RESUMO
ABSTRACT: Differentiated vulvar intraepithelial neoplasia (d-VIN) is an HPV-independent precursor to vulvar squamous cell carcinoma. The histology of d-VIN lesions is difficult to differentiate from that of non-neoplastic epithelial disorders, especially lichen sclerosus (LS). The authors present a case of LS, where relying on histopathology alone could have led to misdiagnosis. The patient was a 17-year-old female patient with clinical features of vulvar dermatitis and LS for 2 years. She was counseled to apply clobetasol 0.05% to the affected area daily but reported no improvement after 6 months. A biopsy of the right labia majora revealed histologic findings typical of d-VIN and near-contiguous p53 expression. These features are characteristic of d-VIN. However, d-VIN is exceedingly rare in young patients. The case was reviewed by 6 dermatopathologists and gynecologic pathologists, who observed that the degree of inflammation would be unusual postclobetasol therapy and could be due to noncompliance. A review of the patient's chart revealed that she "does not always remember to apply" clobetasol. The patient's clinician confirmed that there were compliance issues, and the follow-up biopsy was negative for d-VIN. The case was signed out as LS, with a note describing the above, and to rebiopsy if concern persisted. The authors conjecture that inflammatory infiltrates in the biopsied area caused reactive atypia due to lack of adherence to treatment. Although the patient's age helped rule out d-VIN, similar cases in elderly patients may be occurring. Pathologists must be aware that reactive forms of untreated LS can mimic d-VIN, to avoid misdiagnosis.
Assuntos
Carcinoma in Situ , Clobetasol , Neoplasias Vulvares , Humanos , Feminino , Neoplasias Vulvares/patologia , Neoplasias Vulvares/diagnóstico , Neoplasias Vulvares/tratamento farmacológico , Adolescente , Diagnóstico Diferencial , Carcinoma in Situ/patologia , Carcinoma in Situ/tratamento farmacológico , Clobetasol/uso terapêutico , Líquen Escleroso Vulvar/patologia , Líquen Escleroso Vulvar/tratamento farmacológico , Líquen Escleroso Vulvar/diagnóstico , Líquen Escleroso e Atrófico/patologia , Líquen Escleroso e Atrófico/tratamento farmacológico , Líquen Escleroso e Atrófico/diagnóstico , Biópsia , Adesão à Medicação , Cooperação do Paciente , Erros de DiagnósticoRESUMO
Vulvar lichen sclerosus (VLS) is a chronic and progressive dermatologic condition that can cause physical dysfunction, disfigurement, and impaired quality of life. However, the etiology of VLS remains unknown. The vulvar skin, intestinal and vaginal microbiomes have been postulated to play important roles in the pathogenesis of this disease. The aim of this study was to compare the compositional characteristics of the vulvar skin, vagina, and gut microbiota between perimenopausal or postmenopausal VLS patients and healthy controls. The study involved six perimenopausal or postmenopausal VLS patients which were based on characteristic clinical manifestations and histologic confirmation and five healthy controls. The pruritus severity of each patient was evaluated using the NRS scale, and the dermatology-specific health-related quality of life was assessed using the Skindex-16. Metagenomic sequencing was performed, and the results were analyzed for alpha and beta diversity. LEfSe analysis were used to investigate the microbial alterations in vulvar skin, gut and vagina. KEGG databases were used to analyze differences in functional abundance. The study found significant differences in alpha diversity between the two groups in stool and vaginal samples (P < 0.05). Patients with VLS had a higher abundance of Enterobacter cloacae, Flavobacterium_branchiophilum, Mediterranea_sp._An20, Parabacteroides_johnsoniiand Streptococcus_bovimastitidis on the vulvar skin, while Corynebacterium_sp._zg-913 was less abundant compared to the control group. The relative abundance of Sphingomonas_sp._SCN_67_18, Sphingobium_sp._Ant17, and Pontibacter_sp_BT213 was significantly higher in the gut samples of patients with VLS.Paenibacillus_popilliae,Gemella_asaccharolytica, and Coriobacteriales_bacterium_DNF00809 compared to the control group. Additionally, the vaginal samples of patients with VLS exhibited a significantly lower relative abundance of Bacteroidales_bacterium_43_8, Bacteroides_sp._CAG:20, Blautia_sp._AM28-10, Fibrobacter_sp._UWB16, Lachnospiraceae_bacterium_AM25-39, Holdemania_filiformis, Lachnospiraceae_bacterium_GAM79, and Tolumonas_sp. Additionally, the butyrate-producing bacterium SS3/4 showed a significant difference compared to the controls. The study found a negative relationship between Sphingobium_sp._Ant17 in stool and Skindex-16 (P < 0.05), while Mediterranea_sp._An20 had a positive correlation with Skindex-16 (P < 0.05) in the skin. Additionally, our functional analysis revealed alterations in Aminoacyl_tRNA_biosynthesis, Glutathione_metabolism, the pentose phosphate pathway, and Alanine__aspartate_and_glutamate_metabolism in the VLS patient group. The study suggests that perimenopausal or postmenopausal patients with VLS have a modified microbiome in the vulvar skin, gut, and vagina. This modification is linked to abnormal energy metabolism, increased oxidative stress, and abnormal amino acid metabolism.
