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Objective: To predict preoperative inguinal lymph node metastasis in vulvar cancer patients using a machine learning model based on imaging features and clinical data from pelvic magnetic resonance imaging (MRI)., Methods: 52 vulvar cancer patients were divided into a training set (n=37) and validation set (n=15). Clinical data and MRI images were collected, and regions of interest were delineated by experienced radiologists. A total of 1688 quantitative imaging features were extracted using the Radcloud platform. Dimensionality reduction and feature selection were applied, resulting in a radiomics signature. Clinical characteristics were screened, and a combined model integrating the radiomics signature and significant clinical features was constructed using logistic regression. Four machine learning classifiers (K nearest neighbor, random forest, adaptive boosting, and latent dirichlet allocation) were trained and validated. Model performance was evaluated using the receiver operating characteristic curve and the area under the curve (AUC), as well as decision curve analysis., Results: The radiomics score significantly differentiated between lymph node metastasis positive and negative patients in both the training and validation sets. The combined model demonstrated excellent discrimination, with AUC values of 0.941 and 0.933 in the training and validation sets, respectively. The calibration curve and decision curve analysis confirmed the model's high predictive accuracy and clinical utility. Among the machine learning classifiers, latent dirichlet allocation and random forest models achieved AUC values >0.7 in the validation set. Integrating all four classifiers resulted in a total model with an AUC of 0.717 in the validation set., Conclusion: Radiomics combined with artificial intelligence can provide a new method for prediction of inguinal lymph node metastasis of vulvar cancer before surgery., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose of Review: In the past decade, sentinel lymph node (SLN) mapping has progressively substituted full lymphadenectomies in gynecologic oncology. In this article, we review the most relevant and the latest literature on this topic., Recent Findings: In endometrial and cervical cancer, the current evidence further support the value of indocyanine green (ICG) as tracer of choice for SLN mapping. Experience in vulvar cancer is more limited, with ICG used together with technetium-99 m (Tc-99m) as a dual tracer but ICG, so far, has not been a game changer in this setting as it has been for cervical and endometrial cancer., Summary: For most gynecologic cancers, ICG fluorescence imaging is considered now a days the tracer of choice for lymphatic mapping. However, in early-stage vulvar cancer, SLN biopsy with radioactive tracer continues to be the standard-of-care in lymph node status assessment., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Sentinel lymph node (SLN) detection with superparamagnetic iron oxide (SPIO) nanoparticles has been widely studied and standardized for breast and prostate cancer, but there is scarce evidence concerning its use in vulvar cancer. The objective of this study was to compare SLN detection using a SPIO tracer injected at the time of the surgery detected by a magnetometer, with the standard procedure of using a technetium 99 radioisotope (Tc99) detected by a gamma probe, in patients with vulvar cancer., Methods: The SPIO vulvar cancer study was a single-center prospective interventional non-inferiority study of SPIO compared to Tc99, conducted between 2016 and 2021 in patients who met the GROINSS-V study inclusion criteria for selective sentinel lymph node dissection in vulvar cancer., Results: We included 18 patients and a total of 41 SLNs. The level of agreement between tracers was 92.7% (80.6%-97.4%), corresponding to 38 out of 41 SLNs, which confirms the non-inferiority of SPIO compared to Tc99. The SLN detection rate per groin was 96.3 (81.7%-99.3) using Tc99 and 100% (87.5%-100%) using SPIO. Both tracers had a detection rate of 100% for positive lymph nodes., Conclusions: The use of SPIO as a tracer for detecting SLNs in patients with vulvar cancer has shown to be non-inferior to that of the standard radiotracer, with the advantages of not requiring nuclear medicine and being able to inject it at the time of surgery after induction of anesthesia., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background/aim: Texture analysis is a quantitative imaging technique that provides novel biomarkers beyond conventional image reading. This study aimed to investigate the correlation between texture parameters and histopathological features of lymph nodes in patients with vulvar cancer., Patients and Methods: Overall, nine female patients (mean age 70.1±13.4 years, range=39-87 years) were included in the analysis. All patients had squamous cell carcinomas and underwent upfront surgery with inguinal lymph node resection. Immunohistochemical assessment was performed using several markers of the epithelial-mesenchymal transition. The presurgical magnetic resonance imaging (MRI) was analyzed with the MaZda package., Results: In discrimination analysis, several parameters derived from T1-weighted images showed statistically significant differences between non-metastatic and metastatic lymph nodes. The highest statistical significance was reached by the texture feature "S(0,3)InvDfMom" (p=0.016). In correlation analysis, significant associations were found between MRI texture parameters derived from both T1-weighted and T2-weighted images and the investigated histopathological features. Notably, S(0,3)InvDfMom derived from T1-weighted images highly correlated with the Vimentin-score (r=0.908, p=0.001)., Conclusion: Several associations between MRI texture analysis and immunohistochemical parameters were identified in metastasized lymph nodes of cases with vulvar cancer., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: Sentinel lymph node biopsy with radioactive tracer is the standard-of-care in lymph node status assessment in vulvar cancer. Indocyanine green fluorescence-ICG is a promising detection method, due to its advantages over technetium-99 m. In vulvar cancer, the procedure is controversial due to study heterogeneity and the small sample size in previous studies. This study evaluates ICG sentinel lymph node detection compared with the criterion-standard with technetium (dual modality method)., Methods: Preoperative technetium and intraoperative ICG for sentinel lymph node have been prospectively evaluated in early-stage vulvar cancer. The primary endpoint was to determine accuracy in the detection rate for ICG compared with technetium. Secondary objectives included tracer modality relationship with obesity, tumor size and location., Results: In total, 75 patients participated at 8 centers; 38 had lateral and 37 had midline vulvar tumors. The overall sentinel lymph node detection rate was 85.3 % for technetium and 82.7 % for ICG. For lateral tumors, the detection rate was 84.2 % vs. 89.5 %, while it was 86.5 % vs. 75.7 % for middle tumors, using technetium and ICG, respectively. The median sentinel node harvest was 1.7 (range 1-4), with 24 % metastatic involvement. The sensitivity and positive predictive value for ICG based on the standard technique with technetium was 91.08 % (95 % CI, 83.76-95.84) and 94.8 % (95 % CI, 84.84-96.48), respectively. No significant differences were found comparing the two tracers in patients with midline lesions, obesity (body mass index ≥ 30) and tumor size ≥ 2-4 cm., Conclusion(s): ICG shows comparable performance parameters to the gold-standard of radioisotope localization., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Competing Interests: Competing interests: None declared.

Objective: This study aimed to investigate the feasibility, efficacy, and safety of focused ultrasound (FUS) for the treatment of vulvar low-grade squamous intraepithelial lesions (VLSIL) with persistent symptoms., Methods: This retrospective analysis included 24 VLSIL patients who underwent FUS treatment. At each follow-up visit, the clinical response was assessed including changes in symptoms and signs. In addition, the histological response was assessed based on the vulvar biopsy results of the 3rd follow-up. Clinical and histological response were assessed to elucidate the efficacy., Results: A total of 22 patients completed follow-up and post-treatment pathological biopsies. After treatment, the clinical scores of itching decreased from 2.55 ± 0.51 to 0.77 ± 0.81 ( p  < 0.05). Furthermore, the clinical response rate and histological response rate were 86.4% and 81.8%, respectively. Only two cured patients indicated recurrence in the 3rd and 4th year during the follow-up period and achieved cure after re-treatment. In terms of adverse effects, only one patient developed ulcers after treatment, which healed after symptomatic anti-inflammatory treatment without scarring, and no other treatment complications were found in any patients. None of the patients developed a malignant transformation during the follow-up period., Conclusion: This study revealed that FUS is feasible, effective, and safe for treating VLSIL patients with persistent symptoms, providing a new solution for the noninvasive treatment of symptomatic VLSIL.

