例,采用聚焦超声进行治疗。术后定期随访局部瘙痒症状的改善情况,采用阴道镜检查方法观察体征的变化。结果 聚焦超声治疗后平均随访28．3个月（24～60个月）,有39例患者治愈（27例为鳞状上皮增生型,12例为硬化性苔癣型）,总治愈率为51％（39／76）,总有效率达95％（72／76）,累计复发率为36％（26／72）。对复发病例在间隔一段时间后进行再次聚焦超声治疗,同样可以获得显著的临床治疗效果,18例复发后再治疗患者中,6例完全恢复正常,12例症状明显减轻或缓解。76例患者中,4例（2例鳞状上皮增生型,2例硬化性苔癣型）于治疗后2～4h出现治疗区皮肤少量水疱,经抗炎、对症治疗后均痊愈。另有2例（1例鳞状上皮增生型,1例硬化性苔癣型）在治疗后2周出现治疗区局部皮肤浅表溃疡,经抗炎、对症及促表皮生长等治疗3周后痊愈。76例患者经24～60个月的临床观察未发现有远期并发症。不同的麻醉方式及不同的病理类型对聚焦超声治疗效果的影响比较,差异无统计学意义（P〉0．05）,但病程越短、年龄越小,聚焦超声治疗的临床效果越好。结论 聚焦超声用于治疗外阴上皮内非瘤样病变安全有效,无远期并发症发生。     

CD34、VEGF在外阴白色病变组织中的表达

目的:研究外阴白色病变组织中血管的改变,从而进一步探讨该病的病因及发病机制。方法:采用免疫组织化学的方法,观察CD34和VEGF在37例外阴白色病变(包括SH22例,LS10例,混合型5例)组织中的表达情况。11例正常外阴皮肤组织作对照。结果:外阴白色病变组MVD值显著低于正常外阴皮肤组(P<0.05)且LS组MVD值也低于SH组(P<0.05);VEGF表达阳性率在正常外阴皮肤组织与外阴白色病变组织间无显著性差异(P>0.05)。且LS、SH组中VEGF表达阳性者的病程与阴性者无显著差异(P>0.05)。结论:外阴白色病变组织中的血管存在着异常,主要表现为血管数目的减少,其中LS组患者血管减少最显著,提示血管的异常是外阴白色病变的主要变化之一。     

外阴白色病变患者T细胞亚群及脂质过氧化反应的变化

目的 :探讨外阴白色病变与免疫功能及脂质过氧化反应的关系。方法 :用FCM法检测患者静脉血CD3+、CD4 +、CD8+、CD16 +细胞 ,用亚硝酸盐法检测MDA ,用硫代巴比妥酸法检测SOD。结果 :患者组与对照组的CD3+、CD4 +、CD8+、CD16 +细胞水平无明显差异 ,患者组CD4 + /CD8+细胞比值及SOD明显低于正常对照组 (P <0 .0 5 ) ,而MDA较对照组明显增高 (P <0 .0 5 ) ;不同组织类型外阴白色病变患者之间的T细胞亚群水平和SOD及MDA无明显差异 ;直线相关分析显示 ,SOD变化与CD4 + /CD8+变化及CD 3+、CD4 +变化呈明显正相关 (P <0 .0 1) ,MDA与CD8+、CD16 +变化正相关 (P <0 .0 5 )。结论 :外阴白色病变患者体内存在免疫应答过度和过剩脂质过氧化反应 ,二者共同作用导致了机体自身组织的损伤。     

Receptor modifications in vulvar dystrophies before and after treatment with topical hormones: comparison between the dextran-charcoal technique and immunohistochemical evaluation

