Lichen sclerosus is considered to be the precursor lesion of vulvar squamous cell carcinoma, of which only 2-5% progress to squamous cell carcinoma. Differentiated vulvar intraepithelial neoplasia (VIN) has been proposed to be the direct precursor lesion, but this is a recently recognized, and a difficult to diagnose, entity, which may easily be mistaken for a benign dermatosis. The aim of this study was to test the hypothesis that of all lesions that have been diagnosed as lichen sclerosus in the past, a part might currently be diagnosed as differentiated VIN, and to identify histopathological differences between lichen sclerosus lesions with and without progression to vulvar squamous cell carcinoma. All lichen sclerosus slides were revised by two expert gynecopathologists and histopathological characteristics were documented. After revision of lichen sclerosus biopsies without progression (n ¼ 61), 58 were reclassified as lichen sclerosus. Revision of lichen sclerosus biopsies with progression yielded concordant diagnoses in 18 of 60 cases (30%). Of 60 lesions, 25 (42%) were reclassified as differentiated VIN. The median time from differentiated VIN to vulvar squamous cell carcinoma was shorter (28 months) than that from lichen sclerosus to vulvar squamous cell carcinoma (84 months) (Po0.001). Lichen sclerosus that progressed to squamous cell carcinoma, but did not meet the criteria for differentiated VIN, more often showed parakeratosis (P ¼ 0.004), dyskeratosis (Po0.001), hyperplasia (P ¼ 0.048) and basal cellular atypia (P ¼ 0.009) compared with lichen sclerosus without progression. In conclusion, differentiated VIN diagnosis has been frequently missed and is associated with rapid progression to squamous cell carcinoma. Patients with lichen sclerosus with dyskeratosis and parakeratosis, hyperplasia and/or basal cellular atypia should be kept under close surveillance as these lesions also tend to progress to squamous cell carcinoma.

No abstract

No abstract

The aim of this study was to review the literature on currently available non- and minimally-invasive diagnostic methods and analysis of primary tumor characteristics for prediction of inguinofemoral lymph node metastases in patients with primary squamous cell carcinoma of the vulva. We used the English language literature in Pubmed and reference lists from selected articles. Search terms included vulvar carcinoma, prognosis, lymph node metastases, ultrasound, computer tomography, magnetic resonance imaging, positron emission tomography, and sentinel lymph node. No study type restrictions were imposed. Currently no noninvasive imaging techniques exist that are able to predict lymph node metastases with a high enough negative predictive value. A depth of invasion ≤1 mm is the only histopathologic parameter that can exclude patients for complete inguinofemoral lymphadenectomy. No other clinicopathologic parameter allows exclusion of lymph node metastases with a high enough negative predictive value. The minimally invasive sentinel node procedure is a promising technique for selecting patients for complete lymphadenectomy, but its safety has not been proven yet.

No abstract

Prospectively, the relationship between androgen levels in the utero-ovarian circulation, aromatase activity in endometrial and body fat tissue, and the presence or absence of endometrioid endometrial cancer was studied in postmenopausal women. In 43 women with endometrioid endometrial cancer and 8 women with a benign gynecological condition, a hysterectomy with bilateral salpingo-oophorectomy was performed. Using tritium water-release assays, aromatase activities in endometrial and body fat tissue were determined and related to the steroid levels from the peripheral and the utero-ovarian venous circulation (estradiol, androstenedione, testosterone) and to the presence or absence of endometrial cancer. Significant aromatase activity was found in both benign and malignant endometrial tissue samples. Aromatase activity in samples of endometrial tissue and in samples of body fat did not correlate with steroid levels in peripheral or utero-ovarian venous blood. Aromatase activity in samples of benign or malignant endometrium did not differ. Remarkably, in four women with mainly poorly differentiated endometrial cancer, very high aromatase activity was found in endometrial tissue. It is likely that multiple pathogenetic pathways exist that eventually lead to the formation of endometrioid endometrial cancer. The local availability of androgens and the finding that aromatase activity is present in both endometrial cancer and benign endometrial tissue support the hypothesis that aromatase activity in the endometrium may play a role in malignant transformation by converting androgens into mitogenic estrogens in the endometrial tissue.

Current morphology-based cervical cancer screening is associated with significant false-positive and false-negative results. Tumor suppressor gene hypermethylation is frequently present in cervical cancer. It is unknown whether a cervical scraping reflects the methylation status of the underlying epithelium, and it is therefore unclear whether quantitative hypermethylation specific PCR (QMSP) on cervical scrapings could be used as a future screening method augmenting the current approach. Cervical scrapings and paired fresh frozen cervical tissue samples were obtained from 53 cervical cancer patients and 45 controls. All scrapings were morphologically scored and analyzed with QMSP for the genes APC, DAPK, MGMT, and GSTP1. To adjust for DNA input, hypermethylation ratios were calculated against DNA levels of a reference gene. Hypermethylation ratios of paired fresh frozen tissue samples and scrapings of cervical cancer patients and controls were strongly related (Spearman correlation coefficient, 0.80 for APC, 0.98 for DAPK, and 0.83 for MGMT; P < 0.001). More cervical cancer patients than controls were DAPK positive (P < 0.001). When cutoff levels for ratios were defined to be above the highest ratio observed in controls, QMSP in cervical scrapings identified 32 (67%) of 48 cervical cancer patients. This feasibility study demonstrates that QMSP on cervical scrapings holds promise as a new diagnostic tool for cervical cancer. The addition of more genes specifically methylated in cervical cancer will further improve the assay.

PurposeThere is an ongoing discussion whether ovarian colorectal metastases are the result of peritoneal or hematogeneous dissemination. The metastatic route has implications on the choice of treatment. This study aims to evaluate and discuss the factors indicating peritoneal or hematogenic dissemination and aims to evaluate and discuss the factors indicating peritoneal or haematogenic spreadMethodsA retrospective consecutive series of patients from two tertiary referral centers, who were treated for ovarian metastases from colorectal cancer between 2000 and 2018, was described. Clinical and histopathological characteristics of the primary tumor and the ovarian metastases were collected from patient files, the surgery reports and the pathology files. Statistical analysis included descriptive statistics, whereas binominal testing was used to compare the likelihood of two categories.ResultsData of 141 patients were included. In most cases the ovarian capsule (73.6%) was broken and 120 patients (85.1%) had peritoneal metastases at the time of diagnosis of the ovarian metastases. Most metastatic cells were found deep in the ovarian stroma (80.0%) and 26.2% of patients developed metachronous hematogeneous (distant and/or liver) metastases. ConclusionsIn this study we found characteristics that support a peritoneal as well as a hematogenous dissemination. Therefore, an undoubted conclusion regarding the metastatic route cannot be drawn. Future studies should focus on the biological behavior as well as on the outcome of patients with ovarian metastases after CRS+HIPEC to evaluate its added value in this patient group.