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Purpose The aims of the present study were to evaluate the development of untreated cervical intraepithelial neoplasia (CIN) 3 during pregnancy and to assess persistence, progression, and regression rates postpartum to identify factors associated with regression. Methods In a tertiary gynecology and obstetrics department, a total of 154 pregnant women with CIN 3 were treated in the dysplasia unit. The follow-up findings were analyzed retrospectively on the basis of histological, cytological, and human papillomavirus (HPV) testing of 154 pregnant women confirmed as having CIN 3 in colposcopically guided biopsies. Results The rates of persistence, regression, and progression of CIN 3 in these women were 76.1%, 20% and 3.2%, respectively. Data for the delivery mode was available for 126 women. The rate of regression was almost twice as high with vaginal delivery as with cesarean section, at 27.4 vs. 15.2%, whereas the rate of progression was lower with vaginal delivery, at 2.7 vs. 6.5%. Conclusion The rate of persistence of CIN observed in this study is comparable to that reported in other studies. The study provides strong evidence for greater regression among women who have vaginal deliveries. Careful work-up is recommended postpartum for this group of women in order to rule out persistent CIN 3 or invasive disease.

Primary vaginal carcinoma is rare. There are two pathogenetic pathways, one associated with HPV high-risk infection and another one with inactivation of p53. Vaginal Paget's disease is rare and mostly associated with vulvar disease or represents intravaginal spread of associated locoregional cancer. Diagnostic vaginal biopsies should be examined by step sections on H&E. Sentinel lymph nodes should be processed completely using ultrastaging. Morphology-based prognostic factors with good clinical evidence are tumour stage and lymph node status. Molecular markers are not currently relevant for treatment decision and prognosis.

Purpose Colposcopy-guided punch biopsy is a cornerstone method for diagnosing vulvar diseases. The aim of this study was to evaluate the concordance rate of clinical findings in vulvar diseases during examinations, in comparison with colposcopy-directed punch biopsy. We also developed a new classification to simplify the categorization of vulvoscopic findings. Methods The concordance rate of the clinical findings was compared with the final histology results from punch biopsies. The data were collected between January 2014 and May 2017 at the Erlangen University Hospital. Results A total of 482 colposcopy-directed punch biopsies of the vulva were obtained in 420 women. The overall concordance rate of the clinical findings in comparison with the histological vulvar punch-biopsy findings was 53.9% for all entities — benign lesions, lichen, low- and high-grade squamous intraepithelial lesions (LSIL/HSILs), and vulvar carcinoma. The concordance rate for detecting LSILs was 64.3% (45/70). The concordance rate for detecting HSILs was 62.3% and for Vulvar carcinoma 65.2%. Conclusions Punch biopsy of suspicious lesions continues to be a cornerstone in diagnosing HSILs and carcinoma of the vulva. Careful work-up of the vulva is recommended when patients have symptoms such as pruritus or pain. The new classification is more specific for diagnosing lesions in the vulva.

The current cervical cancer screening program in Germany recommends that the results showing suspected HPV infection should be further examined in specialized colposcopy units. This study aimed to correlate externally documented Pap smear results with in-house colposcopy-guided Pap cytology results and compare colposcopy-guided biopsy and postoperative histopathology results. Clinical data were analyzed from 3627 examinations in 2844 patients who visited a university certified dysplasia unit from 2014 to 2017; 2212 patients underwent complete assessments, including Pap smear, colposcopy, HPV testing, colposcopy-guided biopsy, and/or surgery. The results were analyzed descriptively. External and in-house Pap results were consistent in 1054 ofthe 2212 patients (47.65%). Referral cytology showed a higher grade than in-house in 456 (20.61%) and a lower grade in 702 (31.74%). Using the histopathological findings as the gold standard, overdiagnosis in the referral cytology was noted in 180 patients (13.19%), underdiagnosis in 263 (19.27%), and concordant findings in 922 (67.55%). For in-house cytology, overdiagnosis was found in 133 patients (10.74%), underdiagnosis in 192 (15.51%), and accurate diagnosis with congruent cytology and histopathology findings in 913 (73.75%). The rate of detection of cervical abnormalities differs significantly depending on whether the examination is performed routinely or in specialized units. Colposcopy-guided Pap smears correlate significantly better with histology than referral cytology results without colposcopic guidance. More severe lesions were also detected more accurately.

