Vulvar Malignancies Research Articles

Pedicled Anterolateral Thigh Flap (ALT) for Vulva Reconstruction: Journey to a New Horizon

AbstractSurgery for vulval malignancies necessitates extensive resection necessitating the use of musculocutaneous grafts. We present one such case where the patient needed both a V–Y plasty and an anterolateral thigh flap to ensure a tension-free repair. She underwent a partial deep vulvectomy followed by V–Y plasty and ALT flap. The procedure has been described in detail along with intraoperative photographs. She recovered uneventfully and is receiving post-operative adjuvant radiotherapy. We would like to highlight this “additional skill” of plastic surgery which will empower surgeons to undertake radical surgeries to ensure the best outcomes for patients.

52560 Risk Factors Associated with the Development of Vulvar Malignancy from Lichen Sclerosus

52560 Risk Factors Associated with the Development of Vulvar Malignancy from Lichen Sclerosus

Molecular Classification of Vulvar Squamous Cell Carcinoma and Precursor Lesions Using Immunohistochemistry

Abstract Introduction: Vulvar malignancies are very rare. Two pathogenic pathways have been described in the development of vulvar squamous cell carcinoma.One is related to HPV infection and the other is related to TP 53 mutation. HPV infection related squamous cell carcinomas have a good prognosis and squamous cell carcinomas related to TP 53 mutation have the worst prognosis. Recently a third pathway which is neither HPV dependent nor p53 mutant has been identified. This pathway is found to have intermediate prognosis with better clinical outcome. Aims: The aim of this study was to classify vulvar squamous cell carcinoma and its precursor lesions molecularly using two immunohistochemical stains p16 and p53 in a cohort of South Indian population. Subjects and Methods: A retrospective observational study was conducted between January 2011 and December 2020 in the department of histopathology at a tertiary care hospital in Hyderabad, India. A total of 22 cases including all the vulval biopsies with suspected squamous cell carcinoma or precursor lesions and excision specimens operated for squamous cell carcinoma were included in this study. Paraffin blocks of representative cases were stained with hematoxylin and eosin stain, p16 and p53 immunohistochemistry (IHC) stains. Results: Out of 22 cases, two cases (9.0%) were precursor lesions of the vulva and 20 cases (90.9%) were invasive squamous cell carcinoma. Eleven (50%) of these cases were p53 mutant (p53+/p16−), 10 (45.4%) of these cases were HPV positive (p16+/p53−), and one of these cases (4.5%) was neither HPV positive nor p53 mutant (p16−/p53−). Conclusions: Classification of vulvar squamous cell lesions molecularly using simple immunohistochemical stains in routine diagnostic workup will aid in risk stratification of patients and help in their management and prognostication.

PRAME Immunohistochemistry for Distinguishing Vulvar and Vaginal Melanoma From Benign Melanocytic Nevi.

Vulvovaginal melanoma (VVM) is a rare but deadly disease, accounting for 5% of all vulvar malignancies, with a 5-yr survival rate of only 47% for all stages of the disease. VVM is a distinct subset of melanoma, with a unique genomic profile and underlying pathogenesis unassociated with sun exposure. Distinguishing these rare malignancies from very common pigmented lesions of the vulva and vagina is challenging as histologic features often overlap between entities. PReferentially expressed Antigen in MElanoma (PRAME) is a melanoma-associated protein, and immunohistochemistry (IHC) for PRAME distinguishes cutaneous, oral mucosal, and retinal melanoma from atypical nevi. Given the biological differences between VVM and cutaneous melanoma, the utility of PRAME IHC for the diagnosis of VVM is unknown. We accrued a cohort of 20 VVM and 21 benign vulvar melanocytic nevi. We found that nuclear PRAME IHC staining with 4+ intensity was present in 85% of the VVM and 0% of the nevi. With the assistance of PRAME IHC, we found evidence of close or positive margin involvement in 3 of 10 cases where margins were originally diagnosed as negative for melanoma in situ. Our study is the first to assess PRAME IHC in a cohort of VVM cases and provides confidence for using PRAME IHC to assist with diagnosis and margin assessment in this rare disease.

Our Experience of Distal and Total Urethrectomies in Post Irradiated Vulvar Malignancies in Low Resource Settings: A Single Centre Study.

