Diagnostic Accuracy of "Three Rings Vulvoscopy" for Detection of Vulvar Dermatosis (DATRIV)

The objective of the study was to determine sensitivity, specificity and diagnostic accuracy of "Three Rings Vulvoscopy" for detection of vulvar dermatosis using histopathology as the reference standard.

"Three Rings Vulvoscopy" (TRIV) is a new, and original technique for performing colposcopy of the vulva, taking into account three different skin types and zones as well as morphological evaluation of vulvar lesions according to their specificity (non-specific and lesions specific for dermatosis). To evaluate the clinical value of TRIV, we designed two index tests, a quantitative test called "Vulvoscopy Index" and a semi-quantitative test marked as "N-S-P scheme." The sensitivity, specificity and diagnostic accuracy of both index tests were estimated in comparison with histopathology as the reference test in two groups of 164 consecutive patients with vulvar discomfort (82 patients with vulvar dermatosis and 82 patients with vulvodynia ) and 164 consecutive patients without vulvar discomfort (82 patients with "normal vulva" and 82 patients with "impaired vulvar skin"). The study was performed stratified, on three levels, whereby the first two levels were pre-assignments. The first level of the study was an evaluation of vulvar discomfort during the routine gynecological care in the clinic "Poliklinika Harni" Zagreb, Croatia, where we searched for symptomatic patients; and in the esthetic gynecological unit of the same clinic, where we searched for asymptomatic patients. Vulvar discomfort was evaluated anamnestically by the "International Society for the Study of Vulvovaginal Disease (ISSVD) Vulvodynia Pattern Questionnaire." On the second level, we performed detailed clinical examination (inspection and Cotton-Swab test), searching for non-specific and lesions specific for skin (vulvar) dermatosis, and patients with vulvodynia who fulfilled Friedrich's criteria. Patients with vulvar infection or pre/malignancy were excluded from the study. Vulvar lesions in patients with vulvodynia were not relevant to the diagnosis of vulvodynia. Among women without vulvar discomfort, we described those without any clinical findings ("normal vulva") and those with some non-specific findings on the vulva. We called this group "impaired vulvar skin." The results of the clinical examination were collected using "TRIV Form Data." On this way, we identified four groups of patients during the recruitment: vulvar dermatosis, vulvodynia, impaired vulvar skin, and normal vulva. For each patient with vulvar dermatosis (82 patients), the first consecutive patient with vulvodynia (82), impaired vulvar skin (82) and normal vulva (82) were taken for comparison. The third level of the study presents the investigation and included diagnostic interventions "Three Rings Vulvoscopy" and vulvar biopsy with histopathology. The results of vulvoscopy were collected using "TRIV Form Data" and then assessed by "Vulvoscopy Index" and the "N-S-P Scheme." Biopsy of the vulva from the symptomatic patients was taken to confirm/exclude vulvar dermatosis. Asymptomatic patients, who were recruited from patients undergoing planned labiaplasty, granted vulvar samples to further investigation. The statistical tests were made on a personal computer (PC) in the Statistical Package 12.0. All qualitative variables are shown in the tables with the absolute number and percentage. Quantitative variables are presented with arithmetic mean and standard deviation (if normal distribution), and by the median and range (if not a normal distribution). A chi-squared test was used to test the difference between qualitative variables among the two groups. A chi-squared test with Yates correction was used for 2x2 size tables, and Fisher's exact test was used for small values. T-test proportions were used for the evaluation of the differences between the two percentages. Variance analysis (ANOVA) and post hoc Tukey HSD were used to test quantitative variables with normal distribution between multiple groups. Differences between the arithmetic mean of the two groups were tested by t-test. Variables that did not have normal distribution were tested by nonparametric tests. The differences between several groups were tested by Kruskal-Wallis ANOVA and the differences between the two groups Mann-Whitney U test.