Assuntos
Microbiota , Líquen Escleroso Vulvar , Feminino , Humanos , Líquen Escleroso Vulvar/patologia , Pós-Menopausa , Perimenopausa , Qualidade de Vida , Arritmias Cardíacas , Vagina/patologiaRESUMO
Population-based data on the epidemiology of vulvar lichen sclerosus (LS) are sparse and only few prospective studies have investigated the malignant potential of the disease. We used the nationwide Danish Pathology Registry to first assess the incidence of biopsy-verified vulvar LS in the period 1997-2022 and second to examine the incidence of vulvar high-grade squamous precancer and squamous cell carcinoma (SCC) in women with biopsy-verified vulvar LS (1978-2019) compared with that expected in the general female population. For the latter aim, we computed standardized incidence ratios (SIRs) with 95% confidence intervals (CIs). During our study period, the age-standardized incidence rate of vulvar LS increased from 5.0 (1997-1998) to 35.7 (2021-2022) per 100,000 person-years. Compared with the general female population, women with biopsy-verified vulvar LS had significantly increased rates of vulvar high-grade squamous precancer (SIR = 8.5; 95% CI: 7.2-10.0) and SCC (SIR = 16.2; 95% CI: 14.2-18.4). The SIRs of vulvar high-grade squamous precancer and SCC did not vary substantially according to length of follow-up. This nationwide and population-based study shows a 7-fold increase in the incidence of biopsy-verified vulvar LS since 1997. Data also show that women with biopsy-verified vulvar LS have 8.5 and 16 times higher than expected incidence of vulvar high-grade squamous precancer and SCC, respectively. The substantially increased incidence of vulvar high-grade squamous precancer and SCC following LS is important in relation to the clinical management and follow-up of LS patients.
Assuntos
Carcinoma de Células Escamosas , Lesões Pré-Cancerosas , Líquen Escleroso Vulvar , Neoplasias Vulvares , Humanos , Feminino , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/patologia , Neoplasias Vulvares/epidemiologia , Neoplasias Vulvares/patologia , Incidência , Líquen Escleroso Vulvar/epidemiologia , Líquen Escleroso Vulvar/patologia , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/epidemiologia , Lesões Pré-Cancerosas/patologia , Adulto , Dinamarca/epidemiologia , Idoso , Biópsia , Sistema de Registros , Idoso de 80 Anos ou mais , Adulto Jovem , Fatores de RiscoAssuntos
Doença de Hashimoto , Líquen Escleroso Vulvar , Humanos , Feminino , Prevalência , Líquen Escleroso Vulvar/patologia , Líquen Escleroso Vulvar/complicações , Doença de Hashimoto/complicações , Doença de Hashimoto/patologia , Doença de Hashimoto/epidemiologia , Pessoa de Meia-Idade , Adulto , Idoso , Brasil/epidemiologiaRESUMO
OBJECTIVES: Lichen planus (LP) and lichen sclerosus (LS) are the most common vulvar lichenoid dermatoses. The diagnostic challenges are due to site-specific variation in microscopic appearance and small-sized biopsies. Authentication of diagnostic criteria to distinguish LS and LP to uncover any resemblance or divergence in presentation of these conditions is attempted. METHODS: Cases of vulvar LP and LS diagnosed between January 2012 to December 2022 were included. The clinical details included age, presenting symptoms, examination findings, and other organ involvement. Histopathological analysis of epidermal, dermal, and adnexal findings was done. RESULTS: There were 28 cases of vulvar LP and 72 cases of LS, with a median age of 51 and 60 years, respectively. Depigmentation and atrophy were the major clinical features in LS, whereas ulcers/erosions and erythema were more prevalent in LP with a significantly higher incidence of oral involvement. The most diagnostic feature in LS was diffuse dermal sclerosis (76.8%) and interstitial pattern of inflammation (81.4%), whereas the characteristic features in LP cases was a lichenoid pattern of inflammation (85.7%), necrotic keratinocytes, and lymphocytic exocytosis. In 44.4% of LS, unconventional features like compact orthokeratosis, parakeratosis, thickened/wedge-shaped hypergranulosis, and sawtooth rete pegs were noted. Lichen sclerosus with lichenoid inflammation (21.4%) mimicked LP, from which it was distinguished by presence of thickened or diminished granular layer with basal melanin absence (60%) and dermal homogenization (80%). CONCLUSION: Although the classical, well-established variant of LS poses no diagnostic difficulty, the unconventional variant may mimic LP. Identification of the subtle histological clues demonstrated in this study can help to arrive at the correct diagnosis.