PURPOSE OF INVESTIGATION: The objective of the study was first to quantify estrogen receptors (ERs) and progesterone receptors (PRs) in dystrophic vulvar tissue before and after topical hormone treatment in an attempt to evaluate whether receptor modifications occurred. Second we compared quantitative analysis with immunohistochemical staining of the vulvar specimens. METHODS: We studied 115 vulvar specimens obtained from 75 consenting women ranging from 21 to 78 years of age. Of the patients, 12 had histologically normal vulvar skin, 45 had vulvar dystrophies that were not treated by topical steroid therapy, 28 patients had vulvar dystrophies that were treated by testosterone propionate (TP) 2%, 12 patients had vulvar dystrophies that were treated by progesterone in hydroalcoholic gel and 18 patients had vulvar malignant tumors. For immunohistochemical analysis we considered 25 cases of vulvar dystrophies: 11 cases of squamous hyperplasia (SH) and 14 cases of lichen sclerosus (LS). Among these 25 cases, 15 (5 SH and 10 LS) were treated with TP 2%. RESULTS: After treatment of the vulvar dystrophies with progesterone, the positivity of ERs decreased (58.3% vs 77.8%). After treatment of the vulvar dystrophies with TP 2%, the positivity of PRs significantly decreased (14.3% vs 68.9%) whereas after treatment with progesterone the positivity of PRs increased (83.3%). The immunohistochemical study showed some differences in comparison to the quantitative study. In fact we found low basal positivity especially for PRs (16% vs 68.9% of the quantitative study). This finding was due to the use of a cutoff of at least ++ in order to increase the specificity. After treatment with TP 2%, we observed an increase of immunohistochemical positivity for ERs even in cases that were negative before treatment and a lack of PRs even in cases that were positive before treatment. CONCLUSIONS: These data demonstrate the efficacy of androgen therapy with TP 2% in vulvar dystrophies with increased trophism due to the increase of ERs.     

细胞周期调控因子cyclin D1、p16蛋白表达异常与外阴白色病变发病的关系

目的探讨细胞周期调控因子cyclin D1、p16蛋白表达异常与外阴白色病变发病的关系.方法选择外阴白色病变组织34份,其中硬化性苔藓（LS）12份,鳞状上皮增生（SH）18份,SH合并LS4份;另选择正常外阴皮肤组织11份作为对照.应用免疫组化方法检测上述组织中cyclinD1、p16蛋白的表达,并分析其与外阴白色病变发病的关系.结果外阴白色病变组织中,cyclin D1蛋白阳性表达率为56%,显著高于正常外阴皮肤组织（9%,P＜0.05）;LS和SH组织中,cyclin D1蛋白阳性表达率分别为58%和50%,两者比较,差异无统计学意义（P＞0.05）.外阴白色病变组织中,p16蛋白阳性表达率为6%,与正常皮肤组织（0）比较,差异无统计学意义（P＞0.05）;LS和SH组织中,p16蛋白阳性表达率分别为8%和0,两者比较,差异无统计学意义（P＞0.05）.结论cyclin D1与p16蛋白作为调控细胞增殖周期的重要因子,前者的高表达致两者间的平衡状态被打破,可能是外阴白色病变发病的原因之一.     

Cyclin D1 and retinoblastoma protein in vulvar cancer and adjacent lesions

Abstract. Rolfe KJ, Crow JC, Benjamin E, Reid WMN, Maclean AB, Perrett CW. Cyclin D1 and retinoblastoma protein in vulvar cancer and adjacent lesions.
Abnormalities in the cell cycle are associated with tumorigenesis but have not yet been identified in squamous cell carcinoma (SCC) of the vulva or in adjacent vulvar lesions. The purpose of this study was to identify cell cycle protein expression (cyclin D1 and retinoblastoma protein [pRb]) in vulvar SCC and in adjacent potentially premalignant lesions: lichen sclerosis (LS), squamous cell hyperplasia (SH), and vulvar intraepithelial neoplasia (VIN). Using immunohistochemical techniques, 57 SCCs were analyzed with 19 adjacent areas showing LS, 13 showing SH, 11 VIN, and six normal epithelium. Fifty-one percent of SCCs showed abnormal cyclin D1 expression and 37% showed abnormal pRb. Abnormal cyclin D1 expression in the adjacent areas was as follows: 53% in LS, 31% in SH, 18% in VIN, and 0% in normal. Abnormal pRb expression was as follows: 42% in LS, 62% in SH, 46% in VIN, and 33% in normal. Only 10 lesions showed abnormal expression of both proteins. Abnormal expression of cyclin D1 in SCC was statistically significant compared with adjacent normal epithelium. In SCC lesions, abnormal cyclin D1 expression was associated with greater depth of invasion. Abnormal pRb in SCC was associated with poor tumor grade. Cyclin D1 and pRb are separately involved in the progression of vulvar cancer, and changes in the expression of these proteins may represent an early stage of malignant transformation in vulvar disease.     

