Mucinous cystadenoma and benign mesonephric-like proliferation in the ovary - Further evidence for clonal relationship.

Mesonephric-like adenocarcinomas rarely occur in the uterus and the ovary. Benign mesonephric-like (ML) proliferations and hyperplasia have been described solely within the ovary. Pathogenetic data are very limited. We report a case with microscopic focus of benign ML-proliferation in association with mucinous cystadenoma in the ovary. The immunophenotype was distinct (mucinous tumor: focal weak nuclear positivity for PAX-8, CK 7, patchy cytoplasmic positivity for p16 and negativity for estrogen receptor, CD 10, TTF-1, p53 wildtype; mesonephric component: diffusely positive for PAX-8, CK 7, luminal CD 10, TTF-1, focal staining for estrogen receptor, patchy cytoplasmic for p16, p53 wildtype). On NGS-analysis there was clonal mutation of KRAS p.G12C. The data provide additional evidence for the concept of transdifferentiation (Müllerian tissue representing Wolffian/mesonephric features on histology and immunostaining) within the pathogenesis of mesonephric proliferation of the female genital tract and demonstrate the clonal relationship between these distinct morphologic components.

Cystic Adenomyoma in Pregnancy: A Case Report.

Cystic adenomyomas (CA) are rare. They primarily affect adolescents and young women in their fertile years. Therefore, fertility and pregnancy outcome are of pivotal relevance in this patient collective. Apart from the guidelines of the European Society of Human Reproduction and Embryology (ESHRE) on the management of endometriosis in general, there are no specific treatment recommendations for CA and, as far as our research shows, no data illustrating the behavior of a CA over the course of pregnancy. Thus, we report the case of a 32-year-old 1-gravida, 1-para, preconceptionally diagnosed with a CA by ultrasound. After thoroughly discussing further treatment options, the decision was made to opt for a more conservative approach and not perform surgery before attempting a next pregnancy. The patient conceived spontaneously and sonographic monitoring of the CA throughout pregnancy showed complete regression of the cystic component during the second trimester. A healthy baby was delivered at term by an uncomplicated elective cesarean section. Following a review of the literature and taking into account the course of our case, we propose the feasibility of a conservative, non-surgical approach in women with a CA and the desire to conceive.

Recurrent Pelvic Organ Prolapse after Sacrocolpopexy-A Surgical Challenge.

Background: Repeat sacrocolpopexy (reSCP) for recurrent pelvic organ prolapse (POP) is a rare and complex condition with little understanding of how to manage. Most authors recommend complete reSCP regardless of the underlying cause of the failure. This retrospective cohort study presents our management workflow and how to systematically approach this challenging situation. Methods: From 2017 to 2021, we analyzed all women undergoing surgery for recurrent POP after sacrocolpopexy at our tertiary referral hospital at the department of urogynecology. Preoperatively, all women underwent a structured work-up consisting of answering the validated German female pelvic floor questionnaires, a clinical examination utilizing the POP-Q staging system according to the International Continence Society (ICS), and a pelvic floor ultrasound. The surgical management was based on the preoperative findings and was adapted individually during surgery if indicated according to the estimated underlying problem for recurrence. Results: In total, 377 women underwent a primary laparoscopic sacrocolpopexy. However, ten women presented with a symptomatic recurrent prolapse requiring further surgical intervention. A reSCP was performed in eight women, including two with additional laparoscopic paravaginal repair to correct the displaced mesh placement at initial surgery. A vaginal correction was indicated in two women with an isolated posterior compartment prolapse. The analysis demonstrates that reSCP has a low intraoperative complication rate and high subjective and objective success rates. Conclusions: We could demonstrate that individualized reSCP after initial SCP is a challenging yet feasible and safe treatment option, but there may be suitable alternatives. If women undergo pre- and intraoperative standardized problem-oriented examinations, we can often identify the cause of the recurrent prolapse. Tailored surgery must be subsequently performed.

High concordance of molecular subtyping between pre-surgical biopsy and surgical resection specimen (matched-pair analysis) in patients with vulvar squamous cell carcinoma using p16- and p53-immunostaining.