Assuntos
Líquen Plano , Líquen Escleroso e Atrófico , Líquen Escleroso Vulvar , Feminino , Humanos , Pessoa de Meia-Idade , Líquen Escleroso e Atrófico/patologia , Vulva/patologia , Líquen Plano/patologia , Inflamação/patologia , Biópsia , Líquen Escleroso Vulvar/diagnóstico , Líquen Escleroso Vulvar/patologiaRESUMO
Vulvar lichen sclerosus (VLS) is a chronic non-neoplastic skin lesion characterized by vulvar itching, pain, atrophy, whitening of the skin and mucous membranes, and gradual atrophy and disappearance of the labia minora, which can eventually lead to vulvar scarring, causing functional impairment and seriously affecting the patient's physical and mental health. VLS can occur at any age, however, its pathogenesis and etiology are not fully understood. Considerable progress has been made in related research on genetic susceptibility factors, autoimmune disorders, collagen metabolism abnormalities, and their triggering factors in disease formation and progression. This article reviews the etiology of vulvar lichen sclerosus.
Assuntos
Doenças Autoimunes , Líquen Escleroso Vulvar , Feminino , Humanos , Líquen Escleroso Vulvar/patologia , Atrofia , DorRESUMO
Objective: To analyze and summarize the clinical and pathological characteristics, management, and efficacy of patients with vulvar lichen sclerosus (VLS) through a single center large sample study, and preliminarily to explore the frequency of maintenance treatment medication for VLS. Methods: The clinical data of VLS patients in Obstetrics and Gynecology Hospital of Fudan University from 2018 to 2021 were retrospectively collected. The clinicopathological characteristics (patients' age, course of disease, complicated disease history, family history, symptoms, signs and pathology), treatment and effects were retrospectively analyzed. The patients in the maintenance treatment stage were followed up regularly to explore the minimum frequency of individual medication to maintain the stability of the disease. Results: (1) General situation: a total of 345 patients with VLS were included in this study. The average age was (50.4±14.7) years (ranged from 8 to 84 years old), prevalence was highest in the 50-59 years group (30.1%, 104/345). Immune diseases occurred in 18.6% (33/177) of patients, 24.3% (43/177) of patients had allergic skin diseases, and 5.6% (10/177) of the patients' immediate family members had chronic vulvar pruritus or vulvar hypopigmentation. (2) Clinical features: the most common symptom was vulvar pruritus (96.1%, 196/204) among 204 patients with recorded symptoms. The most common sign was hypopigmentation of the vulva (96.3%, 206/214). The most common involved sites were labia minora (70.3%, 142/202), labia majora (67.8%, 137/202), and labial sulcus (59.4%, 120/202). The cumulative number of sites involved in 62 vulvar atrophy patients (2.7±1.1) was significantly higher than that in 152 non-atrophy patients (2.2±1.0; t=3.48, P=0.001). The course of vulvar atrophy was (9.3±8.5) years, which was significantly longer than that of non-atrophy patients [(6.6±5.6) years; t=2.04, P=0.046]. (3) Pathological features: among the 286 patients with electronic pathological sections, the most common pathological feature in the epidermis was epithelial nail process passivation (71.3%, 204/286). The common pathological features in the dermis were interstitial collagenization (84.6%, 242/286), and inflammatory cell infiltration (73.8%, 211/286). (4) Treatment: 177 patients received standardized treatment after diagnosis and were followed up regularly in our hospital. In the initial treatment stage, 26.0% (46/177) of the patients were treated with 0.05% clobetasol propionate cream, and 74.0% (131/177) of the patients were treated with 0.1% mometasone furoate ointment. The complete remission rates of the two methods were respectively 80.4% (37/46) and 74.0% (97/131), and there was no statistically significant difference (χ²=0.76, P=0.385). During maintenance treatment, 27.1% (48/177) of the patients took the medication twice a week, 35.0% (62/177) took the medication once a week, and 37.9% (67/177) took the medication once every 10 days. During follow-up after 6 months of maintenance treatment, there were no patients with recurrence of pruritus or progression of vulvar signs. Conclusions: The majority of VLS patients have itching, hypopigmentation, involvement of labia minora and labia majora, progressive atrophy, and inflammatory infiltration of dermis. Local treatments of mometasone furoate and clobetasol propionate have good initial therapeutic effects. The frequency exploration of individualized maintenance treatment could minimize the occurrence of adverse reactions when ensuring the stability of the patients' condition.
