Clinical implications of pediatric biliary intraepithelial neoplasia diagnosed from a choledochal cyst specimen.

BACKGROUND: Biliary intraepithelial neoplasia (BilIN), a noninvasive precursor of cholangiocarcinoma, can manifest malignant transformation. Since cholangiocarcinoma (CCA) may progress due to chronic inflammation in the bile ducts and gallbladder, choledochal cysts are considered a precursor to CCA. However, BilIN has rarely been reported in children, to date. METHODS: We reviewed medical records of patients (< 18 years of age, n = 329) who underwent choledochal cyst excision at Asan Medical Center from 2008 to 2022. BilIN was diagnosed in 15 patients. Subsequent analyses were performed of the demographics, surgical procedures, clinical course, and outcomes in these patients. Subgroup analysis and multivariate logistic regression test were performed to identify factors influencing BilIN occurrence. RESULTS: The mean age of the patients included in our study was 40.1 ± 47.6 months. In 15 patients, BilIN of various grades was diagnosed. Todani type I was prevalent in 80% of the patients. The median age at surgery was 17 months. During a mean follow-up of 63.3 ± 94.0 months, no adverse events such as stone formation in the remnant intrapancreatic common bile duct and intrahepatic duct or cholangiocarcinoma were observed, indicating a favorable outcome until now. CONCLUSIONS: The potential progression of choledochal cysts to BilIN in children was demonstrated. These results could underscore the importance of early and comprehensive excision of choledochal cysts, including resection margins for associated lesions and more thorough postoperative surveillance in patients with or at risk of BilIN.

Diagnosis of verruciform acanthotic vulvar intra-epithelial neoplasia (vaVIN) using CK17, SOX2 and GATA3 immunohistochemistry.

AIMS: Verruciform acanthotic vulvar intra-epithelial neoplasia (vaVIN) is an HPV-independent, p53 wild-type lesion with distinct morphology and documented risk of recurrence and cancer progression. vaVIN is rare, and prospective distinction from non-neoplastic hyperplastic lesions can be difficult. CK17, SOX2 and GATA3 immunohistochemistry has emerging value in the diagnosis of HPV-independent lesions, particularly differentiated VIN. We aimed to test the combined value of these markers in the diagnosis of vaVIN versus its non-neoplastic differentials in the vulva. METHODS AND RESULTS: CK17, SOX2 and GATA3 immunohistochemistry was evaluated on 16 vaVINs and 34 mimickers (verruciform xanthoma, lichen simplex chronicus, lichen sclerosus, psoriasis, pseudo-epitheliomatous hyperplasia). CK17 was scored as 3+ = full-thickness, 2+ = partial-thickness, 1+ = patchy, 0 = absent; SOX2 as 3+ = strong staining ≥ 10% cells, 2+ = moderate, 1 + =weak, 0 = staining in < 10% cells; and GATA3 as pattern 0 = loss in < 25% basal cells, 1 = loss in 25-75% basal cells, 2 = loss in > 75% basal cells. For analysis, results were recorded as positive (CK17 = 3+, SOX2 = 3+, GATA3 = patterns 1/2) or negative (CK17 = 2+/1+/0, SOX2 = 2+/1+/0, GATA3 = pattern 0). CK17, SOX2 and GATA3 positivity was documented in 81, 75 and 58% vaVINs, respectively, versus 32, 17 and 22% of non-neoplastic mimickers, respectively; ≥ 2 marker positivity conferred 83 sensitivity, 88 specificity and 86% accuracy in vaVIN diagnosis. Compared to vaVIN, SOX2 and GATA3 were differentially expressed in lichen sclerosus, lichen simplex chronicus and pseudo-epitheliomatous hyperplasia, whereas CK17 was differentially expressed in verruciform xanthoma and adjacent normal mucosa. CONCLUSIONS: CK17, SOX2 and GATA3 can be useful in the diagnosis of vaVIN and its distinction from hyperplastic non-neoplastic vulvar lesions. Although CK17 has higher sensitivity, SOX2 and GATA3 are more specific, and the combination of all markers shows optimal diagnostic accuracy.

Anal and Perianal Preneoplastic Lesions.

