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The 2020 WHO classification is focused on the distinction between HPV-associated and HPV-independent squamous cell carcinoma of the lower female genital organs. Differentiating according to HPV association does not replace the process of grading; however, the WHO classification does not recommend any specific grading system. VIN are also differentiated according to whether they are HPV(p16)-associated. HPV-independent adenocarcinoma (AC) of the cervix uteri has an unfavorable prognosis. Immunohistochemical p16 expression is considered to be a surrogate marker for HPV association. HPV-associated AC of the cervix uteri is determined using the prognostically relevant Silva pattern.

Purpose Epithelial-mesenchymal transition (EMT) is associated with increased metastatic spread and poor prognosis. Data on vulvar carcinoma are limited. Methods Thirty-two cases of squamous cell carcinoma of the vulva (16 with and 16 without inguinal lymph node metastases) and their lymph node deposits were evaluated for immunohistochemical expression of EMT markers (vimentin, cyclin D1, e-cadherin), p16, p53 and Ki-67. Results of EMT-immunostainings were compared to lymph node involvement and expression of p53 and p16. The micro-anatomical staining pattern for EMT markers comparing the tumor center with the front of invasion was analysed in each tumor. Results There was no difference in the expression of EMT markers between node negative and node positive tumors. Staining for vimentin and cyclin D1 was seen within tumor cells at the front of invasion in 100 and 84.4% of the tumors, respectively. The majority of cases (68.7%) showed negative or reduced staining for e-cadherin in this micro-anatomical localization. Tumor cells within the lymph node metastases showed positive staining for e-cadherin in 75% and for cyclin D1 in 49% of the cells but were negative for vimentin in 13 out of 16 cases (81.3%). Tumors with aberrant p53 staining represented a non-significant higher vimentin but significantly higher cyclin D1 expression at the front of invasion than those with p53 wild-type pattern. Conclusion The present study shows no differences in the expression of EMT markers between node positive and node negative vulvar cancers. The evaluation of immunostaining within the micro-anatomical context indicates that an EMT-phenotype is restricted to the tumor cells at the front of invasion. Paired analyses of vulvar carcinomas and their lymph node deposits suggest mesenchymal-epithelial transition (MET) in the metastatic deposits. Immunohistochemical staining results may suggest that EMT is more prevalent in vulvar cancer with aberrant p53 staining.

Purpose Psychological distress affects many cancer patients; however, gynecological cancer patients face unique challenges. We therefore assessed the level of psychological distress and desire for psychosocial support as well as potential determinants of distress levels in 355 gynecological cancer outpatients.Methods Psychological distress was assessed by analyzing data from routine distress screening using the 10-item self-reporting Questionnaire on Stress in Cancer Patients – short form (QSC-R10). A question regarding their desire for psychosocial support was added. First time screenings completed from 11/2013 to 04/2018 were included (N = 355). We investigated prevalences regarding elevated distress and desire for support. Additionally, a multiple linear regression analysis regarding determinants of distress was calculated.Results At the time of data collection, 39.5% showed elevated levels of psychological distress. Overall, 9.9% indicated a desire for support. 7.1% of the patients with little or no distress indicated a desire for support, whereas 18.2% did so of patients with high distress. Younger age, shorter illness duration, a desire for support and progression of disease were significant determinants regarding elevated distress.Conclusion Regarding distress, particular attention needs to be payed to younger cancer patients, those with shorter illness duration or disease progression and patients expressing a subjective need for support. Distressed patients are more likely to express a desire for support; however, some objectively less distressed patients also indicated that desire. Future investigations should explore ways to improve psychosocial care offers for patients in need and focus on the discrepancy between normative and subjective needs for psychosocial support.

Molecular profiling of breast cancer (BC) classifies several intrinsic subtypes based on different patterns of gene expression. Multigene assays estimate the risk of recurrence and help to select high-risk patients for adjuvant chemotherapy. However, these tests are associated with significant costs. Immunohistochemistry (IHC) offers a surrogate classification for molecular subtypes by determining estrogen (ER) and progesterone receptors (PR), human epidermal growth factor (Her2neu), as well as the proliferation marker Ki67. Core needle biopsy (CNB) is well established in BC diagnosis and allows a pre-operative assessment of biomarkers. The aim of this study was to analyze the concordance of these markers between CNB and surgical specimens to assess whether re-testing of the surgical specimen is mandatory. Within a 3-year period, patients with primary BC and paired samples of CNB and surgical specimens were analyzed retrospectively. Concordance rates of ER, PR, Her2neu, Ki67, and the surrogate classification for molecular subtypes were calculated using the Landis and Koch agreement grades. Out of 2254 patients with primary breast cancer, 1307 paired specimens without pre-operative treatment were available for analysis Concordance rates for ER, PR, Her2neu, and Ki67 status showed substantial-to-almost perfect agreement grades (κ = 0.91, 0.75, 0.89, and 0.61, respectively). Though substantial concordance was also found for the subtype classification (κ = 0.70), the molecular subtype changed in 18.5% of patients based on the testing of the surgical specimen, mainly from luminal A-like to luminal B-like. Though the concordance rates for single markers were convincing, a significant proportion of the molecular subtypes differed between CNB and the surgical specimen. Re-testing of PR and Ki67 is mandatory to ensure optimal treatment decisions. Further research is necessary to define safe, efficient, and cost-effective predictive models in adjuvant breast cancer therapy.