Assuntos
Hipopigmentação , Líquen Escleroso Vulvar , Feminino , Humanos , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Líquen Escleroso Vulvar/tratamento farmacológico , Líquen Escleroso Vulvar/complicações , Líquen Escleroso Vulvar/patologia , Clobetasol/efeitos adversos , Estudos Retrospectivos , Furoato de Mometasona/uso terapêutico , Prurido/induzido quimicamente , Prurido/complicações , Prurido/tratamento farmacológico , Atrofia/induzido quimicamente , Atrofia/complicações , Atrofia/tratamento farmacológico , Hipopigmentação/induzido quimicamente , Hipopigmentação/complicações , Hipopigmentação/tratamento farmacológicoRESUMO
As women age, hormonal changes set the stage for a variety of vulvovaginal pathologies. Health care providers in long-term care facilities should be able to recognize and treat these conditions, especially because residents may be unable to communicate their discomfort. The objective of this article is to highlight the major vulvovaginal conditions affecting older women and provide up-to-date information on treatment for providers in long-term care facilities.
Assuntos
Dermatologia , Líquen Escleroso Vulvar , Feminino , Humanos , Idoso , Líquen Escleroso Vulvar/patologia , Líquen Escleroso Vulvar/terapia , Genitália/patologia , Pessoal de SaúdeRESUMO
Objective: To analyze and summarize the clinical and pathological characteristics, management, and efficacy of patients with vulvar lichen sclerosus (VLS) through a single center large sample study, and preliminarily to explore the frequency of maintenance treatment medication for VLS. Methods: The clinical data of VLS patients in Obstetrics and Gynecology Hospital of Fudan University from 2018 to 2021 were retrospectively collected. The clinicopathological characteristics (patients' age, course of disease, complicated disease history, family history, symptoms, signs and pathology), treatment and effects were retrospectively analyzed. The patients in the maintenance treatment stage were followed up regularly to explore the minimum frequency of individual medication to maintain the stability of the disease. Results: (1) General situation: a total of 345 patients with VLS were included in this study. The average age was (50.4±14.7) years (ranged from 8 to 84 years old), prevalence was highest in the 50-59 years group (30.1%, 104/345). Immune diseases occurred in 18.6% (33/177) of patients, 24.3% (43/177) of patients had allergic skin diseases, and 5.6% (10/177) of the patients' immediate family members had chronic vulvar pruritus or vulvar hypopigmentation. (2) Clinical features: the most common symptom was vulvar pruritus (96.1%, 196/204) among 204 patients with recorded symptoms. The most common sign was hypopigmentation of the vulva (96.3%, 206/214). The most common involved sites were labia minora (70.3%, 142/202), labia majora (67.8%, 137/202), and labial sulcus (59.4%, 120/202). The cumulative number of sites involved in 62 vulvar atrophy patients (2.7±1.1) was significantly higher than that in 152 non-atrophy patients (2.2±1.0; t=3.48, P=0.001). The course of vulvar atrophy was (9.3±8.5) years, which was significantly longer than that of non-atrophy patients [(6.6±5.6) years; t=2.04, P=0.046]. (3) Pathological features: among the 286 patients with electronic pathological sections, the most common pathological feature in the epidermis was epithelial nail process passivation (71.3%, 204/286). The common pathological features in the dermis were interstitial collagenization (84.6%, 242/286), and inflammatory cell infiltration (73.8%, 211/286). (4) Treatment: 177 patients received standardized treatment after diagnosis and were followed up regularly in our hospital. In the initial treatment stage, 26.0% (46/177) of the patients were treated with 0.05% clobetasol propionate cream, and 74.0% (131/177) of the patients were treated with 0.1% mometasone furoate ointment. The complete remission rates of the two methods were respectively 80.4% (37/46) and 74.0% (97/131), and there was no statistically significant difference (χ²=0.76, P=0.385). During maintenance treatment, 27.1% (48/177) of the patients took the medication twice a week, 35.0% (62/177) took the medication once a week, and 37.9% (67/177) took the medication once every 10 days. During follow-up after 6 months of maintenance treatment, there were no patients with recurrence of pruritus or progression of vulvar signs. Conclusions: The majority of VLS patients have itching, hypopigmentation, involvement of labia minora and labia majora, progressive atrophy, and inflammatory infiltration of dermis. Local treatments of mometasone furoate and clobetasol propionate have good initial therapeutic effects. The frequency exploration of individualized maintenance treatment could minimize the occurrence of adverse reactions when ensuring the stability of the patients' condition.
