vNOTES retroperitoneal sentinel lymph node dissection for endometrial cancer staging: First multicenter, prospective case series.

INTRODUCTION: The current standard treatment for endometrial cancer is a laparoscopic hysterectomy with adnexectomies and bilateral sentinel node resection. A retroperitoneal vNOTES sentinel node resection has several theoretical potential advantages. These include being less invasive, leaving no visible scars, operating without Trendelenburg, and therefore offering the anesthetic advantage of easier ventilation in obese patients and following the natural lymph node trajectory from caudally to cranially and therefore a lower risk of missing the sentinel node. The aim of this study is to determine the feasibility of a retroperitoneal vNOTES approach to sentinel lymph node dissection for staging of endometrial cancer. MATERIAL AND METHODS: A prospective multicenter case series was performed in four hospitals. A total of 64 women with early-stage endometrial carcinoma suitable for surgical staging with sentinel lymph node removal were operated via a transvaginal retroperitoneal vNOTES approach. The paravesical space was entered through a vaginal incision after injecting the cervix with indocyanine green. A vNOTES port was placed into this space and insufflation of the retroperitoneum was performed. Sentinel lymph nodes were identified bilaterally using near-infrared light followed by endoscopic removal of these nodes. RESULTS: A total of 64 women with early-stage endometrial cancer underwent sentinel lymph node removal by retroperitoneal vNOTES technique. All patients also underwent subsequent vNOTES hysterectomy and bilateral salpingo-oophorectomy. The median age was 69.5 years, median total operative time was 126 min and the median estimated blood loss was 80 mL. In 97% of the cases bilateral sentinel nodes could be identified. A total of 60 patients had negative sentinel nodes, three had isolated tumor cells and one had macroscopically positive sentinel nodes. No complications with sequel occurred. CONCLUSIONS: This prospective multicenter case series demonstrates the feasibility of the vNOTES approach for identifying and removing sentinel lymph nodes in women with endometrial carcinoma successfully and safely. vNOTES allows sole transvaginal access with exposure of the entire retroperitoneal space, following the natural lymph trajectory caudally to cranially, and without the need for a Trendelenburg position.

Can mismatch repair status be added to sentinel lymph node mapping algorithm in endometrioid endometrial cancer?

OBJECTIVE: To evaluate the relation between mismatch repair (MMR) status and the risk of lymph node metastasis in endometrial cancer, and whether this additional data can be incorporated to current SLN (sentinel lymph node) algorithm. METHODS: We included a series of 332 women that underwent SLN mapping ± systematic lymphadenectomy from January 2013 to December 2021. Protein expressions of MLH1, MSH2, MSH6, PMS2 were examined by immuno-histochemistry and considered MMRd (deficient) when at least one protein was not expressed. RESULTS: MMRd was noted in 20.8% of cases and correlated to grade 3 (p = 0.018) and presence of lymphovascular space invasion (p = 0.032). Moreover, MMRd was an independent risk factor for lymph node metastasis (OR 2.76, 95% CI 1.36-5.62). Notably, 21.7% (15/69) cases with MMRd had lymph node metastasis compared to 9.5% (25/263) of cases with MMRp (proficient) (p = 0.005). The overall and bilateral SLN detection rates were 91.9% and 75.9%, respectively. Of the 80 (24%) cases of non-bilateral SLN detection, 66.2% had low-grade tumors (G1/G2) and myometrial invasion <50%. Considering MMR status an independent prognostic factor for lymph node metastasis, a systematic lymphadenectomy (side specific or bilateral) would forgo in 53.7% (43/80) of cases with non-bilateral detection, representing 13% (43/332) of all endometroid tumors. CONCLUSION: MMR status was independently related to lymph node metastasis in endometrioid EC. Moreover, MMR status may help to select patients that can forgo systematic lymphadenectomy in case of undetected SLN.

Does sentinel node mapping impact morbidity and quality of life in endometrial cancer?