Objective POLE-mutant, microsatellite-instable (MSI), p53-mutant and non-specific molecular profile (NSMP) are TCGA-defined molecular subgroups of endometrial cancer (EC). Hypothesizing that morphology and tumor immunology might differ depending on molecular background concerning composition and prognostic impact, we aimed to comprehensively interconnect morphologic, immunologic and molecular data. Methods TCGA-defined molecular groups were determined by immunohistochemistry and sequencing in n = 142 endometrioid EC. WHO-defined histopathological grading was performed. The immunologic microenvironment (iTME) was characterised by the quantification of intraepithelial and stromal populations of tumor-infiltrating lymphocytes (TIL: overall T-cells; T-Killer cells; regulatory T-cells (Treg)). Immunologic parameters were correlated with WHO-grading, TCGA-subgroups and prognosis. Results High density TIL were significantly more frequent in high-grade (G3) compared to low-grade (G1/2) EC in the whole cohort and in the subgroup of POLE-wildtype-/microsatellite-stable-EC. MSI was associated with high-level TIL-infiltration when taking into account the type of mismatch repair defect (MLH1/PMS2; MSH2/MSH6). Prognostic impact of biomarkers depended on molecular subgroups: In p53-mutant EC, Treg were independently prognostic, in NSMP, the unique independently prognostic biomarker was WHO-grading. Conclusions EC morphology and immunology differ depending on genetics. Our study delineated two molecularly distinct subgroups of immunogenic EC characterized by high-density TIL-infiltration: MSI EC and high-grade POLE-wildtype/microsatellite-stable-EC. Prognostic impact of TIL-populations relied on TCGA-subgroups indicating specific roles for TIL depending on molecular background. In NSMP, histopathological grading was the only prognostic biomarker demonstrating the relevance of WHO-grading in an era of molecular subtyping.

Purpose The aim of this multicenter cross-sectional study was to analyze a cohort of breast (BC) and gynecological cancer (GC) patients regarding their interest in, perception of and demand for integrative therapeutic health approaches. Methods BC and GC patients were surveyed at their first integrative clinic visit using validated standardized questionnaires. Treatment goals and potential differences between the two groups were evaluated. Results 340 patients (272 BC, 68 GC) participated in the study. The overall interest in IM was 95.3% and correlated with older age, recent chemotherapy, and higher education. A total of 89.4% were using integrative methods at the time of enrolment, primarily exercise therapy (57.5%), and vitamin supplementation (51.4%). The major short-term goal of the BC patients was a side-effects reduction of conventional therapy (70.4%); the major long-term goal was the delay of a potential tumor progression (69.3%). In the GC group, major short-term and long-term goals were slowing tumor progression (73.1% and 79.1%) and prolonging survival (70.1% and 80.6%). GC patients were significantly more impaired by the side-effects of conventional treatment than BC patients [pain (p = 0.006), obstipation ( Conclusion Our data demonstrate a high overall interest in and use of IM in BC and GC patients. This supports the need for specialized IM counseling and the implementation of integrative treatments into conventional oncological treatment regimes in both patient groups. Primary tumor site, cancer diagnosis, treatment phase, and side effects had a relevant impact on the demand for IM in our study population.

Purpose TP53germline (g) mutations, associated with the Li-Fraumeni syndrome (LFS), have rarely been reported in the context of hereditary breast and ovarian cancer (HBOC). The prevalence and cancer risks in this target group are unknown and counseling remains challenging. Notably an extensive high-risk surveillance program is implemented, which evokes substantial psychological discomfort. Emphasizing the lack of consensus about clinical implications, we aim to further characterize TP53g mutations in HBOC families. Methods Next-generation sequencing was conducted on 1876 breast cancer (BC) patients who fulfilled the inclusion criteria for HBOC. Results (Likely) pathogenic variants in TP53 gene were present in 0.6% of the BC cohort with higher occurrence in early onset BC TP53g variant (c.542G > A; c.375G > A) did not comply with classic LFS/Chompret criteria. Albeit located in the DNA-binding domain of the p53-protein and therefore revealing no difference to LFS-related variants, they only displayed a medium transactivity reduction constituting a retainment of wildtype-like anti-proliferative functionality. Conclusion Among our cohort of HBOC families, we were able to describe a clinical subgroup, which is distinct from the classic LFS-families. Strikingly, two families did not adhere to the LFS criteria, and functional analysis revealed a reduced impact on TP53 activity, which may suit to the attenuated phenotype. This is an approach that could be useful in developing individualized screening efforts for TP53g mutation carrier in HBOC families. Due to the low incidence, national/international cooperation is necessary to further explore clinical implications. This might allow providing directions for clinical recommendations in the future.

Purpose The aim of this study was to investigate whether bone mineral density (BMD) as measured in planning computed tomographies (CTs) by a new method is a risk factor for pelvic insufficiency fractures (PIF) after radio(chemo)therapy (R(C)T) for cervical cancer. Methods 62 patients with cervical cancer who received definitive or adjuvant radio(chemo)therapy between 2013 and 2017 were reviewed. The PIF were detected on follow-up magntic resonance imaging (MRI). The MRI of the PIF patients was registered to the planning CT and the PIF contoured. On the contralateral side of the fracture, a mirrored structure of the fracture was generated (mPIF). For the whole sacral bone, three lumbar vertebrae, the first and second sacral vertebrae, and the PIF, we analyzed the BMD (mg/cm3), V50Gy, Dmean, and Dmax. Results Out of 62 patients, 6 (9.7%) had a fracture. Two out of the 6 patients had a bilateral fracture with only one of them being symptomatic. PIF patients showed a significantly lower BMD in the sacral and the lumbar vertebrae (p p Conclusion The dose does not seem to have a relevant impact on the incidence of PIF in our patients. One of the predisposing factors for developing PIF after radiotherapy seems to be the low BMD. We presented an easy method to assess the BMD in planning CTs.

Accurate disease classification is fundamental for the selection of the treatment approach, prognostication, selection of clinical trials and for research purposes in routine clinical practice. Extrauterine high-grade serous carcinoma (HG-SC) may arise from the ovary, the fallopian tube and rarely from the peritoneal surface epithelium. Regardless of its origin, the vast majority of patients with HG-SC share clinical symptoms, present with advanced stage disease and suffer from a poor prognosis. Recent data suggest that there is an increasing incidence of HG-SC arising from the fallopian tube. Data from the Clinical Cancer Registry of Leipzig of surgically treated non-uterine pelvic carcinomas were analyzed regarding their sites of origin. Depending on the histology, cases were separated into high-grade serous and non-high-grade serous tumors. Based on different approaches in the assessment of the site of origin, three distinct time periods were defined. The frequency of the specific sites of origin was compared to the different time periods and histologic subtypes. The majority of cases (57.9%; 279/482) were high-grade serous carcinomas, 42.1% of the cases presented with endometrioid, clear cell or mucinous histology. Overall, a 1.7-fold decrease of carcinomas with ovarian origin, paralleled by a 10.3-fold increase of tubal carcinomas was noted between 2000 and 2019. Based on the histopathological subtype, there was a 2.1-fold decrease of ovarian and a 7.1-fold increase of tubal carcinomas in patients with HG-SC. In non-high-grade serous tumors, the frequency of the different sites of origin did not change. 83.7% of tumors with non-high-grade serous histology originated from the ovary, whereas 86.8% of the carcinomas with tubal origin were of high-grade serous histology. The present and published data of non-uterine pelvic cancers may suggest an increase of tubal and decrease of ovarian carcinomas. However, there is rising morphologic and molecular evidence that non-uterine HG-SC actually arise from the fallopian tubes via its precursor STIC instead of from the ovary. This evidence has had an impact on the handling and reporting of non-uterine surgical specimens and its definition of the site assessment. In conclusion, the increasing frequency of tubal carcinomas and the associated decrease in ovarian cancer appears to be due to the reclassification of tumors previously classified as ovarian and greater emphasis on examining the resection specimens of non-uterine pelvic carcinomas.