OBJECTIVE: Vulvar squamous cell carcinoma (VSCC) can be stratified into three molecular subtypes based on the immunoexpression of p16 and p53: HPV-independent p53-abnormal (p53abn) (most common, biologically aggressive), HPV-associated, with p16-overexpression (second most common, prognostically more favourable) and more recently recognised HPV-independent p53-wildtype (p53wt) (rarest subtype, prognostically intermediate). Our aim was to determine whether molecular subtypes can be reliably identified in pre-operative biopsies and whether these correspond to the subsequent vulvectomy specimen. METHODS: Matched-paired pre-surgical biopsies and subsequent resection specimen of 57 patients with VSCC were analysed for the immunohistochemical expression of p16 and p53 by performing a three-tiered molecular subtyping to test the accuracy rate. RESULTS: Most cases 36/57 (63.2%) belonged to the HPV-independent (p53-abn) molecular subtype, followed by HPV-associated 17/57 (29.8%) and HPV-independent (p53wt) 4/57 (7.0%). The overall accuracy rate on biopsy was 91.2% (52/57): 97.3% for p53-abnormal, 94.1% for p16-overexpression and 50% for p16-neg/p53-wt VSCC. Incorrect interpretation of immunohistochemical p53 staining pattern was the reason for discordant results in molecular subtyping in all five cases. In one case there was an underestimation of p53 pattern (wildtype instead of abnormal/aberrant) and in one case an overestimation of the p53 staining pattern (abnormal/aberrant instead of wildtype). In 3/5 there was a "double positive" staining result (p16 overexpression and abnormal/aberrant p53 staining pattern). In that cases additional molecular workup is required for correct molecular subtyping, resulting in an overall need for molecular examination of 3/57 (3.5%). CONCLUSIONS: Compared to the final resections specimen, the three-tiered molecular classification of VSCC can be determined on pre-surgical biopsies with a high accuracy rate. This enables more precise surgical planning, prediction of the response to (chemo) radiation, selection of targeted therapies and planning of the optimal follow-up strategy for patients in the age of personalised medicine.

Do PET-positive supradiaphragmatic lymph nodes predict overall survival or the success of primary surgery in patients with advanced ovarian cancer?

OBJECTIVES: Compared to conventional computed tomography (CT), fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) detects higher rates of lymph node and distant metastases in patients with ovarian cancer. However, FDG-PET/CT is not routinely performed during preoperative work-up. Therefore, we investigated the prognostic value of preoperative FDG-PET/CT in advanced epithelial ovarian cancer (EOC) and its predictive value for surgical resection in patients with no residual disease. The potential significance of PET-positive supradiaphragmatic lymph nodes (SDLNs) for these parameters was evaluated. METHODS: All patients with FIGO IIA-IVB EOC diagnosed between March 2014 and January 2021 at our certified gynaecological cancer centre, who underwent FDG PET/CT before primary surgery were retrospectively included. RESULTS: Fifty-three consecutive patients were included in the study. Eighteen (34 %) patients had PET-positive SDLNs. We could not demonstrate a significant correlation between PET-positive SDLNs and median overall survival (OS; SDLN-positive: 58.76 months, SDLN-negative: 60.76 months; p = 0.137) or intra- or perioperative outcomes. CONCLUSIONS: FDG PET/CT has a higher detection rate for SDLNs in patients with ovarian cancer than CT has, as described in the literature. Moreover, PET-positive SDLNs failed to predict intraoperative outcomes or overall survival.

[Molecular classification of endometrial carcinoma-a short summary for clinical use]. / Molekulare Klassifikation des Endometriumkarzinoms ­ ein kurzer Überblick.

BACKGROUND: Histopathological examination is still the backbone for the diagnosis and treatment decision making in endometrial carcinoma (EC). The binary classification of EC into type 1 (mostly endometrioid) and type 2 (mostly serous), although still helpful, showed overlapping clinical, morphological and molecular features and was not very prognostic discriminatory for all subtypes of EC. METHODS: Analysing the most recent studies dealing with the molecular classification of EC and the recommendations of the German S3-guidelines for EC. RESULTS AND CONCLUSION: Based on the comprehensive molecular study of The Cancer Genome Atlas Project (TCGA) four distinct molecular subtypes have been identified: EC with POLE mutation (POLEmut), with loss of mismatch repair proteins (MMR deficiency; dMMR), or with TP53 mutation (p53mut) and without any of these alterations, termed NSMP (no specific molecular profile). The molecular classification of EC presents a morphomolecular approach, based on histopathological evaluation (tumor diagnosis, subtyping, grading), immunohistochemistry (MMR, p53) and molecular analyses for POLE. The incorporation of this molecular classification is recommended for clinical use by the World Health Organisation (WHO) as well as many national guidelines and international societies. Due to the heterogeneity of NSMP-EC, which is the largest molecular group, additional research is indicated to further characterise these tumors.