OBJECTIVES: To evaluate the prevalence of post-operative complications and quality of life (QoL) related to sentinel lymph node (SLN) biopsy vs systematic lymphadenectomy in endometrial cancer. METHODS: A prospective cohort included women with early-stage endometrial carcinoma who underwent lymph node staging, grouped as follows: SLN group (sentinel lymph node only) and SLN+LND group (sentinel lymph node biopsy with addition of systematic lymphadenectomy). The patients had at least 12 months of follow-up, and QoL was assessed by European Organization for Research and Treatment of Cervical Cancer Quality of Life Questionnaire 30 (EORTC-QLQ-C30) and EORTC-QLQ-Cx24. Lymphedema was also assessed by clinical evaluation and perimetry. RESULTS: 152 patients were included: 113 (74.3%) in the SLN group and 39 (25.7%) in the SLN+LND group. Intra-operative surgical complications occurred in 2 (1.3%) cases, and all belonged to SLN+LND group. Patients undergoing SLN+LND had higher overall complication rates than those undergoing SLN alone (33.3% vs 14.2%; p=0.011), even after adjusting for confound factors (OR=3.45, 95% CI 1.40 to 8.47; p=0.007). The SLN+LND group had longer surgical time (p=0.001) and need for admission to the intensive care unit (p=0.001). Moreover, the incidence of lymphocele was found in eight cases in the SLN+LND group (0 vs 20.5%; p<0.001). There were no differences in lymphedema rate after clinical evaluation and perimetry. However, the lymphedema score was highest when lymphedema was reported by clinical examination at 6 months (30.1 vs 7.8; p<0.001) and at 12 months (36.3 vs 6.0; p<0.001). Regarding the overall assessment of QoL, there was no difference between groups at 12 months of follow-up. CONCLUSIONS: There was a higher overall rate of complications for the group undergoing systematic lymphadenectomy, as well as higher rates of lymphocele and lymphedema according to the symptom score. No difference was found in overall QoL between SLN and SLN+LND groups.

Open Versus Minimally Invasive Radical Hysterectomy in Cervical Cancer: The CIRCOL Group Study.

PURPOSE: To analyze the survival outcomes of patients in a Brazilian cohort who underwent minimally invasive surgery (MIS) compared with open surgery for early stage cervical cancer. METHODS: A multicenter database was constructed, registering 1280 cervical cancer patients who had undergone radical hysterectomy from 2000 to 2019. For the final analysis, we included cases with a tumor ≤ 4 cm (stages Ia2 to Ib2, FIGO 2018) that underwent surgery from January 2007 to December 2017. Propensity score matching was also performed. RESULTS: A total of 776 cases were ultimately analyzed, 526 of which were included in the propensity score matching analysis (open, n = 263; MIS, n = 263). There were 52 recurrences (9.9%), 28 (10.6%) with MIS and 24 (9.1%) with open surgery (p = 0.55); and 34 deaths were recorded, 13 (4.9%) and 21 (8.0%), respectively (p = 0.15). We noted a 3-year disease-free survival (DFS) rate of 88.2% and 90.3% for those who received MIS and open surgery, respectively (HR 1.32; 95% CI: 0.76-2.29; p = 0.31) and a 5-year overall survival (OS) rate of 91.8% and 91.1%, respectively (HR 0.80; 95% CI: 0.40-1.61; p = 0.53). There was no difference in 3-year DFS rates between open surgery and MIS for tumors ≤ 2 cm (95.7% vs. 90.8%; p = 0.16) or > 2 cm (83.9% vs. 85.4%; p = 0.77). Also, the 5-year OS between open surgery and MIS did not differ for tumors ≤ 2 cm (93.1% vs. 93.6%; p = 0.82) or > 2 cm (88.9% vs. 89.8%; p = 0.35). CONCLUSIONS: Survival outcomes were similar between minimally invasive and open radical hysterectomy in this large retrospective multicenter cohort.