BACKGROUND Adenoid cystic carcinomas of Bartholin's gland are rare among gynecological malignancies, accounting for 0.1% to 7% of vulvar carcinomas and 0.001% of all female genital tract malignancies. There are no specific guidelines regarding treatment recommendations; therefore, they are commonly treated like vulvar cancer. CASE REPORT We present the case of a 42-year-old premenopausal woman with an adenoid cystic carcinoma of Bartholin's gland diagnosed upon biopsy of a palpable, predominantly vaginally located mass causing foreign-body sensation, vaginal pain, and extreme dyspareunia. The adenoid cystic carcinoma of Bartholin's gland was treated by radical resection in an extensive interdisciplinary surgical approach including bilateral inguinal lymph node dissection, partial posterior colpectomy, amputation of the rectum, and creation of a descendostomy, as well as reconstruction of the vagina and defect coverage using flap plastic. CONCLUSIONS With the presentation of this case, we propose a possible therapeutic approach to adenoid cystic carcinomas of Bartholin's gland with emphasis on surgical management. Especially in young patients, we recommend primary radical surgery with the objective to obtain negative resection margins. However, additional data on the adenoid cystic carcinoma of Bartholin's gland is needed to better understand its biological behavior and thus optimize and standardize treatment. The role of systematic inguinal-femoral lymphadenectomy and adjuvant and neoadjuvant treatment modalities need further evaluation.

Perioperative antibiotic prophylaxis is an established concept to reduce the risk of surgical-site infections; however, the optimal treatment duration in prosthetic breast reconstruction is still controversial. This study evaluated a potential association between the perioperative antibiotic prophylaxis duration (≤24 hours versus24 hours) and incidence of postoperative surgical-site infections in immediate implant-based breast reconstruction in breast cancer patients.A descriptive, retrospective analysis of surgical-site infections after immediate implant-based breast reconstruction in breast cancer patients between January of 2011 and December of 2018 was performed. The incidence of postoperative surgical-site infections in patients with more than 24 hours of perioperative antibiotic prophylaxis was compared to patients treated for 24 hours or less.A total of 240 patients who met criteria were included. There were no relevant epidemiologic, clinical, or histopathologic differences between groups. Surgical-site infections as defined by the Centers for Disease Control and Prevention criteria occurred in 25.8 percent. A risk factor-adjusted analysis by a prespecified multiple logistic regression model showed that 24 hours or less of perioperative antibiotic prophylaxis was not inferior to treatment for more than 24 hours. The upper limit of the one-sided 95 percent confidence interval of the risk difference was 9.4 percent (below the prespecified noninferiority margin of 10 percent leading to statistical significance). Risk factors for a surgical-site infection included obesity and postoperative wound complications.The study found no association between short-course perioperative antibiotic prophylaxis (≤24 hours) and an increased rate of postoperative surgical-site infection. This is of high clinical relevance because short-course treatment can help reduce side effects and the emergence of antimicrobial resistance and prevent surgical-site infections as effectively as a prolonged perioperative antibiotic prophylaxis course.Therapeutic, III.

Ziel dieses Beitrags ist es, einen Uberblick uber neue Techniken der Strahlentherapie in der gynakologischen Onkologie zu geben. Vorgestellt und erlautert werden die technischen und klinischen Aspekte der intensitatsmodulierten Strahlentherapie (IMRT) und der helikalen Tomotherapie, der volumetrisch modulierten Strahlentherapie und der atemgetriggerten Strahlentherapie, insbesondere die Strahlentherapie in tiefer Inspiration („deep inspiration breath hold“, DIBH). Weiterhin werden Hypofraktionierung und stereotaktische Strahlentherapie (Radiochirurgie, stereotaktisch fraktionierte Strahlentherapie und stereotaktische Korperstrahlentherapie) erklart. IMRT gilt als Standardstrahlentherapie fur gynakologische Krebserkrankungen im Becken. Das DEGRO(Deutsche Gesellschaft fur Radioonkologie)-Brustkrebs-Expertengremium empfiehlt DIBH als die beste Technik zur Herzschonung bei Brustkrebspatientinnen.

Endometrial mesonephric-like adenocarcinoma (ML-AC) represents a recently recognized subtype of endometrial adenocarcinoma (AC) associated with a subtle immunophenotype with a characteristic KRAS-mutation. Detailed clinico-pathologic analyses and prognostic data on ML-AC are limited. We report a series of four cases with histopathological, immunohistochemical, and molecular analyses. These cases as well as the data of previously published cases were reviewed for clinico-pathologic variables and clinical follow-up information. Forty cases of ML-AC were identified. ML-AC represents about 1% of all endometrial carcinomas. Similar to other types of endometrial AC, vaginal bleeding was the leading presenting symptom, and the mean age was 60.0 years (range 31–91). More than a half of the patients presented with locally advanced disease (≥ FIGO stage II) at time of diagnosis, developed a recurrence or died of the disease within a mean follow-up period of 24.7 months (range 3–144.5 months). The most common site of distant disease was pulmonary involvement. Microscopically, ML-ACs present with mixed morphology and show a co-expression of so-called mesonephric and Mullerian markers, suggesting a Mullerian origin of the tumors. Immunostaining for PD-L1 was negative in all tested cases, using different antibodies against PD-L1. Retained staining for mismatch repair proteins on immunohistochemistry and a POLE-mutation suggest a copy number low phenotype within the molecular classification of endometrial carcinomas. Almost all cases showed a KRAS-mutation at codon 12 (mostly G12V). Uterine ML-AC represents a distinct subtype of invasive endometrial AC, associated with KRAS-mutations and characteristic immunohistochemical findings. Clinically, ML-AC may show an aggressive behavior with a high rate of recurrent disease and a substantial risk for distant metastatic disease, especially to the lungs.

