OBJECTIVE: To evaluate the management and outcomes of Bartholin gland cancer at a single tertiary institution.
METHODS: A single institution retrospective review of 9 cases of BGC between 2004 and 2022 was conducted. Demographics, pathological characteristics, treatment, follow up and oncologic outcomes were extracted from clinical records. Data are summarised using descriptive statistics and survival probabilities are presented with Kaplan Meier graphs.
RESULTS: Ten cases of BGC were identified at our institution over a period of 18 years. Nine out of ten clinical records were available for analysis. Eight patients presented with vulval swelling and four were treated initially for Bartholin cyst or abscess. One patient had a histological diagnosis of adenoid cystic carcinoma while the remaining were squamous cell carcinomas. With the exception of stage I disease chemoradiation was the primary mode of treatment. Adverse events included skin desquamation (4/9), venous thrombo-embolism (2/9), gastro-intestinal (1/9) and neurotoxicity (1/9). Median follow up was 60 months with a 5-year recurrence free and overall survival at 76 % and 64 % respectively.
CONCLUSIONS: BGC may present after a long duration of symptoms and at advanced stages. Primary chemoradiation appears to be a feasible treatment option in advanced disease with the benefit of decreased morbidity.

UNASSIGNED: Vulvar cancer has an overall low incidence, accounting for approximately 3-5% of all gynecological malignancies.Case: We present a case of locally recurrent Stage IIIA squamous cell carcinoma of the vulva in a 51-year-old healthy African American female. She was initially treated with primary chemoradiation with cisplatin sensitization and boost to primary tumor up to 70 Gray. Post-treatment biopsies revealed complete pathologic response. She later presented with local recurrence to the primary site of the clitoris and vulva, with no evidence of metastasis on imaging, with progressive disease despite treatment with immunotherapy.
UNASSIGNED: Biopsy-proven disease progression was present on the clitoris, entire left labia minora, and a portion of the right labia minora with no evidence of metastasis on imaging. Surgical resection for localized recurrence was recommended, and she underwent radical anterior vulvectomy, distal urethrectomy, and vulvar reconstruction with bilateral Singapore fasciocutaneous flap as part of a multidisciplinary team. Patient underwent several prophylactic hyperbaric oxygen treatments. There were no issues with postoperative wound healing.
UNASSIGNED: Treatment with radical excision often requires multidisciplinary teams for complex reconstructions to restore vulvar anatomy in the setting of prior radiation, especially for those patients desiring the ability to have penetrative intercourse in the future. There are few surgical videos that describe these types of vulvar excisions and subsequent reconstructions. This video provides a unique approach to vulvar reconstruction in a previously irradiated field.

Adenoid cystic carcinoma (ACC) of the vulva represents a highly uncommon type of female malignancy. Due to the absence of specific treatment guidelines, such cases are typically managed by the treatment protocols for vulvar cancer. Here, we report the case of a 52-year-old woman who presented with a painful right vulvar mass, leading to a diagnosis of ACC of the vulva after biopsy and immunohistochemical analysis. She underwent vulvectomy, bilateral inguinal lymphadenectomy, and targeted radiotherapy, and no evidence of recurrence has been found for three years, with ongoing monitoring for post-radiation effects. This case adds valuable insights into the management of ACC of the vulva and underscores the need for further research and guideline development to optimize care for future patients.

UNASSIGNED: Distant metastases of vulvar SCC most commonly involve the lung, liver, bone, skin, and lymph nodes. Metastasis from vulvar SCC to the kidneys is extremely rare, with only one case reported in the literature to date.
UNASSIGNED: We report the case of a 53-year-old postmenopausal female patient was diagnosed with vulvar squamous cell carcinoma in an external hospital and following the diagnosis, she had been performed a vulvectomy for squamous cell carcinoma of the vulva, at that time, the patient had not undergone inguinal lymphadenectomy. In July 2019, she was admitted to our hospital due to upper right quadrant pain. An enhanced whole-body CT scan showed a mixed-density tumor of the right kidney with invasion into the right renal portal vein and multiple enlarged retroperitoneal lymph nodes. Positron emission tomography-computed tomography (PET - CT) scan showed a significantly increased radioactivity uptake in the tumor and enlarged lymph nodes, but PET-CT did not show abnormal enlargement of bilateral inguinal lymph nodes and no abnormal increase in radioactivity uptake. PET-CT examination did not show recurrence in terms of local of vulvar. These results led us to be gravely worried about possible renal carcinoma, so it was agreed upon to perform laparoscopic nephrectomy of the right kidney in the same month. Histology of the resected tumor confirmed it to be poorly differentiated squamous cell carcinoma with invasion consistent with metastatic vulvar carcinoma. Based on clinical history, radiological and histological facts, the patient was diagnosed with kidney metastasis from vulvar squamous cell carcinoma. Recovery from surgery went well and the patient was transferred to the oncology department and underwent a chemotherapy regimen consisting of paclitaxel and nedaplatin for further treatment. After 6 courses of chemotherapy. For a year after treatment, the patient had lived progression-free. Unfortunately, she died of tumor progression in July 2022.
UNASSIGNED: Although renal metastasis from vulvar SCC is rare, renal metastasis should be considered for the patient with a history of vulvar cancer, whenever a mass is identified in the kidney. Timely surgical removal of renal metastasis may prolong the survival time.