Sentinel lymph node mapping versus sentinel lymph node mapping with systematic lymphadenectomy in endometrial cancer: an open-label, non-inferiority, randomized trial (ALICE trial).

BACKGROUND: Growing evidence suggest that sentinel lymph node (SLN) biopsy in endometrial cancer accurately detects lymph node metastasis. However, prospective randomized trials addressing the oncological outcomes of SLN biopsy in endometrial cancer without lymphadenectomy are lacking. PRIMARY OBJECTIVES: The present study aims to confirm that SLN biopsy without systematic node dissection does not negatively impact oncological outcomes. STUDY HYPOTHESIS: We hypothesized that there is no survival benefit in adding systematic lymphadenectomy to sentinel node mapping for endometrial cancer staging. Additionally, we aim to evaluate morbidity and impact in quality of life (QoL) after forgoing systematic lymphadenectomy. TRIAL DESIGN: This is a collaborative, multicenter, open-label, non-inferiority, randomized trial. After total hysterectomy, bilateral salpingo-oophorectomy and SLN biopsy, patients will be randomized (1:1) into: (a) no further lymph node dissection or (b) systematic pelvic and para-aortic lymphadenectomy. MAJOR INCLUSION AND EXCLUSION CRITERIA: Inclusion criteria are patients with high-grade histologies (endometrioid G3, serous, clear cell, and carcinosarcoma), endometrioid G1 or G2 with imaging concerning for myometrial invasion of ≥50% or cervical invasion, clinically suitable to undergo systematic lymphadenectomy. PRIMARY ENDPOINTS: The primary objective is to compare 3-year disease-free survival and the secondary objectives are 5-year overall survival, morbidity, incidence of lower limb lymphedema, and QoL after SLN mapping ± systematic lymphadenectomy in high-intermediate and high-risk endometrial cancer. SAMPLE SIZE: 178 participants will be randomized in this study with an estimated date for completing accrual of December 2024 and presenting results in 2027. TRIAL REGISTRATION NUMBER: NCT03366051.

Predictive Factors for Residual Disease After Conization in Cervical Cancer.

OBJECTIVE: The aim of this study was to evaluate predictive factors for the presence of residual disease after conization followed by definitive surgery in cervical cancer, and suggest a margin distance threshold that could predict residual disease. METHODS: We retrospectively analyzed a series of 42 patients with early-stage cervical cancer who underwent primary conization before definitive surgical treatment from March 2009 to May 2020. All conization specimens were reviewed for endocervical, ectocervical, and radial margins. Cases with residual disease in magnetic resonance imaging before definitive surgery were excluded. RESULTS: Thirty-three (78.6%) patients underwent hysterectomies and 9 (21.4%) trachelectomies ± lymph node staging. Twelve (28.6%) cases were stage IA1, 5 (11.8%) cases were stage IA2, 13 (31%) cases were stage IB1, 11 (26.2%) cases were stage IB2, and 1 (2.4%) case was stage IIIC1 [International Federation of Gynecology and Obstetrics (FIGO) 2019]. We found residual disease in 17 (40.4%) surgical specimens. Of the 20 patients with negative margins, there were still 3 (15%) cases with residual disease. Conversely, residual disease was identified in 14 (63.6%) of the 22 patients with positive cone margins (p = 0.001). Tumor size [odds ratio (OR) 1.71, 95% confidence interval (CI) 1.02-1.33] and positive endocervical margin status (OR 33.6, 95% CI 3.85-293.3) were related to a higher risk of residual disease in multivariate analysis. Notably, all patients with tumors larger than 2 cm had residual disease, in contrast to 29.4% in lesions up to 2 cm (p = 0.002). CONCLUSION: We found that tumor size and positive margin were predictive factors for residual disease. We could not suggest a reliable minimum margin distance threshold that could predict residual disease.

Impact of Sentinel Node Mapping in Decreasing the Risk of Lymphocele in Endometrial Cancer.