Simple Summary HPV-DNA integration into the host genome is a frequent step in cervical carcinogenesis and is considered to be a tumor-driving event. Viral integration sites are unique for each patient and could thus serve as highly specific molecular markers for the detection of recurrent disease. Unexpectedly, our study showed that integration sites as individualized biomarkers could not detect all recurrent pre-cancers (CIN2/3). Nevertheless, this is the first study which has identified and validated integration sites in a large number of CIN3 (n = 445) and as such has unraveled several novel findings: The integration frequency observed in CIN3 was much lower than anticipated (10.8% in CIN3 vs. 80% in cervical cancer). Moreover, in contrast to the monoclonal situation in cervical carcinoma, integrated HPV-DNA in CIN3 is most likely confined to clonally expanding subpopulations. Abstract Purpose: Post-treatment follow-up in women with cervical pre-cancers (CIN3) is mandatory due to relapse in up to 10% of patients. Standard follow-up based on hrHPV-DNA/cytology co-testing has high sensitivity but limited specificity. The aim of our prospective, multicenter, observational study was to test the hypothesis that an individualized viral-cellular-junction test (vcj-PCR) combined with cytology has a lower false positive rate for the prediction of recurrence compared to standard co-testing. Methods: Pre-surgical cervical swabs served for the identification of HPV16/18 DNA integration sites by next-generation-sequencing (NGS). Samples taken at 6, 12 and 24 months post-surgery were evaluated by cytology, hrHPV-DNA and the patients’ individual HPV-integration sites (vcj-PCR on the basis of NGS). Results: Integration sites were detected in 48 of 445 patients (10.8%), 39 of them had valid follow-up data. The false positive rate was 18.2% (95% CI 8.6–34.4%) for standard hrHPV/cytology at six months compared to 12.1% (95% CI 4.8–27.3%) for vcj-PCR/cytology, respectively (McNemar p = 0.50). Six patients developed recurrences (1 CIN2, 5 CIN3) during follow-up. Standard co-testing detected all, whereas vcj-PCR/cytology detected only five patients with recurrences. Data of 269 patients without evidence of HPV16/18 integration were subject to post-hoc analyses. Standard co-testing revealed a false positive rate of 15.7% (95% CI 11.7–20.7%) and predicted ten of fourteen recurrences at six months. Conclusions: Although highly specific on its own vcj-PCR could not detect all recurrent CIN2/3. Possible reasons for this unexpected result may be multifocal lesions, intratumoral heterogeneity with respect to HPV integration and/or incident CIN.

Primary vaginal carcinoma is rare. There are two pathogenetic pathways, one associated with HPV high-risk infection and another one with inactivation of p53. Vaginal Paget's disease is rare and mostly associated with vulvar disease or represents intravaginal spread of associated locoregional cancer. Diagnostic vaginal biopsies should be examined by step sections on HE. Sentinel lymph nodes should be processed completely using ultrastaging. Morphology-based prognostic factors with good clinical evidence are tumour stage and lymph node status. Molecular markers are not currently relevant for treatment decision and prognosis.Das Vaginalkarzinom ist ein seltenes Malignom des weiblichen Genitales. Pathogenetisch können ein HPV-high-risk-Pathogeneseweg und ein p53-abhängiger Pathogeneseweg definiert werden. Der vaginale M. Paget ist selten und zumeist assoziiert mit einem M. Paget der Vulva oder lokoregionären Karzinomen. Diagnostische Biopsien sollen in Stufenschnitten aufgearbeitet werden. Sentinel-Lymphknoten sollen vollständig und mittels Ultrastaging untersucht werden. Etablierte morphologische Prognosefaktoren sind das Tumorstadium und lokoregionäre Metastasen. Molekulare Marker spielen derzeit keine Rolle.

Purpose This is an official guideline, published and coordinated by the Gynecological Oncology Working Group (AGO) of the German Cancer Society (DKG) and the German Society for Gynecology and Obstetrics (DGGG). Vaginal cancers are rare tumors, which is why there is very little evidence on these tumors. Knowledge about the optimal clinical management is limited. This first German S2k guideline on vaginal cancer has aimed to compile the most current expert knowledge and offer new recommendations on the appropriate treatment as well as providing pointers about individually adapted therapies with lower morbidity rates than were previously generally available. The purpose of this guideline is also to set up a register to record data on treatment data and the course of disease as a means of obtaining evidence in future. Methods The present S2k guideline was developed by members of the Vulvar und Vaginal Tumors Commission of the AGO in an independently moderated, structured, formal consensus process and the contents were agreed with the mandate holders of the participating scientific societies and organizations. Recommendations To optimize the daily care of patients with vaginal cancer: 1. Monitor the spread pattern; 2. Follow the step-by-step diagnostic workup based on initial stage at detection; 3. As part of individualized clinical therapeutic management of vaginal cancer, follow the sentinel lymph node protocol described here, where possible; 4. Participate in the register study on vaginal cancer.