Anal cancer, mainly squamous cell carcinoma, is rare but increasing in prevalence, as is its precursor lesion, anal squamous dysplasia. They are both strongly associated with human papillomavirus infection. The 2-tiered Lower Anogenital Squamous Terminology classification, low-grade SIL and high-grade SIL, is preferred to the 3-tiered anal intraepithelial neoplasia classification because of better interobserver agreement and clearer management implications. Immunohistochemistry with p16 is helpful to corroborate the diagnosis of squamous dysplasia. Similarly, immunohistochemistry is helpful to differentiate primary Paget disease from secondary Paget disease, which is usually due to anal squamous mucosal/epidermal involvement by primary rectal adenocarcinoma.

A comprehensive review of anal cancer-with a special focus on anal cytology.

The diagnosis of anal cancer is relatively uncommon, but its incidence has been steadily increasing in high-risk populations. In the 2001 Bethesda System for Reporting Cervical Cytology, anal cytology was introduced as a component. Since then, it has been recognized as a potential tool for screening anal cancer, often in conjunction with high-resolution anoscopy. There are notable similarities between anal cancer and cervical cancer, including the causative role of human papillomavirus. However, there are also significant differences, particularly in terms of disease prevalence. Anal cytology may be used as a primary screening test, and in the event of abnormalities, patients are subsequently directed for high-resolution anoscopy. However, the best approach for anal cancer screening is yet to be determined and uniformly implemented. This comprehensive review article provides an in-depth analysis of the epidemiology and incidence of anal precursor and malignant lesions. It explores the various methods of sample procurement, preparation, interpretation (including sensitivity and specificity), and reporting terminology in anal cytology. The article also addresses the significance of concurrent high-risk human papillomavirus screening in anal cytology and its role in screening programs. Furthermore, it discusses the follow-up, prevention, and subsequent management strategies for anal cancers. By synthesizing current knowledge in these areas, this review aims to provide a comprehensive understanding of anal cytology and its implications in the early detection, prevention, and management of anal neoplasia and cancer.

Management of screening-detected lobular neoplasia in the era of digital breast tomosynthesis: A preliminary study.

PURPOSE: The purpose of this study is to determine upgrade rates of lobular neoplasia detected by screening digital breast tomosynthesis (DBT) and to determine imaging and clinicopathological features that may influence risk of upgrade. METHODS: Medical records were reviewed of consecutive women who presented with screening DBT-detected atypical lobular hyperplasia (ALH) and/or lobular carcinoma in situ (LCIS) from January 1, 2013, to June 30, 2020. Included patients underwent needle biopsy and had surgery or at least two-year imaging follow-up. Imaging and clinicopathological features were compared between upgraded and nonupgraded cases of lobular neoplasia using the Pearson's chi-squared test and the Wilcoxon signed-rank test. RESULTS: During the study period, 107 women (mean age 55 years, range 40-88 years) with 110 cases of ALH and/or LCIS underwent surgery (80.9%, n = 89) or at least two-year imaging follow-up (19.1%, n = 21). The overall upgrade rate to cancer was 5.5% (6/110), and the upgrade rate to invasive cancer was 3.6% (4/110). The upgrade rate of ALH to cancer was 4.1% (3/74), whereas the upgrade rate of LCIS to cancer was 9.4% (3/32) (p = .28). The upgrade rate of cases presenting as calcifications was 4.2% (3/71), whereas the upgrade rates of cases presenting as noncalcified findings was 7.7% (3/39) (p = .44). CONCLUSIONS: The upgrade rate of screening DBT-detected lobular neoplasia is less than 6%. Surveillance rather than surgery can be considered for lobular neoplasia, particularly in patients with ALH and in those with screening-detected calcifications leading to the diagnosis.

Serous endometrial intraepithelial carcinoma: a case report.

Serous endometrial intraepithelial carcinoma (SEIC) is a rare but highly aggressive form of uterine endometrial cancer. We report two cases of post-menopausal, 58-year-old patients with abundant vaginal bleeding and pelvic pain. The first patient had a history of surgical hysteroscopy in 2019 for an endocervical polyp. The second patient had a history of breast resection, axillary lymph node dissection, chemotherapy, radiation therapy, and tamoxifen therapy for breast carcinoma 6 years ago. An abdominal hysterectomy was performed in both patients. The pathological assessment showed serous endometrial intraepithelial carcinoma. Diagnosis of a serous proliferation of the uterus implies the exploration of other genital tract organs as well as distant locations in search of metastatic disease.