OBJECTIVE: Due to the growing evidence of sentinel lymph node (SLN) mapping in endometrial cancer (EC), our aim was to evaluate the impact of SLN mapping and other clinical-pathological variables in the risk of developing lymphocele. METHODS: We retrospectively analyzed a series of patients with ECs who underwent lymph node staging with SLN mapping with or without systematic pelvic ± para-aortic lymphadenectomy from November 2012 to January 2020. The lymphocele diagnosis was performed by computed tomography or magnetic resonance imaging. RESULTS: Of 348 patients included, 178 underwent SLN mapping only and 170 underwent SLN mapping and systematic lymphadenectomy (46.5% pelvic only; 53.5% pelvic and para-aortic). Seventy-three (21%) patients had open surgery and 275 (79%) had a minimally invasive approach. After a median follow-up of 25.4 months, the overall prevalence of lymphocele was 8.6% (n = 30), with 29 cases in a pelvic location. Lymphocele was found in 3.4% (n = 6/178) of patients submitted to SLN mapping only, compared with 14.1% (n = 24/170) among those who underwent SLN with lymphadenectomy (p = 0.009). Among those patients with lymphocele, seven (23.3%) were symptomatic and five (16.6%) required drainage. All symptomatic cases occurred in lymphoceles larger than 4 cm (p = 0.001). Neither resected lymph node count nor the type of systematic lymphadenectomy were related to the presence of lymphocele. Systematic lymphadenectomy was the only factor that emerged as a risk factor for the presence of lymphocele in multivariate analysis (odds ratio 3.68, 95% confidence interval 1.39-9.79; p = 0.009). CONCLUSIONS: Our data suggest that SLN mapping independently decreases the risk of lymphocele formation compared with full lymphadenectomy in EC.

Pathological factors associated with non-sentinel lymph node metastasis in early stage cervical cancer.

OBJECTIVE: To analyze the predictive factors for non-sentinel lymph node (non-SLN) metastasis in early-stage cervical cancer. METHODS: We analyzed a series of 113 patients who underwent sentinel lymph node (SLN) mapping for cervical cancer. The SLNs were examined by immunohistochemistry (IHC) when the hematoxylin-eosin stain was negative. RESULTS: The overall bilateral detection rate was 81.5%, with a median of two SLNs resected. The study ultimately included 92 patients with SLNs that were mapped who had also undergone systematic pelvic lymph node dissection. Thirteen (14.1%) patients had positive SLNs, with a median of one positive SLN. Regarding the size of SLN metastasis, one (1.1%) had isolated tumor cells (ITC), seven (7.6%) had micrometastases, and five (5.4%) had macrometastases. Notably, 46.1% (6/13) had lymph node metastases detected only after IHC. Five (38.5%) cases had positive non-SLNs, with a median count of one positive lymph node. Parametrial invasion was the only risk factor for positive non-SLN (p = .045). Regarding the size of SLN metastasis, non-SLN involvement was present in the only case with ITC (1/1), 42.9% (3/7) of cases with micrometastases, and in 20% (1/5) with macrometastases. CONCLUSIONS: Our data suggest that parametrial invasion correlates with the risk of non-SLN metastasis in cervical cancer.

Size of Sentinel Node Metastasis Predicts Non-sentinel Node Involvement in Endometrial Cancer.