Mesonephric-like adenocarcinoma of the female genital tract: possible role of KRAS-targeted treatment-detailed molecular analysis of a case series and review of the literature for targetable somatic KRAS-mutations.

PURPOSE: Mesonephric-like adenocarcinomas (MLA) of the female genital tract represent a rare and relatively recently described neoplasm exhibiting characteristic morphologic and immunohistochemical findings commonly associated with a KRAS-mutation. Most cases display an aggressive clinical behavior, but knowledge about treatment approaches is limited, especially for targeting KRAS. METHODS: We report a series of eight cases with a detailed molecular analysis for KRAS. These cases as well as the data of previously published cases with detailed information regarding KRAS-mutational events were reviewed for a potential targeted approach and its prognostic impact. RESULTS: Both the uterine and ovarian MLA harbor a somatic KRAS-mutation in about 85% of the reported cases, affecting the hotspot codons 12 and 13. 15.7% of the endometrial and 15.6% of ovarian MLA are wild type for KRAS. A p.G12A-alteration was seen in 5.6% (5/89) of the endometrial and in 6.2% (2/32) of the ovarian tumors, for p.G12C in 7.9% and 6.2%, for p.G12D in 32.6% and 34.5% and for p.G12V in 36% and 37.5%, respectively. Very limited data are available regarding the prognostic impact of different mutational sites within the KRAS-gene without significant prognostic impact. CONCLUSION: Because of a specific p.G12C-KRAS somatic mutation, only the minority of MLA (7.9% with uterine and 6.2% with ovarian primary) are potentially targetable by sotarasib in that rare but aggressive subtype of adenocarcinoma of the female genital tract. Until now, the different location of a somatic KRAS-mutation is of no prognostic impact.

Independent Tissue-Based Biomarkers in Endometrioid Endometrial Cancer: Tumor Budding in Microsatellite Instability and WHO Grading in Copy-Number-Low Patients.

The molecular characterization of endometrial endometrioid adenocarcinomas has provided major advances in its prognostic stratification. However, risk assessment of microsatellite instability (MSI) and copy-number (CN)-low cases remains a challenge. Thus, we aimed to identify tissue-based morphologic biomarkers that might help in the prognostic stratification of these cases. Histomorphologic parameters (WHO grading, tumor budding (TB), tumor-stroma ratio (as a quantitative description of stromal desmoplasia), tumor-infiltrating lymphocytes (TIL), "microcystic, elongated, fragmented" (MELF) pattern) were analyzed in resection specimens of the TCGA-UCEC cohort (n = 228). For each quantitative parameter, a two-tiered system was developed utilizing systematically determined cutoffs. Associations with survival outcomes were calculated in univariate and multivariate analysis and validated in two independent cohorts. In MSI tumors, only TB remained an independent prognostic factor. TB (≥3 buds/high-power field) was associated with inferior outcomes and with lymph node metastases. The prognostic significance of TB was confirmed in two validation cohorts. For CN-low tumors, established grading defined by the WHO was independently prognostic with inferior outcomes for high-grade tumors. The evaluation of TB might help in identifying MSI-patients with unfavorable prognosis who, e.g., could benefit from lymphadenectomy. WHO-based grading facilitates independent prognostic stratification of CN-low endometrioid adenocarcinomas. Therefore, we propose the utilization of TB and WHO-based grading, two tissue-based and easy-to-assess biomarkers, in MSI/CN-low endometrial carcinomas for improved clinical management.

The influence of the menstrual cycle and hormonal contraceptives on cardiorespiratory fitness in physically active women: A systematic review and meta-analysis.

