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Background: Use of liquid biopsy for minimal invasive follow-up diagnostics of non-small-cell lung carcinomas (NSCLCs)., Objectives: Systematic search for new putative blood-based hypermethylation biomarkers to discriminate NSCLC patients from patients without a malign disease., Methods: Quantitative analysis of gene promoter DNA methylation of potential biomarkers from cfDNA (plasma) with pyrosequencing., Results: cfDNA hypermethylation in plasma confirmed significant higher methylation frequencies of the candidate gene CFTR of the NSCLC patients compared to the combined control groups and to NSCLC patients after curative therapy of primary NSCLC (post-NSCLC). ROC-analysis of the best discriminatory CpGs of the CFTR promotor (CpG1-2-4) revealed a sensitivity of 52% in NSCLC patients and a specificity of 90% in the post-NSCLC group (AUC: 0.69; p < 0.05)., Conclusions: Promotor hypermethylation of the potential biomarker CFTR shows a discriminatory potential for differentiation of NSCLC patients to patients without a malign disease and should further be investigated.

Background: Fetal autopsy rates are decreasing in Western countries although post-mortem examinations render important information for the parents concerning the cause of abortion and risk of recurrence in future pregnancies., Objective: The intention of the presented study was to analyze the development of fetal autopsies in Germany during the last decade and to review accessible information obtained by fetal autopsy., Material and Methods: Reports of fetal autopsies conducted in two German university Institutes of pathology between 2005 and 2014 were evaluated retrospectively. Demographic data and the correlation between clinical diagnoses and autopsy findings were assessed. In addition, differences between spontaneous and induced cases of abortion and differences between the institutes were also documented., Results: Overall, 428 fetal autopsies were performed, whereby the number of autopsies decreased by 24.2% during the study period. Of the examined fetuses 29.7% were induced abortions which as expected exhibited different malformations compared to cases of spontaneous abortion (p < 0.001). There was no evidence of a malformation or other cause of death in 27.1% of the cases and 95.7% of these abortions occurred spontaneously. A discrepancy between clinical and autopsy findings was evident in 6.8% of cases and 3.5% of the autopsy examinations revealed at least one additional malformation compared to the prenatal clinical data., Conclusion: Despite improvements in prenatal diagnostics, fetal autopsies remain an important diagnostic tool even today contributing additional information in a considerable number of cases potentially revising clinical diagnoses.

Autopsies are of key importance for the understanding of the anatomy, pathophysiology and pathomorphology. In forensic medicine, the virtual autopsy is a standard instrument in autopsy practice. The advantage of postmortem imaging is the generation of a three-dimensional pre-autopsy snapshot of the body from head to toe with excellent visualization of skeletal pathologies and air inclusions. When angiography is performed, pathologies of the cardiovascular system can additionally be evaluated. The shortcomings of postmortem imaging are the low soft tissue contrast with CT imaging, the lack of haptic, olfactory and color impressions. Another limitation is the access to CT and particularly to magnetic resonance imaging (MRI) facilities and the necessary experience with the peculiarities of postmortem imaging. To date, postmortem imaging can supplement but not replace the traditional autopsy. Nevertheless, postmortem imaging adds valuable technical capabilities to the traditional autopsy. The ability to achieve valid results for the cause of death and additional diagnoses must be evaluated systematically for postmortem imaging, in particular in addition to CT or MR guided biopsies. This article gives an overview of the current state of the technology and encourages its development for application in pathology departments.

As even a mere thickening of the urothelium can harbor genetic changes identical to that of low grade papillary urothelial tumors, it is not always possible to clearly recognize a precursor lesion of urothelial carcinoma by routine histological diagnostics. Complementary immunohistochemical and molecular diagnostic methods assist the recognition of these entities. These methods especially help to identify clinically important genetically unstable cells as the hallmark of carcinoma in situ (CIS). Little is known about the clinical significance of the morphological subtypes of CIS, which range from large cell to micropapillary variants. For a better understanding of special types of bladder cancer (e.g. adenocarcinoma and squamous cell carcinoma), it seems to be important to define the phenotype and the molecular pattern of non-urothelial lesions, such as intestinal metaplasia and squamous metaplasia, better and more precisely.