Introduction: In early-stage vulvar squamous cell carcinoma (VSCC) a sentinel lymph node (SLN) procedure is regarded successful if at least one SLN is removed with minimal residual radioactivity. An inguinofemoral lymphadenectomy is considered if not all SLNs visualized on lymphoscintigraphy can be found, with subsequent increased morbidity. We correlated lymphoscintigraphy findings with surgical outcome and groin recurrence with focus on number of SLNs found., Methods: This study concerns a retrospective cohort of 171 women treated for early-stage VSCC who underwent a SLN procedure between 2000 and 2020. The risk of groin recurrence was compared after either a successful or complete SLN procedure, i.e. removal of all SLNs that were visualized on lymphoscintigraphy., Results: In 13 (7.6%) groins of 171 patients SLN visualization on lymphoscintigraphy failed. In 230 of the 246 (93.5%) groins in which a SLN was visualized, at least one SLN was found during surgery. In 224 of the 246 (91.1%) groins the SLN procedure was regarded either successful (n = 14) or complete (n = 210). An isolated groin recurrence was documented in 5 out of 192 (2.6%, 95%-CI; 0.34 to 4.9) SLN-negative groins after a median follow-up of 47.0 months. All recurrences were noted in the complete SLN group (5/180 groins). The difference with the successful SLN group (0/12 groins) was not significant., Conclusion: Risk of groin recurrence was 2.6% after SLN negative biopsy in early-stage VSCC. The risk appeared not increased if at least one SLN was found with minimal residual radioactivity, in case more SLNs were visualized on lymphoscintigraphy., (© 2023 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Incorrect and delayed diagnosis of vulvar high-grade squamous intraepithelial neoplasia (vHSIL) and lichen sclerosus (LS) increases malignant progression risks and negatively impacts prognosis and quality of life. There is a need to improve diagnosis and monitoring. Reflectance confocal microscopy is a non-invasive imaging tool that visualizes skin structures at cellular resolution. The objectives were to explore feasibility and patient acceptability of vulvar RCM imaging and to identify RCM characteristics that are discriminative for vulvar HSIL and LS. This was a prospective, cross-sectional, observational clinical trial in patients with vHSIL and LS compared to healthy volunteers. RCM images and vulvar tissue samples were obtained. Five (5) patients with vHSIL, 10 patients with LS and 10 healthy volunteers were enrolled. In total, 100 image series of vulvar skin were obtained, including lesional and nonlesional sites. The RCM technique was considered acceptable for application by patients and healthy controls. Healthy vulvar skin was characterized by a homogenous, normal honeycomb patterned epidermis and a clear epidermal-dermal junctions. Vulvar HSIL and LS displayed an atypical honeycomb pattern of the epidermis and lymphocytic influx with presence of melanophages. Distinct features specifically observed in LS included the presence of hyalinised vessels and sclerotic areas in the dermis. RCM is a non-invasive imaging technique that is feasible and clinically acceptable to apply on vulvar skin, both in patients with premalignant lesions and healthy controls. Recognition and validation of disease-specific characteristics could make reflectance confocal microscopy a clinical tool to non-invasively aid identification of vulvar premalignancies., (© 2023 The Authors. Experimental Dermatology published by John Wiley & Sons Ltd.)

Aggressive angiomyxoma is a rare benign tumor with diverse clinical and radiologic presentations, making its differential diagnosis challenging. Here we report the second recurrence of an aggressive angiomyxoma of the vulva in a 33-year-old woman who presented with pain and swelling. Clinical examination revealed a well-circumscribed large palpable mass extending from the inferior part of the right labia major into the right side of the gluteus. A second recurrence of aggressive angiomyxoma was suspected based on the patient's history, clinical examination, and magnetic resonance imaging report, and the patient underwent surgical resection with a negative margin. Histological evaluation of the extracted lesion confirmed the diagnosis of aggressive angiomyxoma. At the 1-year follow-up, the patient was recurrence-free. The present report urges more awareness regarding the aggressiveness of angiomyxoma of the vulva. Closer attention should be given to margin-free removal of such tumors, and patients should be routinely followed up for at least 2 years postoperatively for early diagnosis of recurrence, thereby reducing the risk of morbidity.

Objective: The objective of this study was to examine the feasibility and success rate of intraoperative injection of radiotracer and blue dye performed by the surgeon without the use of preoperative lymphoscintigraphy for the detection of sentinel lymph nodes in clinically early stage vulvar cancer., Methods: All patients with clinically early stage vulvar cancer who underwent attempted sentinel lymph node biopsy using intraoperative injection of Technetium-99 m (99mTc) tracer and blue dye performed by the surgeon after induction of anesthesia at single academic institution from 12/2009 to 5/2022 were identified. Demographic and clinicopathologic variables were collected. Data were compared using descriptive statistics., Results: One hundred sixty-four patients (median age 66.4 years) underwent intraoperative injection of radioactive tracer and dye for sentinel lymph node biopsy. Most patients (n = 156, 95.1%) were white. Squamous cell carcinoma accounted for 138 cases (84.1%), melanoma for 10 (6.1%), extra-mammary invasive Paget's disease for 11 (6.7%), and other histologies for 5 (3%). A majority of cases were stage I disease on final pathology (n = 119, 72.6%). Most patients (n = 117, 71%) had tumors located within 2 cm of the midline and underwent planned bilateral groin assessment, while 47 (29%) had well lateralized lesions and underwent unilateral groin assessment. For the patients undergoing unilateral groin assessment, 44 of 47 (93.6%) had successful unilateral mapping. Of the patients who underwent bilateral groin assessment, 87 of 117 (74.4%) had successful bilateral mapping, and 26 of 117 (22.2%) had successful unilateral mapping. Of the 26 patients who underwent bilateral assessment but only had unilateral mapping, 19 had unilateral mapping to ipsilateral groin but failed contralateral mapping, six had midline lesions with successful mapping to one groin but failed mapping to the other groin, and one had unilateral mapping to the contralateral groin but not ipsilateral groin. The total successful sentinel lymph node mapping rate in this cohort was 86.5% (243/281 total sentinel lymph node attempts)., Conclusion: In this cohort, the overall success rate of sentinel lymph node mapping and biopsy was 86.5%. The high rate of successful sentinel lymph node mapping supports the use of intraoperative radiotracer and blue dye injection by trained providers., Competing Interests: Declaration of Competing Interest The authors report no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Vaginal and vulvar malignancies are rare gynecologic malignancies but can be associated with high morbidity and mortality if undiagnosed and untreated. Advanced imaging modalities such as MRI enable assessment of the local extent of disease and evaluation for regional or distant spread. Accurate identification and description of the primary lesion and sites of involvement as well as detection and localization of suspicious lymph nodes are critical in guiding appropriate management. Additionally, radiologists should be aware of potential mimickers on imaging and the differential diagnoses for vaginal and vulvar lesions., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: This study aimed to examine potential discriminatory characteristics of dermatoscopy and dynamic optical coherence tomography (D-OCT) on vulvar high-grade squamous intraepithelial lesions (vHSIL) and lichen sclerosus (LS) compared with healthy vulvar skin., Methods: A prospective observational clinical trial was performed in 10 healthy volunteers, 5 vHSIL and 10 LS patients. Noninvasive imaging measurements using dermatoscopy and D-OCT were obtained at several time points, including lesional and nonlesional vulvar skin. Morphologic features of vHSIL and LS were compared with healthy controls. Epidermal thickness and blood flow were determined using D-OCT. Patients reported tolerability of each study procedure, including reference vulvar biopsies. The main outcome measures were feasibility and tolerability of imaging modalities, dermatoscopy and OCT characteristics, OCT epidermal thickness and D-OCT dermal blood flow., Results: The application of dermatoscopy and D-OCT is feasible and tolerable. In vHSIL, dermatoscopic warty structures were present. In LS, sclerotic areas and arborizing vessels were observed. Structural OCT in the vulvar area aligned with histology for hyperkeratosis and dermal-epidermal junction visualization. Currently, the OCT algorithm is unable to calculate the epidermal thickness of the uneven vulvar area. Dynamic optical coherence tomography showed statistically significant increased blood flow in LS patients (mean ± SD, 0.053 ± 0.029) to healthy controls (0.040 ± 0.012; p = .0024)., Conclusions: The application of dermatoscopy and D-OCT is feasible and tolerable in vHSIL and LS patients. Using dermatoscopy and D-OCT, the authors describe potential characteristics to aid differentiation of diseased from healthy vulvar skin, which could complement clinical assessments., Competing Interests: J.P. has received grants for projects outside the scope of this article from Philips, KWF, Catharina Onderzoeksfonds, and Ruby and Rose. The other authors have declared they have no conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the ASCCP.)