At diagnosis, women with vulvar cancer often present in locally advanced stage especially in developing countries, owing to the associated ignorance and social stigma. Generally tumour is seen involving adjacent organs, like the vagina, anus, and urethra. Damage to the sphincter system leads to urinary incontinence. Available evidence regarding urethral resections, subsequent lower urinary tract dysfunction and neo-meatus reconstruction in radical vulvar surgeries is scarce and conflicting. Considering, the lack of literature on outcomes of partial and total urethrectomies post chemoradiation in advanced vulvar malignancies from India, in the current study, we analysed our experience of such cases that have been operated post chemoradiation over a span of 2years (from January 2019 to January 2021). DFS ( disease free survival) of more than 6months was seen in 5 of our patients, however in view of local wound complications after primary closure, we recommend reconstruction with myocutaneous flaps. Also in view of incontinence observed in two of our patients who had undergone more than 1⁄2 of urethral resection, as a result of failed suprapubic catheterisation, further plan of urethral reconstruction should be considered especially in patients who have received prior radiation. Our small group of patients represents a unique cohort of patients in whom surgery was attempted after radiation therapy. We have seen that surgery is a feasible option after radiotherapy in patients with advanced disease.

A Pseudo Papillomatous Vulva: A Diagnostic Challenge

Vulvar malignancies are rarely encountered in dermatology. The vulvar intraepithelial neoplasia (VIN) are the most common ones and the incidence of VIN is increasing in younger women. Early diagnosis and tailoring the management on individual basis may help to reduce the long-term morbidity. We report a case of differentiated VIN of the vulva presenting a pseudo papillomatous aspect mimicking a granulomatous disease.

Ten Year Experience of Epidemiological Trends and Clinical Pattern of Vulvar Tumor

Objectives: Vulvar tumor is a relatively uncommon female genito-urinary tumor, occurs mainly in post-menopausal females. Incidence and patterns of vulvar tumor differ from nation to nation, depending upon multiple factors. The aim of this study was to evaluate epidemiological patterns and clinical profile of vulvar tumor in our institution retrospectively. Methods: This is a retrospective study done in a regional cancer centre of India over10-years period. Data of all vulvar tumor patients, regarding demographic profile and tumor characteristics were collected from record section and reviewed. These data were analysed to get an idea about clinic-epidemiological trends of vulvar malignancy. Results: Total 47-patients with biopsy proven vulvar malignancy were found. Mean age at presentation was 63.4 years. Majority of the patients belonged to rural origin, were post-menopausal and multiparous. Most of them had pruritus as typical presenting symptoms. Histopathologically, squamous cell carcinoma constituted the major bulk. Labia was the commonest site of presentation. Bilateralism was found in one-third among them, inguinal lymphadenopathy and extensive disease were found in five and four patients, respectively. Conclusions: The hallmark about the present article is that it was conducted in the only referral cancer institute of this state. Limited studies from different region of India have published local patients’ data on vulvar tumor. A nationwide collaboration in this regard will help to understand the exact burden of this relatively rare malignancy, epidemiological trends and risk factors as well as an idea about how to manage these patients.

Vulvar sarcoma in a young patient with neurofibromatosis syndrome with missed opportunities: A case report

Background: Vulvar malignancies are the fourth commonest of genital malignancies. The sarcoma type is associated with neurofibromatosis disease.
 Case presentation: A 29-year-old nulliparous presented to the outpatient gynecological clinic with a five-year history of a recurrent right vulvar mass. The mass was initially excised without histological analysis. Histological examination of a reexcised mass diagnosed a spindle cell sarcoma. She was then lost to follow-up for one year. The mass recurred and she received external beam radiation. On admission, she was in good general status with generalized café-au-lait spots and neurofibromas. Perineal examination revealed an ulcerated right vulvar mass. Toilet vulvectomy and diversion colostomy were performed followed by chemotherapy. She was discharged after five months with a well-granulated wound. Colostomy was reversed six months later.
 Conclusion: Vulvar sarcoma is a rare vulvar malignancy type usually associated with neurofibromatosis. This case highlights the missed opportunities in its management. A high suspicion threshold is critical for early diagnosis and management to curb the morbidity and mortality rate.

