Depression and anxiety in women with malignant ovarian germ cell (MOGCT) and sex cord stromal tumors (SCST): an analysis of the AGO-CORSETT database.

INTRODUCTION: The intention of this study was to evaluate the level of anxiety and depression of malignant ovarian germ cell (MOGCT) and sex cord stromal tumors (SCST) survivors and to identify possible alterable cofactors. METHODS: CORSETT was an observational, multicenter, mixed retrospective/prospective cohort study of the AGO Studygroup. Women who had been diagnosed with MOGCTs and SCSTs between 2001 and 2011 were asked to complete the Hospital Anxiety and Depression Scale (HADS) to evaluate distress. Predictors of distress (type of surgery, chemotherapy, time since diagnosis, recurrence, second tumor, pain) were investigated using multivariate linear regression analysis. RESULTS: 150 MOGCT and SCST patients with confirmed histological diagnosis completed the questionnaire median seven years after diagnosis. They had a HADS total score ≥ 13 indicating severe mental distress in 34% of cases. Patients after fertility-conserving surgery had lower probability of severe mental distress than those without fertility-conserving treatment (ß = - 3.1, p = 0.04). Pain was associated with the level of distress in uni- and multivariate analysis (coef 0.1, p < 0.01, coef. Beta 0.5). DISCUSSION: Severe mental distress was frequent in patients with MOGCT and SCST and the level of pain was associated with the level of distress. Fertility conserving therapy, however, was associated with less mental distress. Screening and treatment of pain and depression is required to improve mental well-being in survivors of MOGCT and SCST.

Unexpected malignant uterine pathology: Incidence, characteristics and outcome in a large single-center series of hysterectomies for presumed benign uterine disease.

OBJECTIVE: Hysterectomy is a frequently used therapeutic option for benign gynecological conditions. The purpose of this study was to investigate the incidence and characteristics of unforeseen malignant pathologies of the uterine corpus in a large population-based, single center cohort. METHODS: Patients who underwent hysterectomy for presumed benign conditions between 2003 and 2016 were identified. In cases of unexpected malignancies of the uterine corpus (UUM), available tissue samples were collected and a specialized gynecopathological review was performed. RESULTS: A total of 10,756 patients underwent hysterectomy for benign indications. After chart and gynecopathological review, 45/10,756 (0.42%) cases of unexpected uterine malignancies were confirmed. 33/45 (73.3%) were endometrial carcinomas (UEC) and 12/45 (26.7%) were uterine sarcomas (UUS). 27/33 (81.8%) UEC were FIGO IA, 5/33 (15.2%) FIGO IB and 1/33 (3%) FIGO stage II disease. Endometrioid and serous histotype were present in 31/33 (93.9%) and in 2/33 (6.1%) cases, respectively. 8/12 (66.7%) USS were early stage (FIGO IA or IB); only 3/12 (25.0%) were diagnosed at an advanced stage (≥FIGO II). Fatal outcome was observed in 1 patient diagnosed with UEC and 3 patients diagnosed with UUS. CONCLUSION: Our study shows that diagnosis of UUM is rare (0.42%). The majority of UUM tend to be early stage, making preoperative diagnosis difficult. In case of UEC, patient outcome is generally favorable. Nevertheless, the appropriate surgical approach for hysterectomy for a benign indication should be chosen carefully, taking all preoperative findings into account. Patients should always be informed about the residual risk of UUM.

Malignancy rates of B3-lesions in breast magnetic resonance imaging - do all lesions have to be excised?