The incidence of vulvar carcinoma increases with age, though elderly women receive less aggressive cancer therapies and fewer strategies aimed at cancer prevention. Furthermore, elderly women dual enrolled in Medicaid-Medicare experience poor survival rates for vulvar carcinoma. Herein, we provide recommendations for the prevention of and guidelines for the multidisciplinary care of vulvar carcinoma. Prevention of vulvar carcinoma can be categorized into primary, secondary, and tertiary prevention. Primary prevention consists of vaccination, secondary prevention consists of screening, and tertiary prevention is aimed at the management of premalignant and early-stage lesions.

Bartholin gland carcinoma is an extremely rare disease. Information regarding treatment is scarce and there is no strict consensus on best practice. All studies reporting cases of Bartholin\'s gland cancer were screened and evaluated for inclusion. Baseline characteristics of studies were extracted. A total number of 290 manuscripts collected were available for the review process. Studies included in a previous systematic review were not duplicated. In total, details of 367 patients were collected, as follows: histological features, clinical presentation, treatment, recurrent rate, treatment of recurrence and outcome. About 35% of Bartholin gland carcinoma were squamous cell carcinoma. Almost 50% of patients presented with advanced stage. The therapeutic approach was mainly surgery, and in 61% of those women lymph node assessment was performed. Recurrence occurred in 21% of cases. Bartholin gland cancer remains a challenge for gynecologic oncologists. Guidelines, centralization to referral centers and standardized therapy are needed.

The primary aim of this study was to assess the association between human papilloma virus (HPV) and p53 expression and local recurrence (LR), disease specific survival (DSS), and overall survival (OS) in patients with vulvar squamous cell carcinoma (VSCC). Secondary, the accuracy of p16 immunohistochemistry for HPV status was assessed. The tumor tissue of 255 patients, surgically treated for primary unifocal VSCC between 2000 and 2010, was analyzed. HPV-PCR and P16 and p53 immunohistochemical stainings were performed. All histologic slides were independently reviewed by two expert gyneco-pathologists. Time to first LR, DSS, and OS for the variables p16, p53, and HPV-PCR were compared using univariable and multivariable Cox-regression analyses. In 211/255 (83.5%) patients, HPV-PCR was negative. The local recurrence rate was significantly lower in patients positive with HPV-PCR (10-year LR rate 24.6%) versus negative tumors (47.5%), p = 0.004. After multivariable analyses, this difference remained significant (HR 0.23 (95% CI 0.08-0.62) p = 0.004). There was no difference in LR rate correlated to the p53 expression. DSS and OS did not significantly differ after multivariable analyses for all different subgroups. Sensitivity and specificity of p16 staining for presence of HPV detected by HPV-PCR were 86.4% and 93.8%, respectively. In conclusion, patients with HPV-negative VSCCs have significantly more LR compared to patients with HPV-positive VSCCs, and p16 immunohistochemistry is a reliable surrogate marker for HPV status. No relevant subgroup for LR or survival based on HPV/p53 status could be identified. We advise to perform an HPV-PCR or p16 IHC staining in all patients with VSCC.

Vulvar carcinoma is a relatively rare malignancy and there is a paucity of data, especially from India and other developing countries regarding the prognostic factors impacting recurrence and survival. A retrospective observational study was conducted in the Department of Gynecologic Oncology at a tertiary care, regional cancer institute, including all patients with carcinoma vulva who underwent surgery between 2009 and 2018. Demographic profile, surgical-pathological information, details of neo-adjuvant chemotherapy, adjuvant radiation and chemotherapy, and peri-operative complications were analyzed. Long-term follow-up data was gathered, with an evaluation of various prognostic factors impacting recurrence and overall survival outcome. Forty-five cases with mean age of 56.2 years (range 29-82) were treated during the study period. Surgery was the initial treatment modality in 41 (91.1%) cases. Neo-adjuvant chemotherapy prior to surgery was given to four cases. After complete surgico-pathological staging, most patients had stage I disease (26 cases, 57.8%) and 22.2% had stage II disease. Owing to microscopic lymph node involvement, seven cases (15.6%) belonged to FIGO stage III disease. Two cases had stage IVA disease with fixed groin nodes. Adjuvant chemotherapy in the form of 5-fluoro uracil and cisplatin was administered to four out of the nine patients with nodal involvement. The remaining five were advised adjuvant groin radiation. At a median follow-up of 34 months (range 2-114 months), 12 cases (26.7%) experienced a recurrence and one case with stage IVA disease progressed during adjuvant chemotherapy. The 5-year overall survival was 76.6% and the 5-year disease-free survival was 69.6%. There were a total number of 10 deaths, of which seven were due to disease recurrence or progression and the remaining 30% of deaths were due to medical co-morbid conditions. Overall survival was negatively impacted by increasing age (age > 60 years), number of positive nodes, presence of perinodal spread, and stage of the disease. Recurrence-free survival was significantly reduced in those with the presence of peri-nodal spread and lympho-vascular space invasion. The incidence of lymph node metastasis was found to be higher in patients with age > 60 years, increasing tumor size, presence of lympho-vascular space invasion and the number of lymph nodes removed. In carcinoma vulva, treatment should be individualized with multidisciplinary cooperation. In our series, we found that the stage of disease, nodal positivity, and nodal positivity with extra-capsular spread were significant prognostic factors impacting survival on analysis. Lymph nodal positivity was associated with increasing tumour size, presence of lympho-vascular invasion, and patient age.

