Desquamative Inflammatory Vaginitis and Plasma Cell Vulvitis Represent a Spectrum of Hemorrhagic Vestibulovaginitis.

OBJECTIVE: The aim of the study was to identify whether desquamative inflammatory vaginitis (DIV) and plasma cell vulvitis (PCV) are distinct clinicopathologic entities. MATERIALS AND METHODS: The pathology database identified biopsies described as "vaginitis" or "vulvitis" occurring in nonkeratinized epithelium or mucocutaneous junction. Exclusions were age less than 18 years, unavailable slides or records, concurrent neoplasia, or histopathology consistent with other entities. Clinical data included demographics, symptoms, examination, microbiology, treatment, and response. Histopathologic review documented site, epithelial thickness and characteristics, infiltrate, and vascular abnormalities. Cases were analyzed according to histopathologic impression of DIV or PCV based on previous pathologic descriptions. RESULTS: There were 36 specimens classified as DIV and 18 as PCV from 51 women with mean age of 51 years; 3 (6%) had concurrent biopsies with both. Pain was more common in PCV, but rates of discharge, itch, and bleeding were comparable. Rates of petechiae or erythema were similar and vaginal examination was abnormal in 72% of PCV cases. All DIV and 33% of PCV occurred in squamous mucosa; the remaining PCV cases were from mucocutaneous junction. Mean epithelial thickness, rete ridge appearance, exocytosis, and spongiosis were similar in DIV and PCV. Epithelial erosion, wide-diameter lesions, plasma cells, and stromal hemosiderin occurred in both but were more common in PCV. Lymphocyte-obscured basal layer, narrow-diameter lesions, hemorrhage, and vascular congestion were seen in both, but more common and marked in DIV. CONCLUSIONS: Desquamative inflammatory vaginitis and PCV have overlapping symptoms, signs, and histopathologic features. They may represent a single condition of hemorrhagic vestibulovaginitis with varying manifestations according to location and severity.

Is Vulvovaginal Lichen Planus Associated With Squamous Cell Carcinoma?

OBJECTIVE: The aim of the study was to assess for the presence of vulvar lichen planus (LP) in association with human papillomavirus (HPV)-independent squamous cell carcinoma (SCC). MATERIALS AND METHODS: We performed a clinicohistopathologic review of consecutive vulvectomies and wide local excisions for HPV-independent vulvar or vaginal SCC from 2007 to 2017. Data collected included site of SCC, adjacent precursor lesions and dermatoses, dermatologic treatment, and outcome. RESULTS: There were 43 cases of primary HPV-independent vulvar SCC treated by excision, but no vaginal cancers. Eighteen women (42%) had a preoperative diagnosis of lichen sclerosus (LS); none had a diagnosis of LP. Topical corticosteroids were prescribed in 19 (44%) of 43, with 4 women placed on maintenance therapy. Tumors arose from the labia minora, labia majora, and periclitoris, but not from vestibule or perianus. On histopathological review, LS was present in 41 (95%) of 43 specimens, 1 had a nonspecific lichenoid reaction, and 1 had lichen simplex; both of the latter had subsequent biopsies showing LS. Lichen planus was not seen in association with SCC. Differentiated vulvar intraepithelial neoplasia (dVIN) was present in 38 (88%) of 43 specimens, whereas 1 had acanthosis with altered differentiation and 4 (9%) had no precursor lesion. Differentiated vulvar intraepithelial neoplasia had standard, basaloid, and hypertrophic morphology, superficially resembling erosive LP in 9 (24%) of 38 and hypertrophic LP in 6 (16%) of 38. CONCLUSIONS: Lichen planus was not seen in association with HPV-independent vulvar SCC, whereas LS was underrecognized and inadequately treated in this group. Pathologists should be aware that dVIN may superficially resemble erosive or hypertrophic LP.

Effect of Total Laparoscopic Hysterectomy vs Total Abdominal Hysterectomy on Disease-Free Survival Among Women With Stage I Endometrial Cancer: A Randomized Clinical Trial.