BACKGROUND: Approximately 10% of all MRI-guided vacuum-assisted breast biopsies (MR-VAB) are histologically classified as B3 lesions. In most of these cases surgical excision is recommended. The aim of our study was to evaluate the malignancy rates of different B3 lesions which are visible on MRI to allow a lesion-adapted recommendation of further procedure. METHODS: Retrospective analysis of 572 consecutive MR-VAB was performed. Inclusion criteria were a representative (=successful) MR-VAB, histologic diagnosis of a B3 lesion and either the existence of a definite histology after surgical excision or proof of stability or regression of the lesion on follow-up MRI. Malignancy rates were evaluated for different histologies of B3 lesions. Lesion size and lesion morphology (mass/non-mass enhancement) on MRI were correlated with malignancy. RESULTS: Of all MR-VAB 43 lesions fulfilled the inclusion criteria. The malignancy rate of those B3 lesions was 23.3% (10/43). The highest malignancy rate was found in atypical ductal hyperplasia (ADH) lesions (50.0%; 4/8), 33.3% (2/6) in flat epithelial atypia (FEA), 28.6% (2/7) in lobular intraepithelial neoplasia (LIN) and 12.5% (2/16) in papillary lesions (PL). All 6 complex sclerosing lesions were benign. Mass findings were significantly more frequently malignant (31.3%, 10/32; p < 0.05) than non-mass findings (0/11). Small lesions measuring 5-10 mm were most often malignant (35.0%; 7/20). All large lesions (> 20 mm) were not malignant (0/10). Intermediate sized lesions (11-20 mm) turned out to be malignant in 23.1% (3/13). CONCLUSIONS: The malignancy rate of B3 lesions which were diagnosed after MR-VAB was 23.3%. ADH, FEA and LIN showed considerable malignancy rates (50%, 33% and 29%) and should therefore undergo surgical excision. None of the cases, which were diagnosed as radial scars, non-mass enhancement or larger lesions (> 20 mm) were malignant. Here, a follow-up MRI seems to be advisable to avoid unnecessary operations. TRIAL REGISTRATION: Retrospective study design, waived by the IRB.

Final validation of the ProMisE molecular classifier for endometrial carcinoma in a large population-based case series.

Background: We have previously developed and confirmed a pragmatic molecular classifier for endometrial cancers; ProMisE (Proactive Molecular Risk Classifier for Endometrial Cancer). Inspired by the Cancer Genome Atlas, ProMisE identifies four prognostically distinct molecular subtypes and can be applied to diagnostic specimens (biopsy/curettings) enabling earlier informed decision-making. We have strictly adhered to the Institute of Medicine (IOM) guidelines for the development of genomic biomarkers, and herein present the final validation step of a locked-down classifier before clinical application. Patients and methods: We assessed a retrospective cohort of women from the Tübingen University Women's Hospital treated for endometrial carcinoma between 2003 and 2013. Primary outcomes of overall, disease-specific, and progression-free survival were evaluated for clinical, pathological, and molecular features. Results: Complete clinical and molecular data were evaluable from 452 women. Patient age ranged from 29 to 93 (median 65) years, and 87.8% cases were endometrioid histotype. Grade distribution included 282 (62.4%) G1, 75 (16.6%) G2, and 95 (21.0%) G3 tumors. 276 (61.1%) patients had stage IA disease, with the remaining stage IB [89 (19.7%)], stage II [26 (5.8%)], and stage III/IV [61 (13.5%)]. ProMisE molecular classification yielded 127 (28.1%) MMR-D, 42 (9.3%) POLE, 55 (12.2%) p53abn, and 228 (50.4%) p53wt. ProMisE was a prognostic marker for progression-free (P = 0.001) and disease-specific (P = 0.03) survival even after adjusting for known risk factors. Concordance between diagnostic and surgical specimens was highly favorable; accuracy 0.91, κ 0.88. Discussion: We have developed, confirmed, and now validated a pragmatic molecular classification tool (ProMisE) that provides consistent categorization of tumors and identifies four distinct prognostic molecular subtypes. ProMisE can be applied to diagnostic samples and thus could be used to inform surgical procedure(s) and/or need for adjuvant therapy. Based on the IOM guidelines this classifier is now ready for clinical evaluation through prospective clinical trials.

[The 2016 update of the S3 guideline for malignant tumours of the ovary : Role of pathology in diagnosis, therapy and clinical management of epithelial tumours]. / Update der S3-Leitlinie für maligne Ovarialtumoren 2016 : Rolle der Pathologie in Diagnostik, Therapie und Nachsorge epithelialer Tumoren.

Tumor stage, residual postoperative tumor, histological type and grading are considered among the main prognostic parameters in the consensus-based recommendations in the new S3 guidelines for diagnosis, treatment and clinical follow-up of malignant tumours of the ovary. Based on the 2014 update of the WHO Classification of Tumours of the Female Reproductive Organs this article summarizes the most significant changes. For example now the same TNM and FIGO classification applies for tumours of the ovary, peritoneum or fallopian tube. Noninvasive implants of serous borderline tumours are now named implants. In contrast, invasive implants are regarded as low-grade serous carcinoma. By presenting the current background information, we want to provide a basis for discussion, regarding more detailed consensus recommendations for pathologists and clinicians in the future.

