10.5826/dpc.1304a269
Introduction:  Vulvar intraepithelial neoplasia (VIN) is a vulvar skin lesion considered a precursor of vulvar squamous cell carcinoma. No characteristics have been discovered to date that allows us to differentiate between degrees of VIN.
Objectives: The aim of this study was to correlate the clinical and dermoscopic features of VIN cases with histopathological findings.
Methods: A prospective study of the clinical and dermoscopic characteristics of VINs was recruited. Data on clinical and dermoscopic characteristics, histopathology, were collected from the two Italian Dermatology Units from January 2020 and December 2021.
Results: The study population consisted of 20 patients with a histologically confirmed diagnosis of VIN. At the dermoscopic level, VIN1 was characterized by a homogeneous erythematous area that completely involved the entire lesion, with a vascular pattern consisting of regular glomerular vessels. VIN3, was characterized by the presence of compact milky white areas that involved almost the entire lesion. VIN2 was characterized by the presence of non-compact white areas that allowed homogeneous erythematous areas to be seen transparently, without other distinguishing aspects.
Conclusions: Although a definitive diagnosis and grading of VIN remains confirmed only histopathologically, our study shows how dermoscopy may aid the differential diagnosis between the different grades of VIN; the presence of a compact milky white area that involves nearly the entire lesion should be interpreted as an alarming feature, while homogeneous erythematous areas or a glomerular vascular pattern are more typical of the first stage of this neoplasia.
text/xml
2160-9381
3298
en
Daniela Massi
https://creativecommons.org/licenses/by-nc/4.0
Dermatology Practical & Conceptual
CiteSpace
Assessment of Vulvar Intraepithelial Neoplasia (VIN) Grades Based on Dermoscopic Features: A Diagnostic Study
Text.Serial.Journal
https://dpcj.org/index.php/dpc
Original Article
2023-10-31
2023-03-01
2023-10-31
2024-01-16
e2023269
Dermatol Pract Concept
Introduction:  Vulvar intraepithelial neoplasia (VIN) is a vulvar skin lesion considered a precursor of vulvar squamous cell carcinoma. No characteristics have been discovered to date that allows us to differentiate between degrees of VIN.
Objectives: The aim of this study was to correlate the clinical and dermoscopic features of VIN cases with histopathological findings.
Methods: A prospective study of the clinical and dermoscopic characteristics of VINs was recruited. Data on clinical and dermoscopic characteristics, histopathology, were collected from the two Italian Dermatology Units from January 2020 and December 2021.
Results: The study population consisted of 20 patients with a histologically confirmed diagnosis of VIN. At the dermoscopic level, VIN1 was characterized by a homogeneous erythematous area that completely involved the entire lesion, with a vascular pattern consisting of regular glomerular vessels. VIN3, was characterized by the presence of compact milky white areas that involved almost the entire lesion. VIN2 was characterized by the presence of non-compact white areas that allowed homogeneous erythematous areas to be seen transparently, without other distinguishing aspects.
Conclusions: Although a definitive diagnosis and grading of VIN remains confirmed only histopathologically, our study shows how dermoscopy may aid the differential diagnosis between the different grades of VIN; the presence of a compact milky white area that involves nearly the entire lesion should be interpreted as an alarming feature, while homogeneous erythematous areas or a glomerular vascular pattern are more typical of the first stage of this neoplasia.
Daniela Massi
2023/10/31
10.5826/dpc.1304a269
e2023269
Section of Pathology, Department of Health Sciences, University of Florence, Italy
2160-9381
CiteSpace
en
e2023269
Cario M. How hormones may modulate human skin pigmentation in melasma: An in vitro perspective. ExpDermatol. 2019 Jun;28(6):709-718. doi: 10.1111/exd.13915. Epub 2019 May 15. PMID: 30883945.
Assessment of Vulvar Intraepithelial Neoplasia (VIN) Grades Based on Dermoscopic Features: A Diagnostic Study
https://dpcj.org/index.php/dpc/article/download/3298/2390
       Assessment of Vulvar Intraepithelial Neoplasia
       (VIN) Grades Based on Dermoscopic Features:
                    A Diagnostic Study
 Vincenzo De Giorgi1,2, Elisabetta Magnaterra1, Biancamaria Zuccaro1, Manfredi Magliulo1,
 Vincenza Maio3, Angela Muccilli3, Federico Venturi1, Ignazio Stanganelli4,5, Daniela Massi6