Importance: Standard treatment for endometrial cancer involves removal of the uterus, tubes, ovaries, and lymph nodes. Few randomized trials have compared disease-free survival outcomes for surgical approaches. Objective: To investigate whether total laparoscopic hysterectomy (TLH) is equivalent to total abdominal hysterectomy (TAH) in women with treatment-naive endometrial cancer. Design, Setting, and Participants: The Laparoscopic Approach to Cancer of the Endometrium (LACE) trial was a multinational, randomized equivalence trial conducted between October 7, 2005, and June 30, 2010, in which 27 surgeons from 20 tertiary gynecological cancer centers in Australia, New Zealand, and Hong Kong randomized 760 women with stage I endometrioid endometrial cancer to either TLH or TAH. Follow-up ended on March 3, 2016. Interventions: Patients were randomly assigned to undergo TAH (n = 353) or TLH (n = 407). Main Outcomes and Measures: The primary outcome was disease-free survival, which was measured as the interval between surgery and the date of first recurrence, including disease progression or the development of a new primary cancer or death assessed at 4.5 years after randomization. The prespecified equivalence margin was 7% or less. Secondary outcomes included recurrence of endometrial cancer and overall survival. Results: Patients were followed up for a median of 4.5 years. Of 760 patients who were randomized (mean age, 63 years), 679 (89%) completed the trial. At 4.5 years of follow-up, disease-free survival was 81.3% in the TAH group and 81.6% in the TLH group. The disease-free survival rate difference was 0.3% (favoring TLH; 95% CI, -5.5% to 6.1%; P = .007), meeting criteria for equivalence. There was no statistically significant between-group difference in recurrence of endometrial cancer (28/353 in TAH group [7.9%] vs 33/407 in TLH group [8.1%]; risk difference, 0.2% [95% CI, -3.7% to 4.0%]; P = .93) or in overall survival (24/353 in TAH group [6.8%] vs 30/407 in TLH group [7.4%]; risk difference, 0.6% [95% CI, -3.0% to 4.2%]; P = .76). Conclusions and Relevance: Among women with stage I endometrial cancer, the use of total abdominal hysterectomy compared with total laparoscopic hysterectomy resulted in equivalent disease-free survival at 4.5 years and no difference in overall survival. These findings support the use of laparoscopic hysterectomy for women with stage I endometrial cancer. Trial Registration: clinicaltrials.gov Identifier: NCT00096408; Australian New Zealand Clinical Trials Registry: CTRN12606000261516.

Distinguishing Erosive Lichen Planus From Differentiated Vulvar Intraepithelial Neoplasia.

OBJECTIVE: Erosive lichen planus (LP) and differentiated vulvar intraepithelial neoplasia (dVIN) may display overlapping histopathologic features. MATERIALS AND METHODS: We searched the local pathology database for vulvar biopsies reported as dVIN or erosive vulvitis during 2011 to 2013 inclusive. After review of patient notes and slides, there were 5 cases with a clinical appearance and course consistent with erosive LP and histopathology showing epithelial regeneration. We then selected 5 cases of dVIN in which the clinical course and histopathology supported the diagnosis. We performed immunohistochemistry for p16 and p53 on all cases and did copy variant analysis on 1 case each of erosive LP and dVIN. RESULTS: Histopathology of the LP cases showed epithelial thinning, absent stratum corneum, lack of maturation, as well as nuclear changes of enlargement, pleomorphism, and hyperchromasia. Three LP cases (60%) showed a wild-type p53 pattern and 2 (40%) were confluent positive. Two dVIN cases (40%) showed full-thickness loss of differentiation. One case (20%) of dVIN was p53 negative, 2 (40%) were wild-type, 1 was confluent positive, and 1 showed dark suprabasilar staining. All cases were negative for p16. Compared with control, erosive LP epithelium showed a similar copy-number pattern, whereas the dVIN epithelium had many copy-number changes. CONCLUSIONS: A small subset of clinically diagnosed vulvovaginal erosive LP will show on histopathology a regenerative erosive vulvitis with loss of epithelial maturation and nuclear changes, which requires clinicopathologic correlation to distinguish from dVIN.

A clinicopathological review of 33 patients with vulvar melanoma identifies c-KIT as a prognostic marker.