Assuntos
Feminino , Humanos , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Líquen Escleroso Vulvar/patologia , Clobetasol/efeitos adversos , Estudos Retrospectivos , Furoato de Mometasona/uso terapêutico , Prurido/tratamento farmacológico , Atrofia/tratamento farmacológico , Hipopigmentação/tratamento farmacológicoRESUMO
BACKGROUND: Vulvar lichen sclerosus (LS) is a chronic inflammatory dermatosis which can progress to precursor lesion differentiated vulvar intraepithelial neoplasia (dVIN) and vulvar squamous cell carcinoma (VSCC). The risk of developing recurrent vulvar cancer following LS-associated VSCC is high. Evidence suggests that treatment of LS with topical corticosteroids (TCS) can prevent progression to dVIN, VSCC and recurrences. However, current guidelines do not give any recommendation on the management of LS following surgery for VSCC. The aim of this study was to conduct a survey among all registered gynaecologic oncologists (GOs) in the Netherlands to evaluate the current management of LS patients without a history of VSCC (LSnoVSCC) and patients with LS following surgery for VSCC (LSVSCC). METHODS: An online survey was distributed to all registered GOs in the Netherlands. Primary outcome measures were the frequency, type and duration of TCS treatment prescribed for LSnoVSCC and LSVSCC patients, separately. As a secondary outcome measure, reasons for treating or not treating patients with LSnoVSCC and LSVSCC with TCS were analysed. RESULTS: Forty-four GOs completed the survey, resulting in a response rate of 75%. TCS were prescribed more often to patients with LSnoVSCC as compared to patients with LSVSCC (86% versus 52%, respectively, p < 0.001). If treatment was initiated, ultra-potent (class IV) TCS were most commonly prescribed for an indefinite period of time for both patient groups. The most reported reason for treating patients in both groups with TCS was symptoms, followed by clinical aspects of the lesion and prevention of progression to dVIN and VSCC. CONCLUSION: The majority of GOs who participated in our study endorse the utilisation of long-term ultra-potent TCS therapy in both patients with LSnoVSCC and LSVSCC. Nevertheless, Dutch GOs are currently prescribing TCS more frequently to patients with LSnoVSCC than to patients with LSVSCC.
Vulvar lichen sclerosus (LS) is a chronic skin condition which may progress to vulvar squamous cell carcinoma (VSCC) through differentiated vulvar intraepithelial neoplasia (dVIN). LS symptoms are treated with topical corticosteroids (TCS), which can also prevent progression to dVIN and VSCC. However, current international guidelines do not give any recommendation on the treatment of LS following surgery for VSCC. To evaluate the current management of LS patients without a history of VSCC (LSnoVSCC) and patients with LS following surgery for VSCC (LSVSCC), a survey study was conducted among all gynaecologic oncologists (GOs) in The Netherlands. The findings of this study demonstrate that Dutch GOs prescribed TCS more often to patients with LSnoVSCC as compared to patients with LSVSCC. However, when deciding to prescribe TCS, the majority of Dutch GOs prescribed ultra-potent TCS for an indefinite period of time for both LSnoVSCC and LSVSCC patients.
Assuntos
Carcinoma in Situ , Carcinoma de Células Escamosas , Líquen Escleroso e Atrófico , Líquen Escleroso Vulvar , Neoplasias Vulvares , Feminino , Humanos , Líquen Escleroso e Atrófico/tratamento farmacológico , Neoplasias Vulvares/tratamento farmacológico , Neoplasias Vulvares/epidemiologia , Neoplasias Vulvares/cirurgia , Países Baixos/epidemiologia , Prevalência , Recidiva Local de Neoplasia , Líquen Escleroso Vulvar/tratamento farmacológico , Líquen Escleroso Vulvar/epidemiologia , Líquen Escleroso Vulvar/patologia , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/cirurgia , Carcinoma in Situ/patologia , Corticosteroides/uso terapêuticoRESUMO
INTRODUCTION: Vulvar lichen sclerosus (VLS) occurs in at least one in 900 girls. There is limited knowledge as to what extent the disease persists in adulthood and what the repercussions in adulthood may be. The aim of this study is to evaluate the long-term consequences of VLS diagnosed in childhood or adolescence. MATERIAL AND METHODS: The population of females histologically diagnosed with VLS in childhood or adolescence in the Netherlands between 1991 and 2015 was identified through the national pathology database. Histological specimens were retrieved and re-evaluated. Potential participants for whom the diagnosis was reconfirmed and who are now adults, were then traced and surveyed. Descriptive statistics were calculated and compared with the literature. Main outcome measures are the demographics of the cohort, their scores on standardized quality of life (QoL) and sexuality questionnaires and answers to additional questions regarding patients' experience with the disease. The questionnaires used were the Dermatology Life Quality Index (DLQI), the Skindex-29, the Female Sexual Function Index (FSFI) and the Female Sexual Distress Scale-Revised (FSDS-R). Secondary outcome measures include obstetric history and histological features found in the original tissue specimens. RESULTS: A total of 81 women participated, median age 29.0 years, median follow-up from childhood diagnosis 19.5 years. Both QoL and sexuality were somewhat affected in 51.9% of cases. Less than half (45%) reported having regular check-ups. Forty-five (56%) reported symptoms within the past year; of those with symptoms, 14 (31%) were not under surveillance. Cesarean section rate (14.5%) was comparable to the general population, and there were more high-grade obstetric anal sphincter injuries with vaginal deliveries than expected. Sixteen respondents (20%) were not aware of the childhood diagnosis prior to this study. CONCLUSIONS: Symptoms due to VLS are reported by most adults diagnosed as juveniles. QoL and sexuality are affected and correlate to recent symptoms. VLS as a juvenile does not preclude a vaginal delivery. Women diagnosed with VLS in childhood or adolescence are often lost to follow-up.