1 Section of Dermatology, Department of Health Sciences, University of Florence, Florence, Italy
2 Cancer Research “Attilia Pofferi” Foundation, Pistoia, Italy
3 Unit of Histopathology and Molecular Diagnostics, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy
4 Skin Cancer Unit, Scientific Institute of Romagna for the Study of Cancer, IRCSS IRST, Meldola, Italy
5 Department of Dermatology, University of Parma, Parma, Italy
6 Section of Pathology, Department of Health Sciences, University of Florence, Italy



Key words: dysplastic nevus, melanoma, bibliometric analysis, co-citation analysis, CiteSpace
Citation: De Giorgi V, Magnaterra E, Zuccaro B, et al. Assessment of Vulvar Intraepithelial Neoplasia (VIN) Grades Based on Dermoscopic
Features: A Diagnostic Study. Dermatol Pract Concept. 2023;13(4):e2023269. DOI: https://doi.org/10.5826/dpc.1304a269
Accepted: June11, 2023; Published: October 2023
Copyright: ©2023 De Giorgi et al. This is an open-access article distributed under the terms of the Creative Commons
Attribution-NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted
noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited.
Funding: None.
Competing Interests: None.
Authorship: All authors have contributed significantly to this publication.
Corresponding Author: Vincenzo De Giorgi, MD, Department of Dermatology, University of Florence, Via Michelangelo 41,50124 Firenze,
ITALY. Tel: 0039-055-6939632 fax 0039-055-6939632; e-mail:vincenzo.degiorgi@unifi.it




  ABSTRACT             Introduction: Vulvar intraepithelial neoplasia (VIN) is a vulvar skin lesion considered a precursor
                       of vulvar squamous cell carcinoma. No characteristics have been discovered to date that allows us to
                       differentiate between grades of VIN, such as correlating the thickness of involvement of the epithelium
                       (VIN1, VIN2, and VIN3) to the dermoscopic pattern.
                       Objectives: The aim of this study was to correlate the clinical and dermoscopic features of VIN cases
                       with histopathological findings, with the purpose of identifying dermoscopic characteristics that allow
                       us to differentiate between different grades of VIN.
                       Methods: A retrospective study of the clinical and dermoscopic characteristics of VINs was recruited.
                       Clinical and dermoscopic characteristics, as well as histopathology data, were gathered from patients
                       at two Dermatology Units in Italy during the period spanning from January 2020 to December 2021.
                       Results: The study population consisted of 20 patients with a histologically confirmed diagnosis of
                       VIN. The mean age of patients at the time of diagnosis was 55 years. At the dermoscopic level, VIN1
                       was characterized by a homogeneous erythematous area that completely involved the entire lesion,




Original Article | Dermatol Pract Concept. 2023;13(4):e2023269                                                                       1
                     with a vascular pattern consisting of regular glomerular vessels. VIN3, was characterized by the pres-
                     ence of compact milky white areas that involved almost the entire lesion. VIN2 was characterized by
                     the presence of non-compact white areas that allowed homogeneous erythematous areas to be seen
                     transparently, without other distinguishing aspects.
                     Conclusions: Although a definitive diagnosis and grading of VIN remains confirmed only histopatho-
                     logically, our study shows how dermoscopy may aid the differential diagnosis between the different
                     grades of VIN; the presence of a compact milky white area that involves nearly the entire lesion should
                     be interpreted as an alarming feature, while homogeneous erythematous areas or a glomerular vascu-
                     lar pattern are more typical of the first stage of this neoplasia.




