RESUMEN
Vulvar intraepithelial neoplasia, also known as VIN, is a non-invasive squamous lesion and precursor of squamous cell carcinoma (SCC) of the vulva. There is no screening test for vulvar intraepithelial neoplasia. Diagnosis of VIN is made clinically and confirmed with a biopsy. We describe a 66-year-old woman with a condyloma-like tumour located in the skin on the vestibule of the vagina. A biopsy sample was taken from the nodule. The definitive diagnosis is supported by the histological examination (VIN III) and immunohistochemical examination of p16(+), p53(+), and a few cell nuclei. The case provides information on the importance of multidisciplinary cooperation. Lifelong surveillance is essential since the resection of individual lesions does not guarantee the prevention of invasive cancer.
RESUMEN
Objective: To evaluate predictors of recurrence and the risk of progression to carcinoma in patients with dVIN. Methods: 36 self-identified White patients with dVIN from 2011 to 2022 were identified. Demographics, treatment and clinical course were abstracted. Histopathologic features and IHC stains were reviewed by 2 subspecialty pathologists. Standard statistical analyses were applied. Results: Median cohort age was 70 years (range 39-91). Median follow-up was 29.5 months (range 1-123). All patients were Caucasian. 67% had lichen sclerosus (LS) adjacent to dVIN. 56% of patients had recurrent dVIN a median of 11 months from diagnosis. 14 patients had invasive squamous cell carcinoma of the vulva (SCCV) during the study period: 9 (25%) with synchronous dVIN, 5 (14%) developed SCCV after a median of 21.5 months (range 8-57). Patients treated with surgery were more likely to have recurrent/persistent dVIN (p = 0.04) and synchronous or progression to SCCV (p = 0.02) than patients treated with topical therapy. Excluding 9 women with synchronous SCCV, no initial treatment (observation, topical therapy, surgery) was superior at preventing recurrent/ progressive disease in isolated dVIN. Mutation-type p53 expression was identified in 18 (64%) and aberrant GATA3 staining/expression in 20 (56%) of cases. Aberrant GATA3 expression was associated with a higher frequency of synchronous/progression to SCCV (p < 0.05). Conclusion: dVIN has an aggressive clinical course in white patients with a high risk of recurrence/persistence and synchronous/progression to SCCV despite treatment. Close surveillance with a low threshold for additional biopsies is warranted. P53 and GATA3 IHC stains may be useful markers of disease outcome.
RESUMEN
INTRODUCTION: Differentiated vulvar intraepithelial neoplasia (dVIN) is a high-risk preinvasive vulvar lesion and precursor of human papillomavirus-independent vulvar squamous cell carcinoma (VSCC). Due to its rarity, literature data on its malignant potential are scant. The aim of the study is to assess the risk of developing VSCC in patients surgically treated for dVIN not associated with VSCC (solitary dVIN) and the risk of VSCC recurrence in patients treated for dVIN associated with VSCC (dVIN-VSCC) at first diagnosis. MATERIAL AND METHODS: A historical cohort study was performed in a northern Italy referral center for vulvar neoplasms. All consecutive women surgically treated for histologically confirmed dVIN from 1994 to 2021 were collected. Primary outcome was cancer risk or recurrent cancer risk, secondary outcomes were risk factors associated with VSCC development or recurrence. Kaplan-Meier method and log-rank test were used to estimate cancer risk or recurrent cancer risk differences and uni- and multivariate Cox regression analyses to identify risk factors associated with VSCC development in solitary dVIN and recurrence of dVIN-VSCC. RESULTS: Seventy-six patients with dVIN at preoperative biopsy were included: at excisional specimens 44 were solitary dVIN and 32 were dVIN-VSCC. The absolute risk of VSCC development after solitary dVIN treatment was 43.2% with median time to to VSCC diagnosis of 25.4 months (range 3.5-128.0 months). VSCC recurrence absolute risk in treated dVIN-VSCC patients was 31.3% with median time to VSCC recurrence of 52.9 months (range 6.5-94.8 months). At uni- and multivariate regression analyses, only compliant topical ultrapotent corticosteroid treatment after solitary dVIN excision showed an ability to prevent VSCC development. No protective effect by corticosteroid treatment was shown for VSCC recurrence in dVIN-VSCC patients. Smoking was associated with higher cancer recurrence risk in dVIN-VSCC patients on both uni- and multivariate regression analyses. CONCLUSIONS: Patients with dVIN have a high risk of developing both primary and recurring VSCC. Early recognition, long-term follow up, and compliant ultrapotent topical corticosteroid treatment are recommended.