Introduction: In the Netherlands, the sentinel lymph node procedure protocol consists of preoperative lymphoscintigraphy combined with intraoperative blue dye for identifying sentinel lymph nodes in early vulvar squamous cell carcinoma. This study aimed at investigating the role of early and late lymphoscintigraphy., Material and Methods: From January 2015 to January 2019, early and late lymphoscintigraphies of 52 women were retrospectively analyzed. Lymphoscintigraphy was performed 30 minutes (early) and 2.5-4 hours (late) after vulvar injection of 99m Tc-labeled nanocolloid. We calculated the concordance correlation coefficient (CCC) between number of sentinel lymph nodes detected on both images using the Lins concordance coefficient and correlated with clinicopathological data., Results: Thirty-four women had a midline tumor and 18 had a lateral tumor. Detection rates with early and late scintigraphy were 88.5% and 98.1%, respectively. Median number of detected nodes was 1.0 (0-7) and 2.0 (0-7). Good statistical correlation between number of sentinel lymph nodes detected on early and late imaging was found (CCC = 0.76) in most patients. In 18 women (35%) a mismatch occurred: a higher number of nodes was detected on late imaging. In 11 of 18 women re-injection was performed because no sentinel lymph nodes were visualized on early images. Late imaging and intraoperative detection showed a good statistical correlation (CCC = 0.61). One woman showed an isolated groin recurrence despite negative sentinel lymph nodes., Conclusions: This study showed good statistical correlations between early and late scintigraphy in most patients. However, in 35% of women late scintigraphy detected more nodes. In case of poor visualization after the first scintigraphy, re-injection should be considered. Late scintigraphy is probably helpful in confirming successful re-injection and in showing deviating lymph flow in women with failed mapping after the first injection and successful re-injection. Because missing metastatic sentinel lymph nodes often leads to a poor prognosis, we prefer optimal correlations between imaging and intraoperative identification. Hence, late scintigraphy cannot be safely omitted., (© 2022 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Rationale: Granular cell tumor (GCT) of the vulva is an exceptionally rare female genital tract tumor. The majority of these are benign and there are no standardized surgical techniques for the special site to reduce tension of the wound., Patient Concerns: A 47-years-old Chinese woman experienced a nodule on her right vulva with itch sometimes in late 2018., Diagnoses: Magnetic resonance imaging showed a high possibility of vulvar cancer. While Chest X-ray, abdominal sonography, and cystoscopy examination were unremarkable., Interventions: The patient underwent local complete resection of vulvar tumor under general anesthesia on March 24, 2022. The resection scope was approximately 4 cm × 3 cm × 3 cm. Due to the large surgical incision, Z-plasty was performed to achieve the primary closure for decreasing wound tension and improving aesthetic reduction., Outcomes: The final pathological diagnosis was benign GCT of the vulva and surgical margins were uninvolved. At 8 months follow-up, no new lesions were detected., Lessons: Surgery with negative resection margins is the mainstay for benign GCT of the vulva, while Z-plasty is appropriate for decreasing the tension of the wound and improving aesthetic reduction., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background and Purpose: Strategies for minimizing irradiation of organs at risk (OARs) from pathological inguinal lymph node (PILN) boosting are needed to minimize the risk of morbidity. Coverage probability (CovP) is a conformal planning strategy for simultaneously integrated boost (SIB). Our aim was to investigate if SIB of PILN using CovP can be delivered safely in vulvar cancer., Materials and Methods: Ten consecutive patients treated with definitive radiotherapy (RT) including SIB of PILN and with daily cone beam CT (CBCT) were included. Dose prescription was 51.2/32 fx to the elective target and 64 Gy/32 fx to the gross disease at the vulva and to positive lymph nodes (LN). PILN were contoured on both planning CT and MRI (GTV-N) and combined to form ITV-N. Each PILN GTV-N was contoured on every third CBCT, in total 11 CBCT for each patient. OARs were subcutaneous tissue (SC), inguinal vessels, skin rim, bowel, and body contour. Three plans were created for every patient: A) Standard CT-based planning; PTV-N based on GTV-N CT with a 10 mm isotropic margin. B) CT and MRI-based planning with smaller margins: PTV-N based on ITV-N with a 5 mm isotropic margin. C) CovP. The total delivered dose to GTV-Ns was estimated by accumulating dose across all fractions based on GTV-Ns contoured on CBCT., Results: Thirty-five PILNs were boosted. There was no significant difference in accumulated GTV-N D98% between the three plans. CovP delivered a higher mean dose to the GTV-N D50% and D2% ( p  < 0.001). The planned mean doses to the OARs were reduced when applying CovP., Conclusions: SIB of PILN in vulvar cancer based on CovP and a 5 mm PTV margin does not compromise target coverage during RT and reduces the dose to normal tissues in the groin.

Study Objective: The aim of this study was to evaluate the performance of indocyanine green (ICG) compared to that of the gold standard 99mtechnetium (99mTc-nanocolloids) in detecting sentinel lymph nodes (SLN) in early vulvar cancer., Material and Methods: A single-center retrospective cohort study comparing SLN detection by 99mTc-nanocolloids and ICG was performed in patients presenting early vulvar cancer (T1/2), with clinically negative nodes. All SLN showing a radioactive and/or fluorescent signal were resected. The primary endpoints were the sensitivity, positive predictive value (PPV) and false negative (FN) rate of ICG in detecting SLN compared to 99mTc-nanocolloids., Results: Thirty patients were included and 99 SLN were identified in 43 groins. Compared to 99mTc-nanocolloids, ICG had a sensitivity of 80.8% (95% CI [72.6; 88.6%]), a PPV of 96.2% (95% CI [91.8; 100%]) and a FN rate of 19.1% in detecting SLN. Seventeen (17.1%) infiltrated (positive) SLN were identified out of the 99 SLN detected. Compared to 99mTc-nanocolloids, ICG showed a sensitivity of 82.3% (95% CI [73.1; 91.5%]), a PPV of 100% and a FN rate of 17.6% (3/17) in detecting infiltrated SLN., Conclusion: Despite its many advantages, ICG cannot be used as the sole tracer for the detection of SLN in early vulvar cancer and should be employed in conjunction with 99mTc-nanocolloids.