Bladder cancer shows rare variants and special subtypes with diverse prognostic importance and therefore may necessitate different therapeutic approaches. For pathologists it is important to histologically diagnose and specify such variants. Nested variants of urothelial carcinoma with inconspicuous, well-formed tumor cell nests present with an aggressive course. The plasmacytoid variant, which morphologically resembles plasma cells is associated with a shorter survival time and a high frequency of peritoneal metastasis. Micropapillary urothelial carcinoma with small papillary tumor cell islands within artificial tissue retraction spaces and frequent lymphovascular invasion also has a poor prognosis. Other important rare differential variants listed in the World Health Organization (WHO) classification are microcystic, lymphoepithelioma-like, sarcomatoid, giant cell and undifferentiated urothelial carcinomas. Additionally, there are three special types of bladder cancer: squamous cell carcinoma, adenocarcinoma and small cell neuroendocrine carcinoma of the bladder. These tumors are characterized by pure squamous cell or glandular differentiation and are sometimes less responsive to adjuvant (chemo)therapy. Small cell carcinoma of the bladder mimics the neuroendocrine features of its pulmonary counterpart, shows an aggressive course but is sensitive to (neo-)adjuvant chemotherapy. The morphology and histology of the most important variants and special types are discussed in this review.

Testicular tumors can be divided into germ cell tumors and sex cord stromal tumors. Malignant testicular germ cell tumors (TGCT) represent about 90-95 % of all testicular tumors and are the most common solid neoplasms in young men aged 20-40 years with an increasing incidence in industrialized countries. Treatment of TGCT is performed by an individual and risk-adapted approach taking primary tumor histology, histopathlogical and molecular prognostic risk factors, tumor stage and for metastasized tumors the response to systemic chemotherapy into consideration. Knowledge of the specific histopathology of the primary tumor and the prognostic factors is of utmost importance for the treating urologist and oncologist in order to avoid undertreatment or overtreatment. Established risk factors which have been validated in retrospective and prospective studies for clinical stage I non-seminomatous TGCT are the presence of vascular invasion and the percentage of embryonal carcinoma. In clinical stage I seminomas tumor size (> 4 cm) and presence of rete testis infiltration have been identified as risk factors in retrospective but not in prospective studies. Quantitative histopathology of the primary tumor is also important for the management of small residual masses following chemotherapy: if the masses are ≤ 1 cm, postchemotherapy retroperitoneal lymph node dissection is only indicated if the primary tumor contains ≥ 50 % teratoma. Quantitative pathohistology of the resected residual masses is of importance for the decision-making process of a consolidating chemotherapy which is only of benefit if the amount of vital cancer tissue is > 10 %. Resection of residual hepatic and thoracic masses is indispensable. For gonadal stromal tumors knowledge of atypical nuclear forms, increased rate of mitosis and increased growth fractions are important for therapy planning.

Results of molecular pathology have supported changes in the 2004 WHO classification of urothelial cancer. Since then new molecular data such as the distribution pattern of the fibroblast growth factor receptor 3 (FGFR3) has further supported the principle of low and high grade entities of urothelial carcinoma. Animal experiments with knockout mice and conditional knockout systems reveal important parallels to humans and results emphasize the cellular context as a trigger for malignancy. One special feature of the urothelium is its high protection of the urothelial cells by members of the retinoblastoma gene family, efficiently inhibiting invasion even in the presence of p53 mutations. In search of the tumor stem cell phenotype the basal cell phenotype is the focus of attention providing a high clonogenic potential. At the same time detailed analysis of the distribution of mutations in the mitochondrial genome within the urothelium will help to gain insight into the spreading of normal cell or tumor cell clones. The overall data in urological oncology provide evidence that diagnostic and prognostic tools for urothelial cancer can only be reached with multiparametric approaches.