Three-Vulvar-Rings, Three-Rings-Vulvoscopy, N-S-P scheme, Vulvoscopy Index, Vulvar Dermatosis, Vulvar Lichen Sclerosus, Lichen Planus, Lichen Simplex Chronicus, Vulvodynia, Provoked Vestibulodynia, Vulvar Vestibulitis, Vulvar Diseases

We performed the same interventions: Three Rings Vulvoscopy, Vulvar Biopsy and Histopathologically Evaluation in four groups of patients with and without vulvar discomfort, with the aim to detect vulvar dermatosis.

The "Normal vulva" group consisted of patients without vulvar discomfort (ISSVD Questionnaire), and without any vulvar lesion (Clinical examination) undergoing planned labioplasty. For each patient with vulvar dermatosis, the first consecutive patient with normal vulva was taken for comparison. Interventions: Three Rings Vulvoscopy, Vulvar Biopsy, and Histopathology.

The group of "Impaired vulvar skin" was formed by the patients without vulvar symptoms (ISSVD Questionnaire), but with some non-specific vulvar lesions (Clinical examination) undergoing planned labioplasty, before surgery. For each patient with vulvar dermatosis, the first consecutive patient with impaired vulvar skin was taken for comparison. Interventions: Three Rings Vulvoscopy, Vulvar Biopsy, and Histopathology.

The "Vulvodynia" group consisted of patients with vulvar discomfort (ISSVD Questionnaire), who fulfilled Friedrich's criteria (Clinical examination). Non-specific lesions found with TRIV were not relevant for the diagnosis of vulvodynia. For each patient with vulvar dermatosis, the first consecutive patient with vulvodynia was taken for comparison. Interventions: Three Rings Vulvoscopy, Vulvar Biopsy, and Histopathology.

The group of "Vulvar Dermatosis" was formed by the patients with vulvar discomfort (ISSVD Questionnaire) and vulvar lesion specific for dermatosis (Clinical examination). Interventions: Three Rings Vulvoscopy, Vulvar Biopsy, and Histopathology.

Mapping of the vulvar lesions according to the three vulvar rings and specificity of the lesions during "Three Rings Vulvoscopy" technique (TRIV Form Data). Assessing of the data by the "Vulvoscopy Index" and the "N-S-P Scheme".

Biopsy of the vulva in symptomatic patients, vulvar samples after labiaplasty in asymptomatic patients.

Diagnostic Accuracy of "Three Rings Vulvoscopy" by the "Vulvoscopy Index" for Detection of Vulvar Dermatosis

The table shows the distribution of patients with and without vulvar dermatosis diagnosed by "Three Rings Vulvoscopy" (TRIV) using the "Vulvoscopy Index" and histopathology as a reference test. The Vulvoscopy Index as an outcome measure of TRIV is designed as a quantitative test based on five characteristics: vulvar complaints, Marinoff index, Cotton-Swab test, vulvar lesions according to the three vulvar rings and specificity of lesions; with following results: "Normal Vulva" (0-2 points), "Impaired Vulvar Skin" (3-11 points), "Vulvodynia" (12-18 points), and "Vulvar Dermatosis" (19-32 points). Since histopathology distinguishes only patients with and without vulvar dermatosis, the clinical value the Vulvoscopy Index had been estimated according to these two groups of patients. Patients with vulvoscopy diagnoses: "Normal Vulva," "Impaired Vulvar Skin" and "Vulvodynia" were classified into the group "Absent Vulvar Dermatosis."

Distribution of Patients With Vulvar Dermatosis Diagnosed by Vulvoscopy (TRIV) and Histopathology According to Single Categories of the "Vulvoscopy Index"

The table shows the distribution of patients with "Vulvar Dermatosis" diagnosed by "Three Rings Vulvoscopy" and histopathology according to single categories of the "Vulvoscopy Index." We described five categories within the Vulvoscopy Index: Vulvar complaints (present vs. absent), Marinoff index (positive vs. negative), Cotton-Swab test (positive vs. negative), Vulvar lesions according to the vulvar rings (Outer, Middle, and Inner Vulvar Ring Lesion) and Specificity of lesions (Non-specific and Specific Lesions).