Introduction                                                     little has been written about the dermoscopic patterns that
                                                                 characterize the different types and grades of this condition.
Vulvar intraepithelial neoplasia (VIN) is a vulvar skin lesion      Only a few studies exist on this topic; however, some
considered a precursor of vulvar squamous cell carcinoma         common dermoscopic features of VIN have been reported,
(SCC). According to the International Society for the Study      such as a cerebriform pattern, focally distributed glomerular
of Vulvovaginal Disease (ISSVD) [1], a distinction must be       vessels, bluish areas, scales, and blue/brown dots arranged in
made between VIN associated with HPV infection (also             a linear distribution [5-10].These dermoscopic findings are
known as usual type, uVIN) and the HPV-independent form          mostly described in the uVin type. However, no characteris-
(differentiated vulvar intraepithelial neoplasia, dVIN), which   tics have been discovered to date that allows us to differenti-
is related to lichen sclerosus. The ISSVD further divides        ate between grades of uVIN,such as correlating the thickness
uVIN classification as either low-grade squamous intraepi-       of involvement of the epithelium (VIN1, VIN2, and VIN3) to
thelial lesion (L-SIL), which corresponds to VIN1, or high-      the dermoscopic pattern.
grade SIL (HSIL or VIN 2/3) [1,2].                                  Since no pathognomonic features have been described
    The three stages of uVIN are distinguished on the basis of   to identify VIN, a definitive diagnosis of VIN can only be
the thickness of involvement of the vulvar epithelium by the     achieved by biopsy and histological examination. How-
dysplastic cells: VIN1 corresponds to involvement of only        ever, we believe that dermoscopy may introduce important
the lower third of the thickness of the surface layer; VIN2      diagnostic clues and can complement clinical examina-
corresponds to involvement of two-thirds the thickness of        tion, thereby facilitating differential diagnosis (e.g. vulvar
the dysplasia and VIN3 corresponds to involvement of the         melanoma).
entire surface layer. Regarding the risk of progression into
an actual SCC, it must be said that not all VIN types have
the same probability of transformation; although isolated        Objectives
dVIN is significantly less common than uVIN, dVIN bears a
                                                                 Therefore, the objective of this research was to establish a
greater risk for malignant transformation to vulvar SCC and
                                                                 correlation between the clinical and dermoscopic attributes
progresses at a faster rate [3,4]. Furthermore, among uVIN,
                                                                 of VIN cases and their corresponding histopathological find-
VIN1 (or L-SIL) is not considered a precancerous lesion;
                                                                 ings. The ultimate goal was to identify specific dermoscopic
rather, it is considered a benign epithelial change caused
                                                                 characteristics that would enable differentiation among var-
mainly by the low-risk HPV types 6 and 11.
                                                                 ious grades of VIN.
    Despite this well-defined histopathological staging, the
clinical morphology has not been clearly delineated, often
resulting in delayed diagnosis.                                  Methods
    For these reasons, and considering their link with SCC,
it would be important to be able not only to recognize these     This retrospective study examined data about patients who
lesions early, but also to type them according to their level    received a histopathologic diagnosis of vulvar intraepithelial
of atypia. An early treatment of these injuries would save       neoplasia (VIN) between January 2020 and December 2021
the patient considerable inconvenience and discomfort given      at the Skin Cancer Units of the Department of Dermatol-
the particular site. At present, there are no validated clinic   ogy at the University of Florence and of the Department of
and dermoscopic criteria available for VIN diagnosis, and        Dermatology at the University of Parma. The Institutional