Sexually transmitted infections lesions found during colonoscopies

Introduction: Anal examination and videoanoscopy (VA) are rarely performed during colonoscopies. In recent years, there has been a considerable increase in lesions of sexually transmitted anal and rectal infections, but these conditions are not noticed or reported during routine colonoscopy. Objective: To raise awareness regarding the fortuitous findings of lesions and sexually transmitted infections (STIs) in colonoscopy exams and to demonstrate that anal examination and VA provide important information and should be routinely performed. Methods: We conducted a descriptive retrospective study in 16,132 patients screened by colonoscopy and VA between 2006 and 2018. Among numerous other findings, the presence of anal condylomata and sexually transmitted retitis or perianal dermatitis was observed. The rates of each finding were calculated, and the patients were subdivided by sex and into age groups by blocks of ten years. Results: Among the 16,132 colonoscopies performed, 26 cases of condyloma (0.16%) and 50 cases of proctitis or perianal dermatitis suspicious for STI (0.33%) were found. Conclusion: Performing anal examination and VA systematically in all routine colonoscopies enabled the identification of numerous anal conditions, including several fortuitous cases of STIs. The study proposes that anal examination and VA should be performed in all routine colonoscopies and, in suspected cases, complementary tests for STIs. (AU)

Anal Intraepithelial Neoplasia and Anal Squamous Cell Carcinoma: Updates From the Last 3 Years.

ABSTRACT: In the last 3 years, new and relevant information has been published on anal cancer and anal precancerous lesions epidemiology, screening, treatment, and vaccination. This information will likely change prevention and treatment strategies for these patients in the upcoming years.

Management of Lobular Neoplasia Diagnosed by Core Biopsy.

Lobular neoplasia (LN) involves proliferative changes within the breast lobules. LN is divided into lobular carcinoma in situ (LCIS) and atypical lobular hyperplasia (ALH). LCIS can be further subdivided into three subtypes: classic LCIS, pleomorphic LCIS, and LCIS with necrosis (florid type). Because classic LCIS is now considered as a benign etiology, current guidelines recommend close follow-up with imaging versus surgical excision. The goal of our study was to determine if the diagnosis of classic LN on core needle biopsy (CNB) merits surgical excision. This is a retrospective, observational study conducted at Mount Auburn Hospital, Cambridge, MA, from May 17, 2017, through June 30, 2020. We reviewed the data of breast biopsies conducted at our hospital over this period and included patients who were diagnosed with classic LN (LCIS and/or ALH) and excluded patients having any other atypical lesions on CNB. All known cancer patients were excluded. Of the 2707 CNBs performed during the study period, we identified 68 women who were diagnosed with ALH or LCIS on CNB. CNB was performed for an abnormal mammogram in the majority of patients (60; 88%) while 7(10.3%) had an abnormal breast magnetic resonance imaging study (MRI), and 1 had an abnormal ultrasound (US). A total of 58 patients (85%) underwent excisional biopsy, of which 3 (5.2%) showed malignancy, including 2 cases of DCIS and 1 invasive carcinoma. In addition, there was 1 case (1.7%) with pleomorphic LCIS and 11 cases with ADH (15.5%). The management of LN found on core biopsy is evolving, with some advocating surgical excision and others recommending observation. Our data show a change in diagnosis with excisional biopsy in 13 (22.4%) of patients with 2 cases of DCIS, 1 invasive carcinoma, 1 pleomorphic LCIS, and 9 cases of ADH, diagnosed on excisional biopsy. While ALH and classic LCIS are considered benign, the choice of ongoing surveillance versus excisional biopsy should be made with shared decision making with the patient, with consideration of personal and family history, as well as patient preferences.

Changes in cervical dysplasia, carcinoma in situ, and cervical cancer after expanding the National Cancer Screening Program to younger women in Korea.

The National Cancer Screening Program of South Korea for cervical cancer was expanded from women aged ≥30 years to women aged ≥20 years in 2016. This study investigated the effect of this policy on occurrence rates of cervical dysplasia, carcinoma in situ, and cervical cancer in women in their twenties. The National Health Information Database for the years 2012-19 was used. The outcome measures were monthly occurrence rates of cervical dysplasia, cervical carcinoma in situ, and cervical cancer. An interrupted time series analysis was performed to investigate whether the number of occurrences changed after policy implementation. For cervical dysplasia, a pre-intervention decreasing trend of 0.3243 per month (P-value < .0001) was found. The post-intervention trend did not differ significantly, although the slope increased at a rate of 0.4622 per month (P-value < .0001). For carcinoma in situ, a trend of increase at 0.0128 per month (P-value = .0099) was seen before policy implementation. The post-intervention trend did not escalate, but the slope showed an increasing trend of 0.0217 per month (P-value < .0001). For cervical cancer, no significant trend was present before intervention. Occurrences of cervical cancer escalated at a rate of 0.0406 per month (P-value < .0001) after policy implementation, and the slope also showed an increasing trend at a rate of 0.0394 per month (P-value < .0001). Expanding the target population for cervical cancer screening increased detection rates for cervical cancer in women aged between 20 and 29 years.