Malignancies of the vagina are rare, but colposcopy-directed biopsies play a major role in detecting vaginal intraepithelial lesions. Data of accuracy in detecting neoplasia of the vagina are very rare compared to accuracy in detecting cervical neoplasia. The aim of this study was to evaluate the accuracy of colposcopy-directed biopsy in comparison with clinical findings of the examiner. The accuracy of colposcopy-directed biopsy was compared with the clinical finding in relation to the patient’s age and the examiner’s level of training. This was done in combination with PAP-smear, HPV-test results, and the history of other malignancies of the lower genital tract. The data were collected between January 2014 and February 2018 at the certified Dysplasia Unit of the University Hospital Erlangen. In total, 253 biopsies from 253 women from the vagina were obtained. The overall accuracy of biopsy in comparison with clinical finding was 52.17% for all entities—benign lesions, low-grade squamous intraepithelial lesions (LSILs), high-grade squamous intraepithelial lesions (HSILs), and vaginal carcinoma. The accuracy for detecting HSIL was 82.46% (47/57), with an underdiagnosis rate of 15.79% and an overdiagnosis rate of 1.79%. With a sensitivity of over 80%, colposcopy-directed biopsy plays an important role in detecting vaginal–HSIL. A highly experienced practitioner is increasing the sensitivity in detecting vaginal–HSIL. Careful examination is required in women with a history of HSIL of the lower genital tract or with simultaneous neoplasia because they are of greater risk of developing vaginal malignancies. The combination of careful clinical work up, PAP-smear, HPV-testing, and colposcopy-guided biopsy is crucial in detecting vaginal–HSIL.

In Deutschland wachst ein groser Teil der Schuler/innen aus Migrant/innenfamilien mit zwei oder mehreren Sprachen auf. Der Begriff Herkunftssprache (im Folgenden HS) wurde im Deutschen als Entsprechung zum englischen Terminus heritage language gebildet. Neuere Definitionen aus dem angloamerikanischen Kontext (z. B. Polinsky 2015, S. 8) bezeichnen als HS die zuerst erworbene Sprache eines Individuums, das selbst in einer Familie aufwachst, in der nicht (ausschlieslich) die Sprache der umgebenden Mehrheitsgesellschaft verwendet wird.

In Schulfremdsprachen wie Englisch, Franzosisch, Spanisch oder Russisch sind Lerngruppen, in denen Schuler/innen mit unterschiedlich ausgepragten sprachlichen Vorkenntnissen gemeinsam unterrichtet werden, keine Seltenheit. Insbesondere Herkunftssprachenlernende (HSL), fur die die Zielsprache gleichzeitig auch ihre Familiensprache ist, bringen besondere Voraussetzungen mit und haben in der Regel auch andere Erwartungen an diesen Unterricht als ihre Mitschuler/innen (zu den Charakteristika von HSL vgl. Mehlhorn 2017). Dies stellt einerseits eine Bereicherung der Lerngruppe dar, birgt aber auch Herausforderungen: Je nach Gruppenzusammensetzung und -dynamik kommt es z. B. vor, dass Fremdsprachenlernende (FSL) in Anwesenheit von flussig sprechenden HSL Sprechhemmungen zeigen.

A novel histopathological grading system based on tumour budding and cell nest size has recently been shown to outperform conventional (WHO-based) grading algorithms in several tumour entities such as lung, oral, and oesophageal squamous cell carcinoma (SCC) in terms of prognostic patient stratification. Here, we tested the prognostic value of this innovative grading approach in two completely independent cohorts of SCC of the uterine cervix. To improve morphology-based grading, we investigated tumour budding activity and cell nest size as well as several other histomorphological factors (e.g., keratinization, nuclear size, mitotic activity) in a test cohort (n = 125) and an independent validation cohort (n = 122) of cervical SCC. All parameters were correlated with clinicopathological factors and patient outcome. Small cell nest size and high tumour budding activity were strongly associated with a dismal patient prognosis (p < 0.001 for overall survival [OS], disease-specific survival, and disease-free survival; test cohort) in both cohorts of cervical SCC. A novel grading algorithm combining these two parameters proved to be a highly effective, stage-independent prognosticator in both cohorts (OS: p < 0.001, test cohort; p = 0.001, validation cohort). In the test cohort, multivariate statistical analysis of the novel grade revealed that the hazard ratio (HR) for OS was 2.3 for G2 and 5.1 for G3 tumours compared to G1 neoplasms (p = 0.010). In the validation cohort, HR for OS was 3.0 for G2 and 7.2 for G3 tumours (p = 0.012). In conclusion, our novel grading algorithm incorporating cell nest size and tumour budding allows strongly prognostic histopathological grading of cervical SCC superior to WHO-based grading. Therefore, our data can be regarded as a cross-organ validation of previous results demonstrated for oesophageal, lung, and oral SCC. We suggest this grading algorithm as an additional morphology-based parameter for the routine diagnostic assessment of this tumour entity.

