Clinical Impact of Pelvic Sentinel Lymph Node Biopsy for Vulvar Squamous Cell Carcinoma.

BACKGROUND/AIM: This study investigated the clinical impact of resection of pelvic sentinel lymph nodes (PSLNs) in squamous cell vulvar cancer (SCVC). PATIENTS AND METHODS: Sixty-two groins of 33 patients with SCVC who underwent sentinel lymph node (SLN) resection between 2010 and 2021 at the University Hospital of Cologne, Germany, were analyzed in this retrospective cohort study. The frequency of additionally resectable PSLNs, histological findings, and count rates were analyzed and compared to the findings for inguinal sentinel lymph nodes (ISLNs). RESULTS: In all patients and in 61 (98%) of the 62 radiolabeled groins, at least one SLN could be resected. Five (8%) of the 62 groins had histologically confirmed lymph node metastases (4/33 patients, 12%). Twenty (33%) of the 62 groins underwent additional PSLN resection. Resection of these PSLNs was feasible without causing an additional burden for the patients. None of the PSLNs showed signs of tumor infiltration. Information on the extent of radioactivity for ISLNs and simultaneously for PSLNs, expressed as count rate of intraoperative measurement with the gamma probe, was available for 20 (32%) groins. In three (15%) of these cases, the highest count rate in a SLN was found in a PSLN and not in an ISLN. CONCLUSION: Resection of PSLNs is feasible and can be performed without short-term complications. In patients with early SCVC, resection of PSLNs is not necessary, even in those with early infiltration of inguinal lymph nodes. The intraoperative count rate of SLN is not relevant for the decision to perform resection.

MRI Texture Analysis of Inguinal Lymph Node Metastasis in Vulvar Cancer - Associations With Histopathology.

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.

Aggressive angiomyxoma of female pelvis and perineum: Retrospective study of 17 cases.

OBJECTIVE: Aggressive angiomyxoma is an uncommon mesenchymal neoplasm characterized by a high recurrence rate, usually observed in the lower genital tract of women during their reproductive age. STUDY DESIGN: Seventeen cases of aggressive angiomyxoma confirmed by pathology from January 2007 to December 2021 in Beijing Chao-yang Hospital were included. We collected clinical data and summarized the clinical and immunohistochemical features. RESULTS: All seventeen included patients were females, aged between 23 and 57 years (mean, 37.7 years; median, 42 years). Fourteen patients were newly diagnosed and three were recurrent. The tumors were located in vulva (58.8 %), vagina (23.5 %), buttock (11.8 %), and cervix (5.9 %). The tumors size were 2 to 15 cm in greatest dimension (mean 8 ± 4.4 cm, median 6 cm). Follow-up data was available for nine patients, which ranged from 25 to 124 months (mean, 82 months; median, 80 months). At the end of follow-up, no other recurrence or metastasis was reported. Immunohistochemical analysis showed immunoreactive for estrogen (10/11) and progesterone (8/11) receptor, desmin (6/8), smooth muscle actin (4/10), and vimentin (4/4), S-100 (1/8) and CD34 (1/7). The Ki67 level was less than 5 % in five cases. CONCLUSIONS: AAM is a hormone-sensitive, distinct rare mesenchymal neoplasm with high incidence of local recurrence. Surgery is the preferred treatment, with complete resection being an essential prerequisite for minimizing the risk of recurrence.

Update on the Sentinel Node Procedure in Vulvar Cancer.

Early-stage vulvar cancer is managed by a local excision of the primary tumor and, if indicated, a sentinel node (SN) biopsy to assess the need for further groin treatment. With the SN procedure, many patients can be treated less radically and will experience less complications and morbidity compared with an inguinofemoral lymphadenectomy (IFL). Still, the SN procedure can be further optimized. Different tracers for detecting the SN are being investigated, aiming to optimize detection rates and decrease the burden of the procedure and short-term complications. Until now, no standardized protocols exist for the pathologic workup of the SN, possibly leading to discrepancies in detection of metastases between institutes using different methods. New techniques, such as one-step nucleic amplification, seem to have potential in accurately detecting metastases in other cancers, but have not yet been investigated in vulvar squamous cell carcinoma (VSCC). Furthermore, several studies have investigated the possibility to broaden the indications for the SN procedure, such as its use in recurrent disease, larger tumors, or multifocal tumors. Although these studies show encouraging results, cohorts are small and further studies are needed. Prospective studies are currently investigating these subgroups. Lastly, several studies investigated optimization of groin treatment of patients with a metastatic SN. Inguinofemoral radiotherapy is a good alternative to IFL in patients with micrometastases in the SN, with comparable efficacy and less treatment-related morbidity. Reduction of the radicality of groin treatment is also possible in other ways, such as omitting contralateral IFL in patients with lateralized tumors and a unilateral metastatic SN. In conclusion, the SN procedure is an established procedure in early-stage VSCC, although optimization of the technique, pathologic workup, indications, and treatment in the setting of metastatic disease are the subject of ongoing research.