Asunto(s)
Carcinoma in Situ , Carcinoma de Células Escamosas , Recurrencia Local de Neoplasia , Neoplasias de la Vulva , Humanos , Femenino , Neoplasias de la Vulva/patología , Carcinoma in Situ/patología , Carcinoma in Situ/terapia , Persona de Mediana Edad , Recurrencia Local de Neoplasia/epidemiología , Carcinoma de Células Escamosas/patología , Pronóstico , Estudios de Seguimiento , Estudios de Cohortes , Adulto , Factores de Riesgo , Anciano , Italia/epidemiologíaRESUMEN
Herein, the authors evaluate the diagnostic utility and limitations of GATA3 immunohistochemistry for the distinction of differentiated vulvar intraepithelial neoplasia (dVIN) from its potential mimics. Immunohistochemical studies for GATA3, p53, and p16 were performed on 124 pathologic vulvar tissues, inclusive of dVIN (n = 21), vulvar aberrant maturation (n = 10), high-grade squamous intraepithelial lesion (HSIL) (n = 44), and 49 non-neoplastic vulvar dermatoses of various types. GATA3 expression was scored using a modification of previously proposed criteria: pattern 0 (no significant loss of basal layer staining, >75% staining), pattern 1 (25-75% staining), and pattern 2 (<25% staining). With the exception of lichen sclerosus, 8% of which showed pattern 1 or 2 staining, all other non-neoplastic lesions showed pattern 0 expression. Aberrant GATA3 expression (i.e., patterns 1 or 2) was present in 90% of dVIN cases (2 [9.5%], 3 [14.3%], 16 [76.2%] with patterns 0, 1, and 2 respectively), 90% of vulvar aberrant maturation cases (1 [10%],7 [70%], 2 [20%] with patterns 0, 1, and 2 respectively), and 15.9% of HSIL cases (84.1% pattern 0; 2.3% pattern 1; 13.6% pattern 2). All HSIL cases were p16 positive, including the 7 pattern 1 and 2 cases. All cases of dVIN-like HSIL were pattern 0, and all (n = 2) cases of HSIL-like (basaloid) dVIN were pattern 2 (both of the latter cases displayed complete absence of epidermal staining). Only 1 dVIN case was both pattern 0 and p53-wild-type. We conclude that GATA3 is useful for the distinction of dVIN from non-neoplastic dermatoses and from HSIL, but is best used as part of a panel that includes p53 and p16 to mitigate its limitations.