Mit einer Inzidenz von 5,8/100 000 Frauen/Jahr ist das Vulvakarzinom das vierthäufigste Genitalkarzinom der Frau. Meist werden Vulvakarzinome in einem frühen Stadium diagnostiziert. Häufigstes Symptom ist der therapieresistente Pruritus, perineale Schmerzen und/oder beim Sitzen, Dysurie und Brennen. Bei der klinischen Inspektion sollte das komplette äußere Genitale mit Vagina, Perineum, Anus sowie die Zervix inspiziert werden. Liegt eine VIN1, LSIL (vulväre intraepitheliale Neoplasie Grad 1, low-grade squamous intraepithelial lesion) ohne Symptome vor, sind regelmäßige Kontrollen ausreichend. Bei symptomatischer LSIL, HPV-assoziierter VIN2 oder VIN3 (vulväre intraepitheliale Neoplasie Grad 2 oder 3, high-grade squamous intraepithelial lesion) kann eine Laserevaporisation erfolgen. Eine komplette Vulvektomie sollte nur bei multizentrischen Tumoren erfolgen. Eine systematische Lymphonodektomie ist ab Stadium T1b mit Infiltrationstiefe > 1 mm empfohlen. Eine adjuvante Radiotherapie der Primärtumorregion sollte bei non-in-sano-Situation durchgeführt werden, falls eine Nachresektion aus funktionellen Gründen oder Patientenwunsch nicht möglich ist. Eine lebenslange Nachsorge ist notwendig, denn jede dritte Patientin mit Vulvakarzinom erleidet ein Rezidiv. Als Therapie des Lokalrezidivs ohne Beteiligung von Anus, Urethra oder Lymphknoten sollte eine operative Resektion mit R0-Situation angestrebt werden.

The current cervical cancer screening program in Germany recommends that the results showing suspected HPV infection should be further examined in specialized colposcopy units. This study aimed to correlate externally documented Pap smear results with in-house colposcopy-guided Pap cytology results and compare colposcopy-guided biopsy and postoperative histopathology results.Clinical data were analyzed from 3627 examinations in 2844 patients who visited a university certified dysplasia unit from 2014 to 2017; 2212 patients underwent complete assessments, including Pap smear, colposcopy, HPV testing, colposcopy-guided biopsy, and/or surgery. The results were analyzed descriptively.External and in-house Pap results were consistent in 1054 ofthe 2212 patients (47.65%). Referral cytology showed a higher grade than in-house in 456 (20.61%) and a lower grade in 702 (31.74%). Using the histopathological findings as the gold standard, overdiagnosis in the referral cytology was noted in 180 patients (13.19%), underdiagnosis in 263 (19.27%), and concordant findings in 922 (67.55%). For in-house cytology, overdiagnosis was found in 133 patients (10.74%), underdiagnosis in 192 (15.51%), and accurate diagnosis with congruent cytology and histopathology findings in 913 (73.75%).The rate of detection of cervical abnormalities differs significantly depending on whether the examination is performed routinely or in specialized units. Colposcopy-guided Pap smears correlate significantly better with histology than referral cytology results without colposcopic guidance. More severe lesions were also detected more accurately.

Die Heterogenitat der Diagnostik und der Therapie des Zervixkarzinoms bei kaum sinkender Morbiditat und Mortalitat machte ein Upgrade der bestehenden S2k-Leitlinie von 2008 auf S3-Niveau notwendig. Dies fuhrte zur seit 2014 gultigen S3-Leitlinie „Diagnostik, Therapie und Nachsorge der Patientin mit Zervixkarzinom“ (AWMF-Registernummer: 032-033OL). Die vorliegende Ubersichtsarbeit stellt den aktuellen Therapiestandard des Zervixkarzinoms dar und geht dabei im Speziellen auf die medikamentose Therapie ein. Es wird auserdem Stellung zur Diagnostik genommen, die letztlich zur Therapieentscheidung fuhrt. Auf Basis der aufwendigen Evidenzaufarbeitung und der Empfehlungen der S3-Leitlinie werden die aktuellen Therapiealgorithmen dargelegt und diskutiert. Die Therapie des Zervixkarzinoms erfolgt in den fruhen Stadien zumeist operativ. Ab Stadium FIGO IIB besteht die Indikation zur simultanen cisplatinhaltigen Radiochemotherapie. Beim nichtoperablen Rezidiv oder in der metastasierten Situation gibt es palliative Chemotherapieoptionen. Seit 2014 ist auch erstmals die Hinzunahme eines zielgerichteten Therapiekonzepts mit Bevacizumab moglich. Die Behandlung von Zervixkarzinomen hat sich in den letzten Jahren deutlich weiterentwickelt. Die Therapieoptionen sind vielfaltig, sie werden individuell und stadienadaptiert eingesetzt. Die Entscheidung uber die Therapiemodalitat erfolgt interdisziplinar in der Tumorkonferenz. Sie ist individuell angepasst und sollte gemeinsam mit der Patientin getroffen werden. Berucksichtigt werden mussen der Allgemeinzustand und die Lebenssituation der Patientin sowie Erkrankungsstadium, Risikofaktoren und das unterschiedliche Nebenwirkungsprofil der Therapien. Ziel ist eine moglichst geringe Beeinflussung der Lebensqualitat bei maximalem Uberleben.