Solitary fibrous tumors (SFTs) are commonly seen in the pleura. SFT involvement of the vulva is rare, and clinical diagnosis is mainly based on histopathological and immunohistochemical analyses. We herein describe the imaging features of a 69-year-old woman with an SFT of the vulva. The SFT was hypointense on T1-weighted images, similar to muscle; however, it showed inhomogeneous hyperintensity predominantly on fat-suppressed T2-weighted images. An area of low signal intensity was evident on T2-weighted images, and the tumor showed progressive enhancement in delayed phases. The tumor also displayed heterogeneous and prolonged, persistent enhancement, and serpentine vessels were present in the peritumoral area as signal voids. Pathological examination confirmed that the lesion was an atypical SFT originating from the vulva, and it was composed of spindle cells and perivascular and stromal hyalinization. This case reveals the characteristic imaging findings of vulvar SFT and their association with the relevant pathological findings, thus contributing to the primary diagnosis and preoperative evaluation of this potentially aggressive tumor.

Objective: To evaluate the incidence of pulmonary metastases in the preoperative work-up of patients with primary vulvar squamous cell carcinoma (SCC)., Design: Retrospective cohort study., Setting: Tertiary referral centre., Population: Patients treated for primary vulvar SCC from 2000 to 2018., Methods: The pre-operative chest imaging of 452 consecutively treated patients was documented with a minimal follow-up period of 2 years., Mean Outcome Measures: Incidence of pulmonary metastases, frequency of chest imaging and subsequent coincidental findings., Results: In total, 80.8% of patients underwent pre-operative chest imaging. Seven patients (1.9%), with a median tumour size of 80 mm, presented with pulmonary metastases. None of the patients with early stage disease and tumour size <40 mm who underwent radical local excision (RLE) with sentinel node (SN)-procedure, was diagnosed with pulmonary metastasis. Chest imaging was performed by radiography (58.9%) and computerised tomography (CT) (41.1%). Coincidental findings were reported in 40.7% of patients who underwent CT, compared with 15.8% of patients undergoing radiography, resulting in additional diagnostics in 14.7 and 19.7% and being of limited consequence for outcome in 2.9 and 3.3%, respectively., Conclusions: The incidence of pulmonary metastases in patients with primary vulvar SCC is extremely low, and none in patients with early stage disease undergoing the SN procedure. Chest imaging was performed in the majority of patients and was associated with frequent coincidental findings leading to clinically irrelevant diagnostic procedures. Therefore, we recommend omitting chest imaging in patients with early stage disease and tumours <40 mm, considering chest CT only in patients with large tumours and/or advanced stage disease., Tweetable Abstract: The incidence of pulmonary metastases is 1.9%, none in early stage disease planned for SN. Omitting chest imaging in this group is advised., (© 2021 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Gynecological cancers have particularly benefited from the increasing use of imaging to guide radiation treatment planning for both external beam radiation and brachytherapy. While the different gynecological cancers have varying use of imaging, certain trends predominate. CT represents an economical choice for evaluating initial disease extent or potential metastasis at follow-up, particularly for endometrial and ovarian cancers. F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT is particularly useful for assessing the initial disease extent and longer term treatment response of squamous predominant cancers, including cervical, vaginal, and vulvar cancers. With its excellent pelvic soft tissue discrimination, MRI provides the greatest assistance in evaluating the local extent of gynecological tumors, including initial evaluation for non-operative endometrial and vulvar cancer, and assessment before, after and during brachytherapy for cervix, locally recurrent endometrial, and primary vaginal cancers. With more limited availability of MRI, ultrasound can also help guide brachytherapy, particularly during procedures. The benefits of using imaging to better spare bone marrow or earlier assessment of treatment response are topics still being explored, in particular for cervical cancer. As imaging along with radiation oncology technologies continue to evolve and develop, such as with MRI-linacs and ultra high dose rate (FLASH) radiation, we may continue to see increasing use of imaging for advancing gynecological radiation oncology., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Primary vulvar carcinomas are rare gynaecological cancers, for which surgery is the mainstay of treatment. There is however a major place for external beam radiotherapy in the situation of inoperable locally advanced tumours and/or as adjuvant therapy, when there are risk factors for locoregional relapse. We present the recommendations of the French society for radiation oncology on the indications and techniques for radiotherapy in the treatment of primary vulvar cancer., (Copyright © 2021 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Purpose: The aim of this retrospective multicentric study was to investigate the diagnostic performance, the prognostic value and the impact of 18 F-FDG PET/CT on treatment decision-making in patients with suspected recurrent vulvar cancer (VC)., Materials and Methods: Sixty-three patients affected by VC performed 18 F-FDG-PET/CT for restaging purposes in case of suspected clinical and/or radiological recurrence. Histopatology results if available and/or clinical-imaging follow-up for at least 12 months were considered as reference standard. The diagnostic accuracy and the clinical impact of 18 F-FDG PET/CT were investigated. Progression free survival (PFS) and overall survival (OS) were calculated using Kaplan-Meier curves., Results: Fifty-two (82.5%) PET/CT showed the presence of recurrence, while the remaining 11 (17.5%) were negative. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of PET/CT were 100% (95%CI 93-100%), 92% (95%CI 62-100%), 98% (95%CI 89-99%), 100% and 98% (95%CI 92-100%). A relevant impact of 18 F-FDG PET/CT imaging was registered in 28 cases: in 12 cases moving from local therapy to chemotherapy due to the recognition of disseminate localizations; in 10 showing the site of recurrence in presence of negative conventional imaging, and in 6 cases confirming to be true negative and avoiding unnecessary therapies. Beside advanced age and HPV status, a positive restaging 18 F-FDG PET/CT scan was significantly correlated with shorter PFS and OS compared to negative scan (p < 0.001)., Conclusions: 18 F-FDG PET/CT demonstrated to be an accurate tool in the assessing of recurrent VC with high sensitivity and specificity and with a significant impact on clinical decision-making. Restaging 18 F-FDG PET/CT findings were associated with survival., (© 2021. The Author(s).)

Purpose: We aim to establish the prognostic value of metabolic parameters of the primary tumor in patients diagnosed with vulvar squamous cell carcinoma (VSCC) who underwent a pretreatment F-18 FDG PET/CT scan., Materials and Methods: This retrospective study included 47 patients with a histopathologically confirmed diagnosis of VSCC, and who underwent a F-18 FDG PET/CT scan prior to treatment. The disease stage and age at diagnosis, and the maximum standardized uptake value (SUVmax), SUVmean, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) values of the primary tumor, based on a baseline PET scan, were recorded. The relationship between these factors, and progression-free survival (PFS) and overall survival (OS) was evaluated., Results: The mean age of the 47 study patients was 69.6±1.9 years. Among the patients, 18 were in early stage of the disease and 29 were in the advanced stage. The age, and SUVmax, SUVmean, MTV and TLG values were statistically significantly associated with OS and PFS. Furthermore, it was noted that OS and PFS were significantly longer in the early stage patients than in the advanced stage patients, in patients with a tumor size <4cm than those with a tumor size ≥4cm, and in patients with a negative lymph node metastasis than those with a positive lymph node metastasis., Conclusion: Our findings suggest that PET parameters are prognostic factors for VSCC. To the best of our knowledge, this study is the first to investigate the prognostic value of the PET parameters of primary tumors in patients with VSCC, and as such, we believe it contributes to literature., (Copyright © 2020 Sociedad Española de Medicina Nuclear e Imagen Molecular. Published by Elsevier España, S.L.U. All rights reserved.)

Competing Interests: Declaration of interests KJJ reports speaker, advisory board, or consultant roles for Amgen, AstraZeneca, Apo Biologix, Eli Lilly, Esai, Genomic Health, Knight Therapeutics, Merck, Myriad Genetics Inc, Pfizer, Roche, Novartis, and Purdue Pharma, and research funding from Eli Lilly and AstraZeneca. The other authors declare no competing interests.