Vulvar leiomyoma in a postmenopausal woman.

Leiomyomas of the uterus are the most common benign tumours of women in the reproductive age group, affecting up to 40%-50% of women older than 35. In postmenopausal women, the incidence is much lower with an estimated incidence of 1%-2% in women in the 60-80 years old age group. Vulvar leiomyomas are much rarer than their uterine counterparts, accounting for only 0.03% of all gynaecological neoplasms and 0.07% of all vulvar tumours. These tumours are well-circumscribed, painless, solitary growths that affect females of all ages. Given the presentation and rarity of vulvar leiomyomas, they are often misdiagnosed as a Bartholin gland cyst, abscess or even cancer preoperatively. We present a case of a woman in her 70s with a 1.5 cm firm mass that was palpated on the left lower vaginal side wall and was initially suspected to be a Bartholin gland cyst or abscess. Initial treatment included antibiotics and an incision and drainage. Two weeks later, the mass had grown to 3 cm in size. Wide excisional biopsy revealed the mass to be a vulvar leiomyoma.

Evaluation of the impact of a protocol for immediate vulvar reconstruction after vulvectomy.

Vulvar cancers are usually diagnosed at an advanced stage and require wide surgical resections in the form of vulvectomy. Immediate vulvar reconstruction can potentially reduce the reoperation rate and postoperative complications. With this objective, we introduced a protocol for immediate vulvar reconstruction. This study, five years after its introduction, assesses the impact of this intervention on the postoperative evolution of vulvectomy patients. In January 2017 we introduced a protocol for immediate vulvar reconstruction that considered four criteria of high risk for postoperative dehiscence. Patients who meet the criteria were reconstructed at the time of the vulvectomy. To assess the impact of the protocol, we prospectively registered all included patients over a 5 years period (2017-2022). As a control group, we reviewed the vulvectomised patients at our centre from January 2012 to January 2017 (5 years) who would have met the protocol. No statistically significant differences were found in the epidemiological data (age, diabetes mellitus diagnosis, and obesity diagnosis) or in the tumour characteristics (tumour size). We obtained a statistically significant difference in the incidence of complications and need for reintervention, in favour of the reconstruction group. Our study shows the medical and economic benefits for vulvar cancer patients of immediate vulvar reconstruction.

Recurrent ectopic primary breast adenocarcinoma of the vulva with a 19-year follow-up period.

We present a case of an ectopic breast adenocarcinoma of the vulva with metastatic local recurrence and a total follow-up period of 19 years, the longest documented in the literature to our knowledge. Following surgical excision, radiation therapy and hormonal treatment after the recurrence, the patient has remained disease free. This case demonstrates the potential for malignant transformation in accessory breast tissue and highlights the importance of close surveillance and regular physical examinations in patients with a history of ectopic breast malignancy.

Large vulvar fibroepithelial polyp and review of differentials.

Vulval fibroepithelial polyps (FEPs) are a rare type of vulval fibroblastic tumour commonly found in premenopausal women. It is important to obtain an accurate pathological diagnosis because, despite being benign, the condition shares some characteristics with malignant vulva lesions in its differential diagnosis. We present a case of young woman in her 20s with a giant FEP. After surgical excision, the patient did not manifest any signs of recurrence after 1-year follow-up. Our review focuses on the distinguishing characteristics of these rare neoplasms as we explore their differential diagnosis.

High concordance of molecular subtyping between pre-surgical biopsy and surgical resection specimen (matched-pair analysis) in patients with vulvar squamous cell carcinoma using p16- and p53-immunostaining.