2                                                                    Original Article | Dermatol Pract Concept. 2023;13(4):e2023269
Review Board approved this retrospective study. Patients               The mean age of patients at the time of diagnosis was
were ineligible to participate if they were under 18 years old.     55 years (range 41–79), 60% (N= 12) of the patients were
Additional exclusion criteria included a history of vulvo-          in menopause at the time of diagnosis, and 65% (N= 13)
vaginal neoplasia, radiation therapy for other tumors, or           had received hormone therapy or contraceptive or hormone
ongoing or previous immunosuppressive therapy.                      replacement following menopause for a period of at least
    The patient database contains information about patient         12 months before VIN diagnosis. Among these 20 patients,
characteristics, in addition to clinical and dermoscopic fea-       35% (N= 7) were under the age of 50 years (Table 1).
tures of the lesions. Each lesion was photographed clinically          From a clinical point of view, the VIN was pigmented
and dermoscopically. The equipment used for the dermo-              in 10% (2 patients) of cases, and in all of these cases, the
scopic examination consisted of a hand-held dermatoscope            pigmentation was not present in the mucosa but in the
(HEINE DELTA 20, HEINEOptotechnick, Herrsching, Ger-                perivaginal keratinized area. The other lesions (90%) were
many). Both clinical and dermoscopic images of all lesions          non-pigmented erythematous and localized in the mucosa.
were captured with a high-resolution compact digital pho-              Regarding the outcomes of histological examinations,
tographic camera (Olympus E-520, a 7.1megapixel digital             75% (15 patients) were represented by uVIN and only 5 pa-
photo camera with a 3.8 optical zoom lens, a focal length           tients by dVIN, while for the grades of atypia, 50% (10 pa-
of 28–105 mm in a 35-mm format, and a maximum lens                  tients) were VIN1, 15% (3patients) were VIN2, and 35% (7
aperture of f/2.8-f/5.8). Dermoscopic images were captured          patients) were VIN3. All patients diagnosed with VIN3 were
viaDermaphot      (HEINEOptotechnick),         which     connects   over age 65 years, and in three of these cases, a mucosal mel-
the dermatoscope to the camera to generate reproducible,            anosis was also present. In five cases (25%), the lesions were
high-quality dermoscopic pictures at 10-fold magnification.         multiple, and in one patient all levels of VIN were detected
    Biopsies were taken for all lesions. Initially, an incisional   (VIN1, VIN2, VIN3).
biopsy was performed using a 4mm punch. The biopsy site                At the dermoscopic level, VIN1 was characterized by a
was selected based on the most clinically and dermoscop-            homogeneous erythematous area that completely involved
ically significant areas. Subsequently, the entire lesion was       the entire lesion, without disappearing following the applica-
surgically excised. Clinical history, dermoscopic examina-          tion of pressure with the dermatoscope. Within this erythem-
tions, and histopathological features of the lesions were eval-     atous area, in the absence of other dermoscopic parameters,
uated. Three investigators (V.D.G., I.S., and F.V.), who are        a vascular pattern consisting of regular glomerular vessels
skilled in dermoscopy and experienced in assessing genital          arranged throughout the lesion could be seen (Figure 1).
lesions at their affiliated institutions, independently analyzed    VIN3, on the other hand, was characterized by the presence
the archived digital dermoscopic images. They had no prior          of compact milky white areas that involved almost the entire
knowledge of the lesion’s clinical history. The investigators       lesion, replacing the erythematous areas of VIN1 (Figure 2).
completed a printed questionnaire to classify the lesions              In the three cases of VIN2, dermoscopy was charac-
based on typical dermoscopic pattern analysis. These derma-         terized by the presence of non-compact white areas that
tologists had the same level of training and each had more          allowed homogeneous erythematous areas to be seen trans-
than 5 years of practical experience in dermoscopy. Dermo-          parently, without other distinguishing aspects.
scopic pattern and the presence or absence of dermoscopic              Dermoscopically, the pigmented VINs exhibited diffuse
features in a given lesion was defined by the agreement of          pigmentation, with a linear distribution with clearly delim-
at least 2 out of 3 dermatologists. The color of the lesion         ited translucent whitish areas and no pigmented network
was also recorded. Histopathological slides were reviewed           (Figure 3).
by a dermatopathologist with expertise in vulvar lesions               In our case series, two patients presented a non-specific
to confirm the diagnosis and evaluate the dermoscopic-              pattern due to the absence of well-defined or recognizable
histopathological correlates.                                       dermoscopic features. Furthermore, there were no peculiar
                                                                    dermoscopic parameters that would allow us to make a dif-
                                                                    ferential diagnosis between uVIN and dVIN.
Results
Twenty cases were included in the final analysis. Of the 24
                                                                    Conclusions
cases of VIN that were observed between January 2020 and
December 2021, 4cases were excluded because of lack histo-          Owing to the extreme heterogeneity of lesions, little has been
logical data, absence of clear clinical or dermoscopic images,      written about the long-term clinical behavior of VINs, and
or both.                                                            only a few studies to date have analyzed their specific clinical