Preoperative breast MR Imaging in patients with primary breast cancer has the potential to decrease the rate of repeated surgeries.

PURPOSE: The impact of preoperative MRI on re-excisions and mastectomy rate is discussed controversially in the literature. Aim of this study was to evaluate the effect of preoperative breast MRI on the surgical procedure and rate of repeated surgeries. MATERIAL AND METHODS: A total of 991 consecutive patients in the years 2009 and 2010 with 1036 primary breast cancers were retrospectively analyzed. Sixty percent (599 patients with 626 cancers) received preoperative breast MRI. Planned surgical procedures before and after MRI and numbers of repeated surgeries in patients with (MR+ ) and without preoperative MRI (MR-) were compared. RESULTS: The result of preoperative MRI changed the surgical procedure in 25% (157/626) of the cases. In 81% (127/157), MRI was beneficial for the patients, as otherwise occult carcinomas were removed (n=122) or further biopsy could be prevented (n=5). Mastectomy rates did not differ between MR+ and MR- group (39% vs. 39%). On multiple regression analysis, the MR+ group had a lower chance for repeated surgery (p<0.05). CONCLUSION: Preoperative MRI could lower the chance for repeated surgery in patients with primary breast cancer. The rate of mastectomy did not differ between patients undergoing preoperative MRI and those who did not.

Repeated surgeries in invasive lobular breast cancer with preoperative MRI: Role of additional carcinoma in situ and background parenchymal enhancement.

OBJECTIVES: Analysing the influence of additional carcinoma in situ (CIS) and background parenchymal enhancement (BPE) in preoperative MRI on repeated surgeries in patients with invasive lobular carcinoma (ILC) of the breast. METHODS: Retrospective analysis of 106 patients (mean age 58.6±9.9years) with 108 ILC. Preoperative tumour size as assessed by MRI, mammography and sonography was recorded and compared to histopathology. In contrast-enhanced MRI, the degree of BPE was categorised by two readers. The influence of additionally detected CIS and BPE on the rate of repeated surgeries was analysed. RESULTS: Additional CIS was present in 45.4% of the cases (49/108). The degree of BPE was minimal or mild in 80% of the cases and moderate or marked in 20% of the cases. In 17 cases (15.7%) at least one repeated surgery was performed. In n=15 of these cases, repeated surgery was performed after BCT (n=9 re-excisions, n=6 conversions to mastectomy), in n=2 cases after initial mastectomy. The initial surgical procedure (p=0.008) and additional CIS (p=0.046) significantly influenced the rate of repeated surgeries, while tumour size, patient age and BPE did not (p=ns). CONCLUSIONS: Additional CIS was associated with a higher rate of repeated surgeries, whereas BPE had no influence.

Better resource utilisation and quality of care for ovarian cancer patients using internet-based pathology review.

BACKGROUND: The current literature indicates that a considerable number of patients in ovarian carcinoma clinical trials have histopathological diagnoses in conflict with inclusion criteria. It has been suggested that specialised pathology review prior to randomisation should become the standard procedure in study protocols. We hypothesised that our new, internet-based high-throughput infrastructure would be capable of providing specialised pathology review within 10 working days (w.d.). METHODS: Patients scheduled for the AGO OVAR17 ovarian carcinoma chemotherapy trial were registered for expert pathologic case review using a new internet-based central pathology review platform prior to randomisation. All original slides were requested from local pathologists. Slides were scanned and uploaded to a secured internet server. A network of experienced gynaecological pathologists was connected to the server through a custom-designed software platform. If deemed necessary by the expert pathologists, immunohistochemistry was available through a collaborating pathology lab. RESULTS: A total of 880 patients with an original diagnosis of ovarian epithelial carcinoma were registered for expert pathology review from October 2011 to July 2013. For case review, five gynaecopathologists from Austria, Switzerland and Germany were available online. Median number of w.d. required to complete the whole process from patient registration to transmission of final review diagnoses was 4 (range 2-31) (w.d.), and in 848 out of 880 (97.5%) cases, it amounted to ⩽10 w.d. In 2.5% (n=22) of cases, a major diagnostic discrepancy of potential clinical relevance was found leading to exclusion from the chemotherapy trial. CONCLUSIONS: Our results show that the use of a new internet-based infrastructure makes timely specialised case review, prior to patient randomisation feasible within ⩽10 w.d. Our new approach helped to protect against overtreatment with chemotherapy of patients with ovarian borderline tumours and inadequate treatment of patients with ovarian metastases, as a result of their inappropriate entry into a clinical trial designed for patients with primary ovarian carcinoma.