Vulvar melanoma is the second most common vulvar cancer. Patients with vulvar melanoma usually present with the disease at a late stage and have a poor prognosis. The prognostic predictors reported in the literature are not unequivocal and the role of lichen sclerosus and c-KIT mutations in the aetiology of vulvar melanoma is unclear. Breslow staging currently seems to be the most adequate predictor of prognosis. We thus performed a clinicopathological and literature review to identify suitable predictors of prognosis and survival and investigated the expression of c-KIT (by immunohistochemistry) in patients with vulvar melanoma (n=33) from the Gynaecological Cancer Centres of the Royal Hospital for Women (Sydney, Australia) and John Hunter Hospital (Newcastle, Australia). Our series of 33 patients fitted the expected clinical profile of older women: delayed presentation, high stage, limited response to treatment and poor prognosis. We identified 3 patients (9.1%) with lichen sclerosus associated with melanoma in situ, although no lichen sclerosus was found in the areas of invasive melanoma. No patient had vulvar nevi. We identified a) Breslow's depth, b) an absence of any of the pathological risk factors, such as satellitosis, in-transit metastasis, lymphovascular space invasion (LVSI) and dermal mitosis, c) removal of inguino-femoral lymph nodes, d) lateral margin of >1 cm, and e) c-KIT expression as valuable prognostic predictors for disease-free survival. We conclude that c-KIT expression is, apart from Breslow's depth, another valuable predictor of prognosis and survival. Lichen sclerosus may be associated with vulvar melanoma.

Improved surgical safety after laparoscopic compared to open surgery for apparent early stage endometrial cancer: results from a randomised controlled trial.

AIM: To compare Total Laparoscopic Hysterectomy (TLH) and Total Abdominal Hysterectomy (TAH) with regard to surgical safety. METHODS: Between October 2005 and June 2010, 760 patients with apparent early stage endometrial cancer were enroled in a multicentre, randomised clinical trial (LACE) comparing outcomes following TLH or TAH. The main study end points for this analysis were surgical adverse events (AE), hospital length of stay, conversion from laparoscopy to laparotomy, including 753 patients who completed at least 6 weeks of follow-up. Postoperative AEs were graded according to Common Toxicity Criteria (V3), and those immediately life-threatening, requiring inpatient hospitalisation or prolonged hospitalisation, or resulting in persistent or significant disability/incapacity were regarded as serious AEs. RESULTS: The incidence of intra-operative AEs was comparable in either group. The incidence of post-operative AE CTC grade 3+ (18.6% in TAH, 12.9% in TLH, p 0.03) and serious AE (14.3% in TAH, 8.2% in TLH, p 0.007) was significantly higher in the TAH group compared to the TLH group. Mean operating time was 132 and 107 min, and median length of hospital stay was 2 and 5 days in the TLH and TAH group, respectively (p<0.0001). The decline of haemoglobin from baseline to day 1 postoperatively was 2g/L less in the TLH group (p 0.006). CONCLUSIONS: Compared to TAH, TLH is associated with a significantly decreased risk of major surgical AEs. A laparoscopic surgical approach to early stage endometrial cancer is safe.

Risk factors to predict the incidence of surgical adverse events following open or laparoscopic surgery for apparent early stage endometrial cancer: results from a randomised controlled trial.

AIMS: To identify risk factors for major adverse events (AEs) and to develop a nomogram to predict the probability of such AEs in patients who have surgery for apparent early stage endometrial cancer. METHODS: We used data from 753 patients who were randomised to either total laparoscopic hysterectomy or total abdominal hysterectomy in the LACE trial. Serious adverse events that prolonged hospital stay or postoperative adverse events (using common terminology criteria 3+, CTCAE V3) were considered major AEs. We analysed pre-surgical characteristics that were associated with the risk of developing major AEs by multivariate logistic regression. We identified a parsimonious model by backward stepwise logistic regression. The six most significant or clinically important variables were included in the nomogram to predict the risk of major AEs within 6weeks of surgery and the nomogram was internally validated. RESULTS: Overall, 132 (17.5%) patients had at least one major AE. An open surgical approach (laparotomy), higher Charlson's medical co-morbidities score, moderately differentiated tumours on curettings, higher baseline Eastern Cooperative Oncology Group (ECOG) score, higher body mass index and low haemoglobin levels were associated with AE and were used in the nomogram. The bootstrap corrected concordance index of the nomogram was 0.63 and it showed good calibration. CONCLUSIONS: Six pre-surgical factors independently predicted the risk of major AEs. This research might form the basis to develop risk reduction strategies to minimise the risk of AEs among patients undergoing surgery for apparent early stage endometrial cancer.