Distribution of Patients With "Absent Vulvar Dermatosis" Diagnosed by Vulvoscopy (TRIV) and Histopathology According to Single Categories of the "Vulvoscopy Index"

The table shows the distribution of patients with "Absent Vulvar Dermatosis" diagnosed by "Three Rings Vulvoscopy" (patients with vulvoscopical diagnoses "Normal Vulva," Impaired Vulvar Skin "and" Vulvodynia") and histopathology, according to single categories of the "Vulvoscopy Index." The five categories within the Vulvoscopy Index are: Vulvar complaints (present vs. absent), Marinoff index (positive vs. negative), Cotton-Swab test (positive vs. negative), Vulvar lesions according to the vulvar rings (Outer, Middle, and Inner Vulvar Ring Lesion) and Specificity of lesions (Non-specific and Specific Lesions).

"Vulvoscopy Index" (Mean ± SD) in Patients With "Vulvar Dermatosis" Diagnosed by Vulvoscopy (TRIV) and Histopathology

The table shows the results of "Three Rings Vulvoscopy" (TRIV) by single categories of the "Vulvoscopy Index" (mean ± SD) in patients with "Vulvar Dermatosis" diagnosed by TRIV and histopathology. The Vulvoscopy Index is based on five characteristics: Vulvar complaints (negative=0; positive=4 points), Marinoff index (negative=0; positive=3 points), Cotton-Swab test (negative=0; positive=2 points), Vulvar lesions according to the vulvar rings (Outer Vulvar Ring Lesions=4 points; Middle Vulvar Ring Lesions=2 points and Inner Vulvar Ring Lesions=1 point) and Specificity of lesions (Non-Specific Lesions=2 points; Specific Lesions=14 points). According to the Vulvoscopy Index, we have set the diagnoses: "Normal Vulva" (0-2 points), "Impaired Vulvar Skin" (3-11 points), "Vulvodynia" (12-18 points), and "Vulvar Dermatosis" (19-32 points). The likelihood of the diagnosis of "Vulvar Dermatosis" was higher as the value of the Vulvoscopy index was higher.

"Vulvoscopy Index" (Mean ± SD) in Patients With "Absent Vulvar Dermatosis" Diagnosed by Vulvoscopy (TRIV) and Histopathology

The table shows the results of "Three Rings Vulvoscopy" (TRIV) by single categories of the "Vulvoscopy Index" (mean± SD) in patients with "Absent Vulvar Dermatosis" diagnosed by TRIV and histopathology. According to the Vulvoscopy Index, we have set the diagnoses: "Normal Vulva" (0-2 points), "Impaired Vulvar Skin" (3-11 points), "Vulvodynia" (12-18 points), and "Vulvar Dermatosis" (19-32 points). Since histopathology can distinguish only patients with and without vulvar dermatosis, the distribution was estimated according to these two groups of patients. Hence, patients with vulvoscopical diagnoses "Normal Vulva," Impaired Vulvar Skin "and" Vulvodynia" were classified into the one group called "Absent Vulvar Dermatosis." The likelihood of the diagnosis of "Absent Vulvar Dermatosis" was higher as the value of the Vulvoscopy index was lower.

"Vulvoscopy Index" (Median | Range) in Patients With "Vulvar Dermatosis" Diagnosed by Vulvoscopy (TRIV) and Histopathology

The table shows the results of "Three Rings Vulvoscopy" (TRIV) by single categories of the "Vulvoscopy Index" (median ± SD) in patients with "Vulvar Dermatosis" diagnosed by TRIV and histopathology. The Vulvoscopy Index is based on five characteristics: Vulvar complaints (negative=0; positive=4 points), Marinoff index (negative=0; positive=3 points), Cotton-Swab test (negative=0; positive=2 points), Vulvar lesions according to the vulvar rings (Outer Vulvar Ring Lesions=4 points; Middle Vulvar Ring Lesions=2 points and Inner Vulvar Ring Lesions=1 point) and Specificity of lesions (Non-specific Lesions=2 points; Specific Lesions=14 points). According to the Vulvoscopy Index, we have set the diagnoses: "Normal Vulva" (0-2 points), "Impaired Vulvar Skin" (3-11 points), "Vulvodynia" (12-18 points), and "Vulvar Dermatosis" (19-32 points). The likelihood of the diagnosis of "Vulvar Dermatosis" was higher as the value of the Vulvoscopy index was higher.