[Tumor of the mesosalpinx with unclear differentiation]. / Tumor der Mesosalpinx mit unklarer Differenzierung.

Female adnexal tumors of probable Wolffian origin (FATWO) are rare tumors, which are mostly localized in the broad ligament or the mesosalpinx. They show high intratumor and intertumor variability of histological patterns (e.g. solid, tubular, cribriform and cystic) with usually unremarkable cellular and nuclear morphology and a lower mitotic rate. In general, they behave in a benign fashion but there are rare cases with malignant transformation, so that careful examination and surveillance are necessary. Differential diagnoses include Sertoli-Leydig cell tumors, metastasized endometrioid carcinoma and the FATWO-like variant of the endometrioid carcinoma of the fallopian tubes. The FATWOs express pancytokeratin, CD10, vimentin, calretinin and inhibin A. Estrogen and progesterone receptors are expressed in a minority of cases, whereas epithelial membrane antigen (EMA) is not detectable.

Background parenchymal enhancement in breast MRI before and after neoadjuvant chemotherapy: correlation with tumour response.

OBJECTIVES: To correlate the decrease in background parenchymal enhancement (BPE) and tumour response measured with MRI in breast cancer patients treated with neoadjuvant chemotherapy (NAC). METHODS: One hundred and forty-six MRI examinations of 73 patients with 80 biopsy-proven breast cancers who underwent breast MRI before and after NAC were retrospectively analysed. All images were reviewed by two blinded readers, who classified BPE into categories (BEC; 1 = minimal, 2 = mild, 3 = moderate, 4 = marked) before and after NAC. Histopathological and morphological tumour responses were analysed and compared. RESULTS: The distribution of BEC 1/2/3/4 was 25/46/18/11 % before and 78/20/2/0 % after NAC. On average, BPE decreased by 0.87 BEC. Cohen's kappa showed substantial agreement (k = 0.73-0.77) before and moderate agreement (k = 0.43-0.60) after NAC and moderate agreement (k = 0.62-0.60) concerning the change in BEC. Correlating the change in BPE with tumour response, the average decrease in BEC was 1.3 in cases of complete remission, 0.83 in cases with partial response, 0.85 in cases with stable disease and 0.40 in cases with progressive disease. Correlation analysis showed a significant correlation between the decrease in BEC and tumour response (r = -0.24, p = 0.03). CONCLUSIONS: BPE decreased by, on average, 0.87 BEC following NAC for breast cancer. The degree of BPE reduction seemed to correlate with tumour response. KEY POINTS: • BPE decreases by an average of 0.87 categories under neoadjuvant chemotherapy. • The reduction of BPE following neoadjuvant chemotherapy correlates with the tumour response. • The classification of the BPE shows good agreement among trained readers.

CNS metastases in breast cancer patients: prognostic implications of tumor subtype.

Development of brain metastases (BM) in breast cancer leads to limited survival. The therapeutical options are limited. There are less data about the risk factors and prognostic importance in BM. Objective is to investigate predictors of central nervous system metastases and outcome after diagnosis of BM according to tumor subtype. Based on medical records, 80 consecutive patients with primary non-metastatic operable breast cancer, treated at Department of Gynecology, University of Tübingen, and who developed BM during follow-up, were retrospectively analyzed. Clinicopathological parameters and their prognostic impact were evaluated. A node involvement (40 %), ER/PR negative (53.75 vs. 61.25 %), triple negative (28.75 %) and HER2+ status (40 %) were associated with BM. BM in breast cancer patients lead to a shortened survival. In cerebral metastatic breast cancer patients with HER2-negative and triple-negative, patients had significant shorter survival after detection of BM compared with HER2-positive and non-triple-negative patients (p = 0.001; p = 0.03). Risk of BM varies significantly by subtype. Understanding the biology of metastases can help categorize patients into prognostically useful categories and tailor treatment regimens for individual patients. Prospective clinical trials would be required for evaluating the potential role of screening for asymptomatic BM and of treatment of triple-negative patients.