Extraskeletal myxoid chondrosarcoma of the vulva is a very rare tumor, with less than 10 cases reported in the literature. We report a case of a 45-yr-old woman with extraskeletal myxoid chondrosarcoma of the vulva confirmed by EWSR1 fluorescence in situ hybridization. Given the unusual site and prominent myxoid morphology, a broad differential diagnosis and a variety of ancillary testing was required. This article aims to review extraskeletal myxoid chondrosarcoma of the vulva, the differential diagnosis of a myxoid spindle cell neoplasm of the vulva, and the diagnostic importance of immunohistochemistry and EWSR1 fluorescence in situ hybridization., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 by the International Society of Gynecological Pathologists.)

Purpose: This retrospective study aimed to assess the diagnostic performance of preoperative [ 18 F]FDG-PET/CT in predicting the groin and pelvic lymph node (LN) status in a large single-centre series of vulvar cancer patients., Methods: Between January 2013 and October 2018, among all consecutive women with proven vulvar cancer submitted to [ 18 F]FDG-PET/CT, 160 patients were included. LNs were analysed by two qualitative methods assessing PET information (defined as visual assessment) and a combination of PET and low-dose CT information (defined as overall assessment), respectively, as well as semi-quantitative analysis (LN-SUV max ). Sensitivity, specificity, accuracy, positive and negative predictive values (PPV and NPV) in predicting the groin and pelvic LN status were calculated in the overall study population; a subset analysis of groin parameters in clinically/ultrasonography negative patients was also performed. Histopathology was the reference standard., Results: All patients underwent vulvar and inguinofemoral LN surgery, and 35 pelvic LN surgery. Overall, 338 LN sites (296 groins and 42 pelvic sites) were histologically examined with 30.4% prevalence of metastatic groins and 28.6% for metastatic pelvic sites. In the overall study population, sensitivity (95% confidence interval, CI), specificity (95% CI), accuracy (95% CI), PPV (95% CI) and NPV (95% CI) at the groin level were 85.6% (78.3-92.8), 65.5% (59.0-72.0), 71.6% (66.5-76.8), 52.0% (44.0-60.1) and 91.2% (86.7-95.8) for visual assessment; 78.9% (70.5-87.3), 78.2% (72.5-83.8), 78.4% (73.7-83.1), 61.2% (52.3-70.1) and 89.4% (85.0-93.9) for overall assessment; and 73.3% (64.2-82.5), 85.0% (80.1-89.8), 81.4% (77.0-85.8), 68.0% (58.8-77.3) and 87.9% (83.4-92.5) for semi-quantitative analysis (SUV max cut-off value 1.89 achieved by ROC analysis). Similar results were observed in the pelvis-based analysis., Conclusion: In this large single-centre series of vulvar cancer patients, [ 18 F]FDG-PET/CT showed good values of sensitivity and NPV in discriminating metastatic from non-metastatic LNs. In routine clinical practice, qualitative analysis is a reliable interpretative criterion making unnecessary commonly used semi-quantitative methods such as SUV max ., (© 2021. The Author(s).)

Aggressive angiomyxoma is a rare and locally aggressive mesenchymal tumour, predominantly occurring in women of reproductive age group. The term aggressive is attributed to the infiltrative nature and frequent local recurrences. They arise commonly from the vulvovaginal region, perineum or pelvis and are usually misdiagnosed as other common entities in these regions. Radiological investigations aid in the diagnosis and planning of surgery. However, the final diagnosis in most of the cases is established by histopathological examination. We herein report a case of a middle-aged woman presenting with recurrent large right vulvar mass highlighting the surgical challenges posed by its intrapelvic extension., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

In centers with access to high-end ultrasound machines and expert sonologists, ultrasound is used to detect metastases in regional lymph nodes from melanoma, breast cancer and vulvar cancer. There is, as yet, no international consensus on ultrasound assessment of lymph nodes in any disease or medical condition. The lack of standardized ultrasound nomenclature to describe lymph nodes makes it difficult to compare results from different ultrasound studies and to find reliable ultrasound features for distinguishing non-infiltrated lymph nodes from lymph nodes infiltrated by cancer or lymphoma cells. The Vulvar International Tumor Analysis (VITA) collaborative group consists of gynecologists, gynecologic oncologists and radiologists with expertise in gynecologic cancer, particularly in the ultrasound staging and treatment of vulvar cancer. The work herein is a consensus opinion on terms, definitions and measurements which may be used to describe inguinal lymph nodes on grayscale and color/power Doppler ultrasound. The proposed nomenclature need not be limited to the description of inguinal lymph nodes as part of vulvar cancer staging; it can be used to describe peripheral lymph nodes in general, as well as non-peripheral (i.e. parietal or visceral) lymph nodes if these can be visualized clearly. The association between the ultrasound features described here and histopathological diagnosis has not yet been established. VITA terms and definitions lay the foundations for prospective studies aiming to identify ultrasound features typical of metastases and other pathology in lymph nodes and studies to elucidate the role of ultrasound in staging of vulvar and other malignancies. © 2021 International Society of Ultrasound in Obstetrics and Gynecology., (© 2021 International Society of Ultrasound in Obstetrics and Gynecology.)