PURPOSE: To analyze the relationship between the size of metastatic sentinel lymph nodes (SLNs) and the risk of non-sentinel lymph node (non-SLN) metastasis in endometrial cancer. PATIENTS AND METHODS: From a total of 328 patients with endometrial cancer who underwent SLN mapping from January 2013 to April 2019, 142 patients also underwent systematic completion pelvic ± paraaortic node dissections, and they form the basis of this study. The SLNs were examined by immunohistochemistry (IHC) when the hematoxylin-eosin stain was negative. RESULTS: The median age was 60 years. The overall detection rate for SLNs was 87.5%, and bilateral SLNs were observed in 66.2%, with a median of 2 SLNs resected (range 1-8). Twenty-nine (20.4%) cases had positive SLNs, with a median of one positive SLN. Regarding the size of SLN metastasis, 5 (3.5%) cases had isolated tumor cells (ITCs), 13 (9.2%) had micrometastases, and 11 (7.7%) had macrometastases. Notably, 14/29 (48.3%) had node metastases that were detected after IHC. Eight (27.6%) patients had positive non-SLNs, with a median count of 7 positive nodes (range 2-23). Regarding the size of SLN metastasis, non-SLN involvement was not present in cases with ITC (0/5) but was present in 15.4% (2/13) of cases with micrometastases and 54.5% (6/11) of cases with macrometastases. The only risk factor for positive non-SLNs was the size of SLN metastasis. CONCLUSIONS: Our data suggest that size of SLN metastasis is associated with the risk of non-SLN metastasis. No patients with ITCs in SLNs had another metastatic lymph node in this study.

The Impact of Sentinel Node-Mapping in Staging High-Risk Endometrial Cancer.

BACKGROUND: This study aimed to determine the impact of sentinel lymph node (SLN)-mapping on the staging of high-risk endometrial cancer (endometrioid grade 3, serous, clear cell, carcinosarcoma, deep myometrial invasion, or angiolymphatic invasion). METHODS: The study analyzed a series of 236 patients treated at AC Camargo Cancer Center from June 2007 to February 2017. The compared 75 patients who underwent SLN-mapping (SLN group) with 161 patients who received pelvic ± para-aortic lymphadenectomy (N-SLN group). Patients with adnexal, peritoneal, or suspicious node metastases were excluded from the study. RESULTS: The groups did not differ in terms of age, histologic type, or presence of deep myometrial invasion. The overall detection rate for SLNs was 85.3%, and bilateral SLNs were observed in 60% of the patients. Of 20 positive SLNs, 8 (40%) were detected only after immunohistochemistry (IHC). The findings showed an overall sensitivity of 90%, a negative predictive value of 95.7%, and a false-negative predictive value of 4.3%. The SLN group had more pelvic node metastases detected than the N-SLN group (26.7 vs 14.3%; p = 0.02). However, the rate of para-aortic node metastases did not differ between the two groups (13.5 vs 5.6%; p = 0.12). Five patients (3.5%) in the N-SLN group had isolated para-aortic node metastases versus none in the patients with SLN mapped. Additionally, the SLN group received more adjuvant chemotherapy (48 vs 33.5%; p = 0.03). CONCLUSIONS: The data suggest that SLN-mapping identifies more pelvic node metastases than lymph node dissection alone and increases the node detection rate by 12.5% after IHC. Furthermore, no isolated para-aortic node metastases are observed when SLN is detected.

Is parametrectomy always necessary in early-stage cervical cancer?

OBJECTIVE: Increasing data suggest that patients with early-stage cervical cancer and favorable pathological characteristics have a low risk of parametrial invasion (PI) and benefit from less radical surgery. Our aim was to evaluate the clinical-pathological factors that are related to PI and identify a group of patients who are at low risk for PI. METHODS: We analyzed a series of 345 patients with stage Ia2 to Ib2 cervical cancer, for which they underwent radical surgery from January 1990 to October 2016 at AC Camargo Cancer Center. Chi-square and Fisher's exact tests were used to analyze the correlations between PI and clinicopathological variables. RESULTS: A total of 217 (62.9%) patients were classified as having squamous cell carcinoma, and 128(37.1%) had adenocarcinoma or adenosquamous carcinoma. Sixteen (4.6%) patients had PI. The presence of perineural invasion (p=0.003), tumor size >2cm (p=0.044), depth of invasion >10mm (p=0.004), the presence of lymphovascular space invasion(LVSI) (p<0.001), and lymph node metastasis (p<0.001) were related to PI. However, only LVSI (p=0.043) and lymph node metastasis (p<0.001) remained risk factors for PI in the multivariate analysis. Of the patients with tumors ≤2cm and no LVSI, only 1(1.2%) had PI; however, this patient had lymph node metastasis and deep stromal invasion (>10mm). No patient with tumor size ≤2cm and negative lymph nodes had PI. CONCLUSIONS: Patients with tumors ≤2cm and those who lack LVSI are unlikely to have PI, unless lymph node metastasis or deep stromal invasion is present. Our data can help select patients in whom a more conservative approach is warranted, such as simple hysterectomy and simple trachelectomy that is associated with pelvic lymphadenectomy.