Robotic left apicoposterior bisegmentectomy for non–small cell lung cancer

Robotic left apicoposterior bisegmentectomy for non–small cell lung cancer

High-frequency ultrasound assessment of vulvar lichen sclerosus treated with photodynamic therapy.

Patients with vulvar lichen sclerosus (VLS) are faced with a decreased quality of life and an increased risk of vulvar malignancy. 5-Aminolevulinic acid-based photodynamic therapy (ALA-PDT) can serve as an alternative for refractory VLS patients. However, high-frequency ultrasound (HFUS) has never been introduced in the ALA-PDT outcome assessment for VLS patients. A prospective study was conducted. Refractory VLS patients received two treatment courses of ALA-PDT (3 times of remedies at 2-week intervals for each course), and underwent clinical, HFUS and histopathological assessment. Statistical analysis comparing parameters at baseline and after ALA-PDT was performed. Thirty-one VLS patients were included. Both subjective symptoms (itch and burning pain) and objective severity (lesion size and hypopigmentation) were relieved significantly after ALA-PDT treatment. Hypoechoic dermal band (HDB) thickness revealed by HFUS decreased progressively with successive ALA-PDT treatment, and the reduction value had a positive correlation with the reduction of inflammatory infiltration depth in histopathology. Collagen homogenization depth decrease was also noticed. Besides, adverse effects were recorded, mainly as mild and transient post-treatment edema and pain. ALA-PDT is an effective and safe therapeutic option for refractory VLS patients. HFUS can act as a complement to the non-invasive treatment monitoring for its objectivity, quantifiability and precision in the distinct vertical perspective.

Assessing Rates of Positive Surgical Margins After Standard Excision of Vulvar Melanomas.

Vulvar melanoma is a rare malignancy with frequent recurrence and poor prognosis. National guidelines recommend wide local excision of these tumors with allowances for narrower margins for anatomic and functional limitations, which are common on specialty sites. There is presently a lack of data of margin positivity after standard excision of vulvar melanomas. We aim to evaluate the rate of positive margins after standard excision of vulvar melanomas. Retrospective cohort study of surgically excised vulvar melanomas from the NCDB diagnosed from 2004 to 2019. We identified a total of 2,226 cases. Across surgical approaches and tumor stages, 17.2% (Standard Error [SE]: 0.8%) of cases had positive surgical margins. Among tumor stages, T4 tumors were most commonly excised with positive margins (22.9%, SE: 1.5%). On multivariable survival analysis, excision with positive margins was associated with significantly poorer survival (Hazard Ratio 1.299, p = .015). We find that positive margin rates after standard excision of vulvar malignancies are higher than for other specialty site melanomas. Our data suggest that use of surgical approaches with complete margin assessment may improve local control and functional outcomes for patients with vulvar melanoma as they have for patients with other specialty site melanomas.

A Pilot Study of a Screening Program for Human Papillomavirus-Related Squamous Intraepithelial Lesion and Malignancy in Gynecologic Oncology Patients.

Human papillomavirus (HPV)-related squamous intraepithelial lesion (SIL) or malignancy is associated with a significantly increased risk of second-site SIL or malignancy. The primary objective of this study was to determine the feasibility and acceptability of concurrent anal, cervical, and vulvovaginal screening in patients with a history of HPV-related gynecologic high-grade SIL or malignancy. The secondary objective was to assess subjects' knowledge regarding HPV screening and risks. Women with high-grade cervical, vulvar, or vaginal SIL or malignancy were enrolled during a 1-year pilot period. Subjects with cervical SIL or malignancy underwent vulvar examination and anoscopy. Subjects with vulvovaginal SIL or malignancy underwent Pap test if indicated and anoscopy. Appropriate referrals were made for abnormal findings. Feasibility was assessed by compliance using study acceptance rate, screening procedure adherence, and referral adherence. Acceptability was assessed using a Likert-scaled question after completion of screening procedures. One hundred three women with a diagnosis of high-grade vulvovaginal or cervical SIL or carcinoma were approached regarding study enrollment; of these, 74 (71.8%) enrolled. The median score on the HPV knowledge assessment was 8.1 ± 1.6 (max score 10). Seventy-three (98.6%) of 74 patients rated the screening procedures as acceptable (score of 5/5). On examination, 14 (18.9%) subjects had abnormalities noted; 7 (9.5%) were referred for colorectal surgical evaluation, and 6/7 (85.7%) were compliant with their referral appointments. Screening examinations for other HPV-related SILs and malignancies, including Pap tests, vulvovaginal inspection, and anoscopy, are acceptable to patients, with abnormal findings in almost 1 in 5 women.