Phase-rectified signal averaging method (PRSA) represents an analysis method which applied on fetal cardiotocography (CTG) allows the quantification of the speed of fetal heart rate changes. By calculating the average deceleration capacity (ADC) an assessment of the fetal autonomic nervous system (ANS) is possible. The objective of this study was to test its ability to predict perinatal acidosis. A case–control study was performed at a University Hospital in Munich. All intrapartum CTG heart rate tracings saved during a 7-year period were considered for analysis. All neonates born with an umbilical arterial blood pH ≤ 7.10 were considered as cases. Controls were defined as healthy fetuses born with a pH ≥ 7.25. The main matching criteria were gestational age at delivery, parity, birth mode, and birth weight percentile. Exclusion criteria were a planned caesarean section, fetal malformations, and multiple pregnancies. ADC and STV were then calculated during the last 60, the last 45, and the last 30 min intervals prior to delivery. Of all stored birth CTG recordings, 227 cases met the inclusion criteria and were studied. ADC was significantly higher in fetuses born with acidemia (4.85 bpm ± 3.0) compared to controls (3.36 bpm ± 2.2). The area under ROC curve was 0.659 (95% CI 0.608–0.710) for ADC and 0.566 (0.512–0.620) for STV (p = 0.013). This study confirms that the assessment of ADC using PRSA represents a good additional tool for the prediction of acute fetal acidosis during delivery.

Background: Complementary and alternative medicine (CAM) use is common among cancer patients. Data indicated that CAM use correlates with younger age, higher education levels, higher income, and less physician consultations. However, non-CAM use and predictors for non-CAM use are less clear among breast and gynecological cancer patients. Objectives: The purpose of this study was to determine the prevalence of non-CAM use and to investigate factors that might influence non-CAM use. Methods: The survey was conducted in breast cancer patients from January to May 2013 and in gynecological cancer patients from January to May 2014 with 2 pseudoanonymous questionnaires: one for CAM users (109 questions) and one for non-CAM users (85 questions). The survey was conducted via a telephone interview with 333 patients. Eligible participants were women with breast cancer (n = 285) and gynecological cancer (n = 291) who had undergone surgery at the Department of Gynecology and Obstetrics at the Technical University Munich, Germany, in the years 2012 (breast cancer) and 2011–2013 (gynecological cancer). Descriptive statistics were generated to determine patterns of non-CAM use. Univariable analysis was used to detect patient characteristics associated with noninterest in the different CAM therapies. Results: A total of 333 of 576 patients participated in the survey (58%). Fifty-eight percent (n = 192/333) were diagnosed with breast cancer and 42% (n = 141/333) with gynecological cancer. The overall prevalence of non-CAM use was 42% (n = 139/333). Eighty-one percent (n = 112/139) of the non-CAM users stated to have received no recommendation for CAM use, although 53% (n = 73/139) would have liked to receive information from their physician. As reasons for the nonuse of CAM therapies, 76% (n = 106/139) nonusers declared that they did not believe CAM use was necessary since the conventional therapy was considered sufficient, 44% (n = 61/139) reported a lack of information, 31% (n = 43/139) a fear of fraud, and 22% (n = 31/139) a fear of interactions and side effects of CAM. Sixty-eight percent (n = 95/139) of the patients stated that they would resort to CAM if the disease progressed while only 27% (n = 37/139) would still not use any CAM with progression of disease. Five percent (7/139) did not give any information regarding possible future CAM use with disease progression. Seventy-three percent (n = 102/139) would both welcome more physicians with qualifications in complementary medicine and supported an integration of CAM into our health care system. Furthermore, statistically significant correlations between patients’ sociodemographic characteristics and their nonuse of complementary therapies were identified. Conclusions: Our data demonstrate a high overall interest in CAM even in non-CAM users. Health care professionals should be aware of this in order to be able to better address patients’ needs. It is necessary to explore the use of CAM with cancer patients, educate them about potentially beneficial therapies even in the light of the limited available evidence, and work towards an integrated model of health care. Therefore, we implemented a counseling service as an outpatient program (ZIGG) for integrative medicine concepts and evidence-based complementary treatments to discuss integrative health approaches proactively with cancer patients in our cancer center in 2013.

Zahlreiche therapie- und prognoseorientierte Studien zum Zervixkarzinom haben eine Uberarbeitung der FIGO-Klassifikation erforderlich gemacht. Das mikroinvasive Karzinom wird allein durch die Tiefe der Stromainfiltration definiert, die flachige (horizontale) Ausdehnung ist nunmehr irrelevant. Makroinvasive Karzinome, die auf die Cervix uteri begrenzt sind, werden anhand der Tumorgrose subkategorisiert in: FIGO IB1/T1b1 – zervikale Stromainvasion >5,0 mm und ≤2 cm maximale Tumorgrose, FIGO IB2/T1b2 – Tumorgrose >2 cm und ≤4 cm, FIGO IB3/T1b3 – Tumorgrose >4 cm. Sowohl die pelvinen als auch die paraaortalen Lymphknoten werden als regionare Lymphknoten definiert. Der Befall pelviner Lymphknoten wird als FIGO IIIC1/pN1a und eine Metastasierung in paraaortale Lymphknoten mit und ohne Beteiligung pelviner Lymphknoten als FIGO IIIC2/pN1b klassifiziert. Der Nachweis einer Corpusinfiltration und eine adnexale/ovarielle Metastasierung sind nicht stagingrelevant.