Asunto(s)
Carcinoma in Situ , Carcinoma de Células Escamosas , Enfermedades de la Piel , Lesiones Intraepiteliales Escamosas , Neoplasias de la Vulva , Femenino , Humanos , Inmunohistoquímica , Biomarcadores de Tumor/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Carcinoma in Situ/patología , Neoplasias de la Vulva/diagnóstico , Neoplasias de la Vulva/patología , Carcinoma de Células Escamosas/patología , Factor de Transcripción GATA3/metabolismoRESUMEN
Abnormal p53 (p53abn) immunohistochemical (IHC) staining patterns can be found in vulvar squamous cell carcinoma (VSCC) and differentiated vulvar intraepithelial neoplasia (dVIN). They can also be found in the adjacent skin that shows morphology that falls short of the traditional diagnostic threshold for dVIN. Vulvectomy specimens containing human papillomavirus-independent p53abn VSCC with margins originally reported as negative for invasive and in situ disease were identified. Sections showing the closest approach by invasive or in situ neoplasia to margins were stained with p53 IHC stains. We evaluated the following: (1) detection of morphologically occult p53abn in situ neoplasia, (2) rates of margin status change after p53 IHC staining, and (3) effect of p53abn IHC staining at margins on the 2-year local recurrence rates. Seventy-three human papillomavirus-independent p53abn VSCCs were included. Half (35/73, 48%) had documented an in situ lesion in the original report. The use of p53 IHC staining identified 21 additional cases (29%) with the p53abn in situ lesions that were originally unrecognized. The histology of in situ lesions in the p53abn "field" varied and became more subtle (morphologically occult) farther away from the VSCC. Fifteen (21%) cases had a morphologically occult and previously unrecognized p53abn in situ lesion present at a resection margin, which conferred an increased risk of local recurrence (5/7 [71.4%] vs 6/22 [27.3%], P = .036). The p53abn in situ lesions at a margin were confirmed to have TP53 mutations by sequencing. p53 IHC staining identified morphologically occult p53abn in situ lesions surrounding human papillomavirus-independent VSCC. p53abn IHC staining at a margin was associated with a 3-fold increased risk of local recurrence.
Asunto(s)
Carcinoma in Situ , Carcinoma de Células Escamosas , Lesiones Intraepiteliales Escamosas , Neoplasias de la Vulva , Humanos , Femenino , Virus del Papiloma Humano , Proteína p53 Supresora de Tumor , Hiperplasia , Carcinoma de Células Escamosas/cirugíaRESUMEN
A number of changes have been introduced into the 5th Edition of the World Health Organization (WHO) Classification of squamous and glandular neoplasms of the vulva and vagina. This review highlights the major shifts in tumor classification, new entities that have been introduced, recommendations for p16 immunohistochemical testing, biomarker use, molecular findings and practical points for pathologists which will affect clinical care. It also touches upon several issues that still remain answered in these rare but undeniably important women's cancers.
Asunto(s)
Carcinoma in Situ , Carcinoma de Células Escamosas , Neoplasias de la Vulva , Carcinoma in Situ/diagnóstico , Carcinoma in Situ/patología , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patología , Femenino , Humanos , Vagina/patología , Vulva/patología , Neoplasias de la Vulva/diagnóstico , Neoplasias de la Vulva/patologíaRESUMEN
Differentiated vulvar intraepithelial neoplasia (dVIN) is the precursor of human papillomavirus (HPV)-independent vulvar squamous cell carcinoma (VSCC). Given the rare incidence of dVIN, limited information on the exact cancer risk is available. We systematically reviewed the primary and recurrent VSCC risk in patients with dVIN, as well as the time to cancer development. A systematic search was performed up to July 2021 according to the PRISMA guidelines. Five reviewers independently screened articles on title, abstract and full text, followed by critical appraisal of selected articles using the Quality in Prognostic Studies (QUIPS) tool. Of the 455 screened articles, 7 were included for analysis. The absolute risk for primary VSCC in dVIN varied between 33 and 86%, with a median time to progression to VSCC of 9-23 months. The risk of developing recurrent VSCC in dVIN associated VSCC was 32-94%, with a median time to recurrence of 13-32 months. In conclusion, patients with dVIN have a high risk of developing primary and recurrent VSCC with a short time to cancer progression. Increased awareness, timely recognition, aggressive treatment and close follow-up of HPV-independent vulvar conditions including dVIN is therefore strongly recommended.
RESUMEN
Vulvar squamous cell carcinoma (VSCC) develops from high-grade squamous intraepithelial lesions (HSIL) and differentiated vulvar intraepithelial neoplasia (dVIN). This study aimed to assess the diagnostic value of circulating hsa-miR-431-5p in vulvar precancers and VSCC. Expression levels of hsa-miR-431-5p were analyzed by quantitative RT-PCR in plasma samples of 29 patients with vulvar precancers (HSIL or dVIN), 107 with VSCC as well as 15 healthy blood donors. We used hsa-miR-93-5p and hsa-miR-425-5p as normalizers. The levels of miR-431-5p were increased in the blood of patients with VSCC compared to those with vulvar precancers. Statistically significant differences in the survival rates (time to progression) were revealed for VSCC patients categorized by miR-431-5p levels. Low levels of circulating miR-431-5p were found to be indicative of unfavorable survival rates. In summary, our data reveal the diagnostic potential of circulating miR-431-5p in patients with vulvar precancers and VSCC.
