Vulvar Ulcers: An Algorithm to Assist With Diagnosis and Treatment.

OBJECTIVES: Vulvar ulcers can be challenging to diagnose, manage, and treat. Ulcers can be nonspecific in appearance and have many etiologies. Description of the lesion is very important. METHODS: An interactive vulvar ulcer algorithm was created to aid in the evaluation, diagnosis, and treatment of vulvar ulcers. RESULTS: The algorithm flowchart begins with careful history and physical examination. Pending these, specific tests can be obtained to aid in diagnosis. The algorithm also links to appropriate treatments. The algorithm can be accessed on the International Society for the Study of Vulvovaginal Disease Web site ( issvd.org ). Each underlined word in the algorithm is a hyperlink that leads to a wealth of information on the topic that providers can use to direct testing and aid in diagnosis and treatment. CONCLUSIONS: The vulvar ulcer algorithm can help clinicians with diagnosis and treatment plans.

Relationship Between Childhood Sexual Abuse, Obesity, and Vulvodynia in Adulthood.

OBJECTIVE: The aim of the study is to assess the relationship between childhood sexual abuse, obesity, and vulvodynia among adult women participating in a population-based longitudinal vulvodynia study. MATERIALS AND METHODS: Surveys assessed health status, diagnoses, risk factors, and screening test outcomes for women with vulvodynia. Associations between childhood sexual abuse (CSA) and obesity, CSA and vulvodynia, and obesity and vulvodynia were investigated. A multivariate model was used to determine if obesity mediates and/or modifies the relationship between CSA and vulvodynia. RESULTS: Of 2,277 women participating in the study, 1,647 completed survey data on CSA at 18 months, body mass index at 24 months, and vulvodynia over the first 54 months of the survey. Mean age was 50.9 ± 15.8 years. Overall, race and ethnicity were 77.4% White, 15.7% Black, 2.4% Hispanic, and 4.5% other. Five hundred thirty-nine participants (32.7%) were obese (body mass index >30) and 468 (28.4%) were overweight. Physical CSA before age of 18 years was reported by 20.0% ( n = 329). During the study, 22.0% ( n = 362) screened positive for vulvodynia on one or more surveys. After controlling for demographic variables, both obesity and screening positive for vulvodynia were associated with a history of CSA before age of 18 years ( p = .013 and p < .001, respectively), but obesity was not associated with screening positive for vulvodynia ( p = .865). In addition, multivariate analysis indicated no mediation of the CSA/vulvodynia relationship by obesity. CONCLUSIONS: Although obesity and vulvodynia were independently associated with a history of CSA, obesity did not mediate or modify the relationship between CSA and vulvodynia in adulthood.

Outcomes After Lysis of Adhesions and Dilator Placement for Treatment of Vulvovaginal Agglutination Due to Lichen Planus.

OBJECTIVE: The aim of the study is to determine intraoperative and postoperative surgical outcomes for the treatment of vulvovaginal agglutination secondary to lichen planus (LP) following a standard protocol using intraoperative dilator placement and postoperative intravaginal steroid use. MATERIALS AND METHODS: This was a retrospective chart review of patients who underwent surgical management of vulvovaginal agglutination due to LP following a protocol that included surgical lysis of vulvovaginal adhesions, intraoperative dilator placement and removal 48 hours later, and high-potency intravaginal corticosteroid and regular dilator use thereafter. Demographic and clinical data were abstracted from the medical record and analyzed using descriptive statistics. RESULTS: Thirty-four patients, with mean age 51.2 ± 11 years and body mass index 32.8 ± 8.5 kg/m 2 , underwent lysis of vulvovaginal adhesions between 1999 and 2021 with 8 different surgeons at a single institution. The mean preoperative, immediate postoperative, and 6-week postoperative vaginal lengths were 2.8 ± 1.8 cm ( n = 18), 8.0 ± 1.9 cm ( n = 21), and 7.9 ± 2.2 cm ( n = 16), respectively. The mean estimated blood loss intraoperatively was 16 ± 15 mL. No patients had a documented surgical site infection or reoperation within 30 days after surgery. Of patients who had it documented ( n = 26), 70% (18/26) reported postoperative sexual activity. Where documented, 100% (18/18) reported preoperative dyspareunia, while 17% (3/18) did postoperatively. Six percent (2/34) had recurrent severe agglutination and 3% (1/34) underwent reoperation. CONCLUSIONS: Lysis of vulvovaginal adhesions, intraoperative dilator placement, and postoperative intravaginal corticosteroids with dilator use is a safe and effective treatment option to restore vaginal length for those with vulvovaginal LP.