Clinical validation of methylation biomarkers for optimal detection of high-grade vulvar intraepithelial neoplasia.

The precursor lesions of vulvar squamous cell carcinoma (VSCC) include human papillomavirus (HPV)-associated and HPV-independent squamous neoplasia with a varying cancer risk. Our study aimed to validate the accuracy of previously identified DNA methylation markers for detection of such high-grade vulvar intraepithelial neoplasia (VIN). A large clinical series of 751 vulvar lesions, originally diagnosed as high-grade VIN, were reassessed and categorized into HPV-associated or HPV-independent vulvar disease categories. Together with 113 healthy vulvar controls, all samples were tested for 12 methylation markers with quantitative multiplex methylation-specific PCR (qMSP). Performance of individual markers and selection of an optimal marker panel for detection of high-grade VIN was determined by logistic regression analysis. SST was the best-performing individual marker (AUC 0.90), detecting 80% of high-grade VIN cases, with excellent detection of HPV-independent VIN (95%), known to have the highest cancer risk. Merely 2% of controls tested methylation positive for SST. Selection of a marker panel, including ZNF582, SST and miR124-2, resulted in a comparably high accuracy for detection of high-grade VIN (AUC 0.89). In conclusion, we clinically validated the accuracy of 12 DNA methylation markers for detection of high-grade VIN. SST, as a sole marker or in a panel, provides an optimal diagnostic tool to distinguish high-grade VIN in need of treatment, particularly HPV-independent VIN, from low-grade or reactive vulvar lesions. These findings warrant further prognostic validation of methylation biomarkers for cancer risk stratification of patients with VIN.

Consensus based recommendations for the diagnosis of serous tubal intraepithelial carcinoma: an international Delphi study.

AIM: Reliably diagnosing or safely excluding serous tubal intraepithelial carcinoma (STIC), a precursor lesion of tubo-ovarian high-grade serous carcinoma (HGSC), is crucial for individual patient care, for better understanding the oncogenesis of HGSC, and for safely investigating novel strategies to prevent tubo-ovarian carcinoma. To optimize STIC diagnosis and increase its reproducibility, we set up a three-round Delphi study. METHODS AND RESULTS: In round 1, an international expert panel of 34 gynecologic pathologists, from 11 countries, was assembled to provide input regarding STIC diagnosis, which was used to develop a set of statements. In round 2, the panel rated their level of agreement with those statements on a 9-point Likert scale. In round 3, statements without previous consensus were rated again by the panel while anonymously disclosing the responses of the other panel members. Finally, each expert was asked to approve or disapprove the complete set of consensus statements. The panel indicated their level of agreement with 64 statements. A total of 27 statements (42%) reached consensus after three rounds. These statements reflect the entire diagnostic work-up for pathologists, regarding processing and macroscopy (three statements); microscopy (eight statements); immunohistochemistry (nine statements); interpretation and reporting (four statements); and miscellaneous (three statements). The final set of consensus statements was approved by 85%. CONCLUSION: This study provides an overview of current clinical practice regarding STIC diagnosis amongst expert gynecopathologists. The experts' consensus statements form the basis for a set of recommendations, which may help towards more consistent STIC diagnosis.

Urothelial carcinoma in situ with "overriding" features can evade detection by mimicking umbrella cells.