"Vulvoscopy Index" (Median | Range) in Patients With "Absent Vulvar Dermatosis" Diagnosed by Vulvoscopy (TRIV) and Histopathology

The table shows the results of "Three Rings Vulvoscopy" (TRIV) by single categories of the "Vulvoscopy Index" (median ± SD) in patients with "Absent Vulvar Dermatosis" diagnosed by TRIV (patients with vulvoscopical diagnoses "Normal Vulva," Impaired Vulvar Skin "and" Vulvodynia") and histopathology. According to the Vulvoscopy Index, we have set the diagnoses: "Normal Vulva" (0-2 points), "Impaired Vulvar Skin" (3-11 points), "Vulvodynia" (12-18 points), and "Vulvar Dermatosis" (19-32 points). The likelihood of the diagnosis of "Absent Vulvar Dermatosis" was higher as the value of the Vulvoscopy index was lower.

Diagnostic Accuracy of "Three Rings Vulvoscopy" by the "N-S-P Scheme" for Detection of Vulvar Dermatosis

The distribution of patients with and without vulvar dermatosis diagnosed by vulvoscopy ("N-S-P Scheme") and histopathology. According to the specificity of lesions, vulvoscopy results were classified as normal "N" (absence of any lesion), suspect "S" (non-specific lesions) and pathologic "P" results (lesion specific to dermatosis); and each of the three vulvar rings is represented by a single result. The final vulvoscopy result is presented in the form of a three-letter formula, where the first letter indicates the vulvoscopy result in the Outer Vulvar Ring, the mean initial indicates the vulvoscopy result of the Middle Vulvar Ring and the last letter denotes the vulvoscopy result of the Inner Vulvar Ring. "N-S-P Scheme" divides the results of the vulvoscopy into three groups: "Normal Vulvoscopy," "Suspect Vulvoscopy" and "Pathological Vulvoscopy." Diagnosis of vulvar dermatosis was established if one or more vulvar rings showed pathological results ("Pathological Vulvoscopy").

Distribution of Vulvar Lesions According to the "N-S-P Scheme" in Patients With Vulvar Dermatosis Diagnosed by Vulvoscopy (TRIV) and Histopathology

The table shows the distribution of vulvoscopy lesions in relation to the vulvar rings and their specificity according to the "N-S-P Scheme," in patients with vulvar dermatosis diagnosed by vulvoscopy (TRIV) and histopathology. Vulvoscopy findings of each of the three vulvar rings: Outer (first letter in the formula), Middle (second letter), and Inner Vulvar Ring (third letter) were evaluated as normal "N" (absence of any lesions), suspect "S" (non-specific lesions), or pathological "P" (lesions specific for dermatosis). "Normal vulvoscopy" indicated the absence of any lesion in all three vulvar rings ("N-N-N"). "Suspect vulvoscopy" was used to mark findings of non-specific lesions ("S-#*-#"; "S-S-#"; "S-S-S"; "S-N-S" etc.). "Pathological vulvoscopy" spelled out the finding of lesions specific for dermatosis in any of the three vulvar rings ("P-#-#"; "P-P-"; "P-P-P"; "P-N-S" etc.). is the label for any of the three possibilities: N or S or P.