Introduction: Sentinel lymph node biopsy (SLN) helps define lymph node status, a major prognostic factor in vulvar cancer. The aim of the current systematic review was to assess the use of indocyanine green (ICG) coupled with near-infrared (NIR) fluorescence imaging in SLN mapping in vulvar cancer in terms of technique used, feasibility and accuracy., Data Sources: We performed a systematic review using bibliographic citations from PubMed, Clinical Trials.gov, Embase, Cochrane Library, and Web of Science databases. MeSH terms for SLN, ICG and vulvar cancer were combined and restricted to the English language. The final search was performed on May 28, 2020. The primary outcome was to determine if the use of ICG alone in detecting SLN in women with vulvar cancer is as accurate as the gold standard dual labeling technique., Results: Of the 34 studies initially identified, 13 were included for analysis. The SLN detection rate with ICG and NIR fluorescence ranged from 89.7 to 100%. No studies demonstrated the superiority of other detection techniques compared to ICG and NIR imaging. Lower SLN detection rates were found in studies with the most metastatic lymph nodes. No consensus was reached concerning the optimal use of ICG in terms of: injection timing or site; concentrations or volume of ICG; or use of human serum albumin or hybrid tracer. No adverse events were reported., Conclusion: ICG for SLN mapping appears to be safe in women with vulvar cancer with a detection rate similar to the current techniques. A large prospective randomized controlled study with optimization of the technique is necessary to homogenize current practice and determine the true value of ICG in vulvar cancer., Prospero Id: CRD42020178261., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest. No funding sources supported this investigation., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: The aim of this study was to assess the impact of 18F-FDG PET/CT metabolic parameters obtained at initial staging of vulva carcinoma on survival in women with and without HIV infection., Patients and Methods: 18F-FDG PET/CT images of women with vulva cancer who are planned for definitive therapy were analyzed. SUVmax, SUVmean, MTV, and total lesion glycolysis (TLG) as well as whole-body MTV and whole-body TLG were computed., Results: Twenty-five women were included with a mean age of 43.44 ± 10.32. The majority of the patients were HIV infected with a median CD4 count of 444.00 cells/mm3. The HIV-infected women are younger at diagnosis than their HIV-uninfected counterparts. All patients presented with inguinofemoral lymph node involvement, whereas half the patients had pelvic nodal metastasis. All the patients with distant visceral or skeletal metastasis were HIV infected. The lungs were the most common site of distant metastasis. When comparing the SUVmax, SUVmean, MTV, TLG, wbMTV, and wbTLG between HIV-infected and HIV-uninfected patients, we did not find statistical differences. Twelve patients (48%) were upstaged to metastatic disease. Seven patients had died at the time of analysis. The wbMTV and wbTLG were significantly higher in nonsurvivors than survivors., Conclusions: 18F-FDG PET/CT improves initial staging of squamous cell carcinoma among women with and without HIV infection. The whole-body tumor burden assessed by 18F-FDG PET metabolic metrics did not differ between HIV-infected and HIV-uninfected women. A higher whole-burden tumor burden is associated with a higher risk of mortality among women with vulva cancer., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Vulvar cancer is an uncommon gynecologic tumor and one of several human papillomavirus-associated malignancies. Squamous cell carcinoma is the most prevalent histologic subtype of vulvar cancer, accounting for the majority of cases. Imaging plays an important role in managing vulvar cancer. At initial diagnosis, imaging is useful to assess the size and extent of primary tumor and to evaluate the status of inguinofemoral lymph nodes. If recurrent disease is suspected, imaging is essential to demonstrate local extent of tumor and to identify lymph node and distant metastases. In this publication, we summarize the recent literature and describe the panel's recommendations about the appropriate use of imaging for various phases of patient management including initial staging, surveillance, and restaging of vulvar cancer. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment., (Copyright © 2021 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the impact of a preoperative CT on surgical decision making in primary vulvar squamous cell carcinoma (VSCC) and the accuracy of detecting inguinal lymph node metastases (LNM). Secondly to assess prevalence and consequences of incidental findings and comorbidity using a CT., Methods: This population-based study comprised of surgically treated patients with primary VSCC, at a regional tertiary center, using the Swedish Quality Registry for Gynecological Cancer for identification, and medical records were reviewed. Results from the preoperative CT was compared with the histological analysis from the lymphadenectomy in the total cohort and between tumor size <4 cm versus ≥4 cm., Results: In total 134 women had undergone CT before sentinel node (SN) biopsy (n = 83) or inguinofemoral lymphadenectomy (IFL) (n = 51). Fiftyone patients (38%) had groin LNM. Accuracy of CT in detecting groin LNM was 76%; sensitivity 43% and specificity 96%. Positive (PPV) and negative predictive values (NPV) were 88% and 73% respectively. In tumors <4 cm (n = 87), sensitivity, specificity, PPV and NPV were 17%, 95%, 57% and 75% and in tumors ≥4 cm (n = 47) 67%, 100%, 100% and 69% respectively. CT altered surgical method from SN biopsy to IFL in only two cases. Incidental findings led to extra follow-up resulting in a benign diagnosis in 22 patients and major important findings in five patients., Conclusion: In primary VSCC, a preoperative abdominal-inguinal CT is of limited value for surgical decision making. In tumors <4 cm, it may be omitted due to low diagnostic accuracy and disturbing incidental findings., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Aim: The aims of this study were to determine the role of 18F-FDG PET/CT in vulvar cancer patients and to extract summary estimates of its diagnostic performance for preoperative lymph node staging., Patients and Methods: PubMed/Medline and Embase databases were searched to identify studies evaluating 18F-FDG PET/CT in vulvar cancer patients. The assessment of methodological quality of the included articles was performed. Per-patient and per-groin pooled estimates, with 95% confidence intervals (CIs), of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic odds ratio (DOR) were calculated., Results: Ten articles were included in the systematic review, 7 among which evaluated the diagnostic performance of preoperative 18F-FDG PET/CT for lymph node staging. Qualitative per-patient analysis (72 patients from 4 studies) resulted in estimated pooled sensitivity, specificity, PPV, NPV, and DOR of 0.70 (95% CI, 0.44-0.95), 0.90 (95% CI, 0.76-1.04), 0.86 (95% CI, 0.66-1.06), 0.77 (95% CI, 0.56-0.97), and 10.49 (95% CI, 1.68-65.50), respectively. Qualitative per-groin analysis (245 groins from 5 studies) resulted in estimated pooled sensitivity, specificity, PPV, NPV, and DOR of 0.76 (95% CI, 0.57-0.94), 0.88 (95% CI, 0.82-0.94), 0.70 (95% CI, 0.55-0.85), 0.92 (95% CI, 0.86-0.97), and 19.43 (95% CI, 6.40-58.95), respectively., Conclusions: Despite limited literature data, this systematic review and meta-analysis revealed that a negative preoperative PET/CT scan may exclude groin metastases in at least early-stage vulvar cancer patients currently unfit for sentinel node biopsy and select those eligible for a less invasive surgical treatment. A positive PET/CT result should otherwise be interpreted with caution. Larger prospective studies are needed to confirm these results and to evaluate the diagnostic value of standardized semiquantitative analysis compared with the qualitative one., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Vulvar and vaginal melanomas are rare cancers of the female genital tract and account for 1% to 3% of all melanomas diagnosed in women. Due to the rarity of the disease, few data are available on the clinical and pathologic features of these cancers. Furthermore, treatment options are generally based on extrapolations of the information available for the more common cutaneous counterparts. Surgery represents the mainstay of treatment for lower genital tract melanoma. Moreover, the role of sentinel lymph node (SLN) assessment is controversial because no prospective data are available., Evidence Acquisition: Data were collected from Medline, Embase, Web of Sciences and Scopus databases. On July 10, 2020, we used the search comprising the terms "vulvar melanoma," "genital melanoma" and "vulvovaginal melanoma" including only studies in which SLN biopsy was performed., Evidence Synthesis: Ten retrospective studies have been found. No randomized trials have been reported. The studies included 132 patients while only 63 (47%) undergone SLN. 99mTC with or without blue dye followed by ultrastaging was highly accurate and is currently the gold standard. Mean detection rate was 98.3%. No clear evidence supported the execution of back lymphadenectomy (after SLN mapping), in fact, extrapolating data from cutaneous melanomas of other sites, completion of lymphadenectomy does not confer a melanoma-specific survival advantage., Conclusions: Although the small amount of available data, sentinel lymph node procedure is feasible and capable of identifying patients who have occult lymph node metastases. However, the potential role of the sentinel lymph node procedure as an alternative method of lymph node staging in patients with vulvar or vaginal melanoma needs further investigation.

Objectives: Superparamagnetic techniques for sentinel lymph node (SLNs) biopsy in breast cancer is well recognized but remains novel in the literature in relation to early stage vulvar cancer. The aim of this study was to compare and validate SLN detection using a superparamagnetic iron oxide tracer and a magnetometer probe compared with the standard procedure with a radioisotope ( 99 Tc-technetium 99) and a gamma probe, in patients with vulvar cancer., Methods: Patients were included in the study with squamous vulvar tumors less than 4 cm in diameter and without suspicious groin lymph nodes on preoperative magnetic resonance imaging. Patients must have previously qualified for SLN biopsy with a radiotracer as the standard of care. The primary endpoint was the proportion of successful SLN detection with superparamagnetic iron oxide tracer versus 99 Tc. The secondary endpoints were average number of SLNs retrieved per patient, proportion of SLNs detected (nodal detection rate), and proportion of pathologically positive results (malignancy rate) per patient and per node comparing both SLN detection methods., Results: A total of 20 patients were included in the study. SLNs were found in all patients with both methods, resulting in similar average distributions (3.1/3.2 SLN per patient). The SLN detection rate per patient was 100% with both techniques. Nodal detection sensitivity was 98.5% for the superparamagnetic technique and 93.8% for the radiotracer. Percentage of metastatic lymph nodes detected was 100% with both tracers. The rate of lymph node positivity was 21.5% (14 lymph nodes with metastases) and for patients 45% (9 patients with nodal metastases). Additionally, SLN tainted brown due to superparamagnetic iron oxide nanoparticles in 19 of 20 patients., Conclusions: The use of superparamagnetic iron oxide tracer in patients with vulvar cancer seems reliable and not inferior to the standard approach with radiotracer., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

A 67-yr-old female patient was diagnosed with squamous cell vulvar carcinoma and treated with a radical vulvectomy and bilateral sentinel lymphadenectomy. Three months after the surgery, the patient presented with local recurrence and underwent surgical excision of the mass, followed by chemotherapy. Eight months later, the patient was admitted due to weakness and pleural effusion. The patient underwent a chest computed tomography and echocardiogram, which revealed a large mass in the right ventricle penetrating into the pericardium and an additional mass residing on the tricuspid valve. She underwent a pericardial biopsy, and the pathology revealed a moderately differentiated squamous cell carcinoma metastasis. The patient was admitted thereafter in the oncological department for additional chemotherapy treatment. Because of a rapid deterioration in the patient's condition, only palliative treatment was given, and the patient died shortly after. Secondary cardiac tumors are very rare and have not been extensively studied in oncology. Therefore, optimal management is not entirely clear. It is extremely rare for vulvar cancer to metastasize to the heart, and only a handful of cases have been reported in the literature.