Purpose PET-CT has recently been included in the NCCN staging recommendations for cervical cancer stages II–IV and is already routinely applied to radiotherapy planning for other malignancies, as it is expected to provide higher accuracy for the detection of areas with tumor cell spread. In this study, we report on our first experiences of PET-based radiotherapy planning for cervical cancer. Methods 19 patients with cervical cancer that underwent pre-therapeutic PET imaging treated at our institution between January 2016 and April 2019 were included in the study. Information on the primary tumor, lymph node involvement, metastatic spread and changes in the radiotherapy procedure based on the PET findings are described. Results A previously unknown primary tumor extension that was detected by PET imaging in one patient. In patients who underwent a PET before the systematic pelvic and paraaortic lymphonodectomy (n = 2), PET was false negative for pelvic lymph node metastases in 50%. In patients who underwent a PET after the systematic LNE (n = 13), additional lymph node metastases were detected in seven patients (53.80%). Distant metastases were suspected in three patients (15.7%) based on PET imaging. The suspicion was confirmed in one patient (peritoneal spread) and excluded in two patients (supra-diaphragmatic lymph nodes). In 13 patients (68.4%), RT procedures were altered due to findings in PET imaging. Conclusion PET-based radiochemotherapy planning may improve control rates by identifying areas of tumor cell spread eligible for dose escalation. False positivity, however, should be excluded in patients with findings that lead to major modifications of the therapeutic strategy.

Introduction Many gynaecological cancer patients suffer from psychosocial distress. The goal of this evaluation was to assess the level of distress and desire for psychosocial support in this group of patients based on the psychosocial distress screening at the Department of Gynaecology and Obstetrics, University Hospital of the Technical University of Munich, Germany. Methodology As part of the self-reporting 10-item Questionnaire on Stress in Cancer Patients-Revised (QSC-R10), which has been validated for the evaluation of psychosocial distress in oncological patients (Book et al., 2011), patients state whether or not and, if applicable, how severely each item applies to them. Answers range from 0 („the problem does not apply to me’) to 5 („the problem applies to me and is a very serious problem’) and refer to potential disease-related situations. A validated cut-off score >14 indicates significant psychosocial distress. A question regarding the patient’s desire for psychological support was added to the screening. Psychosocial support was actively offered in case of significant distress or patient´s desire. Between November 2013 and April 2018, 860 questionnaires were filled in by 325 outpatients at the Department of Gynaecology and Obstetrics and evaluated for the present study. Results On average, each patient filled in 2.65 questionnaires. The mean patient age on the date of the first filled questionnaire was 60 years. The most frequent cancer diagnosis was ovarian cancer (43%), followed by endometrial cancer (17%). In 10% of questionnaires, patients expressed a desire for psychosocial support, in 74% declined such support and 16% of the surveys showed no answer. 31% of all questionnaires indicated clinically relevant psychosocial distress, 62% remained under the cut-off and 6% were not evaluable due to missing information. Of those exceeding the cut-off, 14% desired psychosocial support, 73% declined support and in 13% of the questionnaires, patients did not comment on their desire. Conclusion 31% of questionnaires showed clinically relevant psychosocial distress of patients. However, only in 14% of these cases patients showed desire for psychosocial support. This discrepancy is a common phenomenon described in the literature. Further research concerning potential causes and factors associated with high distress-levels will be necessary. For this analysis, the development of the score and the desire for support over time in patients who received several questionnaires has not been taken into account yet. Further investigations in this regard should be considered in order to facilitate needs-based support over time of treatment and disease. Disclosures Authors did not state any conflicts of interest within the last three years.

For some gynecologic malignancies, there are disagreements between the most recent WHO and TNM classifications and the recommendations of the International Collaboration of Cancer Reporting. These discrepancies are addressed and discussed in this paper. The WHO definition for primary vaginal cancer does not match the TNM definition. The paper also discusses and provides TNM classifications for rare gynecologic tumors like primary malignant vulvar melanomas, sarcomas of the vulva, perivascular epithelioid cell tumor (PECom) of the uterus, undifferentiated uterine sarcomas, and extra-intestinal gastrointestinal stromal tumors (GIST), and provides some recommendations for the reporting and categorization of regional lymph nodes in nonuterine serous pelvic cancer.

Tumor grade is one of the more controversial factors with limited prognostic information in squamous cell carcinomas (SCC) of the uterine cervix. Histologic slides of 233 surgically treated cervical SCC (FIGO IB1) were re-examined regarding the prognostic impact of the WHO-based grading system, using the different degree of keratinization, categorizing the tumors in G1, G2 and G3 (conventional tumor grade). 45.1% presented with well-differentiated tumors (G1), 29.2% with moderate (G2) and 25.8% with poor differentiation (G3). Tumor grade significantly correlated with decreased recurrence-free and overall survival. However, detailed analyses between G1- and G2-tumors failed to show any correlation with either recurrence-free or overall survival. G1- and G2-tumors were therefore merged into low-grade tumors and were compared to the high-grade group (G3-tumors). This binary conventional grading system showed an improved 5-years recurrence-free (low-grade: 90.2% vs. high-grade: 71.6%; p = 0.001) and overall survival rates (low-grade: 89.9% vs. high-grade: 71.1%; p = 0.001) for low-grade tumors. On multivariate analysis adjusted for lymph node metastasis, high-grade tumors represented a hazard ratio of 2.4 (95% CI 1.3–4.7) for reduced recurrence-free and 2.4 (95% CI 1.2–4.6) for overall survival. High-grade tumors showed a significantly higher risk for pelvic lymph node involvement [OR 2.7 (95% CI 1.4–5.5); p = 0.003]. The traditional three-tiered grading system failed to predict pelvic lymph node metastases. A binary grading model for the conventional tumor grade (based on the degree of keratinization) in SCC of the uterine cervix may allow a better prognostic discrimination than the traditionally used three-tiered system.