Clinical characteristics, pathological reevaluation, surgical management and adjuvant therapy of patients with endometrial stromal tumors.

PURPOSE: To review a single-center experience over a 27-year period in the management of endometrial stromal sarcoma (ESS) and undifferentiated endometrial sarcoma (UES) for insight into clinical characteristics, pathological diagnosis, surgical practice, adjuvant therapy and clinical outcome. MATERIALS AND METHODS: This was a retrospective study of women with histologically proven ESS and UES who were treated at the Department of Obstetrics and Gynecology, University of Tuebingen, Germany, between 1983 and 2010. Available tumor tissue, as well as inpatient and ambulatory records were reviewed; follow-up and survival data were ascertained. RESULTS: The study sample comprised ten patients with ESS and seven patients with UES. Primary surgical treatment consisted of total hysterectomy in nine patients (90.0 %) with ESS and six patients (85.7 %) with UES; one patient (10.0 %) with ESS and one patient (14.3 %) with UES underwent debulking surgery. All patients (100 %) from the ESS group and six patients (85.7 %) from the UES group underwent bilateral salpingo-oophorectomy. Seven women (70.0 %) with ESS and six women (85.7 %) with UES underwent lymphadenectomy. Median DFS was 83.8 months (95 % CI 80.6-87.0) and median OS was 232.6 (95 % CI 49.3-415.9) for patients with ESS; median DFS was 12.9 months (95 % CI 0-284.1) and median OS was 17.6 (95 % CI 0-37.0) for patients with UES. There was no significant difference in DFS between patients with ESS as compared with patients with UES. However, patients with ESS had a significantly better OS when compared to patients with UES (p = 0.011). CONCLUSION: ESS and UES are very rare uterine neoplasms. Surgery consisting of total hysterectomy with or without bilateral salpingo-oophorectomy is the most important treatment-element in patients with ESS or UES.

[Mucinous ovarian neoplasms. Prognostically mostly excellent, infrequently a wolf in sheep's clothing]. / Muzinöse Ovarialtumoren. Prognostisch meist exzellent, selten Wölfe im Schafspelz.

Mucinous ovarian neoplasms represent the second largest group of epithelial ovarian tumors after serous neoplasms, of which benign cystadenomas constitute more than 80 %. Mucinous cystadenomas and carcinomas cannot be distinguished by the clinical features or the mean age of onset of the disease. They typically occur unilaterally, are confined to the adnexae (FIGO stage I) and clinically present with non-specific abdominal symptoms or are diagnosed by chance. The mean age of disease onset is around 50 years old. The prognosis is excellent. Implants, peritoneal metastases and bilateral occurrence of ovarian mucinous neoplasms should lead to the suspicion of metastasis particularly from a gastrointestinal tumor. Neither microinvasion defined as a maximum extent of invasion of 5 mm, nor intraepithelial carcinoma characterized by high grade atypia without invasion, affect the prognosis of mucinous borderline tumors. Mucinous carcinomas typically show confluent glandular, expansile growth that leads to a labyrinth-like pattern. A destructive infiltrative or nodular growth pattern, however, should lead to the consideration of metastasis. Mural nodules that may reveal a spindle cell sarcomatous or anaplastic carcinomatous pattern occur infrequently in mucinous and do not affect the prognosis. Pax8 positivity is indicative of a primary ovarian neoplasm. In this case, however, mucinous tumors associated with teratomas may show the colonic immunoreaction pattern (CK7-/CK20+/CDX2+). The rare mucinous tumors with endocervical differentiation are now designated as seromucinous tumors and consist of two or more distinct cell types, are frequently associated with endometriosis and seem to show a molecular genetic relationship to endometrioid neoplasms.

MR imaging-guided vacuum-assisted breast biopsy: reduction of false-negative biopsies by short-term control MRI 24-48 h after biopsy.