Assuntos
Líquen Escleroso e Atrófico , Líquen Escleroso Vulvar , Adulto , Humanos , Feminino , Adolescente , Gravidez , Líquen Escleroso Vulvar/diagnóstico , Líquen Escleroso Vulvar/complicações , Líquen Escleroso Vulvar/patologia , Estudos de Coortes , Qualidade de Vida , Cesárea , Comportamento Sexual , Líquen Escleroso e Atrófico/complicaçõesRESUMO
Vulvar lichen sclerosus (VLS) is a chronic inflammatory dermatosis of unknown pathogenesis, characterized by porcelain-white atrophic plaques around the vulvar and anal areas in girls. With this communication, we performed the study on 16 female girls with clinically and histologically confirmed VLS, described the main identifying characteristics of the lesions in reflectance confocal microscopy (RCM) and elucidated the corresponding relationship between RCM findings and histology. We recommend RCM, a noninvasive technique, as a complementary diagnostic tool for VLS.
Assuntos
Líquen Escleroso e Atrófico , Líquen Escleroso Vulvar , Neoplasias Vulvares , Feminino , Humanos , Líquen Escleroso Vulvar/diagnóstico por imagem , Líquen Escleroso Vulvar/patologia , População do Leste Asiático , Líquen Escleroso e Atrófico/diagnóstico por imagem , Líquen Escleroso e Atrófico/patologia , Vulva/diagnóstico por imagem , Vulva/patologia , Microscopia ConfocalRESUMO
ABSTRACT: Several vulvar lichen sclerosus (VLS) clinical severity scales have recently been proposed. In this prospective case series, we characterized histopathology in the context of clinical severity in 6 treatment-naïve postmenopausal patients with VLS. The Vulvar Quality of Life Index (VQLI) and an adaptation of the 2018 International Society for the Study of Vulvovaginal Disease Delphi consensus VLS severity score were administered. Vulvar skin punch biopsies were obtained to measure inflammatory density, constituent inflammatory cells, thickness of the stratum corneum and other epidermal layers, dermal edema, and dermal sclerosis. Clinicopathologic correlations were assessed. Two cases demonstrated sparse inflammatory densities, 1 case demonstrated patchy and nodular inflammatory density, 1 case demonstrated dense lichenoid inflammatory density, and 2 cases demonstrated dense lichenoid and epitheliotropic inflammatory densities. Those patients who reported severe pruritus demonstrated the greatest lymphocytic inflammatory densities on histopathological examination. Both cases of ulceration or erosion were associated with severe VQLI scores. Severe VQLI scores were also associated with trends for higher average thickness of the epidermal layers and of dermal sclerosis. Altogether, histopathologic grading of biopsy sites may reflect clinical severity in patients with VLS.
Assuntos
Líquen Escleroso e Atrófico , Líquen Escleroso Vulvar , Feminino , Humanos , Líquen Escleroso Vulvar/patologia , Qualidade de Vida , Esclerose/patologia , Vulva/patologia , Epiderme/patologia , Líquen Escleroso e Atrófico/patologiaRESUMO
Vulvar lichen planus (VLP) is a chronic inflammatory disease which adversely affects patients' quality of life. The pathogenesis of VLP is unknown although Th1 immune response has been implicated. We aimed to discover specific tissue-based protein biomarkers in VLP compared to normal vulvar tissue (NVT), vulvar lichen sclerosus (VLS) and oral lichen planus (OLP). We used laser capture microdissection-liquid chromatography- tandem mass spectrometry to assess protein expression in fixed lesional mucosal specimens from patients with VLP (n = 5). We then compared proteomic profiles against those of NVT (n = 4), VLS (n = 5), OLP (n = 6) and normal oral mucosa (n = 5), previously published by our group. IL16, PTPRC, PTPRCAP, TAP1 and ITGB2 and were significantly overexpressed in VLP compared to NVT. Ingenuity pathway analysis identified antigen presentation and integrin signalling pathways. Proteins overexpressed in both VLP versus NVT and OLP versus NOM included IL16, PTPRC, PTPRCAP, TAP1, HLA-DPB1, HLA-B and HLA-DRA. This proteomic analysis revealed several overexpressed proteins in VLP that relate to Th1 autoimmunity, including IL16. Overlapping pathways, including those involving IFNγ and Th1 signalling, were observed between VLP, VLS, and OLP.