Ovarian carcinomas (OCX) have traditionally been thought to arise from the ovarian surface epithelium. However, recent (immuno-) histopathological and molecular analyses suggest that OCX consist of morphological subtypes with different epidemiologic features and a varying prognosis.The data of 482 OCX from the Clinical Cancer Registry of Leipzig who were surgically treated between 2000 and 2019 and were evaluated regarding incidence, clinico-pathologic characteristics and prognostic factors. Cases were separated into high-grade and non-high-grade serous tumors. Both groups were analyzed regarding the tumor stage, lymph node involvement, site of origin and prognosis.The overall incidence for OCX was 17.9. The most common histological subtype was high-grade serous OCX (57.9%; 279/482). Patients with high-grade were significantly older than those with a non-high-grade serous OCX (63.9 versus 58.5 years; p 0.001), more frequently diagnosed at an advanced stagepT3 (78.5% (219/279) versus 42.8% (87/203); p 0.001) and showed a 2.4-fold higher frequency of lymph node metastases (53.4% vs. 21.2%; p 0.02) with a 4.6-fold higher rate of 1 cm metastatic deposits (pN1b) within the lymph nodes (14.8% vs. 4.6%; p 0.02). Irrespective of tumor stage and morphological subtype, the 1- and 5-year overall survival (OAS) was 72.9% and 40.8%, respectively. Patients with high-grade serous OCX showed a shorter 5-year OAS compared to non-high-grade serous OCX (34.1% vs. 57.0%; p 0.001). This association was reproducible in patients with an advanced tumor stage irrespective of the histopathologic tumor type serous OCX (pT3: 32.4% vs. pT1: 75.1%; p 0.001) as well as within high-grade (pT3: 28.7% vs. pT1: 55.5%; p = 0.003) and non-high-grade serous OCX (pT3: 43.0% vs. 80.0%; p 0.001). There were no differences in OAS depending on the site of origin (fallopian tube, ovary, peritoneum) within the two histologic subgroups.OCX cases from a single institution with uniform surgical treatment and a standardized histopathological workup were evaluated. The poor prognostic outcome of patients with high-grade serous compared non-high-grade serous OCX as well as an advanced stage of the disease was confirmed. This study demonstrates for the first time that the histopathological distinction into high-grade serous and non-high-grade serous tumors may be much more prognostically relevant than the site of origin.

Die extrauterine Graviditat (EUG) geht mit einer klinisch relevanten Morbiditat und Mortalitat im ersten Trimester einher. In der Majoritat ist die EUG im ampullaren Teil der Tube lokalisiert. Die Haufigkeit steigt im Rahmen einer kunstlichen Befruchtung, bei einer Erstschwangerschaft in hoherem Alter und bei vorherigen Adnexeingriffen. Es soll ein Uberblick uber die klinischen Aspekte und die diagnostischen Herausforderungen einer EUG fur den Pathologen gegeben werden. Ein Review der relevanten Literatur wurde durchgefuhrt. Der Nachweis von Gestationsgewebe ist von hochster Wichtigkeit bei der pathologisch-anatomischen Beurteilung einer EUG. Die Aufarbeitung muss so erfolgen, dass der Nachweis schwangerschaftsspezifischen Gewebes gelingt. Eine vollstandige Bewertung der Probe nach einer vermuteten tubularen Ablosung oder nach „milking out“ der Ektopie sollte durchgefuhrt werden. Anormale Plazentationen (Schwangerschaft ohne Embryonenentwicklung, embryonale molare Schwangerschaft) wie auch gestationelle Tophoblasterkrankungen (GTD, z. B. teilweise/vollstandige molare Schwangerschaft, Chorionkarzinom) konnen im Rahmen einer EUG auftreten. Vorsicht ist geboten bei der Abgrenzung einer Trophoblasthyperplasie zu einer tubularen Mikroumgebung einer GTD. Um eine molare Schwangerschaft auszuschliesen, kann p57-Immunhistochemie helfen. Nur 50 % der EUG sind mit tubularen Pathologien assoziiert (z. B. Entzundungen, tubulare Verwachsungen). Chorionzotten und Trophoblastepithelien konnen nach vorhergehender Methotrexatbehandlung regressiven Veranderungen unterworfen sein. Selten kann Immunhistochemie mit GATA-3, p63, HCG, PAX-8 und WT-1 zur Differenzialdiagnose eines Trophoblastenepithels angewendet werden. Die EUG ist mit einer relevanten Morbiditat und Mortalitat assoziiert. Eine grundliche Analyse der Gewebeproben kann bei der Behandlung und Verlaufskontrolle helfen.

Synchronous endometrial and ovarian malignancies occur in 5% of women presenting with endometrial cancer and 10% of patients presenting with ovarian malignancy. When a high-grade serous carcinoma concurrently involves both ovary and endometrium, pathological determination of whether they are synchronous primaries or metastatic tumors from one primary site can be challenging. MicroRNAs (miRNA) are 22-nucleotide noncoding RNAs that are aberrantly expressed in cancer cells and may inherit their cellular lineage characteristics. We explored possible differential miRNA signatures that may separate high-grade ovarian serous carcinoma from primary endometrial serous carcinoma. Forty-seven samples of histologically pure high-grade serous carcinoma of both uterine (16 case) and ovarian primaries (31 cases) were included. Expression of 384 mature miRNAs was analyzed using ABI TaqMan Low-Density Arrays technology. A random forest model was used to identify miRNAs that together could differentiate between uterine and ovarian serous carcinomas. Among 150 miRNAs detectable at various levels in the study cases, a panel of 11-miRNA signatures was identified to significantly discriminate between ovarian and uterine serous carcinoma (P < .05). A nested cross-validated convergent forest plot using 6 of the 11 miRNA signature was eventually established to classify the tumors with 91.5% accuracy. In conclusion, we have characterized a miRNA signature panel in this exploratory study that shows significant discriminatory power in separating primary ovarian high-grade serous carcinoma from its endometrial counterpart.