Objective: To systematically review and summarize the existing evidence related to the influence of the menstrual cycle (MC) and hormonal contraceptive (HC) use on V˙O2max in physically active women. Methods: This systematic review and meta-analysis conforms to the PRISMA statement guidelines. Four (sub-)meta-analyses were performed. Two focused on longitudinal studies examining the same women several times to compare the V˙O2max during the different menstrual phases or oral contraceptive (OC) use and withdrawal. Two meta-analyses examined if there is a difference in V˙O2max between OC users and normally menstruating women by analyzing cross-sectional studies assigning physically active women to one of these two groups as well as intervention-based studies (cross-over studies, randomized controlled trials considering only the data of the intervention group) comparing women intra-individually with and without OCs. Results: Nine of the included studies (107 women) evaluated the influence of the MC, five studies (69 women) the impact of OCs on V˙O2max, and six studies investigated both topics (88 women). A mean difference of V˙O2max -0.03 ml/kg/min (95%CI -1.06 to 1.01) between the early follicular and luteal menstrual phase was observed. Between the active and inactive phases of OCs, a mean difference of -0.11 ml/kg/min (95%CI -2.32 to 2.10) was found. The inter-individual comparison of naturally menstruating women and OC users showed a mean difference in V˙O2max of 0.23 ml/kg/min (95% CI -2.33 to 2.79) in favor of OC use. The intra-individual comparison of the same women showed a mean decrease in V˙O2max of -0.84 ml/kg/min (95% CI -2.38 to 0.70) after a new start with OCs. Conclusions: Our meta-analyses showed no effects of the MC or the OCs on V˙O2max. More high-quality studies are needed determining the MC phases more precisely, including OCs with the current standard formulations and comparing the influence of different progestins.

Vulvar Leiomyosarcomas: A Case Series with Clinical Comparison to Uterine Leiomyosarcomas and Review of the Literature.

BACKGROUND Leiomyosarcomas of the vulva (VLMS) are very rare among gynecological malignancies, with a lack of knowledge on clinical presentation, prognosis, and therapeutic management. CASE REPORT The database of the German Clinical Center of Competence for Genital Sarcomas and Mixed Tumors in Greifswald (DKSM) was reviewed between the years 2010 and 2020. A total of 8 cases of VLMS were retrieved and analyzed retrospectively. One exemplary case of VLMS was outlined in detail: A 45-year-old premenopausal woman presented with increasing vulvar swelling and discomfort. Given the suspicion of a Bartholin's gland abscess, the mass was excised. Final pathology revealed a solid tumor consistent with a moderately differentiated leiomyosarcoma of the vulva. A wide local excision was subsequently performed followed by adjuvant external beam radiation. The clinical features of these 8 cases of VLMS were compared to 26 cases of VLMS found in a review of the literature and to a total of 276 cases of uterine leiomyosarcoma (ULMS) from the same database (DKSM). CONCLUSIONS In addition to rapid growth, observed in both tumor entities, VLMS most commonly presented as Bartholin's gland abscess or cyst and ULMS as leiomyoma. In this cohort, the prognosis of VLMS was much better than that of ULMS, most probably due to the significantly smaller tumor size of VLMS at diagnosis. Further data and larger studies on VLMS are needed to calculate recurrence and survival rates more accurately and define the role of adjuvant radiotherapy.

Incidence and predictors for chemotherapy modifications and their impact on the outcome of ovarian cancer patients.

PURPOSE: Chemotherapy (CTX) is an important part of the treatment strategy of stage II-IV ovarian cancer. CTX modifications, such as delays, dose reductions or premature terminations might have a negative impact on overall survival (OS) and progression free survival (PFS). The goal of this study was to determine the incidence and predictors of CTX modifications and their influence on survival. METHODS: An observational retrospective cohort analysis of 192 ovarian cancer patients who were treated at the Department of Obstetrics and Gynaecology, Technical University Munich, Germany, according to international guidelines was performed including from 2009 to 2013. A potential association between patient and disease characteristics and CTX modifications was tested with multivariate logistic regression. OS and PFS were estimated by Kaplan-Meier analysis. RESULTS: 44.8% (86/192) received a modification of CTX. 34 (17.7%) women discontinued CTX prematurely, 17 (8.9%) underwent a dose reduction, 16 (8.3%) experienced a CTX delay and 10 (5.2%) had both a delay and a dose modification. In nine (4.7%) patients, the dose needed to be divided. Leukopenia (p < 0.001) and anaemia (p = 0.003) were significantly more common in patients with CTX modifications. Significant predictors for CTX modifications were a history of thrombosis or embolism (p < 0.001) and residual tumour postoperatively (p = 0.003). Patients with CTX modifications showed a significantly lower OS as well as PFS (p < 0.001), even after adjustment for prognostic factors such as age, body-mass-index, residual tumour, histology, FIGO stage and grading (p = 0.005 for OS and p = 0.001 for PFS). CONCLUSION: CTX modifications have a negative impact on survival. Significant predictors for such modifications are a history of thrombosis or embolism and the presence of residual postoperative tumour. Further studies are needed to avoid CTX modifications and to improve survival of ovarian cancer patients.