RESUMEN
AIMS: Differentiated vulvar intraepithelial neoplasia (dVIN), the precursor lesion to human papillomavirus-independent vulvar squamous cell carcinoma (VSCC), can be difficult to distinguish from vulvar inflammatory dermatoses. Our goal was to determine if p53 could be a useful biomarker for dVIN, by characterizing p53 percentage, intensity and patterns of staining in dVIN and its histological mimics. METHODS AND RESULTS: We studied p53 immunohistochemical staining patterns in 16 dVIN cases and 46 vulvar non-neoplastic squamous lesions [12 lichen sclerosus (LS); seven lichen simplex chronicus; three lichen planus (LP); six psoriasis; 13 spongiotic dermatitis (SPO); and five candidiasis]. dVIN cases were adjacent to a p16-negative invasive VSCC in resection specimens. All dVIN cases showed null-type or moderate to strong uniform p53 staining in >70% of basal cells, with moderate to strong continuous parabasal staining extending to two-thirds of the epidermis. This was in contrast to weak or weak to moderate patchy p53 staining in the majority of other lesions. Moderate to strong and increased basal p53 staining (≥70%) was also observed in a subset of LS cases (5/12, 42%), LP cases (1/3, 33%), and SPO cases (36%, 4/11); however, in all categories, this was limited to the basal layer, and any staining in the parabasal layers was patchy. CONCLUSION: Strong and uniform p53 staining of basal cells, extending into the parabasal layers, and a complete absence of staining (null type) is useful in distinguishing dVIN from other mimics in the vulva. p53 staining of lesser intensity or quantity, particularly basal overexpression only, overlaps with that in vulvar inflammatory lesions.
Asunto(s)
Carcinoma in Situ/diagnóstico , Inmunohistoquímica/métodos , Proteína p53 Supresora de Tumor/análisis , Neoplasias de la Vulva/diagnóstico , Biomarcadores de Tumor/análisis , Candidiasis/diagnóstico , Candidiasis/patología , Carcinoma in Situ/patología , Dermatitis/diagnóstico , Dermatitis/patología , Diagnóstico Diferencial , Técnicas y Procedimientos Diagnósticos , Femenino , Humanos , Liquen Escleroso y Atrófico/diagnóstico , Liquen Escleroso y Atrófico/patología , Neurodermatitis/diagnóstico , Neurodermatitis/patología , Psoriasis/diagnóstico , Psoriasis/patología , Sensibilidad y Especificidad , Enfermedades de la Piel/diagnóstico , Enfermedades de la Piel/patología , Vulva/patología , Neoplasias de la Vulva/patologíaRESUMEN
Vulvar squamous cell carcinomas (VSCC), which constitute over 90% of vulvar malignancies in adults, are classifiable into 2 subgroups that are mostly clinicopathologically distinct, a classification that is fundamentally based whether or not the tumors are HPV-mediated. In this review, we aim to summarize the recent advances in the understanding of molecular events in the pathogenesis of VSCC, including common and targetable mutations, copy number alterations, epigenetics, noncoding RNAs, and tumor immune microenvironment, which may provide insight into the future management of the disease. These events show substantial differences between the 2 subgroups, although significant areas of overlap exist. Recurrent, driver mutations appear to be substantially more prevalent in HPV(-) VSCC. TP53 mutations are the most common somatic mutations in VSCC overall, and are notably predominant in the HPV(-) VSCC, where 30-88% show a mutation. TP53 mutations are associated with worse patient outcomes, and co-mutations between TP53 and either HRAS, PIK3CA or CDKN2A appear to define subsets with even worse outcomes. A wide variety of other somatic mutations have been identified, including a subset with different mutational frequencies between HPV(+) and HPV(-) VSCC. CDKN2A mutations are common, and have been identified in 21 to 55% of HPV(-) VSCC, and in 2 to 25% of HPV(+) VSCC. Hypermethylation of CDKN2A is the most frequently reported epigenetic alteration in VSCC and the expression of some microRNAs may be associated with patient outcomes. The PTEN/PI3K/AKT/mTOR pathway is commonly altered in HPV(+) VSCC, and is accordingly potentially targetable. HPV-positivity/p16 block expression by immunohistochemistry has been found to be an independent prognostic marker for improved survival in VSCC, and may have some predictive value in VSCC patients treated with definitive radiotherapy. 