The handling and reporting of resected lymph nodes in gynecologic cancer follows the recommendations of the German national guidelines and the recommendations of the International Collaboration of Cancer Reporting (ICCR) and the International Society of Gynecologic Pathologists (ISGyP). The definitions of micrometastases and isolated tumor cells are in accordance with the definition of the UICC (Union Internationale Contre le Cancer) and TNM system. Both findings must be reported as part of the pathology report and final tumor classification. It is mandatory to examine all excised lymph nodes with complete processing of all nodes up to 0.3 cm and slicing of all larger nodes in 0.2-cm wide intervals with complete processing of all lamellae. The amount of the resected lymph nodes in correlation to positive nodes, the metric dimension of the largest lymph node metastasis per lymph node region, and the presence of extracapsular extension of the lymph node deposits must be part of the pathology report. The handling and cutting of sentinel lymph nodes are similar to nonsentinel nodes. Within frozen section analyses and final processing from paraffin-embedded sentinel nodes, all nodes should be examined by three-step sections with an interval of about 200 µm. In cases of negative sentinel nodes on HE staining, immunohistochemical ultrastaging should be performed.Die Aufarbeitung von Lymphonodektomiepräparaten gynäkologischer Malignome orientiert sich an den nationalen AWMF-Leitlinien und internationalen Empfehlungen. Die Definition von Mikrometastasen und isolierten Tumorzellen entspricht den Festlegungen der UICC(Union Internationale Contre le Cancer)/TNM(TNM-Klassifikation maligner Tumoren). Deren Nachweis soll im Befundbericht erwähnt werden sowie in die Tumorklassifikation einfließen. Alle übersandten Lymphknoten (LK) sollen untersucht werden mit vollständiger Einbettung aller LK bis 0,3 cm und Lamellierung aller größeren Lymphknoten parallel zu ihrer kurzen Achse in ca. 0,2 cm dicken Scheiben. Bestandteile des histologischen Befundberichtes sind: Zahl der befallenen LK im Verhältnis zur Zahl der entfernten/untersuchten LK entsprechend der Entnahmelokalisationen, metrische Ausdehnung der größten LK-Metastase, Fehlen/Nachweis einer extrakapsulären Ausbreitung. Zuschnitt und Einbettung von Sentinel-LK mit oder ohne Schnellschnittuntersuchung erfolgt in Analogie zu Nicht-Sentinel-LK mit Anfertigung von ca. 3 HE-gefärbten Stufenschnitten in einem Abstand von ca. 200 µm sowohl vom Gefrier- als auch Paraffinblock. Stellen sich die Sentinel-LK in der HE-Färbung negativ dar, soll ein immunhistochemisches Ultrastaging erfolgen.

Cervical cancer metastases to the ovary may occur with advanced tumor stage, deep cervical stromal involvement and corpus involvement. Endocervical adenocarcinoma in situ (AIS) with ovarian involvement is exceptionally rare with about twelve reported cases. Here we present a case of endocervical AIS with ovarian and pulmonary involvement 39 months after the initial diagnosis. The characteristics of that case were compared and summarized with the eleven previously published cases. The patients’ age ranged between 30 and 40 years (median 37.4 years). The time interval between the diagnosis of AIS and ovarian involvement was 26.7 months (range 2–84 months). Majority of the patients are alive without evidence of disease after a median time of 63.4 months (range 9–156 months). All reported cases were positive for high-risk HPV which was associated with strong p16 expression on immunohistochemistry. The ovarian involvement by endocervical AIS suggests the concept of a transtubal spread of the neoplastic cervical cells with or without previous colonization within the endometrium without evidence of invasive growth, suggesting a seed and soil spread of the disease. In cases with ovarian involvement by the AIS and without additional extragenital spread, the prognosis may be favorable.

Die WHO-Klassifikation von 2014 nimmt eine Unterteilung in verschiedene Subtypen des muzinosen Adenokarzinoms vor. Kurzlich beschrieben wurde der gastrische Subtyp, der keine Assoziation zu einer High-risk-HPV-Infektion (humane Papillomviren) zeigt, prognostisch ungunstig ist sowie bevorzugt bei Asiatinnen auftritt und beim Peutz-Jeghers-Syndrom vorkommen kann. Mittelfristig ist zu erwarten, dass sich beim Adenokarzinom der Cervix uteri ein auf verschiedenen Invasionsmustern beruhendes Grading etabliert. Die tiefe Stromainfiltration makroinvasiver Karzinome ist definiert als eine Infiltration von >66 % des zervikalen Stromas. Zukunftig konnte eine maximale Tumorgrose von 2 cm ein Parameter zur Planung einer eingeschrankt-radikalen Operation sein. Parameter des histopathologischen Befundberichts, die relevant fur die Prognoseabschatzung und Auswahl der adjuvanten Therapie sind und als Qualitatsindikatoren im Rahmen von Zertifizierungen dienen, werden beschrieben. Der histologische Typ Adenokarzinom hat fur sich allein genommen keine pradiktive bzw. prognostische Bedeutung bei Patientinnen mit primar operativer Therapie, einer neoadjuvanten Chemotherapie, einer kombinierten Radiochemotherapie bzw. dem Einsatz von Angiogeneseinhibitoren. Molekulare Parameter und Biomarker besitzen derzeit keine Relevanz.

Die Mehrzahl der Prakanzerosen (intraepitheliale Neoplasien, IN) des Plattenepithels des unteren weiblichen Genitaltrakts beruht auf einer HPV-Infektion (humane Papillomviren). Diese fuhrt zum Auftreten zellularer Atypien mit der Folge eines gestorten geweblichen Aufbaus. In Abhangigkeit von ihrer Pathogenese werden bei den vulvaren intraepithelialen Neoplasien (VIN) die HPV-high-risk-assoziierte klassische VIN („usual“, u‑VIN) und die mit einem Lichen sclerosus assoziierte differenzierte VIN („differentiated“, d‑VIN) mit p53-Alteration unterschieden. In der aktuellen WHO-Klassifikation wird fur die plattenepithelialen Prakanzerosen des unteren weiblichen Genitaltrakts ein neues System zur Graduierung vorgeschlagen mit Unterteilung in L‑SIL („low-grade squamous intraepithelial lesions“; Kondylome/HPV-assoziierte Veranderungen plus VIN 1, vaginale intraepitheliale Neoplasie 1 [VaIN 1] bzw. zervikale intraepitheliale Neoplasie 1 [CIN 1]) und H‑SIL („high-grade squamous intraepithelial lesions“; VIN 2 und 3, VAIN 2 und 3 bzw. CIN 2 und 3). Bei der Unterscheidung kann die p16-Immunhistochemie hilfreich sein. Diese binare Einteilung lauft jedoch der zytologischen Nomenklatur in Deutschland (Munchner Nomenklatur III) zuwider, die zur Vermeidung einer Ubertherapie von Patientinnen mit einer masiggradigen intraepithelialen Neoplasie eine Unterteilung in 3 Dysplasiegrade vornimmt. Die einzelnen Nomenklaturen werden einander gegenuber gestellt. Es wird empfohlen, zusatzlich zur SIL-Klassifikation der WHO den Grad der jeweiligen Prakanzerosen anzugeben.