Intracavitary brachytherapy with additional Heyman capsules in the treatment of cervical cancer.

PURPOSE: Brachytherapy is a mandatory component of primary radiochemotherapy in cervical cancer. The dose can be applied with a traditional intracavitary approach (IC alone) or with multiple catheter brachytherapy to optimize dose distribution in an individual concept. We therefore evaluated whether the utilization of a tandem-ring applicator plus additional intracavitary applicators (add IC) provides an advantage over the traditional IC alone approach, as this method is less time consuming and less invasive compared to a combined intracavitary/interstitial brachytherapy. METHODS: Twenty three procedures of intracavitary brachytherapy for cervical cancer with additional intracavitary applicators performed in seven patients treated between 2016 and 2018 in our institution were included in this study. Plans were optimized for D90 HR-CTV with and without the utilization of the additional applicators and compared by statistical analysis. RESULTS: D90 for HR-CTV was 5.71 Gy (±1.17 Gy) for fractions optimized with add IC approach and 5.29 Gy (±1.24 Gy) for fractions without additional applicators (p < 0.01). This translates to a calculated mean EQD2 HR-CTV D90 of 80.72 Gy (±8.34 Gy) compared to 77.84 Gy (±8.49 Gy) after external beam therapy and four fractions of brachytherapy for add IC and IC alone, respectively (p < 0.01). The predictive value of improved coverage of HR-CTV in the first fraction was high. CONCLUSION: In a subgroup of cases, the addition of intracavitary Heyman capsules can be an alternative to interstitial brachytherapy to improve the plan quality compared to standard IC alone brachytherapy. The benefit from the addition of applicators in the first fraction is predictive for the following fractions.

Combined Expression of HGFR with Her2/neu, EGFR, IGF1R, Mucin-1 and Integrin α2ß1 Is Associated with Aggressive Epithelial Ovarian Cancer.

Hepatocyte growth factor receptor (HGFR), also known as c-mesenchymal-epithelial transition factor (c-MET), plays a crucial role in the carcinogenesis of epithelial ovarian cancer (EOC). In contrast, the mechanisms contributing to aberrant expression of HGFR in EOC are not fully understood. In the present study, the expression of HGFR with its prognostic and predictive role was evaluated immunohistochemically in a cohort of 42 primary ovarian cancer patients. Furthermore, we analyzed the dual expression of HGFR and other druggable biomarkers. In the multivariate Cox regression analysis, high HGFR expression was identified as an independent prognostic factor for a shorter progression-free survival (PFS) (hazard ratio (HR) 2.99, 95% confidence interval (CI95%) 1.01-8.91, p = 0.049) and overall survival (OS) (HR 5.77, CI95% 1.56-21.34, p = 0.009). In addition, the combined expression of HGFR, human epidermal growth factor receptor 2 (Her2/neu), epithelial growth factor receptor (EGFR), insulin-like growth factor 1 (IGF1R), Mucin-1 and Integrin α2ß1 further significantly impaired PFS, platinum-free interval (PFI) and OS. Protein co-expression analyses were confirmed by transcriptomic data in a large, independent cohort of patients. In conclusion, new biomarker-directed treatment targets were identified to fight poor prognosis of primary EOC.

NCALD as a potential predictive biomarker for the efficacy of platinum-based chemotherapy in ovarian cancer.

Aim: Since reliable response predictors to platinum-based chemotherapy in ovarian cancer (OC) are scarce, we characterize NCALD as a predictive biomarker. Materials & methods: NCALD mRNA (n = 100) and protein (n = 102) expression was analyzed in OC samples and associated with patient outcome. A stable OC cell line knockdown was generated and cellular response to platinum was explored. Results: High NCALD mRNA and protein expression was significantly associated with longer overall patient survival (p = 0.037/0.002). Knockdown experiments revealed a significant association between cisplatin sensitivity and NCALD expression. Conclusion: Low NCALD expression was associated with reduced sensitivity to platinum-based chemotherapy. NCALD may be a new biomarker candidate to identify patients who might benefit from platinum-based chemotherapy.