Para-aortic lymphadenectomy can be omitted in most endometrial cancer patients at risk of lymph node metastasis.

OBJECTIVES: To determine the predictive factors of para-aortic lymph node (PALN) metastasis in endometrial cancer (EC) and recommend a subgroup of patients who can safely forgo PALN dissection. METHODS: We analyzed a series of 255 patients who were at risk of lymph node metastasis and treated from June 2007 to June 2015. All patients underwent systematic pelvic and para-aortic lymphadenectomy. RESULTS: The median number of pelvic lymph nodes (PLN) and PALNs that were resected was 33 and 15, respectively. Fifty (19.6%) patients had LN metastasis-43 (16.9%) pelvic, 28 (11%) para-aortic, 21 (8.2%) pelvic and para-aortic, and 7 (2.7%) isolated PALN metastasis. PALN metastasis was significantly associated with PLN metastasis, the presence of lymphovascular space invasion, deep myometrial invasion (MI), and histological grade 3. In the multivariate analysis, only pelvic LN metastasis and deep MI remained independent risk factors of PALN metastasis. For patients without LN enlargement ± adnexal metastasis, when deep MI and PLN metastasis were absent, the risk of PALM was 0.8%. CONCLUSIONS: Our series supports that PALN metastasis is a rare event in the absence of PLN metastasis and that most patients can safely forego PALN dissection. This subgroup can be identified by the combined absence of PLN metastasis and deep MI.

HER-2 Expression and Response to Radiotherapy in Patients with Advanced Cervical Cancer.

Glauco Baiocchi, M.D., Ph.D., Maria Dirlei Begnami, M.D., Ph.D., Michael Jenwei Chen, M.D., Elza Mieko Fukazawa, M.D., Ph.D., Levon Badiglian-Filho, M.D., Ph.D., Antonio Cassio Assis Pellizzon, M.D., Ph.D., Fernando Augusto Soares, M.D., Ph.D., and Ademar Lopes, M.D., Ph.D. OBJECTIVE: To evaluate HER-2 expression as a predictor of the response to radiotherapy and its value as a prognostic marker. STUDY DESIGN: A retrospective analysis was performed in a series of 34 individuals with advanced stage cervical cancer who underwent radiotherapy followed by radical hysterectomy. HER-2 expression was measured by immunohistochemistry in biopsies from all patients prior to radiotherapy and in 14 patients with residual tumors after radiotherapy. The presence of gene amplification was also examined. RESULTS: Eighteen (53%) patients had residual disease after radical hysterectomy. HER-2 was expressed in 26.5% of cases. Gene amplification by FISH was detected in 2.9% of cases. HER-2 expression was associated with a higher risk of residual disease after radiotherapy (p= 0.019). HER-2 expression did not correlate with the risk of recurrence or death. CONCLUSION: The prevalence of HER-2 expression is low in cervical cancer, and although HER-2 can predict the response to radiotherapy, it does not correlate with poor outcomes.

Cox-2, EGFR, and ERBB-2 expression in cervical intraepithelial neoplasia and cervical cancer using an automated imaging system.