Sexual Functions and Depressive Symptoms after Photodynamic Therapy for Vulvar Lichen Sclerosus in Postmenopausal Women from the Upper Silesian Region of Poland

IntroductionAlthough lichen sclerosus (LS) may affect women's physical functioning, mood, and quality of life, restricting their physical activities, sexual, and non‐sexual contacts, there are limited data on the sexual functioning of women diagnosed with LS.AimsThe aim of the study was to evaluate the influence of photodynamic therapy for vulvar LS on sexual functions and depressive symptoms in postmenopausal women from the Upper Silesian Region of Poland.MethodsA total of 65 women aged 50–70 visiting an outpatient clinic for assessment of vulvar dermatoses were screened for the clinical trial. Finally, 37 women who met all the inclusion/exclusion criteria were included in the study. All the subjects were treated by topical laser therapy (photodynamic therapy). Sexual functions and depressive symptoms were assessed before and after the therapy using Female Sexual Function Index and Beck Depression Inventory, respectively.Main Outcome MeasuresSexual behaviors, sexual functions, and depressive symptoms in females after photodynamic therapy for vulvar LS.ResultsThe total FSFI score was significantly lower after the treatment of vulvar LS as compared with the baseline (median 24.6 vs. 15.9). However, the prevalence of clinically significant FSD was stable throughout the medical intervention except lubrication disorders (higher prevalence after the treatment: 40% vs. 68.57%). Although the scores of BDI at the baseline dropped significantly after the photodynamic therapy (median 12.0 and 9.0, respectively), there were no significant differences in the prevalence of depressive symptoms (48.65% vs. 45.94%).ConclusionsTopical laser therapy for vulvar LS has a good clinical outcome, especially in the context of no major negative effects on sexual functioning and the positive impact on the severity of depressive symptoms in postmenopausal women. However, patients should be informed about the possible lubrication disorders following the treatment. Skrzypulec V, Olejek A, Drosdzol A, Nowosielski K, Kozak‐Darmas I, and Wloch S. Sexual functions and depressive symptoms after photodynamic therapy for vulvar lichen sclerosus in postmenopausal women from the Upper Silesian region of Poland.     

聚焦超声治疗外阴上皮内非瘤样病变900例临床疗效分析

目的 探讨聚焦超声治疗外阴上皮内非瘤样病变的临床疗效,评价聚焦超声治疗的有效性、安全性及可行性。方法 对2003年6月至2005年8月,采用聚焦超声治疗的941例外阴上皮内非瘤样病变患者的临床资料进行回顾性分析,其中鳞状上皮增生型498例（占52．9％）,硬化性苔癣型342例（占36．4％）,硬化性苔癣伴增生（混合）型101例（占10．7％）。患者年龄18～70岁,平均年龄40．8岁。平均病程为6．2年（3个月～45年）,于治疗后6、12个月评价其疗效（分为治愈、有效、无效,以治愈及有效例数计算有效率）。结果 941例患者中900例患者随访资料完整,治疗后6个月,临床治愈434例（占48．2％）,有效420例（占46．7％）,无效46例（占5．1％）,治疗后6个月的有效率为94．9％。治疗后12个月的有效率为83．7％。治疗后12个月有101例患者再次出现明显的外阴瘙痒症状（占11．2％）,再次给予聚焦超声治疗,其中90例达到临床有效。900例患者中,无一例出现阴道周围组织（尿道或直肠）损伤等并发症,但有50例患者（5．6％）在治疗中及1周后出现皮肤水泡及局部浅表溃疡,经对症治疗后全部愈合。结论 聚焦超声是当前治疗外阴上皮内非瘤样病变行之有效的新方法,值得在临床上进一步推广应用。     

Cell cycle proteins as molecular markers of malignant change in vulvar lichen sclerosus