Preoperative smoking cessation program in patients undergoing intermediate to high-risk surgery: a randomized, single-blinded, controlled, superiority trial.

BACKGROUND: At present, effectively implementing smoking cessation programs in the health care system constitutes a major challenge. A unique opportunity to initiate smoking cessation focuses on smokers scheduled for surgery. These patients are not only highly motivated to quit smoking but also likely to benefit from a reduction in postoperative complications which may translate into a decrease of costs. Nevertheless, surgical patients are not routinely informed about the benefits of preoperative smoking cessation. Potential reasons for this missed opportunity may be the lack of time and training of surgeons and anaesthesiologists. We therefore aim to analyse the impact of a preoperative high-intensity smoking cessation intervention on surgical complications up to a 90-day postoperative period in patients of various surgical disciplines. The hypothesis is that a preoperative smoking cessation program improves outcomes in smokers undergoing intermediate to high-risk surgery. METHODS: The present study is a single-centre, randomized trial with two parallel groups of smokers scheduled for surgery comparing surgery alone and surgery with preoperative smoking cessation. We plan to randomize 251 patients. The primary objective is to compare complications between patients with an institutional multifaceted smoking cessation intervention starting 4 weeks before surgery compared to patients in the advice-only group (control group) within a 90-day postoperative period. The primary endpoint is the Comprehensive Complication Index (CCI®) within 90 days of surgery. Secondary outcomes include the length of hospital stay, cost of care, quality of life, smoking abstinence, and reduction in nicotine consumption. DISCUSSION: The hypothesis is that a preoperative smoking cessation program improves outcomes in smokers undergoing surgery. TRIAL REGISTRATION: BASEC #2021-02004; ClinicalTrials.gov: NCT05192837 . Registered on January 14, 2022.

Interpatient Heterogeneity in Drug Response and Protein Biomarker Expression of Recurrent Ovarian Cancer.

Recurrent ovarian-cancer patients face low 5-year survival rates despite chemotherapy. A variety of guideline-recommended second-line therapies are available, but they frequently result in trial-and-error treatment. Alterations and adjustments are common in the treatment of recurrent ovarian cancer. The drug response of 30 lesions obtained from 22 relapsed ovarian cancer patients to different chemotherapeutic and molecular agents was analyzed with the patient-derived ovarian-cancer spheroid model. The profile of druggable biomarkers was immunohistochemically assessed. The second-line combination therapy of carboplatin with gemcitabine was significantly superior to the combination of carboplatin with PEGylated liposomal doxorubicin (p < 0.0001) or paclitaxel (p = 0.0007). Except for treosulfan, all nonplatinum treatments tested showed a lesser effect on tumor spheroids compared to that of platinum-based therapies. Treosulfan showed the highest efficacy of all nonplatinum agents, with significant advantage over vinorelbine (p < 0.0001) and topotecan (p < 0.0001), the next best agents. The comparative testing of a variety of treatment options in the ovarian-cancer spheroid model resulted in the identification of more effective regimens for 30% of patients compared to guideline-recommended therapies. Recurrent cancers obtained from different patients revealed profound interpatient heterogeneity in the expression pattern of druggable protein biomarkers. In contrast, different lesions obtained from the same patient revealed a similar drug response and biomarker expression profile. Biological heterogeneity observed in recurrent ovarian cancers might explain the strong differences in the clinical drug response of these patients. Preclinical drug testing and biomarker profiling in the ovarian-cancer spheroid model might help in optimizing treatment management for individual patients.

Clinico-pathologic characteristics and prognostic factors of ovarian carcinoma with different histologic subtypes - A benchmark analysis of 482 cases.

PURPOSE: 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. METHODS: 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. RESULTS: 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 stage >pT3 (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. CONCLUSION: 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.

Adenoid Cystic Carcinoma of Bartholin's Gland: A Case Report with Emphasis on Surgical Management.

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.

First experiences with PET-MRI/CT in radiotherapy planning for cervical cancer.

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.