Vulvar cancer in young woman—case report

Vulvar cancer is rare with incidence of 45,240 new cases globally which account for 4% of all genitourinary tract neoplasma. It is considered as a postmenopausal disease, however incidence age has decreased over the years because of high prevalence of persistent high-risk human papillomavirus (hrHPV) infection. Vulvar cancer diagnosis in young women is challenging. Prompt and adequate diagnosis, and treatment can ensure the life quality. A 23 years old patient was admitted to Department of Operative Gynecology for treating malignant vulvar neoplasma. She was reffered to our clinic for electrocauterization after being diagnosed of condylomata accuminata. Physical examination revealed vulva atrophy with smooth discolored skin patches on both sides. A 2 cm exophytic lesion was noted ~10 mm from clitoris on right labia majora. Multifocal biopsy was performed for suspect finding which proved invasive vulvar squamous keratinizing cancer. Positron emission tomography-computed tomography (PET/CT) scan showed individual lymph nodes on right inguinofemoral region which were moderately metabolically active. Wide excision of cancer was performed with unilateral inguinofemoral lymphadenectomy. Macroscopic evaluation of entire specimen depicted 2.4 × 2.2 × 0.5 cm HPV associated invasive vulvar squamous keratinizing cancer, vulvar high grade squamous intraepithelial lesion (vHSIL) or usual type vulvar intraepithelial neoplasia (uVIN3) and lichen sclerosus. Healthcare professionals in primary care centers should be adequately trained, aware of and familiar with vulvar malignancies in younger women despite their rarity. Early diagnosis can improve outcomes in vulvar cancer via reducing morbidity and mortality. The individualized surgical treatment is the preferred strategy for patients at present.

Mixed warty and sarcomatoid squamous cell carcinoma of vulva: a rare occurrence

Vulvar cancer is a rare tumor accounting for <5% of female genital tract tumors. The most common type of vulvar malignancy is squamous cell carcinoma. There are many histological variants of squamous cell carcinoma, keratinizing type being the most common one. Sarcomatoid variant is an extremely rare variant in vulva and comprises both epithelial and mesenchymal features. Due to the rarity of this tumor in the vulva and limited cases reported in the literature, no proper management guidelines have been established yet. In the current case report, we describe a case of mixed warty and sarcomatoid squamous cell carcinoma of vulva.

GSOR23 Presentation Time: 12:20 PM: Clinical Outcomes of Interstitial High-Dose Rate Brachytherapy with and without Concurrent Interstitial Hyperthermia for Gynecologic Malignancies