AIM: To evaluate whether another contrast-enhanced (CE) magnetic resonance imaging (MRI) examination 24-48 h after MRI-guided vacuum-assisted breast biopsy (MRI-VAB) can reduce the rate of false-negative cases. MATERIALS AND METHODS: The study included 252 patients who underwent MRI-VAB for the clarification of 299 lesions. The success of MRI-VAB was assessed at interventional MRI and another CE MRI 24-48 h after the intervention. In cases of successful MRI-VAB (complete or partial lesion removal) and benign histological results, follow-up breast MRI was performed. In cases of unsuccessful biopsy (unchanged lesion), tissue sampling was repeated. False-negative cases were calculated to assess the diagnostic value of MRI follow-up within 2 days after intervention. RESULTS: Ninety-eight malignant (32.8%) and 201 (67.2%) benign lesions were diagnosed using MRI-VAB. At immediate unenhanced control MRI, all lesions were assessed as successfully biopsied. In 18 benign cases (6%), CE MRI after 24-48 h showed an unsuccessful intervention. Further tissue sampling revealed another 13 cancers in these patients. This results in a false-negative rate of 11.7%. Follow-up MRI of the benign lesions presented no further malignancy. CONCLUSIONS: MRI-VAB with immediate unenhanced control offers a success rate of 94%. The rate of false-negative biopsies (11.7%) could be reduced to zero by using short-term follow-up MRI. Therefore, a further CE breast MRI 24-48 h after benign MRI-VAB to eliminate missed cancers is recommended.

Clinical value of magnetic resonance imaging in patients with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome: diagnosis of associated malformations, uterine rudiments and intrauterine endometrium.

OBJECTIVES: The aim of this study was to evaluate the accuracy of preoperative magnetic resonance imaging (MRI) in the diagnosis of malformations associated with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome and identification of uterine endometrium to optimise the clinical management. METHODS: We retrospectively reviewed 214 consecutive MRKH patients, mean age 19 years, who underwent laparoscopy-assisted neovagina creation. A total of 115 patients (53.7%) met the inclusion criterion of sufficient preoperative MRI. In 110 of them (95.7%), MRI findings were correlated with laparoscopy and associated malformations. In 39 cases (35.5%) uterine rudiments were removed and analysed histopathologically. RESULTS: Ten per cent (11/110) of the patients showed complete uterine agenesis. The others presented with either unilateral (n = 16; 14.5%) or bilateral (n = 83; 75.5%) uterine rudiments. MRI detection of uterine rudiments agreed in 78.2% (86/110) with laparoscopy. In 85.4% of the removed rudiments, MRI could correctly diagnose the existence of the endometrium. Compared to laparoscopy, MRI could exactly detect ovaries in 97.3% (107/110). Renal or ureteral malformations were seen in 32 cases (27.8%). In 83% of unilateral renal agenesis and unilateral rudiment, the latter was located at the side of the kidney. CONCLUSIONS: MRI is useful for preoperative detection of MRKH-associated malformations and assessment of the endometrium to further optimise MRKH patient treatment. KEY POINTS: • Pelvic MRI is useful for preoperative detection of MRKH-associated malformations. • MRI can diagnose uterine endometrium in MRKH patients with high precision. • Preoperative MRI can optimise clinical management of patients with MRKH syndrome.

Risk factors and survival outcome in cerebral metastatic breast cancer.

The development of brain metastases (BM) of primary breast cancer patients leads to limited survival. HER2-positive and triple-negative status are risk factors for the development of BM. Estrogen receptor (ER)/progesterone receptor (PR)/HER2 are important prognostic markers and are essential for effective treatment decisions. We retrospectively analyzed the impact of known risk factors and the outcome after the development of BM. Eighty consecutive patients, treated between January 1, 2001, and June 30, 2012, on the basis of primary non-metastatic operable breast cancer and who developed BM, were enrolled. Clinical parameters (TNM; ER, PR, HER2) and their impact on the occurrence of BM and additionally their prognostic influence after the occurrence of BM were investigated. A small tumor size, ductal histology, grade 3, hormone receptor-negative, triple-negative and HER2+ tumors were associated with BM. Median time from breast cancer diagnosis to BM was 35 months (range 26.2-43.8). Grade 3 versus 2 has significantly negative prognostic impact with earlier development of BM (median 23 vs. 41 months; p=0.033). HER2-positive patients had significantly longer survival after the occurrence of BM than HER2-negative patients (p=0.009). The risk of BM varies significantly by subtype. In high-risk patients, the occurrence of BM must be considered, and possibly, general screening in these patients is warranted. The survival advantage of HER2-positive breast cancer patients compared with HER2-negative patients after the occurrence of BM is possibly explainable by systemic control of disease. Standard of care for patients with BM is whole-brain radiotherapy, with/without surgery, or stereotactic radiosurgery. Perhaps novel therapies may additionally improve survival in these patients.