Quality of life after total laparoscopic hysterectomy versus total abdominal hysterectomy for stage I endometrial cancer (LACE): a randomised trial.

BACKGROUND: This two-stage randomised controlled trial, comparing total laparoscopic hysterectomy (TLH) with total abdominal hysterectomy (TAH) for stage I endometrial cancer (LACE), began in 2005. The primary objective of stage 1 was to assess whether TLH results in equivalent or improved quality of life (QoL) up to 6 months after surgery compared with TAH. The primary objective of stage 2 was to test the hypothesis that disease-free survival at 4.5 years is equivalent for TLH and TAH. Here, we present the results of stage 1. METHODS: Between Oct 7, 2005, and April 16, 2008, 361 participants were enrolled in the QoL substudy at 19 centres across Australia, New Zealand, and Hong Kong; 332 completed the QoL analysis. Randomisation was done centrally and independently from other study procedures via a computer-generated, web-based system (providing concealment of the next assigned treatment), using stratified permuted blocks of three and six patients. Patients with histologically confirmed stage I endometrioid adenocarcinoma and Eastern Cooperative Oncology Group performance status less than 2 were randomly assigned to TLH (n=190) or TAH (n=142), stratified by histological grade and study centre. Patients and study personnel were not masked to treatment assignment. QoL was measured at baseline, 1 and 4 weeks (early), and 3 and 6 months (late) after surgery, using the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire. The primary endpoint was the difference between groups in QoL change from baseline at early and late timepoints (a 5% difference was considered clinically significant). Analysis was done according to the intention-to-treat principle. Patients for both stages of the trial have now been recruited and are being followed up for disease-specific outcomes. The LACE trial is registered with ClinicalTrials.gov, number NCT00096408. FINDINGS: Eight of 332 patients (2.4%) had treatment conversion-seven from TLH to TAH and one from TAH to TLH (patient preference). In the early phase of recovery, patients who had TLH reported significantly greater improvement in QoL from baseline compared with those who had TAH, in all subscales apart from emotional and social wellbeing. Improvements in QoL up to 6 months after surgery continued to favour TLH, except in the emotional and social wellbeing measures of FACT and the visual analogue scale of the EuroQoL five dimensions (EuroQoL-VAS). Operating time was significantly longer in the TLH group (138 min [SD 43]) than in the TAH group (109 min [34]; p=0.001). Although the proportion of intraoperative adverse events was similar between groups (TAH eight of 142 [5.6%] vs TLH 14 of 190 [7.4%]; p=0.53); postoperatively, twice as many patients in the TAH group experienced adverse events of grade 3 or higher (33 of 142 [23.2%] vs 22 of 190 [11.6%] in the TLH group; p=0.004). Postoperative serious adverse events occurred more in the TAH group (27 of 142 [19.0%]) than in the TLH group (16 of 190 [7.9%]; p=0.002). INTERPRETATION: QoL improvements from baseline during early and later phases of recovery, and the adverse event profile, favour TLH compared with TAH for treatment of stage I endometrial cancer. FUNDING: Cancer Council Queensland, Cancer Council New South Wales, Cancer Council Victoria, Cancer Council Western Australia; NHMRC project grant 456110; Cancer Australia project grant 631523; The Women and Infants Research Foundation, Western Australia; Royal Brisbane and Women's Hospital Foundation; Wesley Research Institute; Gallipoli Research Foundation; Gynetech; TYCO Healthcare, Australia; Johnson and Johnson Medical, Australia; Hunter New England Centre for Gynaecological Cancer; Genesis Oncology Trust; and Smart Health Research Grant QLD Health.