Introduction: Metastatic involvement of groin nodes can alter radiation therapy planning for pelvic tumors. 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography/computed tomography (PET/CT) can identify nodal metastases; however, interpretation of PET/CT-positive nodes can be complicated by non-malignant processes. We evaluated quantitative metrics as methods to identify groin metastases in patients with pelvic tumors by comparison with standard subjective interpretive criteria, with pathology as the reference standard., Methods: We retrospectively identified patients with vulvar, vaginal, or anal cancers who underwent 18 F-FDG PET/CT before pathologic evaluation of groin nodes between 2007 and 2017. Because patho-radiologic correlation was not possible for every node, one index node identified on imaging was selected for each groin. For each index node, standardized uptake value measurements, total lesion glycolysis, metabolic tumor volume, CT-based volume, and short and long axes were measured. Multivariate logistic regression was used to identify metrics predictive for pathologically positive groins and generate a probabilistic model. Area under the receiver-operating characteristic curves (AUCs) for the model were compared with clinical interpretation from the diagnostic report via a Wald's χ 2 test., Results: Of 55 patients identified for analysis, 75 groins had pathologic evaluation resulting in 75 index groin nodes for analysis with 35 groins pathologically positive for malignancy. Logistic regression identified mean standardized-uptake-value (50% threshold) and short-axis length as the most predictive imaging metrics for metastatic nodal involvement. The probabilistic model performed better at predicting pathologic involvement compared with standard clinical interpretation on analysis (AUC 0.91, 95% CI 0.84 to 0.97 vs 0.80, 95% CI 0.71 to 0.89; p<0.01)., Discussion: Accuracy of 18 F-FDG PET/CT for detecting groin nodal metastases in patients with pelvic tumors may be improved with the use of quantitative metrics. Improving prediction of nodal metastases can aid with appropriate selection of patients for pathologic node evaluation and guide radiation volumes and doses., Competing Interests: Competing interests: BAS has no relevant disclosures to this work, but reports serving in a consultant role for Curium Pharma, ImagingAB, Inc, and Progenics Pharmaceuticals, Inc, serving as advisory board member for GE Healthcare, and his spouse has received lecture honoraria from Siemens. DGM has no relevant disclosures to this work but reports speaking for Clovis and AstraZeneca. MAP has no relevant disclosures to this work but does report relationship with Merck, AstraZeneca, Tesaro, and Clovis Oncology. SM has no relevant disclosures but is supported by NIH K08 CA237822. The contents of this manuscript are solely the responsibility of the authors and do not necessarily represent the official views of the NIH., (© IGCS and ESGO 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: This study aimed to update the clinical practice applications and technical procedures of sentinel lymph node (SLN) biopsy in vulvar cancer from European experts., Methods: A systematic data search using PubMed/MEDLINE database was performed up to May 29, 2019. Only original studies focused on SLN biopsy in vulvar cancer, published in the English language and with a minimum of nine patients were selected., Results: Among 280 citations, 65 studies fulfilled the inclusion criteria. On the basis of the published evidences and consensus of European experts, this study provides an updated overview on clinical applications and technical procedures of SLN biopsy in vulvar cancer., Conclusions: SLN biopsy is nowadays the standard treatment for well-selected women with clinically negative lymph nodes. Negative SLN is associated with a low groin recurrence rate and a good 5-year disease-specific survival rate. SLN biopsy is the most cost-effective approach than lymphadenectomy in early-stage vulvar cancer. However, future trials should focus on the safe extension of the indication of SLN biopsy in vulvar cancer. Although radiotracers and optical agents are widely used in the clinical routine, there is an increasing interest for hybrid tracers like indocyanine- 99m Tc-nanocolloid. Finally, it is essential to standardise the acquisition protocol including SPECT/CT images, and due to the low incidence of this type of malignancy to centralise this procedure in experienced centres for personalised approach.

Introduction: Vulvar squamous cell carcinoma (VSCC) commonly metastasises through groin lymphatics. However, the use of pre-operative imaging in detecting inguinal nodal metastasis before staging surgery or to triage patients for sentinel node biopsy remains unclear. Here, we investigated if pre-operative CT scan, the imaging choice in our cancer centre, influences the overall course of VSCC management in those patients without clinical evidence of groin lymphadenopathy., Method: The study comprised of a prospective cohort of 225 patients with VSCC who underwent staging surgery within a regional tertiary gynaecological cancer centre. Comprehensive information of the cohort's demography, clinicopathological variables and outcome data were collected and analysed. Findings of pre-operative imaging were compared with histological findings of inguinal lymph nodes following groin lymphadenectomy. Statistical analyses were performed using SPSS V24., Results: Pre-operative CT scan was performed on 116 (56.6%) patients. The sensitivity and specificity of cross-sectional imaging in detecting groin lymphatic metastasis were 59.1% and 77.8%, respectively; while the positive (PPV) and negative predictive value (NPV) were 61.9% and 75.7%, respectively. In patients who had sentinel inguinal nodes biopsy, the sensitivity, specificity, PPV and NPV of CT scan in detecting inguinal node metastasis were 30.0%, 85.7%, 33.3% and 83.7%, respectively. There was no difference in disease-free and overall survival in those who received pre-operative imaging when compared to those who did not., Conclusion: Pre-operative CT scan may be omitted in early stage VSCC prior to surgical staging as it does not affect overall management and surgical outcomes., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: Application of radioactive tracers for sentinel lymph node biopsy (SLNB) in vulvar cancer has been established, however, the use of radioisotopes is expensive and requires complex logistics. This exploratory study evaluated the feasibility of near-infrared fluorescence-based SLNB in comparison to the gold standard using radioactive guidance., Methods: At Evangelische Kliniken Essen-Mitte (Essen, Germany) between 02/2015 and 04/2019, 33 patients with squamous cell vulvar cancer and unifocal tumors (32 midline, 1 lateral) smaller than 4 cm underwent SLNB as part of their routine primary surgical therapy. Radiolabeled nanocolloid technetium 99 ( 99m Tc) was injected preoperatively and indocyanine green (ICG) intraoperatively. Demographic and clinical data were retrieved from patients' records, and descriptive statistics were applied. The detection rate of the ICG fluorescence technique was compared with the standard radioactive approach., Results: In patients with midline tumors, bilateral SLNB was attempted. SLNB was feasible in 61/64 (95.3%) groins with 99m Tc and in 56/64 (87.5%) with ICG. In total, 125 SLNs were excised; all SLNs were radioactive and 117 (93.6%) also fluorescent. In 8 patients with BMI > 30 kg/m 2 , SLNB was successful in 14/15 groins (93.3%) with 99m Tc and 13/15 groins (86.7%) with ICG. Upon final histology, infiltrated nodes were present in 9/64 (14.1%) groins and 10/125 SLNs; one positive SLN was not detected with ICG., Conclusions: SLNB using ICG is a promising technique, however, the detection rate obtained was slightly lower than with 99m Tc. The detection rate increased over time indicating that experience and training may play an important role besides further methodological refinements.