Histopathological assessment of the tumor grade and cell type is central to the management and prognosis of various gynecological malignancies. Conventional grading systems for squamous carcinomas and adenocarcinomas of the vulva, vagina and cervix are poorly defined. For endometrioid tumors of the female genital tract as well as for mucinous endometrial, ovarian and seromucinous ovarian carcinomas, the 3-tiered FIGO grading system is recommended. For uterine neuroendocrine tumors the grading system of the gastrointestinal counterparts has been adopted. Uterine leiomyosarcomas are not graded. Endometrial stromal sarcomas are divided into low and high grades, based on cellular morphology, immunohistochemical and molecular findings. A chemotherapy response score was established for chemotherapeutically treated high-grade serous pelvic cancer. For non-epithelial ovarian malignancies, only Sertoli-Leydig cell tumors and immature teratomas are graded. At this time molecular profiling has no impact on the grading of tumors of the female genital tract.

Invasive stratified mucin-producing carcinoma (i-SMILE) represents a recently recognized subtype of cervical adenocarcinoma (AC) developing in a background of a stratified mucin-producing intraepithelial lesion (SMILE). Clinical and prognostic data on i-SMILE are limited. We report a series of five cases with histopathological, immunohistochemical (p16) and PCR analyses. The cases as well as the patients previously published in the literature were reviewed for follow-up information. Thirteen cases were identified. The mean age of 47.1 years (range 34–66) was not different from the usual type of cervical AC. 10/13 cases presented with tumors > 2 cm and a polypoid-exophytic appearance. Regardless of tumor size and stage of the disease, 7 out of 11 patients developed recurrent disease after a mean of 7.8 months (range 6 weeks–36 months). Five patients developed distant metastases (three of them in the lungs). Five out of the 11 informative cases died of the disease. All reported cases were positive for high-risk HPV (mainly HPV type 18) and associated with p16-overexpression. i-SMILE represent a distinct subtype of invasive endocervical AC, associated high-risk HPV infection and strong p16-overexpression. Clinically, i-SMILE may represent an aggressive tumor with early recurrent disease and substantial risk of distant metastatic disease, especially to the lungs.

BACKGROUND According to current treatment guidelines, comprehensive surgical staging procedures in endometrial cancer confined to the uterus depend on uterine risk factors: a systematic lymph node dissection (LND) is recommended in high risk patients and should be omitted in low risk patients. Its role in intermediate and high intermediate risk patients is inconclusive. The aim of this analysis was to review the implementation of this risk-adopted strategy. MATERIALS AND METHODS Data were provided by the population-based Munich Cancer Registry. Patients with endometrial cancer diagnosed between 1998 and 2016 were included. RESULTS Of 5446 eligible patients, 58.5%, 30.1% and 11.4% belonged to the low risk, intermediate/high-intermediate and high risk group, respectively. Lymph node dissection was performed in 20.2%, 53.0% and 63.7% within these groups. Lymph node involvement was diagnosed in 1.7%, 9.6% and 19.3%, respectively. Within these risk groups, there was no significant difference in the time to local recurrence, lymph node recurrence or distant metastases between patients with and without LND. After adjusting for age and comorbidity-status, no significant difference in overall survival was found. CONCLUSIONS The application of a risk-adopted management of LND in early endometrial cancer in real-life is associated with a high rate of surgical under- and overtreatment. Corresponding survival data do not show a significant benefit of a systematic lymph node dissection. In order to improve the management and outcome of early endometrial cancer in the future, prospective trials, new surgical concepts and prognostic markers will be primary and necessary.

Background Tumor grade is one of the more controversial factors, and the data regarding its prognostic impact in squamous cell carcinoma (SCC) of the uterine cervix are controversial. Methods The histological slides of 467 surgically treated FIGO stage IB1 to IIB cervical SCC were re-examined regarding the prognostic impact of the histological tumor grade based on the degree of keratinization (conventional tumor grade) according to the WHO recommendation on recurrence-free and overall survival as well as on the prediction of pelvic lymph node involvement. Results 46.0% presented with well-differentiated tumors (G1, n = 215), 30.6% with moderate (G2, n = 143) and 23.3% with poor differentiation (G3, n = 109). The recurrence-free survival was significantly reduced in patients with poorly differentiated tumors (G1: 81.4%, G2: 70.6%, G3: 64.2%; p = 0.008). There was no impact on overall survival. Because of the lack of survival differences between G1- and G2-tumors, they were merged into low-grade tumors, and their prognostic outcome was compared to the high-grade group (G3-tumors). Based on this binary conventional grading system there was a significantly longer recurrence-free (low-grade: 77.1% vs. high-grade: 64.2%; p = 0.008) and overall survival (low-grade: 76.0% vs. high-grade: 65.1%; p = 0.031) in the low-grade group. However, both the conventional three-tiered and the binary grading systems (separating tumors into a low- and high-grade group) failed to predict pelvic lymph node involvement (p = 0.9 and 0.76, respectively). Conclusion A binary grading model for the conventional tumor grade (based on the degree of keratinization) in SCC of the uterine cervix may be suitable for the prognostic survival evaluation but failed to predict pelvic lymph node involvement.

Introduction: Integrative medicine is becoming increasingly relevant to modern oncology. The present study aims to assess the demand for integrative therapeutic approaches including complementary and alternative medicine (CAM), body and mind practices, nutritional counseling, and psychological assistance among breast and gynecological cancer patients. Methods: From April to July 2017, a pseudo-anonymous questionnaire was distributed to cancer patients at the Department of Gynecology and Obstetrics, Technical University of Munich. Patterns of CAM use and demand for integrative health approaches were investigated by generating descriptive statistics. Results: 182 (90%) of 203 patients participated in the survey. 59% indicated the use of CAM practices in general, and 41% specifically in relation to their oncological disease. Most frequently used modalities were herbal supplements (32%), homeopathy (29%), vitamins (28%), and selenium (21%). Integrative health approaches that patients would have desired alongside conventional oncological treatment were CAM (54%), relaxation therapies (44%), and dietary counseling (43%). Conclusion: There is a considerable demand for integrative medicine among breast and gynecological cancer patients. Our results underline the need for the implementation of evidence-based integrative treatments in cancer care in order to meet the standards of modern oncology.