Urothelial carcinoma in situ (uCIS) is typically recognized by overtly malignant cells with characteristic nuclear features; multiple histologic patterns have been described. A rare "overriding" pattern, in which uCIS tumor cells extend on top of normal urothelium, has previously been mentioned in the literature, but not well described. Herein, we report 3 cases of uCIS with "overriding" features. Detailed morphologic evaluation revealed somewhat subtle cytologic atypia: variably enlarged hyperchromatic nuclei and scattered mitotic figures but with abundant cytoplasm and limited to superficial urothelium. Immunohistochemical (IHC) analysis showed a distinctive diffuse positive aberrant p53 pattern, limited to the atypical surface urothelial cells; these cells also showed CK20+, CD44-, and increased Ki-67. In 2 cases, there was a history of urothelial carcinoma and adjacent conventional uCIS. In the third case, the "overriding" pattern was the first presentation of urothelial carcinoma; therefore, next-generation sequencing molecular testing was also performed, revealing pathogenic mutations in TERTp, TP53, and CDKN1a to further support neoplasia. Notably, the "overriding" pattern mimicked umbrella cells, which normally line surface urothelium, can have abundant cytoplasm and more variation in nuclear and cell size and shape, and show CK20+ IHC. We therefore also evaluated umbrella cell IHC patterns in adjacent benign/reactive urothelium, which showed CK20+, CD44-, p53 wild-type, and very low Ki-67 (3/3). We also reviewed 32 cases of normal/reactive urothelium: all showed p53 wild-type IHC in the umbrella cell layer (32/32). In conclusion, caution is warranted to avoid overdiagnosis of usual umbrella cells as CIS; however, "overriding" uCIS should be recognized, may have morphologic features that fall short of the diagnostic threshold of conventional CIS, and requires further study.

Vulvar intraepithelial neoplasia, grade III, treated with photodynamic therapy: A case report.

Vulvar intraepithelial neoplasia (VIN) is a precancerous lesion on the vulvar epidermis that does not invade or metastasize to surrounding stroma; it manifests as atypical intraepithelial hyperplasia on the vulva. Most patients with VIN are diagnosed early, and treatment with standardized therapy often leads to complete regression of symptoms. The treatment of VIN is still a challenge for clinicians because, in most cases, surgery is destructive and risky. However, photodynamic therapy (PDT) was recommended as a new treatment for VIN. Herein, we report the case of a patient with a large-area high-grade VIN lesion complicated by human papillomavirus infection. The patient could not undergo surgical treatment. However, treatment with PDT was performed in our outpatient department. There was slight pain during the treatment after multi-point injection of micro-lidocaine (0.05 mL/dot) was given. No recurrence was noted after 13 months of follow-up. More importantly, scarring and other major side effects were not detected. Therefore, PDT can be a useful alternative treatment for patients with VIN with large lesions or multifocal high-grade VIN.

Nuestra experiencia en el manejo diagnóstico-terapéutico a corto plazo del paciente con displasia anal / Our experience in the short-term diagnostic-therapeutic management of the patient with anal dysplasia

Introducción: La neoplasia intraepitelial anal (NIA) es una lesión premaligna del carcinoma escamoso anal. Los varones VIH que tienen sexo con varones, es la población de riesgo más afectada. La citología y anuscopia son los métodos mejor aceptados para su diagnóstico, aunque es controvertido qué pacientes deben completarlo con una biopsia. Tampoco está bien establecido qué pacientes deben someterse a tratamiento y cuál es el mejor. Con este estudio, queremos exponer nuestra experiencia en el manejo diagnóstico-terapéutico de la NIA a corto plazo. Métodos: Estudio observacional retrospectivo de pacientes con riesgo de NIA con una citología anal alterada a los que se les realizó una anuscopia de alta resolución con biopsia. Tras la confirmación histológica de displasia iniciaron tratamiento con ácido tricloroacético. Se comprobó su efectividad con una citología posterior. Se analizaron las variables demográficas de la muestra y los resultados de las pruebas diagnósticas y de tratamiento. Resultados: La mayoría eran varones VIH positivos (104/115) y el 50% mantenían relaciones sexuales con otros varones. Se incluyeron 115 pacientes con citología anal alterada, de los cuales el 92% presentaron displasia en la biopsia. El 97% con atipia de significado incierto en la citología presentaron displasia histológicamente. El 60% de los pacientes normalizó la citología tras el tratamiento. Conclusión: Se debe considerar de forma sistemática la detección precoz de la NIA en poblaciones de riesgo conocidas. Cualquier anormalidad citológica debe ser biopsiada. El ácido tricloroacético puede ser un tratamiento efectivo consiguiendo un alto porcentaje de regresión, aunque actualmente la información con la que contamos es de bajo nivel de evidencia. (AU)