OBJECTIVE: Vulvar squamous cell carcinoma (VSCC) can be stratified into three molecular subtypes based on the immunoexpression of p16 and p53: HPV-independent p53-abnormal (p53abn) (most common, biologically aggressive), HPV-associated, with p16-overexpression (second most common, prognostically more favourable) and more recently recognised HPV-independent p53-wildtype (p53wt) (rarest subtype, prognostically intermediate). Our aim was to determine whether molecular subtypes can be reliably identified in pre-operative biopsies and whether these correspond to the subsequent vulvectomy specimen. METHODS: Matched-paired pre-surgical biopsies and subsequent resection specimen of 57 patients with VSCC were analysed for the immunohistochemical expression of p16 and p53 by performing a three-tiered molecular subtyping to test the accuracy rate. RESULTS: Most cases 36/57 (63.2%) belonged to the HPV-independent (p53-abn) molecular subtype, followed by HPV-associated 17/57 (29.8%) and HPV-independent (p53wt) 4/57 (7.0%). The overall accuracy rate on biopsy was 91.2% (52/57): 97.3% for p53-abnormal, 94.1% for p16-overexpression and 50% for p16-neg/p53-wt VSCC. Incorrect interpretation of immunohistochemical p53 staining pattern was the reason for discordant results in molecular subtyping in all five cases. In one case there was an underestimation of p53 pattern (wildtype instead of abnormal/aberrant) and in one case an overestimation of the p53 staining pattern (abnormal/aberrant instead of wildtype). In 3/5 there was a "double positive" staining result (p16 overexpression and abnormal/aberrant p53 staining pattern). In that cases additional molecular workup is required for correct molecular subtyping, resulting in an overall need for molecular examination of 3/57 (3.5%). CONCLUSIONS: Compared to the final resections specimen, the three-tiered molecular classification of VSCC can be determined on pre-surgical biopsies with a high accuracy rate. This enables more precise surgical planning, prediction of the response to (chemo) radiation, selection of targeted therapies and planning of the optimal follow-up strategy for patients in the age of personalised medicine.

Surgery as primary treatment improved overall survival in vulvar squamous cancer: A single center study with 108 women.

OBJECTIVE: To describe a single-center experience managing women with vulvar squamous cancer and analyze factors influencing their survival. STUDY DESIGN: It is an observational longitudinal retrospective study that reviewed medical records of patients admitted for treatment at the University of Campinas between 2010 and 2019, followed up until June 2022. The final sample was 108 cases. The main outcomes were disease-free survival (DFS) and overall survival (OS). Other variables were age, stage, relapse, and race. Vital status was accessed by medical records, active search, or public online register. Survival analysis was performed by the Kaplan-Meier method and Log-rank Test, and Regression Cox-Model assessed risks. RESULTS: The mean age in stages IA and IB were 65.0 years, and in stages II + III + IVA 71.1 years. Women 70 years or older were more related to diagnosis in stages II + III + IVA (p = 0.019). Progression was observed in 7 (16.7 %) patients in stage IB and 30 (65.2 %) in stage II + III + IVA. Both five-year (5y) DFS and OS were significantly different in stage IB and II + III + IVA (5y-DFS 70.5 % and 39.3 %, p = 0.024; 65.1 % and 24.3 %, p < 0.001). In stages II + III + IVA, most deaths happened before 24 months of follow-up. The primary treatment was surgery in 81.0 % of stage IB and 47.8 % of stage II + III + IVA. A higher OS was observed in patients treated primarily by surgery compared to radiotherapy in stage IB (p = 0.008), and in stages II + III + IVA (p = 0.013). Surgery followed or not by adjuvant radiotherapy was independently associated with a 60 % adjusted death protection compared to radiotherapy alone as primary treatment (0.40, 0.23;0.70). CONCLUSIONS: Half of the patients have been diagnosed in stage I. The progression rate was high in the advanced stages of the disease. Overall survival by stage was improved when surgery was the primary treatment. Surgery was independently associated with death.

Inguinal nodal metastatic squamous cell carcinoma of unknown primary (CUP) detected 7 years before the diagnosis of vulvar squamous cell carcinoma: A case report.

OBJECTIVE: Metastatic squamous cell carcinoma (SCC) of inguinal lymph node region with unknown origin is a rare condition. A patient was diagnosed to have vulvar SCC 7 years after the initial diagnosis of inguinal nodal metastatic SCC of unknown primary. CASE REPORT: A 59-year-old woman with metastatic SCC of unknown origin in the right inguinal lymph node underwent tumor resection and no evidence of residual disease or possible tumor origin was detected after the surgery and a comprehensive work-up. Seven years later, she was diagnosed to have invasive right vulvar SCC with right pelvic lymph node metastasis. We performed a series of tests to evaluate the relationship between these two events. CONCLUSION: According to our investigation, the possible relationship between the two events could not be ruled out. This case emphasizes the possibility of late recurrence and the importance of long-term follow up for patients with isolated nodal CUP.