Introduction: Vulvar squamous cell carcinoma (VSCC) is a rare malignancy with an increasing incidence, especially in young women. Surgical treatment of VSCC is associated with significant morbidity and high recurrence rates, which is related to the limited ability to distinguish (pre)malignant from healthy tissue. There is a need for new tools for specific real-time detection of occult tumor lesions and localization of cancer margins in patients with VSCC. Several tumor-specific imaging techniques are developed to recognize malignant tissue by targeting tumor markers. We present a systematic review to identify, evaluate, and summarize potential markers for tumor-specific imaging of VSCC., Methods: Relevant papers were identified by a systematic cross-database literature search developed with assistance of an experienced librarian. Data were extracted from eligible papers and reported based on the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. VSCC-specific tumor markers were valued based on a weighted scoring system, in which each biomarker was granted points based on ranked eligibility criteria: I) percentage expression, II) sample size, and III) in vivo application., Results: In total 627 papers were included of which 22 articles met the eligibility criteria. Twelve VSCC-specific tumor markers were identified and of these 7 biomarkers were considered most promising: EGFR, CD44v6, GLUT1, MRP1, MUC1, CXCR-4 and VEGF-A., Discussion: This overview identified 7 potential biomarkers that can be used in the development of VSCC-specific tracers for real-time and precise localization of tumor tissue before, during, and after treatment. These biomarkers were identified in a small number of samples, without discriminating for VSCC-specific hallmarks such as HPV-status. Before clinical development, experimental studies should first aim at validation of these biomarkers using immunohistochemistry and cell line-based examination, discriminating for HPV-status and the expression rate in lymph nodes and precursor lesions., Competing Interests: Declaration of competing interest Authors report no conflict of interest., (Copyright © 2019. Published by Elsevier Inc.)

Objective: To assess the accuracy of preoperative ultrasound examination for predicting lymph-node (LN) status in patients with vulvar cancer., Methods: This was a single-institution retrospective observational study of all women with a histological diagnosis of vulvar cancer triaged to inguinal surgery within 30 days following ultrasound evaluation between December 2010 and January 2016. For each groin examined, 15 morphological and dimensional sonographic parameters associated with suspicion for LN involvement were examined. A morphometric ultrasound pattern (MUP) was expressed for each groin, classifying the inguinal LN status into five groups (normal; reactive-but-negative; minimally suspicious/probably negative; moderately suspicious; and highly suspicious/positive) according to subjective judgment, followed by stratification as positive or negative for metastasis according to morphometric binomial assessment (MBA). In cases of positive MBA, fine-needle aspiration cytology was performed. Combining the information obtained from MUP and cytologic results, a binomial final overall assessment (FOA) was assigned for each groin. The final histology was considered as the reference standard. Comparison was performed between patients with negative and those with positive LNs on histology, and receiver-operating-characteristics curves were generated for statistically significant variables on univariate analysis, to evaluate their diagnostic ability to predict negative LN status., Results: Of 144 patients included in the analysis, 87 had negative inguinal LNs and 57 had positive LNs on histology. A total of 256 groins were analyzed, of which 171 were negative and 85 showed at least one metastatic LN on histology. The following parameters showed the greatest accuracy, with the best balance between specificity and sensitivity, in predicting negative LN status: cortical (C) thickness of the dominant LN (cut-off, 2.5 mm; sensitivity, 90.0%; specificity, 77.9%); short-axis (S) length of the dominant LN (cut-off, 8.4 mm; sensitivity, 63.9%; specificity, 90.6%); C/medulla (M) thickness ratio of the dominant LN (cut-off, 1.2 mm; sensitivity, 70.4%; specificity, 91.5%), the combination of S length and C/M thickness ratio (sensitivity, 88.9%; specificity, 82.4%); and the FOA analysis (sensitivity, 85.9%; specificity, 84.2%)., Conclusions: Preoperative ultrasound assessment, with or without the addition of cytology, has a high accuracy in assessing inguinal LN status in patients with vulvar cancer. In particular, the combination of two ultrasound parameters (S length and C/M thickness ratio) provided the greatest accuracy in discriminating between negative and positive LNs. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.)

Background/aim: Differentiated vulvar intraepithelial neoplasia (dVIN) and lichen sclerosus (LS) can give rise to vulvar squamous cell carcinoma (VSCC), but genetic evidence is currently still limited. We aimed to determine genetic abnormalities in VSCC and backtrack these abnormalities in the dVIN and LS lesions., Materials and Methods: DNA from VSCC and patient-matched dVIN and LS samples of twelve patients was collected. High-resolution genome-wide copy number analysis was performed and subsequently, we sequenced TP53., Results: Copy number alterations were identified in all VSCC samples. One dVIN lesion presented with three copy number alterations that were preserved in the paired VSCC sample. Targeted sequencing of TP53 identified mutations in five VSCCs. All five mutations were traced back in the dVIN (n=5) or the LS (n=1) with frequencies ranging from 3-19%., Conclusion: Our data provide genetic evidence for a clonal relationship between VSCC and dVIN or LS., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Introduction: To evaluate clinical outcomes, pattern of failure, and toxicity after high-dose intensity-modulated radiation therapy (IMRT) for advanced vulvar cancer., Methods: In this IRB approved retrospective study, the charts of women with histologically confirmed, non-metastatic vulvar cancer consecutively treated at our institution from 2012 to 2018 were reviewed to identify patients that received high-dose IMRT with curative intent. The treatment compliance, toxicities, and patterns of failure were investigated. Actuarial local, regional and distant recurrence and survival were estimated using Kaplan-Meier method and compared using log rank test., Results: Twenty-six patients were identified, 23 were unresectable, and 3 refused surgery. Fifteen patients (58%) had inguinal node metastases; 10(38%) had pelvic node metastases. Elective surgical staging of groins was performed in 9-patients. Median tumor dose was 65.4Gy. Concurrent platinum-based chemotherapy was administered in 22(84.6%) patients. Complete response (CR) was achieved in 21/26 (80.7%) patients. Five patients had persistent disease following treatment and one sustained recurrence 5-months following radiotherapy. All persistent or recurrent disease occurred inside the irradiated volume. Median follow-up was 19 months (3-52 months). Actuarial 1-year local, regional and distant controls were 72.4%, 85.4%, and 86%, respectively. One and 2-year overall survivals were 91% and 62%, respectively. Complete response at 3-months was a strong predictor for overall survival (1-yr OS 73% vs 27%, HR 7.1 (95% CI 1.2-44); p = 0.01). Lymph node metastases adversely affected overall survival (2-yr OS 49% vs. 83%, p = 0.09). Grade 3-4 late urinary and soft-tissue toxicity was seen in 5 patients. Tumor doses >66 Gy (p = 0.03) and prior pelvic radiotherapy (p = 0.002) predicted grade 3-4 toxicity., Conclusion: High-dose IMRT for vulvar cancer achieves high rates of local control with acceptable dose dependent long-term toxicity., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Epidermolytic acanthoma is a rare benign lesion that most often presents as a solitary or multiple small papular lesions on the trunk, face, limbs or external male genitalia. Only a small number of cases have been reported occurring on the vulva and clinically and histologically they may mimic and be misdiagnosed as viral warts. We report 2 cases of multiple epidermolytic acanthomas localized to the vulva. Molecular tests (in situ hybridization and polymerase chain reaction) showed no evidence of human papillomavirus infection and p16 staining was negative. We stress the need for pathologists to consider epidermolytic acanthoma in the differential diagnosis of multiple vulval lesions resembling viral warts.