<h3>Purpose</h3> Radiosensitization with external hyperthermia (HT) has demonstrated improved oncologic outcomes for patients with gynecological (GYN) malignancies. However, similar data for multicatheter interstitial HT (IHT) with interstitial high-dose rate (IHDR) brachytherapy is limited. We present a single-institution experience of patients with GYN cancers treated using IHDR with and without concurrent IHT (IHDR-IHT). <h3>Materials and Methods</h3> We retrospectively analyzed 63 patients with locally advanced GYN malignancies treated with IHDR using a Syed-Neblett template (IHDR: 29 and IHDR-IHT: 34 patients). Primary indication for adding IHT was bulky, residual or recurrent disease guided by number, location and geometry of needle placement within HRCTV to allow placement of IHT antennae and thermistors. IHT (target temperature 40-44°C) was performed after IHDR treatment using the same set of interstitial catheters. The median age was 60 yrs (27- 89). Primary sites included cervical (n=40), endometrial (n=9), vaginal (n=10), vulvar (n=3), and non-GYN malignancy with vaginal invasion (n=1). Pelvic radiation therapy was performed prior to IHDR in all but one patient with median dose of 45 Gy (Range, 30.6-55.0 Gy) and 52 patients received concurrent chemotherapy. Median IHDR dose was 23.75 Gy (10-30.0) and number of fractions was 5 (2-5). IHDR and IHDR-IHT groups had similar proportion of reirradiation (p=0.55), stage ≥ III (p=0.11) and HRCTV volume (p=0.65) with marginally higher recurrent cases in the IHDR cohort (p=0.07). Median D90 HRCTV EQD2 was higher in IHDR-IHT (78.2 Gy; 14-105) vs IHDR group (75.9 Gy; range 61-86); p = 0.005. Respective median HRCTV volume were 61.3 cc (25-376) and 48.6 cc (12-175); p = 0.21. Chi -square and Mann-Whitney tests were done to compare variables between the two cohorts. The Kaplan-Meier method with Cox Regression was used to estimate overall survival (OS), local control (LC), locoregional control (LRC) and distant control (DC) and evaluate predictors of LC. <h3>Results</h3> IHDR-IHT and IHDR were well tolerated with no acute procedure-related adverse events. With a median follow up of 12.1 months (<1-59) in IHDR group and 11.0 months (1-76), 1 IHDR-HT patient developed acute CTCAE grade 3+ toxicity (grade 3 urinary obstruction in a patient with horseshoe kidney). Late Grade 3+ toxicity was seen in 9 patients (IHDR: 5, IHDR-IHT: 4 patients); ureteral stricture/incontinence (4), fistula (3) and radiation proctitis (2). Median OS was 31 versus 42 months (p=0.55) in the IHDR and IHDR-IHT groups, respectively. 1 yr LC for IHDR vs IHDR-IHT of 86.9% vs 77.8% (p=0.051). Corresponding, 1-yr LRC and DC were 82.5 vs 74.8% (p=0.056) and 81 vs 77.6% (p=0.84), respectively. On cox regression undergoing IHT (HR 4.7 [95% CI 1.3-16.9] p=0.02) was associated with worse local control. <h3>Conclusions</h3> To our knowledge, this is the largest report describing outcomes from the addition of IHT to IHDR in patients with locally advanced GYN malignancies. Use of IHT had excellent tolerance without any procedural complications. With possible group imbalances, trend to shorter LC and LRC was seen in IHT. Prospective controlled studies will be needed to evaluate clinical benefits.

Molecular Features of Preinvasive and Invasive Vulvar Neoplasms.

Neoplasms arising from the vulva are uncommon and comprise various subtypes. Given the recent advancements in the molecular aspects of oncologic pathology and how they have impacted cancer treatment, an understanding of recent innovations in the molecular features of vulvar lesions is important. Systematic literature search was performed on PubMed, Google Scholar, and Scopus databases for molecular and genetic characteristics of vulvar neoplasms. Peer-reviewed literature published in English is included. Squamous cell carcinoma (SCC) and its precursors are the predominant neoplasm at this site. Human papillomavirus (HPV) plays a crucial role in the pathogenesis of some of these lesions. Human papillomavirus-associated SCC follows the carcinogenic pathway driven by viral proteins E6 and E7 while HPV-independent SCC shows a high incidence of mutation of TP53 and CDKN2A genes. Mutations in the genes involving the PI3K-Akt pathway play an important role in the pathogenesis of both types of SCC. Among other vulvar malignancies, melanoma, and vulvar Paget disease (VPD) pose a significant clinical challenge and have unique molecular characteristics. Compared with dermal cutaneous melanoma, vulvar melanoma shows a higher rate of mutation of cKIT and NRAS genes and a lower rate of mutations in BRAF . Less than 20% of VPD shows amplification of ERBB2 and seldom shows mutation in genes involving the PI3K-Akt pathway. Several potentially targetable molecular pathways have emerged as they have been shown to be involved in the tumorigenesis of SCC, melanoma, and VPD.