22-39.3% and 68% of VSCC show EGFR amplification and protein overexpression respectively, although the prognostic and predictive value of an EGFR alteration requires additional study. Recurrent chromosomal gains in VSCCs have been found at 1q, 2q, 3q, 4p, 5p, 7p, 8p, 8q, and 12q, and there may be differential patterns of alterations depending on HPV-status. At least one-third of VSCC patients may potentially benefit from immune checkpoint inhibition therapy, based on a high frequency of PD-L1 expression or amplification, or a high tumor mutational burden. Additional studies are ultimately required to better understand the global landscape of genetic and epigenetic alterations in VSCC, and to identify and test potential targets for clinical application.
Asunto(s)
Carcinoma in Situ/genética , Carcinoma de Células Escamosas/genética , Variaciones en el Número de Copia de ADN , Transducción de Señal , Neoplasias de la Vulva/genética , Carcinoma in Situ/patología , Carcinoma in Situ/terapia , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/terapia , Fosfatidilinositol 3-Quinasa Clase I/genética , Fosfatidilinositol 3-Quinasa Clase I/metabolismo , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , Epigenómica , Femenino , Humanos , Inmunohistoquímica , Mutación , Fosfohidrolasa PTEN/genética , Fosfohidrolasa PTEN/metabolismo , Infecciones por Papillomavirus/patología , ARN no Traducido/genética , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/metabolismo , Microambiente Tumoral , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Neoplasias de la Vulva/patología , Neoplasias de la Vulva/terapiaRESUMEN
BACKGROUND/AIM: Differentiated vulvar intraepithelial neoplasia (dVIN) and lichen sclerosus (LS) can give rise to vulvar squamous cell carcinoma (VSCC), but genetic evidence is currently still limited. We aimed to determine genetic abnormalities in VSCC and backtrack these abnormalities in the dVIN and LS lesions. MATERIALS AND METHODS: DNA from VSCC and patient-matched dVIN and LS samples of twelve patients was collected. High-resolution genome-wide copy number analysis was performed and subsequently, we sequenced TP53. RESULTS: Copy number alterations were identified in all VSCC samples. One dVIN lesion presented with three copy number alterations that were preserved in the paired VSCC sample. Targeted sequencing of TP53 identified mutations in five VSCCs. All five mutations were traced back in the dVIN (n=5) or the LS (n=1) with frequencies ranging from 3-19%. CONCLUSION: Our data provide genetic evidence for a clonal relationship between VSCC and dVIN or LS.
Asunto(s)
Carcinoma in Situ/genética , Carcinoma de Células Escamosas/genética , Liquen Escleroso y Atrófico/genética , Neoplasias de la Vulva/diagnóstico por imagen , Neoplasias de la Vulva/genética , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Persona de Mediana EdadRESUMEN
The pathogenesis of vulvar squamous neoplasia has 2 pathways: human papillomavirus (HPV)-dependent and HPV-independent. The HPV-dependent pathway in the vulva follows the same progression as HPV-dependent lesions elsewhere in the gynecologic tract-HPV infection results in high-grade squamous intraepithelial lesion with subsequent progression to basaloid squamous cell carcinoma. The HPV-independent pathway is more complex, with a variety of precursor lesions and molecular alterations. Although the most recognized form of HPV-independent vulvar lesion is differentiated vulvar intraepithelial neoplasia, recent explorations have elucidated new precursors. This review provides an update on HPV-independent risk factors and precursor lesions for squamous cell carcinoma of the vulva.