Abstract. Rolfe KJ, Eva LJ, MacLean AB, Crow JC, Perrett CW, Reid WMN. Cell cycle proteins as molecular markers of malignant change in vulvar lichen sclerosus.
Lichen sclerosus (LS) has a known association with the development of squamous cell carcinoma of the vulva. The purpose of this study was to investigate molecular markers, which could indicate premalignant changes. Multiple sequential vulvar biopsies were taken over a period of 11 years from a patient with longstanding LS. Immunohistochemical staining was used to demonstrate a range of molecular markers.
Increased expression of p53 and Ki67 was found in areas of squamous hyperplasia (SH) and differentiated vulvar intraepithelial neoplasia (dVIN) which correlated with the subsequent development of invasive squamous cell carcinoma (SCC). Molecular changes have been found to accompany histologic changes in the progression of vulvar LS to malignancy. Such markers may prove a useful addition in the clinical management of these conditions.     

Vulvar carcinoma associated with lichen sclerosus. Experience at the Florence,Italy, Vulvar Clinic

OBJECTIVE: To compare demographic and clinical characteristics of patients with lichen sclerosus (LS)-associated squamous cell carcinoma (SCC) of the vulva with those of patients with tumors not histologically associated with LS in a series of patients with vulvar SCC not HPV correlated. STUDY DESIGN: We retrospectively reviewed histologic specimens and clinical files of all vulvar SCCs referred to the Vulvar Clinic, University of Florence, Florence, Italy, since 1990. RESULTS: Twenty-five out of the 72 cases in this study (34.7%) were LS associated. Among these cases, 8 (32%) were diagnosed with LS before occurrence of the cancer and received treatment for the disease. In 17 cases the diagnosis of LS was simultaneous with that of SCC; in 13 cases the diagnosis was achieved by clinical examination and confirmed afterwards histologically. In 4 cases this was confirmed only by means of histologic examination. The shared profile of patients with LS-associated vulvar SCC was a subject (mean age, 72 years) seldom with a past medical history of vitiligo (16% of cases), with invasive cancer (92% of cases), clinically characterized by an exophitic tumor (73%), seldom ulcerated (18%) or showing hyperkeratosis (9%). Labia majora (32%), labia minora (27%) and vestibule (23%) were the most frequently involved sites. In most cases (80%) the cancer was limited to 1/3 of the vulvar region. An itch was the most frequent symptom. However, for all of these variables, no overall statistically significant difference was found with patients who had SCCs not associated with LS. CONCLUSION: The experience of the Vulvar Clinic, University of Florence, confirms the suggested role of LS as a possible precursor of vulvar carcinoma since 32% of our cases not HPV related were LS associated. We demonstrated that the profile of patients with LS-associated cancer does not differ from that of patients with cancer not associated with LS, excluding HPV-related cases. The existence of accessory conditions, probably needed to promote the progression from LS to cancer in a minority of subjects remains to be established.     

High-intensity focused ultrasound treatment for non-neoplastic epithelial disorders of the vulva

Objective

To assess the efficacy of high-intensity focused ultrasound (HIFU) treatment in patients with non-neoplastic epithelial disorders of the vulva.

Method

We reviewed 41 cases of lichen sclerosus, 38 cases of squamous cell hyperplasia, and 17 mixed cases treated by HIFU from April 2004 to July 2008 at the Women's Hospital of Zhejiang University School of Medicine. Biopsy specimens were assessed with light microscopy before and after treatment.

Results

Pruritus and signs of vulvar lesions were dramatically improved following HIFU treatment, without severe complications, and 90.23% of the patients were cured or had their symptoms improved 6 months after treatment. On light microscopy, pigmentation and epithelial structures were recovered and dermal lymphocytic infiltration was reduced. The response rates were lower and complication rates higher among lichen sclerosus than among squamous cell hyperplasia cases (P < 0.05 for both).

Conclusion

Treatment with HIFU may be safe and effective in cases of vulvar dystrophy.     