Comorbid Vulvar Lichen Sclerosus and High-Grade Squamous Intraepithelial Lesions: A Management Conundrum.

OBJECTIVE: This study aimed to determine if treating lichen sclerosus (LS) with high-potency topical corticosteroids (TCS) increases the risk of high-grade squamous intraepithelial lesion (HSIL) recurrence in patients with comorbid vulvar LS and HSIL. METHODS: This is a retrospective study of patients with comorbid vulvar LS and HSIL treated with TCS between 2015 and 2020. Patients with clinically diagnosed or biopsy-proven LS and biopsy-proven HSIL of the vulva were included. Clinical data included demographics, tobacco use, immune-modifying conditions, specimen pathology, treatment types, and HSIL recurrence. Bivariate analysis was performed to compare demographic and clinical characteristics between patients with and without HSIL recurrence. RESULTS: Twenty-six patients with comorbid LS and HSIL were identified. The median age was 66.0 years and median time in treatment for LS was 5.5 years. Thirteen (50%) had recurrence of HSIL and 13 (50%) did not have recurrence. Exposure to high-potency TCS was present in 20 (77%) patients, with 17 (65%) having use of more than 1-year duration and 9 (35%) having use at the time of HSIL diagnosis. When comparing the groups with and without HSIL recurrence, there was no significant difference in high-potency TCS exposure, duration of use, or use at time of HSIL diagnosis. CONCLUSIONS: High-potency TCS use for the treatment of LS did not seem to increase the risk of HSIL recurrence in patients with comorbid vulvar LS and HSIL. This suggests that high-potency TCS can be appropriately used for the treatment of LS even when HPV-associated disease is present.

Expanding the Morphologic, Immunohistochemical, and HPV Genotypic Features of High-grade Squamous Intraepithelial Lesions of the Vulva With Morphology Mimicking Differentiated Vulvar Intraepithelial Neoplasia and/or Lichen Sclerosus.

Squamous cell carcinoma of the vulva can arise through 2 pathways: human papillomavirus (HPV)-dependent high-grade squamous intraepithelial lesions (previously termed usual vulvar intraepithelial neoplasia) or HPV-independent (differentiated vulvar intraepithelial neoplasia, dVIN). Distinguishing between the 2 types can be clinically and histologically difficult. A subset of high-grade squamous intraepithelial lesions with superimposed chronic inflammation mimicking dVIN has recently been reported; p53 shows characteristic mid-epithelial staining (with basal sparing) in such cases. The pathology databases of 2 academic institutions were searched for vulva specimens with corresponding p53 and p16 immunohistochemical stains, yielding 38 specimens (from 27 patients). In situ hybridization and multiplex polymerase chain reaction-MassArray for high-risk HPV were performed on at least 1 block from each patient. All cases resembled dVIN or lichen sclerosus morphologically, but with a higher degree of atypia. All but 1 case demonstrated mid-epithelial p53 staining with basal sparing by immunohistochemistry. All cases showed block positivity for p16 and at least patchy positivity by HPV in situ hybridization. Of the 23 cases with valid HPV DNA polymerase chain reaction results, 15 were positive and 8 were negative. Of the positive cases, HPV16 was identified in 10 cases, with other high-risk types in the remaining 5. To our knowledge, this is the largest cohort of high-grade squamous intraepithelial lesions mimicking dVIN reported to date. Prior studies reported positivity for HPV16 in all cases tested, however, we found HPV16 in only 67% of HPV positive cases. This case series highlights the importance of immunohistochemistry, and occasionally HPV in situ hybridization, for accurate diagnosis, and expands the spectrum of associated HPV types.