Distribution of Vulvar Lesions According to the "N-S-P Scheme" in Patients With Absent Vulvar Dermatosis Diagnosed by Vulvoscopy (TRIV) and Histopathology

The table shows the distribution of lesions according to their specificity and vulvar rings in patients without vulvar dermatosis diagnosed by vulvoscopy (TRIV) and histopathology, as a reference test. According to the "N-S-P scheme," we have set the diagnoses: "Normal result" (no lesion), "Suspect result" (non-specific lesion in any of the vulvar rings), and "Pathological result" (specific for dermatosis in any of the vulvar rings). Since histopathology can distinguish only patients with and without dermatosis, the distribution was estimated according to these two groups of patients. Hence, patients with normal and suspect vulvoscopic results were classified into one group called "Absent Vulvar Dermatosis."

The table shows the body mass index (Mean ± SD) in four groups of patients with and without vulvar discomfort.

The table shows demographic data - age: more or less than 65 years, reproductive age, menopause, domicile country as a country of birth, the degree of education (more and less than 12 years), marital status, births, abortions, and using of contraception among four groups of patient.

Various Characteristics and Duration of Vulvar Discomfort in Patients With Vulvar Dermatosis and Vulvodynia

The table shows various characteristics of vulvar pain (complaints) in patients with vulvar dermatosis or vulvodynia. Generally, we can differentiate between two categories of pain - the dull pain vs. the sharp pain depending on the nerve fibers in the skin, which are involved in the provocation of the pain. The symptoms of the dull pain are burning, stinging, soreness, irritation, itching, feeling of inflammation and aching. The symptoms of the sharp pain are a knife-like pain, paper-cuts pain, stabbing and sticking. We do not know, are there some symptoms characteristic for vulvar dermatosis or vulvodynia.

The table shows sexual activity and sexual abstinence due to dyspareunia or lack of a sexual partner in four groups of patients.

The table shows the degree of dyspareunia in sexually active patients with and without vulvar discomfort. We used Marinoff Index as a measure of the degree of dyspareunia. Negative Marinoff Index (0) is a sign of the absence of dyspareunia. Four grades of Marionoff Index are: Marinoff Index 0 = no dyspareunia; Marinoff Index 1= discomfort/pain with intercourse that doesn't interfere with the frequency of sex; Marinoff Index 2= pain with intercourse which sometimes prevents intercourse and Marinoff Index 3= pain with intercourse preventing any intercourse.

Aggravation Of Vulvar Complaints Depending On Sexual Intercourse In Patients With Vulvar Dermatosis And Vulvodynia

The relationship between sexual vulvar discomfort and sexual intercourse (provocation and aggravation) in patients with vulvar dermatosis and vulvodynia, as recommended in the ISSVD Questionnaire.

Aggravation of Vulvar Discomfort Through Various Triggers in Patients With Vulvar Dermatosis and Vulvodynia

The table shows the relationship among worsening of vulvar discomfort by using tampons, cycling, wearing tight clothes, menstruation, and urination in patients with vulvar dermatosis and vulvodynia.

The table shows the incidence of the problems with urination and defecation in four groups of patients with and without vulvar discomfort.

The table shows the incidence of the other associated symptoms and diseases in four groups of patients, as recommended in the ISSVD Questionnaire.

The table shows the incidence of the previous treatment in patients with vulvar dermatosis and vulvodynia.

The table shows the results of Cotton-Swab Test in four groups of patients. Cotton-Swab Test or Q-Tip Testing is part of a multidisciplinary approach to the assessment of sexual pain, especially, vulvodynia or vestibulodynia, in women. ISSVD recommended the Cotton-Swab test for the differential diagnosis of vulvodynia. The test consists of using a cotton-swab to palpate multiple vulvar and vestibular site while recording the woman's pain. We performed Cotton-Swab Test by touching the vulva at 6 points (each vulvar ring), organized into locations based on a clock face and marked like the hours on the clock: 2h, 4h, 6h, 8h, 10h, and 12 h.