Vulvar Dystrophies: An Evaluation

EDITORIAL COMMENT: This paper provides readers with a logical plan of treatment for patients presenting with pruritus, vulvitis or visible vulvar disease who are found on directed biopsy to have vulvar dystrophy (hyperplasia, lichen sclerosus or mixed dystrophy). Excellent results were obtained using topical corticosteroid therapy for patients with hyperplasia, and topical testosterone for those with lichen sclerosus. In presenting the results in this series of 86 patients the authors do not explain the criteria for directed vulvar biopsy in women presenting with pruritus or vulvitis. These excellent results suggest that vulvar biopsy should be performed not only in all patients with clinical suspicion of carcinoma, but also in all those who fail to respond to initial therapy. The results presented here seem almost too good to believe because in this reviewer's experience vulvar biopsies in many patients with intractable pruritus and vulvitis show coexistence of hyperplasia and lichen sclerosus — in this series only 7 of 86 patients had mixed dystrophy. Readers should note that medical treatment was not used in patients with atypia on biopsy — these patients require a surgical approach to their treatment.
Summary: Of 86 patients diagnosed as having vulvar dystrophy in a 10-year period 56 (65.1%) had hyperplastic dystrophy, 23 (26.7%) had lichen sclerosus and 7 (26.7%) had mixed vulvar dystrophy. The diagnoses were made by colposcopic or toluidine blue directed biopsies. Fluorinated corticosteroids were given to patients with hyperplastic dystrophy with a response rate of 90.1%. Patients with lichen sclerosus received topical testosterone propionate and the response rate was 87.7%. Topical fluorinated corticosteroids followed by testosterone propionate was given to patients with mixed dystrophy and 85.8% of the patients responded. Surgical therapy was reserved for patients with failed medical treatment.     

Topical testosterone versus clobetasol for vulvar lichen sclerosus.

OBJECTIVE: To compare the effects of topical testosterone and clobetasol treatments on symptoms remission and recurrence rates in patients with vulvar lichen sclerosus (LS). METHODS: A retrospective review of the records showed that, of 140 patients with biopsy-proven vulvar LS, 80 were treated with applications of testosterone propionate 2% in petrolatum and 60 with clobetasol 17-propionate 0.05%. RESULTS: The response rates after 6 months were 77.5% for patients treated with testosterone and 91.7% for those treated with clobetasol (P=0.02). The recurrence rates were 20% and 6.7% in the 2 groups, respectively (P=0.02). Premenopausal patients had higher remission rates and lower recurrence rates than postmenopausal patients (P>0.05). Considering whole patients, low remission rates and high recurrence rates were observed in patients who had had a hysterectomy (P>0.05). CONCLUSION: Treatment of LS with a corticosteroid provided excellent remission rates. In this study, clobetasol 17-propionate 0.05% was superior to testosterone for both remission induction and maintenance therapy.     

Pseudoepitheliomatous hyperplasia in lichen sclerosus of the vulva.

Small tentacles or separated nests of squamous cells in the dermis are not uncommonly seen in long-standing vulvar lichen sclerosus (LS) associated with epidermal thickening. We recently encountered a case where separated nests of well-differentiated squamous cells in the dermis were difficult to distinguish from squamous cell carcinoma (SCC). Further biopsies showed similar nests originating from every hair follicle. We postulated a diagnosis of multifocal pseudoepitheliomatous hyperplasia (PEH) to explain this phenomenon. Because we could find no reference to PEH in the setting of LS, we reviewed the biopsies of 92 women with extragenital and vulvar LS with and without carcinoma to determine its frequency and histological appearance. The study population, which excluded the index case, comprised 10 women with extra-anogenital LS, 58 with vulvar LS without carcinoma, and 24 with vulvar LS with carcinoma. The presence of PEH, epidermal thickness, predominant dermal collagen change, degree of inflammation, and presence of fibrin and red blood cells were recorded. The presence or absence of lichen simplex chronicus (LSC), squamous cell hyperplasia (SCH), and differentiated vulvar intraepithelial neoplasia (VIN) were recorded. PEH was identified only in vulvar LS, where it was seen in 7/58 (12.1%) women without carcinoma, 1/24 (8.3%) with carcinoma, and 0/10 (0%) with extra-anogenital LS. Two forms of PEH were seen: predominantly epidermal 7/8 (87.5%) and predominantly follicular 1/8 (12.5%). PEH was associated with increased epidermal thickness, less dermal edema, more dermal inflammation, fresh fibrin, and red blood cell extravasation. In all cases, there was associated LSC, but there was no SCH or differentiated VIN. In conclusion, PEH may explain many of the cases of dermal tentacles and separated squamous nests in vulvar LS with LSC. The association with fresh fibrin and red blood cells suggests that PEH might be a reaction to tissue damage. PEH is distinguished from SCC by its lack of atypia, confinement to the abnormal collagen, and limited growth. The pathologist must be careful about making a diagnosis of PEH in LS with epidermal thickening, looking carefully for basal atypia and other features of differentiated VIN in the overlying epidermis or dermal proliferation. We do not know whether PEH occurs in differentiated VIN and, if it does, how it could be distinguished from SCC.     