Facility level volume of surgical lymph node assessment for patients with vulvar cancer: A multi-institutional database analysis (368)

<b>Objectives:</b> To investigate surgical lymph node assessment (LND) facility level volume for patients with vulvar cancer using a large hospital-based database and evaluate the potential impact on perioperative and survival outcomes. <b>Methods:</b> The National Cancer Database was accessed, and patients who were diagnosed between 2004 and 2016 with a pathologically confirmed invasive vulvar malignancy, who received all treatment at the reporting facility and underwent surgical lymph node assessment (LND) (including lymph node sampling, dissection, or sentinel lymph node biopsy) were identified. Annual LND volume was calculated for facilities that reported at least 12 cases. High-volume facilities were defined as those performing at least ten LND annually. The impact of facility volume on perioperative and survival outcomes was examined in a cohort of patients with apparent stage IB squamous cell carcinoma, and available data on lymph node status from the pathology report. Clinical-pathologic and demographic characteristics of patients managed in low and high-volume facilities were compared with the Chi-square test while overall survival (OS) was compared with the log-rank test. A Cox model was constructed to control for a priori selected confounders. <b>Results:</b> A total of 376 facilities performed at least 12 cases of LND in vulva cancer patients between 2004 and 2016. The median annual facility volume was 2.9 cases; 10^th and 90^th percentiles were 1.81 and 6.41 cases, respectively. Only eight facilities performed at least ten vulvar cancer LND cases annually. The analysis cohort included 10821 patients with apparent stage IB SCC who met the inclusion criteria; 990 (9.1%) were managed at high-volume centers. There was no difference between patients managed in low and high-volume facilities in terms of patient age, insurance status, and presence of comorbid conditions. Rate of lymph node metastases (22.4% vs 24%, p=0.24) and 90-day mortality (1.5% vs 1.4%, p=0.66) were comparable between low and high-volume facilities. The rate of prolonged hospital stay (defined as >3 days) was higher in low-volume facilities (26.2% vs 21.2%, p<0.001); however, the rate of unplanned re-admission 30 days from discharge was lower (5.2% vs 7.8%, p<0.001). There was no difference in OS between low and high-volume facilities (median OS: 106.9 and 108.9 months, respectively, p=0.21). However, patients who had negative lymph nodes who were managed at highvolume facilities had better OS (p=0.024); 5-year OS rates were 80% and 75%, respectively. After controlling for patient age, race, insurance status, presence of comorbid conditions, history of another tumor, tumor size, and status of lymph nodes, there was no difference in OS between low and high-volume centers (HR: 0.93; 95% CI: 0.83, 1.04). <b>Conclusions:</b> The majority of institutions in the United States perform very few LND for vulvar cancer. Although facility volumes do not appear to affect OS, lymph node assessments appear to be more accurate at high-volume centers.

Association of vulvar lichen sclerosus with endometrial and ovarian cancer

Association of vulvar lichen sclerosus with endometrial and ovarian cancer

Analysis of clinical outcomes of patients with primary rare carcinoma of Bartholin gland: six case series report and review of the literature.

BackgroundBartholin gland carcinoma (BGC) is an unusual malignancy representing less than 5% of all vulval carcinomas. Due to the limited published information on the diagnosis and treatment of BGC, this tumor is prone to misdiagnosis; most cases are found in an advanced stage once the diagnosis is delayed.MethodsThis was a retrospective study of six patients with BGC in the West China Second University Hospital between January 2011 to August 2021.ResultsIn our study, BGC was 4.4% in all vulvar malignancies. The average age of six patients was 40.83 years old, with the tumor size ranging from 2 to 5 cm, and time of onset ranging from 2 to 3 years. Based on the retrospective clinical staging, there were three patients in stage I, one in stage II, and two in stage IVb. The human papillomavirus (HPV) 16 was detected in tissue samples of three patients. Two patients with excision of the vulvar mass and wide local excision (WLE) had local recurrence at 32 and 18 months, respectively. One patient died of distant metastasis of tumor, one died of non-tumor cause, and the others survived to this day.ConclusionsSix patients with BGC were reviewed in this study, and their characteristics of baseline information, clinicopathology, treatment approaches, and prognosis were described and analyzed, hoping to provide new insights for the diagnosis or treatment in this rare malignancy.

Vulvar melanoma with multisystemic metastases: A rare case presentation

Malignant melanoma is the second most common vulvar malignancy which occurs in elderly females. In advanced stages of the disease, distant metastases can occur to any organ; hence, comprehensive radiological evaluation is necessary. We report a case of a 45-year-old female who presented with progressively increasing growth over the vulva for 6 months. On detailed clinical, pathological, and radiological workup, multiple metastases were found in the brain, liver, pancreas, peritoneum, lungs, and pleura. The final diagnosis of vulvar melanoma with multisystemic metastases was made after the histopathological examination.