Original Article | Dermatol Pract Concept. 2023;13(4):e2023269                                                                    3
             Table 1. Demographic, clinical and dermoscopic characteristics of the study cases.
                              N° patients         Age
                                  (%)            Range              Clinic Characteristics             Dermoscopic Characteristics
 Enrolled patients                 20            41-79.     N/A                                        N/A
 Under 50 years                  7 (35)                     N/A                                        N/A
 Menopause                       12 (60)                    N/A                                        N/A
 Hormonal Therapy/               13 (65)                    N/A                                        N/A
 Contraceptive/
 Hormone replacement
 Clinical aspect
 Pigmented VIN                   2 (10)                     Pigmented lesion with a color              Diffuse pigmentation, linear
                                                            spectrum from light brown to               distribution with delimited
                                                            dark brown in the perivaginal              translucent whitish areas and
                                                            keratinized area (not in the mucosa)       no pigmented network
 Non-Pigmented VIN               18 (90)                    red to white non-pigmented lesions         atypical vascular pattern
                                                            localized in the mucosa                    with a variable red to white
                                                                                                       background
 Histopathology
 uVIN                            15 (75)                    N/A                                        N/A
 dVIN                            5 (25)                     N/A                                        N/A
 Degree of atypia
 VIN1                            10 (50)                    Reddish shiny lesions with clear           Homogeneous erythematous
                                                            margins                                    area (entire lesion), does not
                                                                                                       disappear under pressure with
                                                                                                       the dermatoscope. Vascular
                                                                                                       pattern: regular glomerular
                                                                                                       vessels.
 VIN2                            3 (15)                     whitish erythematous discromic             Non-compact white
                                                            lesion                                     areas, homogeneous with
                                                                                                       erythematous areas to be seen
                                                                                                       transparently.
 VIN3                            7 (35)                     Whitishdiscromic lesion                    Compact milky white areas
                                                                                                       (entire lesion)

N/A = not applicable; VIN = vulvar intraepithelial neoplasia.




       Figure 1. A 55-year-old patient affected by multiple vulvar intraepithelial neoplasia1. (A) Clinically, reddish papillomatous
       shiny lesions of the vulva. (B) Dermoscopy showed a homogeneous pink to red background. (C) Dermoscopically, a vascular
       pattern consisting of regular glomerular vessels arranged throughout the lesion could be seen.



4                                                                           Original Article | Dermatol Pract Concept. 2023;13(4):e2023269
                 Figure 2. A 72-year-old patient affected by multifocal vulvar intraepithelial neoplasia (VIN). (A)­Clinically,
                 numerous erythematous and white areas, some infiltrated with areas of peripheral brown-like pigmenta-
                 tion of the labia minora and vaginal introitus, can be seen. (B)Dermoscopy revealed compact milky-white
                 areas involving areas affected by VIN grade 3. (C)Dermoscopy shows non-compact white areas that al-
                 lowed homogeneous erythematouszones to be seen transparently, involving area affected by VIN grade 2.
                 (D)Dermoscopically, diffuse pigmentation with a linear arrangement can be seen, with a clearly delimited
                 translucent whitish area involving areas affected by multifocal VIN.




and dermatoscopic features. In this study, we aimed to in-                patient. Several biopsies or a so-called vulvar mapping are
vestigate the dermoscopic characteristics of these conditions,            commonly performed in patients with multifocal VIN to
which might be useful not only for VIN characterization and               confirm the clinical diagnosis and to exclude the presence
diagnosis, but also to help guide treatment, in order both to             of underlying invasive neoplasia [12]. We believe that the
assess the efficacy of topical therapy and to ensure conserva-            identification of specific dermoscopic features that allow for
tive excisions in such critical areas.                                    differentiation between grades of intraepithelial neoplasia
    It is known that it is possible to find multiple sites and            could help minimize the number of unneeded genital biop-
different degrees of intrahepitelial neoplasia in the same                sies and guide topical treatment with imiquimod.



Original Article | Dermatol Pract Concept. 2023;13(4):e2023269                                                                        5
     Figure 3. A 70-year-old patient affected by pigmented vulvar intraepithelial neoplasia3. (A) Clinically, flat pigmented perivaginal
     macule with well demarcated edges, but with inhomogeneous color distribution, can be seen. (B) Dermoscopically, the lesion
     showed diffuse pigmentation with a linear distribution, with clearly delimited translucent whitish islands and no pigmented
     network.