Distribution of Non-Specific and Specific Vulvar Lesions in Relation to The Three Vulvar Rings (TRIV)

The table shows the distribution of non-specific and specific vulvar lesions in relation to the three vulvar rings (TRIV). The "OUTER Vulvar Ring" includes vulvar skin, the "MIDDLE Vulvar Ring" encompasses the modified mucosa, and the "INNER Vulvar Ring" is presented with glicogenized mucosa. "Non-Specific Lesions" include non-specific erythema, punctuations, papillae, paleness and smoothness, fissures or sores in the absence of infection and pre/malignancy in any part of the vulva. "Specific Lesions" comprise eczematous inflammation with thickened, excoriated skin within chronic lichen simplex; hypopigmented or white lesions, fusion or resorption of the labia minora and clitoral hood, loss of vulvar architecture and sclerotic changes in lichen sclerosis; white reticular pattern to extensive erosion with agglutination or resorption of the labia within lichen planus and psoriatic erythematous papules with silver, scaly plaques.

Distribution of Non-Specific and Specific Lesions of the Outer Vulvar Ring According to the "Three Rings Vulvoscopy"

The table shows the distribution of the non-specific and specific lesions of the vulva according to individual structures of the Outer Vulvar Ring according to the TRIV. The "OUTER Vulvar Ring" includes vulvar skin with the following structures: mons pubis, labia majora, and the perineum. "Non-Specific Lesions" include non-specific erythema, punctuations, papillae, paleness and smoothness, fissures or sores in the absence of infection and pre/malignancy in any part of the vulva. "Specific Lesions" (lesions specific for vulvar dermatosis) comprise eczematous inflammation with thickened, excoriated skin within chronic lichen simplex; hypopigmented or white lesions, fusion or resorption of the labia minora and clitoral hood, loss of vulvar architecture and sclerotic changes in lichen sclerosis; white reticular pattern to extensive erosion with agglutination or resorption of the labia within lichen planus and psoriatic erythematous papules with silver, scaly plaques.

Distribution of Non-Specific and Specific Lesions of the Middle Vulvar Ring According to the "Three Rings Vulvoscopy"

The table shows the distribution of non-specific and specific lesions of the vulva in relation to the individual structures of the Middle vulvar ring according to the "Three Rings Vulvoscopy." The "MIDDLE vulvar ring" includes the anterior commissure with the prepuce of the clitoris, interlabial sulci, labia minora, and the posterior commissure. "Non-Specific Lesions" include non-specific erythema, punctuations, papillae, paleness and smoothness, fissures or sores in the absence of infection and pre/malignancy in any part of the vulva. "Specific Lesions" comprise eczematous inflammation with thickened, excoriated skin within chronic lichen simplex; hypopigmented or white lesions, fusion or resorption of the labia minora and clitoral hood, loss of vulvar architecture and sclerotic changes in lichen sclerosis; white reticular pattern to extensive erosion with agglutination or resorption of the labia within lichen planus and psoriatic erythematous papules with silver, scaly plaques.

Distribution of Non-Specific and Specific Lesions of the Inner Vulvar Ring According to the "Three Rings Vulvoscopy"

The table shows the distribution of non-specific and specific lesions of the vulva in relation to the individual structures of the Inner vulvar ring according to the "Three Rings Vulvoscopy." The "INNER vulvar ring" includes clitoris, Hart's line, urethral sulcus, urethral meatus, hymenal remnants, Bartholin's gland opening, and the vestibule. "Non-Specific Lesions" include non-specific erythema, punctuations, papillae, paleness and smoothness, fissures or sores in the absence of infection and pre/malignancy in any part of the vulva. "Specific Lesions" comprise eczematous inflammation with thickened, excoriated skin within chronic lichen simplex; hypopigmented or white lesions, fusion or resorption of the labia minora and clitoral hood, loss of vulvar architecture and sclerotic changes in lichen sclerosis; white reticular pattern to extensive erosion with agglutination or resorption of the labia within lichen planus and psoriatic erythematous papules with silver, scaly plaques.