Asunto(s)
Carcinoma de Células Escamosas/etiología , Neoplasias de la Vulva/etiología , Carcinoma in Situ/etiología , Carcinoma in Situ/patología , Carcinoma de Células Escamosas/patología , Diagnóstico Diferencial , Progresión de la Enfermedad , Femenino , Humanos , Liquen Escleroso y Atrófico/complicaciones , Liquen Escleroso y Atrófico/diagnóstico , Liquen Escleroso y Atrófico/patología , Neurodermatitis/complicaciones , Neurodermatitis/diagnóstico , Neurodermatitis/patología , Infecciones por Papillomavirus/complicaciones , Lesiones Precancerosas/etiología , Lesiones Precancerosas/patología , Pronóstico , Neoplasias de la Vulva/patologíaRESUMEN
Differentiated vulvar intraepithelial neoplasia (dVIN) is the precursor lesion of HPV-negative vulvar squamous cell carcinoma (VSCC). The histopathological diagnosis of dVIN can be challenging, as it often resembles vulvar non-neoplastic epithelial disorders (NNED), especially lichen sclerosus (LS). We aimed to establish the most specific and reproducible histological features of dVIN and assessed cytokeratin 13 (CK13) and cytokeratin 17 (CK17) immunohistochemistry as a diagnostic aid. Consecutive cases of dVIN (n = 180) and LS (n = 105) from the period 2010 to 2013 were reviewed using a checklist of histological features. Each feature was recorded as 'present' or 'absent' and statistical comparison (dVIN vs LS) was made. Interobserver agreement between two pairs of pathologists was assessed for a subset of cases of dVIN (n = 31) and LS and other NNED (n = 23). Immunohistochemistry with CK13, CK17, MIB1 and p53 was performed on dVIN, LS, and other NNED cases. Macronucleoli, features of disturbed maturation and angulated nuclei were significantly more common in dVIN than LS (p < 0.001). We found 'substantial agreement' for the diagnosis of dVIN (κ = 0.71). Macronucleoli and deep keratinisation had the highest agreement. In dVIN, the mean percentage of cells staining with CK13 was 15 and with CK17, this was 74. For LS, the mean percentage of cells staining with CK13 was 31, and with CK17, this was 41. By plotting receiver operating characteristic curves (ROC), an area under the curve (AUC) of 0.52 was obtained for CK13, and an AUC of 0.87 was obtained for CK17. The most helpful histological features for diagnosing dVIN were macronucleoli, features of disturbed maturation, and angulated nuclei. Increased CK17 expression may have promise for supporting dVIN diagnosis.
Asunto(s)
Biomarcadores de Tumor/análisis , Carcinoma in Situ/diagnóstico , Queratina-13/biosíntesis , Queratina-17/biosíntesis , Neoplasias de la Vulva/diagnóstico , Área Bajo la Curva , Carcinoma in Situ/patología , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patología , Diagnóstico Diferencial , Femenino , Humanos , Queratina-13/análisis , Queratina-17/análisis , Curva ROC , Sensibilidad y Especificidad , Liquen Escleroso Vulvar/diagnóstico , Neoplasias de la Vulva/patologíaRESUMEN
Cutaneous vulvar neoplasms are commonly encountered at gynecology visits, with 2% of women having a benign vulvar melanocytic nevus and 10% to 12% of nevi being vulvar. High-grade squamous intraepithelial lesions (vulvar intraepithelial neoplasia 2 or 3) occurs in 5 per 100,000 women, with increasing incidence in the past 30 years. The recognition of these lesions and differentiation between benign, premalignant, and malignant stages are crucial for adequate diagnosis, clinical monitoring, and treatment. The presentation, diagnosis, and management of benign and malignant vulvar proliferations are discussed with focus on practical aspects of clinical care.