Background and Objectives Chylous ascites, an accumulation of milky-white lymph fluid in the peritoneal cavity, is a rare complication following retroperitoneal lymphadenectomy. This study evaluated the appearance and management of chylous ascites following lymphadenectomy for gynecological malignancies. Methods A total of 931 patients who underwent lymphadenectomy for gynecological malignancies at Erlangen University Hospital between 2002 and 2013 were reviewed retrospectively. Results Chylous ascites occurred postoperatively in 28 of the 931 patients (3.0%). All patients with chylous ascites had undergone combined systematic para-aortic and pelvic lymphadenectomy (SAPL). Patients with chylous ascites had a larger mean number of lymph nodes removed (51.9 vs. 40.0, P = 0.002) and the proportion of laparoscopic SAPLs was significantly higher (20/28; 71.4%) in comparison with open surgery (8/28; 28.6%) (P

Colposcopy-directed biopsy is a cornerstone method for diagnosing cervical intraepithelial neoplasia. The aim of this study was to evaluate the accuracy of colposcopy-directed biopsy in comparison with definitive surgery. The accuracy of colposcopy-directed biopsy was compared with the final histology in relation to different types of transformation zone (TZ), the patient’s age, and the examiner’s level of training. The overall accuracy of biopsy in comparison with definitive surgery was 71.9% for all entities—benign lesions, low-grade squamous intraepithelial lesions, high-grade squamous intraepithelial lesions (HSILs), and cervical carcinoma—with an underdiagnosis rate of 11.8% and an overdiagnosis rate of 16.5%. The accuracy for detecting HSIL was 88% (401/455), with an underdiagnosis rate of 10.5% and overdiagnosis rate of 1.3%. The accuracy rates for detecting HSIL in women with TZ 1, TZ 2, or TZ 3 were 92.2, 90.5, and 76.5%, respectively. The accuracy rates for detecting HSIL in the different age groups were 93.1% (age 0–34), 83.6% (age 34–55), and 80% (age 55 or older). A combination of the colposcopic findings, cytology, human papillomavirus testing, and colposcopy-directed biopsy is necessary for the correct diagnosis of HSIL. The accuracy rate depends on the TZ and the patient’s age. The examiner’s level of training does not have any substantial influence on the accuracy.

Die Haufigkeit der VaIN ist nicht genau bekannt: Fur Deutschland werden 100–200 Falle pro Jahr geschatzt. Als Risikofaktoren werden HPV-Infektion, Immuninsuffizienz und Nikotinabusus genannt. Als Primarpravention ist ein Effekt von der HPV-Impfung zu erwarten. Fruherkennung ist nur moglich durch positive Zytologien bei unauffalliger oder fehlender Zervix. Therapiegrundlage ist die histologische Sicherung und die Ausbreitungsdiagnostik durch Differenzialkolposkopie. Therapiebedurftig sind die VaIN 2/3. Bei der Therapie kommen sowohl lokal medikamentose Applikationen zum Einsatz als auch operative Verfahren. Die Brachytherapie ist in Deutschland wegen der ausgepragten Nebenwirkungen nicht verbreitet. Als operative Verfahren werden die Laservaporisation und die Exzision mittels Skalpell oder Laserskalpell eingesetzt. Wegen der fehlenden Einsehbarkeit im oberen Scheidendrittel, insbesondere nach Hysterektomie, wird dort die Scheidenkuppelresektion als Vollhautexision oder Skinning-Verfahren empfohlen. Die klinische/zytologische Nachsorge sollte lebenslang erfolgen.

Vaginalkarzinome gehoren zu den seltenen Tumoren (etwa 500 Falle pro Jahr in Deutschland). Risikofaktoren sind die HPV-Infektion, Immundepression, Nikotinabusus und HPV-assoziierte Vorerkrankungen der Cervix uteri und der Vulva. Als teilweise Primarpravention kann die HPV-Impfung gelten. Eine systematische Fruherkennung existiert angesichts der Seltenheit der Erkrankung nicht. Auffallige zytologische Befunde bei fehlender oder unauffalliger Zervix sollten zu einer intensivierten Untersuchung mit Inspektion und Kolposkopie veranlassen. Es handelt sich uberwiegend um Plattenepithelkarzinome. Die definitive Diagnostik erfolgt durch histologische Sicherung. Zum Staging werden erst in fortgeschritteneren Stadien bildgebende Verfahren eingesetzt. Im Stadium I kann eine operative Resektion durchgefuhrt werden, die ubrigen Stadien werden einer Radio(chemo)therapie zugefuhrt. Als Lymphabflussgebiete der Vaginalkarzinome mussen sowohl inguinofemoralen als auch die pelvinen Lymphknoten gelten. Das Sentinel-Verfahren kann zur Beschrankung der Therapieausdehnung eingesetzt werden.