The table shows the presence, the quality, and the distribution of the aceto-whitening reaction after 5% acetic acid application (Aceto-Whitening Test), in relation to the three vulvar rings. The "OUTER Vulvar Ring" includes vulvar skin, the "MIDDLE Vulvar Ring" encompasses the modified mucosa, and the "INNER Vulvar Ring" is presented with glicogenized mucosa. Acetic acid is thought to cause swelling of the epithelial tissue through reversible coagulation or precipitation of the nuclear proteins and cytokeratins. Areas of pre-/malignant lesions turn densely white and opaque immediately after application of acetic acid, due to the presence of large numbers of dysplastic cells in the superficial layers of the epithelium. The acetowhite appearance is not unique to pre-/malignancy; it is also seen in other conditions with increased nuclear protein. The acetowhite reaction varies in intensity, within and between patients.

The table shows the velocity (Mean ± SD) of the aceto-whitening occurrence after 5% acetic acid application (AWR - aceto-whitening reaction) in patients with positive AWR classified into four groups based on anamnestic data and clinical examination. Acetic acid is thought to cause swelling of the epithelial tissue through reversible coagulation or precipitation of the nuclear proteins and cytokeratins. Areas of pre-/malignant lesions turn densely white and opaque immediately after application of acetic acid, due to their higher concentration of abnormal nuclear protein and the presence of large numbers of dysplastic cells in the superficial layers of the epithelium. The acetowhite appearance is not unique to pre-/malignancy; it is also seen in other conditions with increased nuclear protein like immature squamous metaplasia, regeneration, inflammation, HPV-infection, hyperkeratosis, etc. The acetowhite reaction varies in intensity, within and between patients.

The table shows the velocity (Median | Range) of the aceto-whitening occurrence after 5% acetic acid application (AWR - aceto-whitening reaction) in patients with positive AWR classified into four groups based on anamnestic data and clinical examination. Acetic acid is thought to cause swelling of the epithelial tissue through reversible coagulation or precipitation of the nuclear proteins and cytokeratins. Areas of pre-/malignant lesions turn densely white and opaque immediately after application of acetic acid, due to their higher concentration of abnormal nuclear protein and the presence of large numbers of dysplastic cells in the superficial layers of the epithelium. The acetowhite appearance is not unique to pre-/malignancy; it is also seen in other conditions with increased nuclear protein like immature squamous metaplasia, regeneration, inflammation, HPV-infection, hyperkeratosis, etc. The acetowhite reaction varies in intensity, within and between patients.

The table shows the distribution of aceto-whitening occurrence (AWR) after 5% acetic acid application in relation to the structures of the Outer Vulvar Ring. The "OUTER Vulvar Ring" is presented with the following structures: Mons Pubis, Labia Majora, and the Perineum. Acetic acid is thought to cause swelling of the epithelial tissue through reversible coagulation or precipitation of the nuclear proteins and cytokeratins. Areas of pre-/malignant lesions turn densely white and opaque immediately after application of acetic acid, due to the presence of large numbers of dysplastic cells in the superficial layers of the epithelium. The acetowhite appearance is not unique to pre-/malignancy; it is also seen in other conditions with increased nuclear protein. The acetowhite reaction varies in intensity, within and between patients.

The distribution of aceto-whitening occurrence after 5% acetic acid application (AWR - aceto-whitening reaction) in relation to the structures of the Middle Vulvar Ring. The "MIDDLE vulvar ring" encompasses the following structures: the anterior commissure with the prepuce of the clitoris, interlabial sulci, labia minora, and the posterior commissure.

The table shows the distribution of aceto-whitening reaction (AWR) after 5% acetic acid application (AWR - aceto-whitening reaction) in relation to the structures of the Inner Vulvar Ring. The "INNER Vulvar Ring" is presented with the following structures: the clitoris, Hart's line, the urethral sulcus, the urethral meatus, hymenal remnants, Bartholin's gland opening, and the vestibule. Acetic acid is thought to cause swelling of the epithelial tissue through reversible coagulation or precipitation of the nuclear proteins and cytokeratins. Areas of pre-/malignant lesions turn densely white and opaque immediately after application of acetic acid, due to the presence of large numbers of dysplastic cells in the superficial layers of the epithelium. The acetowhite appearance is not unique to pre-/malignancy; it is also seen in other conditions with increased nuclear protein. The acetowhite reaction varies in intensity, within and between patients.

