Simona Maria Fragomeni

Trans-inguinal pelvic lymphadenectomy in vulvar cancer patients: TRIPLE pilot study

The goal of this study was to assess the feasibility and safety of a retrograde extraperitoneal trans-inguinal novel approach to pelvic lymphadenectomy in vulvar cancer patients. The secondary objectives were to assess complications (early and late) and oncological outcomes. In this pilot study, all patients referred to our institution from November 2019 to May 2021 were evaluated. The inclusion criteria were patients diagnosed with primary/recurrent vulvar cancer and who were candidates for concomitant groin and pelvic lymph node dissection. A consecutive sampling was planned during the study period. After conventional inguino-femoral lymph nodal dissection, ipsilateral extraperitoneal trans-inguinal pelvic lymphadenectomy (TRIPLE) was performed through a groin incision. Clinical data, type of treatment, perioperative complications, and follow-up were evaluated. 13 patients (8 primary, 5 recurrent vulvar cancer) underwent 16 TRIPLE procedures (10 unilateral, 3 bilateral). The median age was 69 years (range 58-93 years); 8 patients had comorbidities (61.5%). Up front locoregional radiotherapy was previously performed in two cases (15.4%). The pathology report showed metastatic lymph nodes in 20 (87%) groins and 11 (68.8%) pelvic sites; the mean number of removed and metastatic pelvic lymph nodes was 12.1 (range 5-33) and 2.9 (range 0-18), respectively. No intra-operative site-specific complications occurred. One (5.9%) post-operative site-specific complication was reported (pelvic abscess, grade 2), which was treated with antibiotics. One patient died due to concomitant pneumonia. No unilateral pelvic lymph node recurrence occurred during follow-up (median 13 months, range 2-43 months); 3 patients (23.1%) had distant site recurrence (median disease-free survival 9 months). TRIPLE seems to be a feasible and safe technique, providing adequate lymph node dissection. Despite being a high-risk and fragile population, morbidity was similar to previously reported data for conventional mini-invasive approaches. Prospective larger comparative series are necessary.

“Clock mapping” prior to excisional surgery in vulvar Paget’s disease: tailoring the surgical plan

Paget disease is a rare neoplasm of the skin that mainly involves the vulvar region. Vulvar Paget's disease (VPD) can spread beyond the apparent edges of the lesion resulting in a high risk of involved surgical margins. Our aim is to verify the efficacy of a preoperative vulvo-vaginal intensive clock mapping in the prediction of the invasiveness and the extension of VPD. All consecutive patients with primary VPD referred to our institution from July 2005 to December 2018 were subjected to a preoperative intensive biopsy mapping (clock mapping) of the vulvo-vaginal area: inside and outside the vulvar skin visible lesion, according to o'clock positions, and in the vagina. Patients with positive biopsies "only inside" or "also beyond" the visible lesion were included, respectively, in Group A and B. Surgical excision was drawn passing by the points with negative histology. Pathological findings of mapping biopsies were compared with those from radical surgery. A total of 28 women were enrolled. After clock mapping definitive histology: 17 (60.7%) and 11 (39.3%) patients were included in Group A and B. Definitive histology showed non-invasive, micro-invasive and invasive VPD, respectively, in 13 (46.4%), 11 (39.3%) and 4 (14.3%) patients, with 4 patients further upstaged. Overall, negative margins were found in 14 (50%) patients: 9 (32.1%) from Group A and 5 (17.9%) from Group B. In 23 cases (82.1%), clock mapping identified free surgical margins along the vulvo-perineal skin excision front. Preoperative clock mapping emerged as potentially useful workup tool to predict invasiveness and extension of VPD, to tailor surgical excision.

Terms, definitions and measurements to describe sonographic features of lymph nodes: consensus opinion from the Vulvar International Tumor Analysis (VITA) group

ABSTRACTIn 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.

Personalizing vulvar cancer workflow in COVID-19 era: a proposal from Vul.Can MDT

Since the community spread of Coronavirus disease 2019 (COVID-19), the practice of oncologic care at our comprehensive cancer center has changed. Postponing cancer treatment without consideration of its implications could cost more lives than can be saved. In this special situation, we must continue to provide our cancer patients with the highest quality of medical services assuring the safety. This article provides general guidance on supporting curative treatment strategies in vulvar cancer patients. At our institution, a vulvar cancer multidisciplinary team (Vul.Can MDT) of specialists is responsible for personalized treatment of this disease. The phase 2 period necessarily requires specific procedures for both outpatient and inpatient pathways and to provide strategies concerning the management of vulvar cancer patients even in case of an eventually concomitant SARS-CoV-2 infection. In brief, an accurate remote and in person triage must be provided routinely and patients submitted to specific diagnostic tests prior to every major treatment or procedure (surgery, RT, and CT) or in case of suspicion for COVID-19 syndrome. The decisional workflow for these women often old and frail, have been rapidly adjusted by our Vul.Can MDT to mitigate the potential risks of COVID-19. The team produced two types of recommendations concerning: (1) safety regulations of care pathways, patients and health care providers, (2) personalized treatment strategies. We present a protocol that can be applied in clinical practice: the flowcharts provided, include the modulation of treatment intensity designed for surgical procedures and radiation, stratified for FIGO stage of disease and intention. We suggest that our proposals are applicable in this setting of patients, considering anyway current international recommendations and guidelines.