Vulvakarzinome werden immer haufiger. Als Risikofaktoren gelten HPV-Infektion, Lichen sclerosus und Nikotinabusus. Damit wird ein primarer Praventionseffekt durch die HPV-Impfung erwartet. Eine spezifische Fruherkennungsuntersuchung ist nicht etabliert. Die definitive Diagnose wird histologisch gesichert, in fortgeschrittenen Stadien erfolgt ein Staging durch zusatzliche apparative Diagnostik. Eine Metastasierung in die Leistenlymphknoten ist nicht zu erwarten bei Basalzellkarzinomen und verrukosen Karzinomen und bei Karzinomen mit einer Infiltrationstiefe ≤1 mm. Die Therapie erfolgt uberwiegend operativ. Zumeist erfolgt nach weiter lokaler Resektion ein primarer Wundverschluss, nur bei grosen Resektionen sind plastische Rekonstruktionen erforderlich. Bei multifokalen Primartumoren ist eine Vulvektomie indiziert. Das Lymphknoten-Staging wird durch getrennte Leistenschnitte durchgefuhrt (“triple incision”). Die inguinalen und femoralen Lymphknoten mussen entfernt werden (LNE). Die postoperative Morbiditat der Lymphonodektomie ist hoch, das Sentinel-Verfahren verspricht bessere Vertraglichkeit. Dafur bestehen onkologische Risiken, die sich genau beziffern lassen. Prazise Aufklarung und Abwagung sind unabdingbar.

Vulvare intraepitheliale Neoplasien (VIN) sind uberwiegend plattenepithelial und HPV-assoziiert. Zwei Unterformen werden unterschieden: die HPV-assoziierte uVIN und die seltenere HPV-unabhangige dVIN. Neben der HPV-Infektion gelten Immunsuppression und Nikotinabusus sowie ein Lichen sclerosus als Risikofaktoren. Damit bieten sich die HPV-Impfung und das Nichtrauchen zur primaren Pravention an. Therapieresistente Symptome vermeldet die Halfte der Patientinnen. Die Diagnose kann histologisch zumeist an Stanzbiopsaten gestellt werden. Die Behandlung hat die Entfernung der Lasion im Gesunden zum Ziel. Als wesentliche Verfahren gelten die Exzision und die Laserdestruktion. Bei uVIN konnen Immunmodulatoren lokal in speziellen Fallen eingesetzt werden (“off-label use”). Die Rezidivraten liegen bei 25 %, davon sind etwa 3 % invasiv. VIN-Patientinnen sollen nach der Behandlung regelmasig in einer qualifizierten Nachsorge verbleiben, im besten Fall lebenslang. Als Sonderform einer intradermalen potenziellen Praneoplasie gilt der Morbus Paget der Vulva. Die Therapie bestand uber lange Zeit in der chirurgischen Entfernung der Haut. In neuerer Zeit werden die Lasionen – insbesondere bei wiederholten Rezidiven nach operativer Therapie – erfolgreich lokal mit immunmodulatorischen Substanzen behandelt (“off-label use”).

To analyze reoperation rates and perioperative outcomes after long-term follow-up of two surgical approaches in the treatment of endometrial cancer when the standard of care shifts from open surgery to laparoscopy at a university hospital. In this retrospective monocenter study a total of 267 patients with endometrial cancer were included; 107 women underwent laparoscopy and 160 laparotomy. All of the patients received total hysterectomy, bilateral salpingo-oophorectomy, and pelvic and para-aortic lymphadenectomy, depending on individual pathological features (e.g. high risk for positive lymph nodes) and the expertise of the surgeon. Repeat surgery was needed significantly more often in the laparotomy group in comparison with the laparoscopy group (11.9 vs. 0.9 %, respectively; P