Assuntos
Líquen Plano Bucal , Líquen Plano , Líquen Escleroso Vulvar , Feminino , Humanos , Líquen Escleroso Vulvar/patologia , Interleucina-16 , Proteômica , Qualidade de Vida , Líquen Plano/patologia , Mucosa BucalRESUMO
Vulvar lichen sclerosus is a chronic inflammatory disease involving vulvar skin. The risk of developing invasive vulvar cancer for women with LS is reported in the literature, but the risk of extra-vulvar tumors has been under-investigated. This multicentric study aims to estimate the risk of developing cancers in a cohort of women with a diagnosis of vulvar lichen sclerosus. METHODS: A cohort of women diagnosed with and treated for vulvar lichen sclerosus in three Italian gynecological and dermatological clinics (Turin, Florence, and Ferrara) was retrospectively reviewed. Patient data were linked to cancer registries of the respective regions. The risk of subsequent cancer was estimated by dividing the number of observed and expected cases by the standardized incidence ratio. RESULTS: Among 3414 women with a diagnosis of vulvar lichen sclerosus corresponding to 38,210 person-years of follow-up (mean 11.2 years) we identified 229 cancers (excluding skin cancers and tumors present at the time of diagnosis). We found an increased risk of vulvar cancer (standardized incidence ratio = 17.4; 95 % CL 13.4-22.7), vaginal cancer (standardized incidence ratio = 2.7; 95 % CL 0.32-9.771), and oropharyngeal cancer (standardized incidence ratio = 2.5; 95 % CL 1.1-5.0), and a reduced risk of other gynecological tumors (cervical, endometrial, ovarian) and breast cancer. CONCLUSIONS: Patients with vulvar lichen sclerosus should undergo annual gynecological check-up with careful evaluation of the vulva and vagina. The increased risk of oropharyngeal cancer also suggests the need to investigate oropharyngeal cavity symptoms and lesions in patients with vulvar lichen sclerosus.
Assuntos
Carcinoma de Células Escamosas , Líquen Escleroso e Atrófico , Neoplasias Orofaríngeas , Líquen Escleroso Vulvar , Neoplasias Vulvares , Humanos , Feminino , Líquen Escleroso Vulvar/complicações , Líquen Escleroso Vulvar/epidemiologia , Líquen Escleroso Vulvar/patologia , Líquen Escleroso e Atrófico/complicações , Líquen Escleroso e Atrófico/epidemiologia , Líquen Escleroso e Atrófico/patologia , Neoplasias Vulvares/complicações , Neoplasias Vulvares/epidemiologia , Estudos Retrospectivos , Carcinoma de Células Escamosas/complicações , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/patologia , Vulva/patologia , Neoplasias Orofaríngeas/complicações , Neoplasias Orofaríngeas/patologiaRESUMO
BACKGROUND: Vulvar lichen sclerosus (VLS) is a chronic and recurrent dermatosis of an inflammatory nature with severe focal atrophy of the skin. Connective tissue changes are polymorphic and are still not taken into account in histological diagnostics due to the difficulty of interpreting routine histological methods. In this work, we use multiphoton microscopy (MPM) as a new imaging technique that provides detailed information about the organization of collagen fibers in the dermis based on a non-linear second harmonic generation (SHG) process. OBJECTIVE: To determine the degree of connective tissue damage in lichen sclerosus using standard histological techniques and to reveal the diagnostic capabilities of multiphoton microscopy. MATERIAL AND METHODS: We studied 42 biopsies with a histopathological diagnosis of VLS and 10 biopsies of normal vulvar skin. Histological, histochemical and immunohistochemical evaluation was used in comparison with MPM data. Quantitative analysis included the determination of the thickness, length of collagen fibers and the average intensity of the SHG signal. RESULTS: A comprehensive study of the skin showed 4 groups of changes that can be regarded as the degree of the dermis damage: initial, mild, moderate, severe. The affected area at the initial and mild degree has subtle changes, however, it is reliably identified by quantitative analysis of the SHG signal. So, the initial degree is characterized by thin (1.3-1.8 µm) long (56-69 µm) collagen fibers, with a moderate degree, the fibers are thickened (3.4-4.3 µm) and fragmented (22-37 µm). The affected area in moderate and severe cases undergoes homogenization, which is associated with the deposition of extremely thin (0.6-0.9 µm) short (16-28 µm) collagen fibers and the expression of type V collagen. CONCLUSION: Multiphoton microscopy in the second harmonic generation mode is a reliable method for identifying collagen fibers in tissues. The study made it possible to identify 4 degrees of the dermis damage in vulvar lichen sclerosus.