Asunto(s)
Lesiones Precancerosas/patología , Vulva/patología , Neoplasias de la Vulva/patología , Femenino , Humanos , Lesiones Precancerosas/diagnóstico , Neoplasias de la Vulva/diagnósticoRESUMEN
This review article discribes the genesis and development of vulvar squamous precancerous lesions terminology and discusses the consensus of the International Society for the Study of Vulvovaginal Disease, the American Society for Colposcopy and Cervical Pathology, College of American Pathologists and the World Health Organization on the current terminology. The article describes the different types of vulvar squamous precancerous lesions, according to their etiology, incidence and malignant potential.
Asunto(s)
Carcinoma in Situ/patología , Carcinoma de Células Escamosas/patología , Infecciones por Papillomavirus/patología , Lesiones Precancerosas/patología , Neoplasias de la Vulva/patología , Transformación Celular Neoplásica/patología , Femenino , Humanos , Pronóstico , Vulva/patologíaRESUMEN
Vulvar cancer is the fourth most common gynecological cancer worldwide. However, limited studies have been completed on the molecular characterization of vulvar squamous cell carcinoma resulting in a poor understanding of the disease initiation and progression. Analysis and early detection of the precursor lesion of HPV-independent vulvar squamous cell carcinoma (VSCC), differentiated vulvar intraepithelial neoplasia (dVIN), is of great importance given dVIN lesions have a high level of malignant potential. Here we present an examination of adjacent normal vulvar epithelium, dVIN, and VSCC from six patients by peptide Matrix-assisted laser desorption/ionization Mass Spectrometry Imaging (MALDI-MSI). The results reveal the differential expression of multiple peptides from the protein cytokeratin 5 (CK5) across the three vulvar tissue types. The difference observed in the relative abundance of CK5 by MALDI-MSI between the healthy epithelium, dVIN, and VSCC was further analyzed by immunohistochemistry (IHC) in tissue from eight VSCC patients. A decrease in CK5 immunostaining was observed in the VSCC compared to the healthy epithelium and dVIN. These results provide an insight into the molecular fingerprint of the vulvar intraepithelial neoplasia that appears to be more closely related to the healthy epithelium than the VSCC.
Asunto(s)
Carcinoma de Células Escamosas/patología , Queratina-5/análisis , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Neoplasias de la Vulva/patología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/metabolismo , Cromatografía Líquida de Alta Presión , Epitelio/metabolismo , Epitelio/patología , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Estadificación de Neoplasias , Péptidos/análisis , Neoplasias de la Vulva/metabolismoRESUMEN
BACKGROUND: Vulvar squamous cell carcinomas (SCCs) arising in association with vulvar lichen planus (LP) are poorly documented. OBJECTIVES: We sought to present clinicopathological features of 38 patients (median age 61 years, range 39-90 years) with LP-associated vulvar SCCs. METHODS: Evaluated were location of vulvar SCC and metastases at presentation, recurrences, survival, precursor lesions, presence of human papillomavirus DNA, p16ink4a, and p53 expression. RESULTS: In all, 32 solitary (5 pT1a, 20 pT1b, 7 pT2) and 6 multifocal SCCs, located in the vestibulum (n=20) and in nonhair-bearing modified and glycogenated mucosa (n=18), arose in erosive (n=13) and nonerosive (n=25) LP. All SCCs were human papillomavirus DNA and p16ink4a negative. Sixteen of 38 (42%) women had inguinal metastases at presentation. Treatment was surgery with clear margins (36/38) and chemoradiation (2/38). Fourteen of 36 (39%) surgically treated patients developed between 1 and 5 new SCCs in the residual diseased mucosa. Of all recurrences, 68% developed within 12 months via precursors revealing various histologic features including elongated, but also flat rete ridges, basaloid and hypertrophic differentiation with inconsistent p53 expression. Fourteen of 38 (37%) patients died of SCCs. LIMITATIONS: Retrospective study and lack of a standardized treatment protocols are limitations. CONCLUSION: LP-associated SCCs were located in nonhair-bearing vulvar mucosa. Patients had a high rate of inguinal metastases, recurrent vulvar cancers in diseased mucosa, and disease-related death.