Introduction: Anal intraepithelial neoplasia (AIN) is a premalignant lesion of anal squamous cell carcinoma. HIV-positive males who have sex with males, are the most affected at-risk population. Cytology and anuscopy are the best accepted methods for its diagnosis, although it is controversial which patients should complete it with a biopsy. Neither which patients should undergo treatment nor which is the best treatment is not well established. With this study, we would like to present our experience in the diagnostic-therapeutic management of AIN in the short term. Methods: Retrospective observational study of patients at risk of AIN with altered anal cytology who underwent high-resolution anuscopy with biopsy. After histological confirmation of dysplasia, they started treatment with trichloroacetic acid. Its effectiveness was verified by subsequent cytology. The demographic variables of the sample and the results of both diagnostic and treatment tests were analyzed. Results: The majority were HIV-positive males (104/115) and 50% had sexual relations with other men. We included 115 patients with altered anal cytology, of whom 92% had dysplasia on biopsy. 97% with atypia of uncertain significance on cytology had histological dysplasia. Cytology normalized after treatment in 60% of patients. Conclusion: Early detection of AIN should be routinely considered in known at-risk populations. Any cytological abnormality should be biopsied. Tricholoroacetic acid can be an effective treatment achieving a high percentage of regression, although currently, the information we have is of low level of evidence. (AU)

Interobserver Agreement Across Subspecialties for Diagnosis of Differentiated Vulvar Intraepithelial Neoplasia and Predictive Values of 20 Histologic Features.

CONTEXT.­: Differentiated vulvar intraepithelial neoplasia (dVIN) is a human papillomavirus-independent lesion with the potential for rapid progression to invasive squamous cell carcinoma (SCC). The histopathologic features of dVIN are diverse, have overlapping characteristics with lichen sclerosus (LS) and lichen simplex chronicus (LSC), and may be diagnosed by dermatopathologists or gynecologic pathologists because of the vulva's anatomic location. OBJECTIVES.­: To identify the salient histopathologic features of dVIN, particularly those that predict progression to SCC, and to evaluate interobserver agreement in diagnosing dVIN within the same subspecialty and across subspecialties. DESIGN.­: One general surgical pathologist, 2 pathology-trained dermatopathologists, and 1 gynecologic pathologist blinded to the final diagnoses were asked to record 20 histopathologic features and to provide their final interpretations on cases of dVIN (n = 65), LS (n = 126), LSC (n = 112), and LS with LSC (n = 6). RESULTS.­: Interobserver agreement for the 4 diagnoses and 10 histopathologic features was moderate. Logistic regression analysis indicated that keratin pearls, basal pleomorphism, and basal layer disarray were independent variables for diagnosing dVIN (coefficients 1.95, 1.97, and 0.91, respectively; P < .001) and progression to SCC (coefficients 1.96, 1.20, and 1.08, respectively; P < .001). CONCLUSIONS.­: There is no single histopathologic feature pathognomonic for dVIN; however, the presence of keratin pearls, basal pleomorphism, and basal layer disarray should raise high suspicion for dVIN and concurrent SCC. Expertise in both dermatologic and gynecologic pathology is beneficial for diagnosing dVIN.

Extramammary Paget's Disease of the Vulva and Concomitant Premalignant/Malignant Vulvar Lesions: A Potential Challenge in Diagnosis and Treatment.

The aim of the present study was to evaluate the incidence of concomitant vulvar cancers or premalignant lesions in women surgically treated for extramammary Paget's disease of the vulva (EMPDV) through a multicenter case series. The medical records of all women diagnosed with and treated for EMPDV from January 2010 to December 2020 were retrospectively analyzed. Women with EMPDV and synchronous vulvar cancer, vulvar intraepithelial neoplasia (VIN) and/or lichen sclerosus (LS) at the histology report were included in the study. A total of 69 women eligible for the present study were considered. Concomitant vulvar lesions occurred in 22 cases (31.9%). A total of 11 cases of synchronous VIN (50%) and 14 cases (63.6%) of concomitant LS were observed. One patient (4.5%) had synchronous vulvar SCC (FIGO stage 1B). Women with EMPDV and concomitant premalignant/malignant vulvar lesions had a significantly higher rate of invasive EMPDV and wider lesions with an extravulvar involvement. The specific meaning of the association between EMPDV, VIN, SCC and LS remains unclear. The potential overlapping features between different vulvar lesions highlight the importance of dedicated gynecologists and pathologists in referral centers.