Association Between Vulvar Squamous Intraepithelial Lesions and Psychiatric Illness.

OBJECTIVES: The aims of the study were to describe and to compare demographics and the prevalence of psychiatric disorders among patients with low- and high-grade vulvar squamous intraepithelial lesions. METHODS: A retrospective chart review was performed for patients presenting to a vulvar diseases clinic between 1996 and 2019 (N = 2,462). Intake questionnaire data were entered into a deidentified database. Results were compared between 80 patients with biopsy-confirmed high-grade squamous intraepithelial lesions (HSILs) and 48 patients with biopsy-confirmed low-grade squamous intraepithelial lesions (LSILs). Bivariate analysis was performed to compare demographics and psychiatric treatment and outcomes across HSIL and LSIL groups. RESULTS: Among 128 patients with vulvar disease, 80 (62.5%) had HSILs and 48 (37.5%) had LSILs. Patients with HSILs were significantly older (HSIL median [interquartile range] = 49.0 (39.0-61.0) vs LSIL = 36.0 [29.0-53.0], p = .006). There were no significant differences between groups across race/ethnicity, education, marital status, or self-reported household income categories. Forty percent of HSIL patients reported depression compared with 20.8% of LSIL patients (p = .03), whereas 31.3% of HSIL patients and 8.3% of LSIL patients reported anxiety (p = .002). Bipolar disorder was reported in 3.8% of HSIL patients and no LSIL patients (p = .29). There were no differences in the proportion of patients receiving psychiatric counseling, medications, or hospitalizations between groups. CONCLUSIONS: Squamous intraepithelial lesions of the vulva are associated with psychiatric disorders above age-matched national averages; these disorders are more prominent in the HSIL group. Combining mental health services with ongoing disease treatment seem to be part of a comprehensive approach to caring for this patient population.

Fertility and Pregnancy Outcomes After Conservative Management of Adenocarcinoma In Situ of the Cervix.

OBJECTIVE: The aim of the study was to evaluate the pregnancy outcomes of women who underwent conservative management of adenocarcinoma in situ (AIS). MATERIALS AND METHODS: We conducted a retrospective chart review of patients diagnosed with AIS at a single tertiary institution between January 1, 1991, and December 31, 2019. We collected demographic data, AIS-specific information, and fertility outcomes and performed bivariate analyses to compare demographic characteristics and AIS-specific information between patients with and without hysterectomy after diagnosis. Patients with conservative management who achieved pregnancy were described. RESULTS: Among 87 patients with AIS, 38 (44%) underwent a hysterectomy within 6 months of diagnosis and 49 (56%) underwent conservative management. Six of 19 patients (32%) had residual AIS despite undergoing definitive management after an excisional procedure with negative margins and negative endocervical curettage (ECC). Nine of 19 patients (47%) had residual AIS after an excisional procedure with positive margins and/or a positive ECC. Patients who opted for conservative management were younger (median = 31.6 [interquartile range = 27.4-34.9] vs 38.5 y [32.3-44.8 y], p < .001) and nulligravid. Among patients with conservative management, there were 15 pregnancies and 14 live births (29%). Seven were preterm, although 2 were for medical indications. CONCLUSIONS: Residual AIS in patients with negative margins and ECC leading to definitive hysterectomy (32%) and the rate of preterm birth (36%) were higher than previous reports and nationally reported rates. However, only 1 patient had a preterm birth before 34 weeks. These findings reflect important information for counseling patients who elect for conservative management of AIS.