Accuracy of ICG compared with technetium-99 m for sentinel lymph node biopsy in vulvar cancer.

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.

Vulvar Adenoid Cystic Carcinoma with Squamous Cell Carcinoma Component.

Adenoid cystic carcinoma (ACC) is a major histological type of salivary gland cancer but an uncommon form of vulvar cancer. Salivary gland ACC occasionally dedifferentiates into high-grade carcinoma, resulting in poor prognoses. The dedifferentiated component is usually a poorly differentiated cribriform or solid carcinoma, whereas squamous cell carcinoma (SCC) is exceptional. Herein, we report the case of a 78-year-old woman with vulvar ACC, including an SCC component. She presented with a vulvar nodule that had been present for 30 years and increased in size over the past few years. Magnetic resonance imaging showed a ball-like mass with high intensity on T1-weighted images and high intensity with non-uniformity on T2-weighted images. Considering the systemic and social conditions, the tumor was maximally resected without lymphadenectomy. Histologically, the tumor was composed of a marginal ACC component with a central SCC component. Stage IB vulvar cancer, which was assumed to originate from the Bartholin's gland, was diagnosed. She has survived over 2 years without additional treatments after the surgery. In this case, we assumed that slowly progressive indolent ACC could be dedifferentiated to high- grade SCC. According to our review of available literature, dedifferentiation of vulvar ACC with a high-grade SCC component has not been specifically documented. Although the nature of dedifferentiated vulvar cancer is unclear, it should be noted that high-grade dedifferentiation can occur in long-lasting vulvar masses.

Sentinel Lymph Node Evaluation in Early-Stage Vulvar Cancer.

OPINION STATEMENT: Sentinel lymph node mapping (SLNM) and dissection (SLND) should be used as an alternative to full inguinofemoral lymph node dissection (IFLND) in select patients with early-stage vulvar cancer. IFLND is associated with high postoperative complications such as wound breakdown, lymphedema, lymphocyst formation, and infection. SLND in select patients offers a safe, effective, and less morbid alternative. Candidates for SLND include patients with a unifocal vulvar tumor less than four centimeters, clinically negative lymph nodes, and no prior inguinofemoral surgeries. SLND should ideally be performed by a high-volume SLN surgeon. Most commonly, SLND is performed using both radiocolloid lymphoscintigraphy (e.g., Technetium-99) and a visual tracer such as blue dye; however, near infrared imaging with indocyanine green injection is becoming more widely adopted. Further prospective studies are needed to examine the safety and efficacy of various techniques for SLND. SLND has been demonstrated to be cost-effective, especially when including perioperative complications. Further studies are needed to demonstrate quality of life differences between IFLND and SLND.

Management of primary and recurrent Bartholin's gland carcinoma: A systematic review on behalf of MITO Rare Cancer Group.

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.

Predictive factors of surgical complications after pelvic exenteration for gynecological malignancies: a large single-institution experience.

OBJECTIVE: To evaluate pre-operative predictors of early (<30 days) severe complications (grade Dindo 3+) in patients with gynecological malignancy submitted to pelvic exenteration (PE). METHODS: We retrospectively analyzed 129 patients submitted to surgery at Fondazione Policlinico Gemelli between 2010 and 2019. We included patients affected by primary or recurrent/persistent cervical, endometrial, or vulvar/vaginal cancers. Post-operative complications were graded according to the Dindo classification. Logistic regression was used to analyze potential predictors of complications. RESULTS: We performed 63 anterior PE, 10 posterior PE, and 56 total PE. The incidence of early severe post-operative complications was 27.9% (n=36), and the early mortality rate was 2.3% (n=3). More frequent complications were related to the urinary diversion and intestinal surgery. In univariable analysis, hemoglobin ≤10 g/dL (odds ratio [OR]=4.2; 95% confidence interval [CI]=1.65-10.7; p=0.003), low albumin levels (OR=3.9; 95% CI=1.27-12.11; p=0.025), diabetes (OR=4.15; 95% CI=1.22-14.1; p=0.022), 2+ comorbidities at presentation (OR=5.18; 95% CI=1.49-17.93; p=0.012) were predictors of early severe complications. In multivariable analysis, only low hemoglobin and comorbidities at presentation were independent predictors of complications. CONCLUSION: Pelvic exenteration is an aggressive surgery characterized by a high rate of post-operative complications. Pre-operative assessment of comorbidities and patient health status are crucial to better select the right candidate for this type of surgery.