Childhood vulvar lichen sclerosus. The course after puberty

OBJECTIVE: To identify girls with vulvar lichen sclerosus (LS) and to follow them through puberty, documenting the course of the disease. STUDY DESIGN: Twenty-one postpubertal girls were identified from a cohort of 75 girls with LS presenting prepubertally and attending a pediatric vulvar clinic. Details of current symptoms, findings on examination and treatment needs were recorded. A database of 263 women with LS was reviewed for onset of LS premenarche. RESULTS: Of the 21 postpubertal girls, 16 reported an improvement in symptoms, but 11 stated that they still experienced occasional pruritus, requiring intermittent topical steroid application. Although the disorder appeared less active in most cases, definite physical signs persisted in 16 patients (75%); in 5 patients no physical signs of the disease remained. Of 251 postmenopausal women with LS, < 5 could recall symptoms in childhood. Of 12 young adult premenopausal patients with vulvar LS, 4 could recall symptoms in childhood. One of these, a 32-year-old with well-documented LS in childhood resolving at puberty, presented with and died of vulvar squamous cell carcinoma (SCC). CONCLUSION: Patients should be aware that LS may improve symptomatically but usually does not entirely resolve at puberty and that the disease in women may be associated with development of vulvar SCC. Ideally, long-term follow-up should be the standard of care.     

NASPAG Clinical Opinion: Diagnosis and Management of Lichen Sclerosis in Pediatric and Adolescent Patients

This Clinical Opinion replaces the NASPAG Clinical Recommendation: Pediatric Lichen Sclerosus published in 2014. The objective of this document is to provide guidance in the diagnosis and management of vulvar lichen sclerosus (LS) in the pediatric and adolescent patient in order to treat patient symptoms and reduce long-term sequelae. LS is a chronic inflammatory condition affecting the anogenital region that may present in the prepubertal or adolescent patient. Clinical presentations include significant pruritus, loss of pigmentation and vulvar adhesions with loss of normal vulvar architecture. Management includes topical agents for induction and maintenance therapy, as well as long-term follow-up for identification and treatment of recurrence and sequelae. This document is intended for use by both primary and specialty pediatric and adolescent gynecology (PAG) providers, including specialists in pediatrics, gynecology, adolescent medicine, and dermatology.     

Topical mometasone furoate for vulvar lichen sclerosus

OBJECTIVE: To assess the efficacy and safety of treating vulvar lichen sclerosus with mometasone furoate, a synthetic analogue of beclomethasone. STUDY DESIGN: Thirty-one consecutive patients with biopsy-proven vulvar lichen sclerosus (LS) seen at the Florence Vulvar Clinic were entered into the study. Each subject's symptoms and the gross appearance of the lesions were recorded using a severity score according to the authors' previous studies. The patients were treated with a regimen of 0.1% mometasone furoate cream applications to the affected areas once daily for 4 weeks and then twice weekly for 8 weeks. After 12 weeks of treatment, the subjects were asked to rate the changes in their symptoms and were reevaluated by the same examiner for the gross appearance of the lesions. In every patient the before/after treatment total severity scores were compared using Wilcoxon's signed-rank test for statistical significance. RESULTS: With mometasone furoate all the patients had a significant improvement (P < .001) in the gross aspects of the disease and a very dramatic decrease in symptoms (P < .001), with nearly all the subjects having complete symptomatic remission. Compliance was excellent, and no side effects were observed. CONCLUSION: The improved risk/benefit ratio of mometasone furoate may minimize the possible long-term side effects expected when using a very potent topical steroid. Therefore, momentasone furoate cream may be an alternative to clobetasol propionate for treatment of vulvar LS, with similar efficacy but higher levels of safety and tolerability.     