Genomic Profiling of Vulvar Lichen Sclerosus Patients Shows Possible Pathogenetic Disease Mechanisms.

OBJECTIVE: Vulvar lichen sclerosus (LS) is known to occur in families, suggesting a genetic link. Genomic profiling of patients with vulvar LS was investigated to find underlying pathogenetic mechanisms, with the hope that targeted therapies and future clinical research will arise. METHODS: Two unrelated families with vulvar LS were investigated using whole-exome sequencing. Five affected sisters from 1 family were compared with their unaffected paternal aunt (unaffected control). A mother-daughter pair from a second affected family was compared with the first family. The results of the sequencing were compared with population-specific allele frequency databases to prioritize potential variants contributing to vulvar LS development. RESULTS: Recurrent germ-line variants in 4 genes were identified as likely to be deleterious to proper protein function in all of the 7 affected patients, but not in the unaffected control. The genes with variants included CD177 (neutrophil activation), CD200 (inhibitory signal to macrophages), ANKRD18A (ankyrin repeat protein, epigenetic regulation), and LATS2 (co-repressor of androgen signaling). CONCLUSIONS: Although many providers may see a mother and daughter with vulvar LS, this condition is rarely seen in multiple family members who are available for genetic testing. This is the first report to detail genomic profiling related to a familial association of vulvar LS.

Maternal plasma LPCAT 1 mRNA correlates with lamellar body count.

Human lysophosphatidylcholine acyltransferase 1 (hLPCAT1) is a protein which helps produce surfactant in the fetal lung. We previously reported that levels of cell-free fetal mRNA for hLPCAT1 in amniotic fluid are correlated with lamellar body count (LBC) (r2=0.93). This short communication demonstrates that fetal hLPCAT1 mRNA is also present in maternal blood. Its quantity also correlates with amniotic fluid LBC (r2=0.81). Research in maternal plasma hLPCAT1 may assist in understanding fetal and placental maturational processes.

Amniotic fluid LPCAT1 mRNA correlates with the lamellar body count.

Lysophosphatidylcholine acyltransferase 1 (LPCAT1) is required in the biosynthesis of pulmonary surfactant. This short communication describes our assessment of LPCAT1 mRNA levels in human amniotic fluid. We found a direct correlation between LPCAT1 mRNA copies and the amniotic fluid lamellar body count (LBC). This finding corroborates an association between LPCAT1 and surfactant phospholipid biosynthesis in humans. It may provide a model for future research in perinatal medicine.

A Novel Technique for Securing a Bolster For Skin Grafting after Extensive Vulvar Resection.

Patients with stage III hidradenitis suppurativa of the vulva and adjacent areas, unresponsive to other therapies, may require extensive surgeries. These include excision of diseased areas on the buttocks, vulva, groins, and abdomen, followed by delayed skin grafting. Negative pressure wound therapy has been used over grafts, but it can be difficult to maintain a seal when extensive areas have been resected. We present a novel technique to bolster skin grafts for optimal success. A total vulvectomy and resection of the buttocks, groins, and abdomen are first performed for stage III HS, incorporating all diseased tissue. Negative pressure wound therapy is applied and changed on postoperative day 3-4. On postoperative day 7, split-thickness skin grafts are applied. The skin grafts are covered by Adaptic gauze (3M Company, Minn.), cotton, and a layer of Reston foam (3M Company, St. Paul, Minn.) which is cut to fit the size of the wound. Ostomy skin barriers (Hollister Incorporated, Libertyville, Ill.) are placed on the skin surrounding the excised areas. Pediatric Foley catheters are then placed through the ostomy skin barriers and tied together to prevent movement of the bolster. The use of ostomy skin barriers and pediatric Foley catheters to secure bolsters has not previously been described. We demonstrate a well-tolerated technique, using common surgical supplies, to provide consistent uniform pressure over the graft site. This technique also allows for easy bedside dressing change(s) when indicated.