    Although a definitive diagnosis and grading of VIN re-                  We hardly found typical features of VIN2, which was
mains confirmed only histopathologically, our study shows               partially due to the lack of VIN2 cases in our cohort and
how dermoscopy may aid the differential diagnosis between               partially to the fact that VIN2 is considered a type of “gray
the different grades of VIN; the presence of a compact milky            zone” between VIN1 and VIN3.
white area that involves nearly the entire lesion should be                 According to the few studies published on this topic,
interpreted as an alarming feature, while homogeneous ery-              10–15% of VINs are grossly hyperpigmented.7,13 Pigmented
thematous areas or a glomerular vascular pattern are more               VINs accounted for only 10% of the VINs in our study and
typical of the first stage of this neoplasia. This dermoscopic          were present in keratinized perimucosal regions. The clinical
compact milky white area corresponds histopathologically                picture was characterized by a pigmented lesion with sharp
to an important hyperkeratosis, typical of VIN3 (Fig.4).                edges but inhomogeneous in pigment distribution. Accord-
Therefore, as happens in the dermoscopic evaluation of                  ing to some reports, a cerebriform pattern as well as parallel
mucosal melanomas and mucosal melanosis, in the dermo-                  pigmented dots are possible findings in pigmented VIN [6-8].
scopic diagnosis of vulvar VIN, a correct evaluation of the             However, these patterns are also typically found in other
colors present in the lesion is important, rather than the              skin conditions such as seborrheic keratosis, Bowen disease,
presence of isolated dermoscopic parameters. So, the whiter             and bowenoid papulosis. In our study, dermoscopically, we
is present, the greater the likelihood that the VIN is at grade         can see the presence of whitish islands within the lesion, with
3 (VIN3).                                                               a brown background pigment. This dermoscopic pattern is
    In our study, all patients diagnosed with VIN3 were over            difficult to find in other skin lesions and can, therefore, be
65 years of age. Furthermore, all three grades of VIN (VIN1,            useful in a preoperative diagnostic process.
VIN2, VIN3) were detected in one of our patients, testifying                In our cohort, the association with vulvar melanosis
to the slow progression of cytoarchitectural atypia through             seems to be strictly linked with VIN grade 3. This finding
the vulvar epithelium. In our cohort, we did not observe any            could either be random or linked to hormonal stimulation. It
distinctive dermoscopic clues that allowed the differentia-             is well known that estrogens that increase melanin synthesis
tion between uVIN and dVIN. In a case-series of four female             are involved in the genesis of vulvar melanosis [14,15]. In-
patients [7], Barisani et al. observed differences in vessel            fact, 65% of our patients underwent hormonal therapy for a
morphology between these two entities. Specifically, they               period of at least 12 months before VIN diagnosis.
reported that uVIN presented with dotted or glomerular                      The strength of this study lies in the number of cases;
vessels, while dVIN presented with many curvy teleangecta-              as far as we know, this case series has the largest number of
sias [7]. However, this distinction has not been investigated           patients reported to date. Nevertheless, further studies are
thoroughly, and these findings may not be relevant given the            needed to better characterize the dermoscopic features of
limited number of cases.                                                VIN and to corroborate our findings.



6                                                                            Original Article | Dermatol Pract Concept. 2023;13(4):e2023269
Figure 4. Histological appearance of high grade squamous intraepithelial lesion (vulvar intraepithelial neoplasia III, usual type).The lesion
at scanning magnification shows a complete loss of maturation, an increased nuclear density and hyperkeratosis (left image, scale bar 200
micron, original magnification x10). A band of inflammatory cells in the superficial derma can be seen (middle image, scale bar 100-micron,
original magnification x20). Higher magnification demonstrates cellular loss of polarity, an increased number of mitoses and nuclear atypia
involving all the epithelial layers (right image, scale bar 50 micron, original magnification x40).




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Original Article | Dermatol Pract Concept. 2023;13(4):e2023269                                                                                   7