The table shows the distribution of histopathological findings of vulvar epidermis among patients with and without vulvar discomfort, classified into four groups based on anamnestic data, clinical examination and "Three Rings Vulvoscopy." Histopathological characteristics of vulvar epidermis included hyperkeratosis, parakeratosis, acanthosis, and epidermal atrophy. In the vulvar dermis, there were evaluated presence of inflammatory infiltrates (monocytes, lymphocytes, mastocytes), collagen fibers, hyalinization, hyperpigmentation, elongated dermal papillae, blood vessels, sebaceous glands, and nerve fibers.

Histopathological Features of the Vulvar Epidermis and Vulvar Discomfort in Patients With Vulvar Dermatosis

The table shows the relationship between histopathological features of the vulvar epidermis (normal versus abnormal) and single vulvar symptoms from the categories of the dull ("slow") and sharp ("fast") pain of the vulva in 82 patients with vulvar dermatosis. The dull pain comprises sensations of burning, stinging, soreness, irritation,itching, inflammation and aching. The fast pain includes sensations like sticking and stabbing, paper-cut or knife-like pain.

The table shows the relationship between histopathological features of the vulvar epidermis (normal versus abnormal), and single vulvar symptoms from the categories of the dull ("slow") and sharp ("fast") pain of the vulva in 82 patients with vulvodynia diagnosed anamnestically and clinically following Friedrich's criteria. The "dull" pain comprises sensations of burning, stinging, soreness, irritation, itching, inflammation and aching. The "fast" pain includes sensations like sticking and stabbing, paper-cut or knife-like pain.

Histopathological Features of Vulvar Dermis in Patients With Vulvar Dermatosis Depending On The Duration of Vulvar Discomfort

The table shows the relationship between histopathological features of the vulvar dermis depending on the duration of vulvar discomfort (less or more than 24 months) in 82 consecutive patients with vulvar dermatosis. Histopathological characteristics of vulvar dermis included inflammatory infiltrates (mononuclear, lymphocytes, mastocytes), collagen fibers, hyalinization, hyperpigmentation, elongated dermal papillae, blood vessels, sebaceous glands, and nerve fibers.

Histopathological Features of the Vulvar Dermis in Patients With Vulvodynia Depending on The Duration of Vulvar Discomfort

The table shows the relationship between histopathological features of the vulvar dermis depending on the duration of vulvar discomfort (less or more than 24 months) in 82 patients with vulvodynia, diagnosed anamnestically and clinically following Friedrich's criteria. Histopathological characteristics of vulvar dermis included inflammatory infiltrates (mononuclear, lymphocytes, mastocytes), collagen fibers, hyalinization, hyperpigmentation, elongated dermal papillae, blood vessels, sebaceous glands, and nerve fibers.

Inclusion Criteria: "Three Rings Vulvoscopy" performed at Poliklinika Harni, during the period from December 2011 - December 2016. Ability to provide Informed Consent and complete Questionnaire. Exclusion Criteria: Incomplete medical records. Lack of histopathology. Vulvo-vaginal infection. Benign tumors of the vulva. Pre-/malignant conditions of the vulva.

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Raspollini MR, Asirelli G, Moncini D, Taddei GL. A comparative analysis of lichen sclerosus of the vulva and lichen sclerosus that evolves to vulvar squamous cell carcinoma. Am J Obstet Gynecol. 2007 Dec;197(6):592.e1-5. doi: 10.1016/j.ajog.2007.04.003. Epub 2007 Aug 21.

Shier M, El-Khatib S. Vulvar lichen sclerosus. J Obstet Gynaecol Can. 2010 Oct;32(10):929-30. doi: 10.1016/s1701-2163(16)34676-x. No abstract available. English, French.

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