We hypothesized that the activation of cyclooxygenase (COX)-2, epidermal growth factor receptor (EGFR), and ErbB-2 signaling is required for cervical intraepithelial neoplasia (CIN) lesions to progress to cervical cancer. A retrospective analysis was performed in 179 patients with Stage I squamous cell carcinoma (SCC) and 233 patients with CIN (112 CIN I, 47 CIN II, and 74 CIN III). COX-2, EGFR, and ErbB-2 expression was analyzed by immunohistochemistry using the ACIS III automated imaging system. The mean expression of COX-2, EGFR, and ErbB-2 was compared between the various stages of CIN and SCC. COX-2 mean expression was predominantly cytoplasmic, increasing significantly from CIN I to CIN II, CIN III, and SCC (P<0.001). EGFR mean expression also rose significantly during tumor progression from CIN I to SCC (P=0.001). CIN I samples were negative for ErbB-2 expression. CIN II, CIN III, and SCC were considered positive for ErbB-2 expression in 2.2%, 14%, and 16.2% of cases, respectively. There was also a statistically significant correlation between increase of ErbB-2 positivity from CIN to SCC. We conclude that COX-2, EGFR, and ErbB-2 expression increase significantly during the progression of CIN to cancer.

Intraoperative ultrasound for benign cystic teratoma. Report of two cases.

PURPOSE: Teratoma is one of the most common ovarian neoplasms and frequently leads to laparoscopic surgical procedure. When this tumor is small and the ovarian surface seems regular during the surgery, it is difficult to localize the tumor. METHODS: We used a standard transvaginal ultrasound probe during the procedure and filled the pelvic cavity with saline solution of 0.9% in order to create an interface between the saline solution and the surgical instruments. RESULTS: We could localize the teratoma with confidence and precision, allowing to perform a sparing surgery. CONCLUSION: This is a simple, secure and efficient technique that can be performed in most of the institutions.

Conservative management of extramammary paget disease with imiquimod.

OBJECTIVE: Extramammary Paget disease is a rare cutaneous neoplasm that most frequently affects the vulva. Surgery remains the preferred treatment, despite its association with high recurrence rates. Few reports have described conservative treatments for vulvar Paget disease. Our aim was to evaluate the efficacy of conservative treatment with imiquimod. MATERIALS AND METHODS: We performed a retrospective analysis of 4 patients who were treated with topical imiquimod 5% cream. RESULTS: One patient underwent vulvectomy after imiquimod therapy, and 3 patients experienced extensive recurrent disease that was unsuitable for surgical resection and were treated successfully with imiquimod. CONCLUSIONS: Imiquimod is an effective therapeutic agent for the conservative treatment of vulvar Paget disease.

Immunohistochemical expression of ErbB/HER family proteins in patients with vulvar cancer.

OBJECTIVE: To investigate the immunohistochemical (IHC) expression of the ErbB/HER family in primary vulvar squamous cell carcinoma (VSCC). METHODS: We analyzed a series of 125 patients who were surgically treated for VSCC from January 1980 to June 2016. All cases had lymph node (LN) staging and 80 had LN metastasis. A tissue microarray was built for epidermal growth factor receptor (EGFR), HER2, HER3, and HER4 IHC staining. RESULTS: In the primary tumor we found positive expressions for EGFR, HER2, HER3, and HER4 in 5%, 0.9%, 0.9%, and 22.8%, respectively. For the LN metastasis, expressions of EGFR and HER4 were positive in 22.2% and 39.1%, respectively. No cases had positive staining for HER2 and HER3 in the LN metastasis. For HER4, positive expression correlated with smaller tumor sizes (P = 0.02). However, positive HER4 was related to adverse prognostic factors such as: histological grade (P = 0.012), presence of lymphovascular space invasion (40.9% vs 16.2%; P = 0.035), and perineural invasion (57.1% vs 16.7%; P = 0.006). Notably, all cases with LN metastasis had positive HER4 in the primary tumor (P < 0.001). ErbB/HER family expression was not related to worse survival. CONCLUSION: EGFR, HER2, and HER3 were infrequently expressed in VSCC by IHC. HER4 IHC expression was found in 22.8% of cases and was related to adverse prognostic factors.