HPV (humanes Papillomavirus) ist ein Hauptrisikofaktor fur die Entstehung des Vulva- und Vaginalkarzinoms. Eine Zunahme der HPV-Infektionen konnte mit einer Zunahme beider Karzinomentitaten korrelieren. Eine Impfung gegen HPV ist seit einigen Jahren verfugbar. Ziel der Recherche war es, eine Ubersicht uber die aktuelle Datenlage bezuglich epidemiologischer und atiologischer Faktoren des Vulva- und Vaginalkarzinoms zu prasentieren. Es wurde eine Recherche der vorhandenen Literatur in etablierten medizinischen Datenbanken (Medline, Cochrane Database) sowie ein Review der vorhandenen epidemiologischen und atiologischen Daten durchgefuhrt. Innerhalb der letzten Jahrzehnte kam es zu einer Zunahme der HPV-Infektionen bei jungen Frauen und dadurch zu einer steigenden Inzidenz der HPV-induzierten Karzinome von Vulva und Vagina. Dies betraf die Gesamtpopulation, jedoch insbesondere auch jungere Frauen. Das Wissen um die Epidemiologie und die Atiologie des Vulva- und Vaginalkarzinoms ist nicht nur wichtig fur die Therapieentscheidung und die Therapieart, sondern auch von Bedeutung hinsichtlich des postoperativen Managements der Patientin im Sinne einer Risikostratifizierung. Eine besondere Bedeutung haben v. a. die rezidiv-gefahrdeten Patientinnen mit einem HPV-negativen Vulvakarzinom oder einer differenzierten VIN (d-VIN). Das Wissen um die Zunahme der HPV-Infektionen und die dadurch steigende Inzidenz der HPV-induzierten Vulva- und Vaginalkarzinome sollte aktiv in die Fruherkennung durch eine obligate und genaue Inspektion von Vulva und Vagina mit einbezogen werden. Inwieweit die HPV-Impfung Einfluss auf epidemiologische Grosen wie die Inzidenz und Pravalenz der Vulva- und Vaginalkarzinome nehmen wird bleibt in den kommenden Jahren abzuwarten. Dies ist stark abhangig von der Entwicklung der Durchimpfungsrate der Bevolkerung auch in Deutschland.

5592 Background: Currently, there are two major pathways for tumorigenesis of vulvar squamous cell carcinoma (VSCC) – an HPV-dependent with p16 overexpression as a surrogate for HPV-associated transformation and an HPV-independent route linked to lichen sclerosus, characterized by p53 mutation. A possible correlation of HPV dependency with a favourable prognosis has been proposed. Methods: The AGO CaRE-1 study is a retrospective survey of pts with primary VSCC FIGO stage ≥1B (UICC-TNM version 6) treated at 29 gynecologic cancer centers in Germany 1998-2008 (n = 1,618). For this CaRE-translational sub-study available FFPE tissue was collected centrally (n = 648). A tissue micro array (TMA) was constructed; p16 and p53 expression was determined by immunohistochemistry (IHC). HPV status and subtype were analyzed by PCR. Results: p16 IHC was interpretable in 550 TMA spots and considered positive in 166/550 (30.2%). HPV DNA was detected in 78.4% of the p16+ tumors, with HPV 16 being the most common subtype (88.3%) . Pts with p16+ tumors were younger at diagnosis (63 vs. 70 yrs for p16- tumors; p = 0 < 0.01) and showed lower rates of lymph-node involvement (29.0% vs. 39.7%; p = 0.021). p53 IHC was interpretable in 597 spots, 187/597 (31.3%) were considered positive. Pts with p53+ tumors were older at first diagnosis (71 vs. 66 yrs; p = 0.001 for p53- tumors) and showed lymph-node involvement more often (43.3% vs. 31.1%; p = 0.007). There was a relevant number of tumors with neither p16 nor p53 overexpression (221/535); while co-expression of p53 and p16 was rare (12/535). For survival analyses, three groups were defined: p53+ (n = 163), p16+/p53- (n = 151) and p16-/p53- (n = 221). 2-y-disease-free (DFS) and overall survival (OS) rates were significantly different between the groups: DFS: p53+ 47.0%; p16-/p53- 53% and p16+/p53- 65.5% (p < 0.001); OS: 70.4%, 72.6% and 82.7% (p = 0.003), respectively. Adjustment for age and nodal status showed consistent p16 and p53 effects regarding DFS. Conclusions: p16 overexpression is associated with an improved prognosis in VSCC while p53 positivity is linked to an adverse outcome. Our data provide evidence of a clinically relevant third subgroup of VSCC with a p53-/p16- phenotype showing an intermediate prognosis that needs to be further characterized.

Summary Aims The pathogenesis and classification of multicentric smooth muscle tumours with benign appearance and concurrent/metachronous uterine and peritoneal involvement is controversial and may on occasion be diagnostically challenging. Leiomyomatosis peritonealis disseminata (LPD) is a rare condition affecting women of reproductive age, characterised by the occurrence of multiple small peritoneal smooth muscle nodules with bland histology. Methods We investigated a total of 12 uterine and seven concurrent/metachronous peritoneal smooth muscle nodules with benign appearance from two females for mutations in the mediator complex subunit 12 (MED12), which has recently been identified as the most frequent genetic aberration in uterine leiomyomas. Results The first case harboured different MED12 mutations in the peritoneal nodules. Mutational status of peritoneal nodules was discordant with that of the uterine leiomyomas. The second case displayed the same MED12 mutation in all five peritoneal nodules, but this mutation was not detected in her current uterine leiomyomas. Conclusions Our results suggest that smooth muscle neoplasms with benign appearance of the primary and secondary mullerian system share a similar genetic background of MED12 mutation in combination with oestrogen dependency. Analysis of MED12 mutation status might be a valuable adjunct tool for the future classification of these sometimes diagnostically challenging multicentric tumours.