Molecular pathways in vulvar squamous cell carcinoma: implications for target therapeutic strategies

Additional prognostic factors and personalized therapeutic alternatives for vulvar squamous cell carcinoma (VSCC), especially for advanced stages with poor prognosis, are urgently needed. To review and assess literature regarding underlying molecular mechanisms of VSCC target therapeutic and prognostic approaches. We performed a narrative literature review from the inception of the database up to January 2020 limited to English language, organizing knowledge in five main fields: extracellular and intracellular cell cycle deregulation, tumor immune microenvironment, tumor angiogenesis and hormones. EGFR immunohistochemical overexpression/gene amplification, representing early events in VSCC carcinogenesis, have been correlated with a worse prognosis and led to inclusion of erlotinib in cancer guidelines. p16 expression and HPV positivity are linked to a better prognosis, while p53 overexpression is linked to a worse prognosis; thus, biomarkers could help tailoring conventional treatment and follow-up. The implications of PD-L1 positivity in reference to HPV status and prognosis are still not clear, even though pembrolizumab is part of available systemic therapies. The role of tumor angiogenesis emerges through data on microvessel density, immunohistochemical VEGF staining and evaluation of serum VEGF concentrations. Few data exist on hormonal receptor expression, even though hormonal therapy showed great manageability. We suggest adding p16, p53 and HPV status to routine hystopathological examination of vulvar biopsies or surgical specimens. Predictive biomarkers for anti-EGFR and anti-PD-1/PD-L1 drugs are needed. Enough preclinical data supporting anti-angiogenic target therapies in clinical trials are existing. Hormonal receptor expression deserves further investigation.

Ultrasound morphometric and cytologic preoperative assessment of inguinal lymph‐node status in women with vulvar cancer: MorphoNode study

ABSTRACTObjectiveTo assess the accuracy of preoperative ultrasound examination for predicting lymph‐node (LN) status in patients with vulvar cancer.MethodsThis 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.ResultsOf 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%).ConclusionsPreoperative 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.

Subjective assessment and IOTA ADNEX model in evaluation of adnexal masses in patients with history of breast cancer

ABSTRACTObjectiveTo evaluate the performance of subjective assessment and the Assessment of Different NEoplasias in the adneXa (ADNEX) model in discriminating between benign and malignant adnexal tumors and between metastatic and primary adnexal tumors in patients with a personal history of breast cancer.MethodsThis was a retrospective single‐center study including patients with a history of breast cancer who underwent surgery for an adnexal mass between 2013 and 2020. All patients had been examined with transvaginal or transrectal ultrasound using a standardized examination technique and all ultrasound reports had been stored and were retrieved for the purposes of this study. The specific diagnosis suggested by the original ultrasound examiner in the retrieved report was analyzed. For each mass, the ADNEX model risks were calculated prospectively and the highest relative risk was used to categorize each into one of five categories (benign, borderline, primary Stage I, primary Stages II–IV or metastatic ovarian cancer) for analysis of the ADNEX model in predicting the specific tumor type. The performance of subjective assessment and the ADNEX model in discriminating between benign and malignant adnexal tumors and between primary and metastatic adnexal tumors was evaluated, using final histology as the reference standard.ResultsIncluded in the study were 202 women with a history of breast cancer who underwent surgery for an adnexal mass. At histology, 93/202 (46.0%) masses were benign, 76/202 (37.6%) were primary malignancies (four borderline and 72 invasive tumors) and 33/202 (16.3%) were metastases. The original ultrasound examiner classified correctly 79/93 (84.9%) benign adnexal masses, 72/76 (94.7%) primary adnexal malignancies and 30/33 (90.9%) metastatic tumors. Subjective ultrasound evaluation had a sensitivity of 93.6%, specificity of 84.9% and accuracy of 89.6%, while the ADNEX model had higher sensitivity (98.2%) but lower specificity (78.5%), with similar accuracy (89.1%), in discriminating between benign and malignant ovarian masses. Subjective evaluation had a sensitivity of 51.5%, specificity of 88.8% and accuracy of 82.7% in distinguishing metastatic and primary tumors (including benign, borderline and invasive tumors), and the ADNEX model had a sensitivity of 63.6%, specificity of 84.6% and similar accuracy (81.2%).ConclusionsThe performance of subjective assessment and the ADNEX model in discriminating between benign and malignant adnexal masses in this series of patients with history of breast cancer was relatively similar. Both subjective assessment and the ADNEX model demonstrated good accuracy and specificity in discriminating between metastatic and primary tumors, but the sensitivity was low. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.