The role of angiogenesis and COX-2 expression in the evolution of vulvar lichen sclerosus to squamous cell carcinoma of the vulva

OBJECTIVES: We aimed to determine whether premalignant changes in vulvar lichen sclerosus (LS) could be identified by analysing markers of angiogenesis and the expression of the enzyme cyclooxygenase-2 (COX-2). METHODS: Eight cases of histologically diagnosed vulvar LS, which showed an evolution to carcinoma of the vulva histologically documented, were compared to 10 cases of vulvar LS, for which follow-up information was available for at least 9 years, and to 10 cases of LS adjacent to squamous cell carcinoma (SCC) of the vulva. The microvessel density (MVD), and the expression of vascular endothelial growth factor (VEGF) and of COX-2 were analysed. RESULTS: Difference of MVD between unchanged LS cases and LS cases evolving to SCC and LS adjacent to SCC cases was statistically significant (P=0.008, Wilcoxon Mann-Whitney test). Difference of VEGF and COX-2 expression between unchanged LS cases and LS cases evolving to SCC and LS adjacent to SCC cases were statistically significant (P=0.007 and P=0.01, respectively; Fisher's exact test). CONCLUSIONS: Our study addresses the possibility that immunohistochemical studies may add information to permit the identification of LS as a precursor lesion that has a greater potential to evolve into SCC. These data may identify characteristics of vulvar LS disclosing alterations that indicate the further development to cancer; therefore, it may allow the identification of a group of LS patients who need a careful follow-up and adjunctive biopsies.     

p53抑癌基因蛋白在外阴鳞癌和不典型增生组织中的表达

应用免疫组化方法，对外阴鳞癌、外阴白色病变和不典型增生组织中ｐ５３基因蛋白的表达进行检测。并与胸腹壁、腿部及外阴鳞癌旁正常皮肤（正常皮肤）组织进行对照。结果：外阴鳞癌组织中ｐ５３基因蛋白的阳性率为５２．９％（９／１７）；外阴硬化苔癣型营养不良组织中为１３．６％（３／２２）；增生型营养不良组织中为１４．７％（５／３４）；混合型营养不良组织中为２０．８％（１０／４８）；不典型增生组织中为５４．５％（６／１１）。正常皮肤组织中均为阴性。提示：ｐ５３基因蛋白在外阴鳞癌和外阴白色病变的各型营养不良组织中，均有不同程度的过度表达，外阴鳞癌和不典型增生组织中的表达阳性率，显著高于外阴白色病变的各型营养不良组织（Ｐ＜０．０１）。     

Decorin and chondroitin sulfate distribution in vulvar lichen sclerosus: correlation with distinct histopathologic stages

OBJECTIVE: To characterize decorin and chondroitin sulfate (CS) expression in lichen sclerosus (LS). STUDY DESIGN: Thirty-one untreated vulvar LS lesions were biopsed, and hematoxylin-eosin-stained cases were graded according to Hewitt's classification. Immunohistochemistry was performed using antibodies directed against human decorin diluted 1:500 and CS diluted 1:200. The control group, made up of cutaneous fragments from vulvoperineal corrective surgeries or nymphoplasties, represented 22 patients. RESULTS: Decorin and CS were present at the LS hyaline zone in different moments of matrix modulation. In all Hewitt stages CS prevailed at the extracellular matrix in cases with a compact aspect of the hyaline zone, while decorin was seen only in areas of less compactness. Normal vulvar tissue revealed only the presence of CS in juxtaepithelial zones. No decorin immunoexpression was found in normal vulvar skin. CONCLUSION: Decorin and CS deposition in vulvar LS varies in the distinct histologic stages, which probably reflect the importance of these molecules in matricial remodeling in this disorder. Decorin may play an important role in cases of LS.