Clear cell carcinoma (CCC) of the vulva is extremely rare. We report a case of a 54-year-old woman who presented with a 5 cm mass of the mons pubis. She underwent needle biopsy demonstrating CCC. She then underwent radical vulvectomy with bilateral inguinofemoral lymph node dissection. Surgical pathology revealed CCC of the vulva with lymphovascular space invasion (LVSI) and metastatic carcinoma in 1/7 inguinal lymph nodes. The patient has a history of endometriosis, raising suspicion that her CCC could have arisen from endometriosis in the mons. She completed adjuvant treatment with cisplatin and concurrent external beam radiation therapy with radiographic evidence of complete response. However, short-interval imaging demonstrated multi-focal recurrence, which was confirmed with supraclavicular lymph node biopsy. She then completed 8 cycles carboplatin, paclitaxel, and biosimilar bevacizumab-bvzr with favorable response on imaging. She was continued on bevacizumab maintenance. She was later started on pembroluzimab for disease progression based on new mediastinal adenopathy and worsening retroperitoneal lymphadenopathy. She received eight cycles of pembrolizumab with ongoing disease progression before enrolling in hospice and discontinuing cancer-directed treatment. As described in the related literature which we summarize here, the majority of reported cases of vulvar CCC arise from endometriosis implants at the site of prior episiotomy or from the Bartholin\'s gland. This patient had clinical history of endometriosis; prior tissue sampling was not performed to support the diagnosis. Given the absence of data regarding this rare type of primary vulvar cancer, treatment of this patient\'s disease was based on existing data specific to squamous cell carcinoma of the vulva and extrapolated from treatment guidelines for CCC of the ovary and endometrium. Continued research is needed on this rare form of vulvar carcinoma to determine the risk factors, prognostic factors, and treatment recommendations specific to this disease.

Whether G protein-coupled estrogen receptor 1 (GPER1) is tumor-promoting or tumor-suppressive depends in part on tumor entity. Little is known about the function of GPER1 in vulvar carcinoma. In this work, we aim to clarify what role GPER1 plays in vulvar cancer, tumor-promoting or tumor-suppressive. Localization of GPER1 in A431 and CAL-39 vulvar carcinoma cells was examined by immunofluorescence. Using a tissue microarray of vulvar neoplasias, the correlation between GPER1 expression and grade of malignancy was investigated. A431 and CAL-39 cells were treated either with GPER1 agonist G1 or antagonist G36. Proliferation was quantified by BrdU assay and viability examined using Resazurin assay. Morphological changes were analyzed by microscopy and measured using ImageJ. Cell migration was analyzed by gap closure assay. Clonogenic potential was tested by colony and sphere formation. Expression of estrogen receptors was examined by Western blot. GPER1 was found consistently expressed in vulvar neoplasia tissues. The immune-reactive score was found to be significantly higher in tissue samples of lymph node metastases and neoplasias with grade 3. In A431 and CAL-39 vulvar carcinoma cells, GPER1 expression was mainly found in the cytoplasm and nuclei. Treatment of A431 and CAL-39 cells with GPER1 agonist G1 resulted in a decrease in proliferation and migration. In addition, colony formation and tumor sphere formation were reduced. Furthermore, morphological signs of necrosis and reduction in cell viability after G1 treatment were observed. The GPER1 antagonist G36 did not have significant effects on vulvar carcinoma cells. Neither agonist G1 nor antagonist G36 treatment resulted in altered expression of estrogen receptors. Activation of GPER1 with GPER1 agonist G1 reduces the tumorigenic potential of the vulvar carcinoma cells. It can be deduced from this that GPER1 appears to have a tumor-suppressive effect in vulvar carcinoma.