Assuntos
Líquen Escleroso e Atrófico , Líquen Escleroso Vulvar , Feminino , Humanos , Líquen Escleroso Vulvar/diagnóstico , Líquen Escleroso Vulvar/patologia , Microscopia , Líquen Escleroso e Atrófico/diagnóstico , Líquen Escleroso e Atrófico/patologia , Pele/patologia , ColágenoRESUMO
OBJECTIVE: Oral lichen planus (OLP) is a mucosal variant of lichen planus. Lichen sclerosus (LS) is an inflammatory disorder with a predilection for genital skin. We aimed to identify the characteristics of patients with both mucosal diagnoses. STUDY DESIGN: This retrospective study included 86 women with both OLP and vulvar LS diagnosed from June 1, 1991 through November 30, 2020 at a Mayo Clinic campus in Rochester, Minnesota; Scottsdale, Arizona; or Jacksonville, Florida. Data included treatments, other cutaneous diagnoses, comorbidities, and information on patch testing and malignant transformation. RESULTS: The median patient age at diagnosis was 64.5 years for OLP and 65.6 years for vulvar LS. A diagnosis of OLP before vulvar LS was most common (50.0%). The most frequently used treatment for both conditions was topical corticosteroids. Oral squamous cell carcinoma (SCC) did not develop in any patient, but vulvar SCC developed in 2 (2.3%). CONCLUSIONS: OLP and vulvar LS may coexist, commonly beginning in the patient's seventh decade. Topical corticosteroids are often used to manage both conditions. The coexistence of both diseases did not seem to portend a greater malignancy risk.
Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Líquen Plano Bucal , Líquen Plano , Neoplasias Bucais , Líquen Escleroso Vulvar , Humanos , Feminino , Líquen Escleroso Vulvar/complicações , Líquen Escleroso Vulvar/tratamento farmacológico , Líquen Escleroso Vulvar/patologia , Líquen Plano Bucal/complicações , Líquen Plano Bucal/tratamento farmacológico , Líquen Plano Bucal/patologia , Estudos Retrospectivos , Carcinoma de Células Escamosas/complicações , Carcinoma de Células Escamosas/patologia , Líquen Plano/complicações , Neoplasias de Cabeça e Pescoço/complicações , Corticosteroides/uso terapêuticoRESUMO
OBJECTIVES: To investigate the histologic characteristics of vulvar tissues before and after completion of fractionated carbon dioxide (CO2 ) laser therapy (FxCO2) for vulvar lichen sclerosus (LS). The secondary objective was to assess subjective improvement in symptoms via the Skindex-16 questionnaire. METHODS: This prospective single-arm study was conducted from April 2021 to August 2022 at one academic medical center. Ten postmenopausal women with biopsy-proven LS planning FxCO2 laser treatment were enrolled. Exclusion criteria included prior transvaginal mesh for prolapse, topical corticosteroid use within 8 weeks, prior pelvic radiation, malignancy, active genital infection, or pregnancy. The vulvovaginal SmartXide2-V2-LR laser system fractionated CO2 laser (DEKA) was utilized to treat visually affected areas of vulvar and perianal LS with a single pass. Subjects underwent three treatments 4-6 weeks apart. Subjects completed the Skindex-16 questionnaire and had vulvar biopsy at baseline and at 4 weeks after completion of fractionated CO2 laser therapy. Blinded histologic slides were scored by one dermatopathologist (Michael A. Cardis) rating from 1 to 5 the degree of dermal sclerosis, inflammation, and epidermal atrophy. Change scores were calculated as the difference between pre- and post-treatment scores for each subject. RESULTS: The 10 subjects enrolled had a mean age of 61 and most were white, privately insured, and had a college/graduate-level education. Post-fractionated CO2 laser treatment vulvar biopsies showed significant improvement in sclerosis and epidermal atrophy compared with pretreatment baseline biopsy specimens (p < 0.05) with no statistically significant change found in inflammation score. Skindex-16 and FSFI scores showed a trend towards improvement (p > 0.05 for both). A statistically significant correlation was found between change in sclerosis and Skindex-16 symptoms scores with an average change of 21.4 units in Skindex-16 symptoms score for every one-point change in histologic sclerosis score (p = 0.03). CONCLUSIONS: In postmenopausal women with vulvar LS undergoing fractionated CO2 laser, symptomatic improvements correlated with histologic change in degree of sclerosis on vulvar biopsy. These results demonstrate FxCO2 laser therapy as a promising option for the treatment of LS and suggest that further studies should assess degree of sclerosis on histopathology.