Purpose: This is an official guideline, published and coordinated by the Arbeitsgemeinschaft Gynakologische Onkologie (AGO, Study Group for Gynecologic Oncology) of the Deutsche Krebsgesellschaft (DKG, German Cancer Society) and the Deutsche Gesellschaft fur Gynakologie und Geburtshilfe (DGGG, German Society for Gynecology and Obstetrics). The number of cases with vulvar cancer is on the rise, but because of the former rarity of this condition and the resulting lack of literature with a high level of evidence, in many areas knowledge of the optimal clinical management still lags behind what would be required. This updated guideline aims to disseminate the most recent recommendations, which are much clearer and more individualized, and is intended to create a basis for the assessment and improvement of quality care in hospitals. Methods: This S2k guideline was drafted by members of the AGO Committee on Vulvar and Vaginal Tumors; it was developed and formally completed in accordance with the structured consensus process of the Association of Scientific Medical Societies in Germany (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften, AWMF). Recommendations: 1. The incidence of disease must be taken into consideration. 2. The diagnostic pathway, which is determined by the initial findings, must be followed. 3. The clinical and therapeutic management of vulvar cancer must be done on an individual basis and depends on the stage of disease. 4. The indications for sentinel lymph node biopsy must be evaluated very carefully. 5. Follow-up and treatment for recurrence must be adapted to the individual case.

Chylous ascites, an accumulation of milky-white lymph fluid in the peritoneal cavity, is a rare complication following retroperitoneal lymphadenectomy. This study evaluated the appearance and management of chylous ascites following lymphadenectomy for gynecological malignancies.A total of 931 patients who underwent lymphadenectomy for gynecological malignancies at Erlangen University Hospital between 2002 and 2013 were reviewed retrospectively.Chylous ascites occurred postoperatively in 28 of the 931 patients (3.0%). All patients with chylous ascites had undergone combined systematic para-aortic and pelvic lymphadenectomy (SAPL). Patients with chylous ascites had a larger mean number of lymph nodes removed (51.9 vs. 40.0, P = 0.002) and the proportion of laparoscopic SAPLs was significantly higher (20/28; 71.4%) in comparison with open surgery (8/28; 28.6%) (P 0.0001). Additional parameters, such as the number of positive lymph nodes, were not significantly associated with the occurrence of chylous ascites. Conservative management was sufficient to resolve chylous ascites in all observed cases, with a mean time to resolution of 8 days.Postoperative chylous ascites was more frequently observed in patients with laparoscopic SAPL in comparison with open SAPL and was strongly associated with a larger mean number of removed lymph nodes. J. Surg. Oncol. 2016;114:613-618. © 2016 Wiley Periodicals, Inc.

Nichtneoplastische, durch HPV bedingte Veranderungen an Vulva und Vagina sind haufig und teilweise mit einer kondylomatosen Lasion assoziiert. Die klassische Einteilung der Prakanzerosen der Vulva in vulvare intraepitheliale Neoplasien (VIN) 1–3 wird zunehmend durch die Definition einer klassischen und differenzierten VIN abgelost. Die Einteilung der Prakanzerosen der Vagina (vaginale intrapepitheliale Neoplasie, VAIN) folgt dem Konzept wie bei der Cervix uteri. Zur Abgrenzung einer kondylomatosen Lasion gegenuber einer Prakanzerose ist der immunhistochemische p16-Nachweis hilfreich. HPV-assoziierte Karzinome der Vulva und Vagina sind das verrukose, das kondylomatose („warty“) Karzinom und das (nicht)verhornende Plattenepithelkarzinom ohne besondere Differenzierung (NOS) sowie in der Vagina das sehr seltene squamotransitionelle Karzinom.

An incidental finding of atypical endometrial hyperplasia (AEH) in women who have undergone laparoscopic supracervical hysterectomy (LASH) is a rare phenomenon, and it is unclear whether laparoscopic extirpation of the cervical stump (LECS) is justified in these patients.LECS due to AEH found incidentally in the morcellated uterus after LASH.A total of 332 women underwent LASH between January 2002 and September 2010. Five of the women (1.5%) underwent secondary LECS procedures due to histological evidence of AEH or focal atypical endometrial cells found incidentally in the morcellated uterus. No atypical endometrial cells were histologically diagnosed in the cervical stump in any of the cases, nor were any endometrial cells found in the cervical stumps in any of the 5 patients. There was no abdominal evidence at all of any disseminated endometrial cells. In all 5 cases, cytological examination of peritoneal fluid confirmed the absence of adenocarcinoma cells.No signs of AEH were found in the removed cervical stumps. However, women should receive counseling regarding the need for secondary LECS to minimize any risks in such cases.