Dural ectasia in Loeys-Dietz syndrome: comprehensive study of 30 patients with a TGFBR1 or TGFBR2 mutation.

The purpose of this study was to assess the frequency, severity, and clinical associations of dural ectasia (DE) in Loeys-Dietz syndrome (LDS). Database analysis of three German metropolitan regions identified 30 patients with LDS and TGFBR1 mutation in 6 and a TGFBR2 mutation in 24 individuals (17 men; mean age: 31 ± 19 years), as well as 60 age and sex-matched control patients with Marfan syndrome carrying a FBN1 mutation. DE was present in 22 patients with LDS (73%), and it related to skeletal score points (p = 0.008), non-skeletal score points (p < 0.001), and to the presence of ≥7 systemic score points (p = 0.010). Similarly, the severity of DE was related to body height (p = 0.010) and non-skeletal score points (p = 0.004). Frequency (p = 0.131) and severity of DE (p = 0.567) was similar in LDS and Marfan syndrome. DE is a manifestation of LDS that occurs with similar frequency and severity as in Marfan syndrome. Severity of DE may serve as a marker of the overall connective tissue disease severity. LDS may be considered in patients with DE.

Comprehensive analysis of dural ectasia in 150 patients with a causative FBN1 mutation.

The purpose of this study was to perform a comprehensive study of dural ectasia (DE) related to FBN1 mutations. We performed a database analysis of two German metropolitan regions of 150 patients (68 men, 82 women; mean age 35 ± 16 years). All patients had a FBN1 mutation and underwent dural magnetic resonance imaging. Age was <16 years in 20, 16-25 in 27, 26-35 in 67, and >35 in 36 patients. Prevalence of dural ectasia was 89% with criteria of Oosterhof and Habermann, 83% with Fattori, 78% with Lundby, and 59% with Ahn. DE was less frequent in patients <16 years with Ahn and Fattori. DE related to skeletal manifestations with all criteria, to aortic Z-scores and mitral valve prolapse with criteria of Habermann and Lundby, and to age with criteria of Fattori. The Fattori-grade of DE increased with age, aortic Z-scores, and skeletal score points. There was no consistent relationship of DE with any type of FBN1 mutation. DE is frequent in patients with FBN1 mutations irrespective of age and its severity increases during life. Criteria of Oosterhof and Habermann yielded most consistent diagnostic results. DE relates to skeletal involvement, aortic Z-scores, and mitral valve prolapse.

Receptor change-clinicopathologic analysis of matched pairs of primary and cerebral metastatic breast cancer.

OBJECTIVE: A challenge in the management of breast cancer is development of brain metastases (BM) with limited survival. In primary breast cancer, ER/PR/HER2 are important prognostic markers and are important for making effective treatment decisions. Changes in immunohistochemical markers of metastases are with unclear clinical significance, and mechanisms of resistance to endocrine therapy are an additional challenge. The aim of this retrospective study is to detect changes in immunohistochemical markers of primary and BM and to recognize if receptor change has prognostic impact. METHODS: Twenty-four consecutive primary breast cancer patients who developed BM and got surgical resection of BM were enrolled. Matched pair analyses of primary and BM were done with evaluation by immunostaining (ER/PR/HER2). RESULTS: A small tumor size, ductal histology and HER2+ tumors were associated with BM. Loss of ER/PR receptor positivity was observed in BM compared to primary (ER: 50.0 %/22.7 %; p = 0.004; PR: 45.8 %/9.1 %; p = n.s), respectively, and almost no change in HER2 status (>80 %; p = 0.012). Patients with ER-/PR-negative or HER2-positive primary had shorter time to recurrence than ER-/PR-positive and HER2-negative patients. Receptor change has negative prognostic impact. CONCLUSION: With the observed loss of receptor positivity, therapeutic options are diminished. Identification of patients with a high risk for BM is warranted to evaluate preventive strategies.