[Mimickers and diagnostic pitfalls of urinary bladder cancer]. / Nachahmerläsionen/diagnostische Fallstricke des Harnblasenkarzinoms.

Urothelial carcinoma (UC) is by far the most common malignant neoplasm of the urinary bladder; however, there are both benign and malignant changes of the urothelium which morphologically resemble urothelial carcinomas or other carcinomas of the urinary bladder. Thus, these mimickers can cause problems in the histomorphological diagnosis. This article provides an overview of possible mimickers and pitfalls of bladder cancer as well as practical notes on the diagnostic procedure, partly using case studies.

[Cytology in uropathological diagnostics]. / Zytologie in der uropathologischen Diagnostik.

Cytology in uropathological diagnostics is mainly performed for oncological purposes. The assessment of malignancy by urothelial cell morphology is therefore decisive; however, cytology is only sensitive enough to detect high-grade tumor cells and the different low-grade tumors cannot be reliably diagnosed. Thus, the four-tier classification system of cytological findings (i.e. negative, atypical cells but significance uncertain, suspicious and positive) refers to high-grade tumor cells only. Furthermore, for valid cytological diagnostics not only the cytological specimen but also clinical information on cystoscopy findings and, if applicable, a biopsy should be evaluated together. In difficult differential diagnostic settings, e.g. differentiation between reactive versus neoplastic atypia or difficult to access lesions in the upper urinary tract, additional fluorescence in situ hybridization of cytological preparations might be helpful. At the moment there are no indications for further immunocytology or additional biomarker tests.

[Non-invasive and invasive urothelial tumours: special challenges in uropathological diagnostics]. / Nicht-invasive und invasive Urothelneoplasien : Besondere Herausforderungen in der uropathologischen Diagnostik.

The current 2004 WHO classification of bladder tumors categorizes non-invasive and invasive urothelial neoplasms into prognostically relevant groups according to the histopathological cell morphology and underlying genetic changes. Although many parts of the classification have not been changed dramatically, even small changes have caused uncertainty and scepticism among urologists and pathologists in recent years. The following review article is structured into various challenges for urologists and pathologists and provides an overview of rare but clinically relevant subgroups and diagnostics, interpretation of diagnoses and pathological findings with respect to consequences for the daily clinical routine (extended diagnosis, therapy and prognosis).

[Urine markers with special regard to fluorescent in situ hybridization (FISH)]. / Uringebundene Marker mit besonderer Berücksichtigung der Fluoreszenz-in-situ-Hybridisierung (FISH).

Patient care with noninvasive or minimally invasive methods is appealing for the patient. It has to be assessed in terms of validity to guarantee improvement of patient care. Urine cytology for the detection of tumour cells can be considered a valid method since its specificity and sensitivity is high when high-grade tumour cells are sought. High-grade tumour cells are considered the clinically most relevant finding in urine specimens. Fluorescent in situ hybridization of interphase nuclei on centromeric and gene loci has been optimized for urothelial carcinoma and increases the sensitivity of tumour findings. It also gives a valid chance to adapt the number of cystoscopies in the follow-up of bladder cancer patients more individually.

[Current knowledge in molecular pathology of urothelial cancer]. / Stand des Wissens zur molekularen Pathologie des Urothelkarzinoms.

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.

[Urine-based tumour diagnostics for bladder cancer: effects of the new histopathological classification--food for thought]. / Urinbasierte Tumordiagnostik des Harnblasenkarzinoms: Auswirkungen der neuen histopathologischen Klassifikation--ein Denkanstoss.

The new WHO classification of bladder cancer was published in 2004 and consequently cannot be regarded as very recent. However, it is still timely since it picks up considerations affecting other schemes of tumour classification as well. Genetic results are included in the context of morphology, and at the same time a high inter- and intra-observer agreement is striven for as a matter of high quality patient care. The WHO classification of 2004 does not include cytological diagnosis. Thinking about and considering tumour tissue diagnosis, the style of cytological diagnoses is also affected. For tissue diagnoses, low- and high-grade tumours are differentiated from benign lesions including reactive changes. The element of this classification which has to be transferred to cytology is especially the unequivocal diagnosis of high-grade lesions. The low-grade lesion, correlating with tissue of well-differentiated papillary tumours and dysplasias, mostly cannot be distinguished cytologically with certainty from a broad spectrum of non-malignant lesions (papillomas, reactive urothelial detachment in urolithiasis patients, cytology specimen from vigorously irrigated bladders). For the latter group our aim should be to establish an additional diagnostic tool of high quality driven by clinical questions (e.g. potential of tumour progression).

[Update on urothelial carcinoma histopathology]. / Aktuelles zur Histopathologie des Harnblasenkarzinoms.

Urothelial carcinoma comprise a heterogenous group of diseases with very different clinical outcome: 70%-80% of urothelial carcinoma are genetically stable and associated with a favorable prognosis, while 20%-30% are genetically unstable and have a high progression rate. Therefore, the current WHO Classification (2004) reduces the histologic grade to simply 'low grade' and 'high grade'. In addition to TNM classification and histologic grade, genetic factors such as p53 mutations, fibroblast growth factor receptor 3 (FGFR3) and phosphatidylinositol-3-kinase (PIC(3)CA) are relevant in a patient's prognosis.

[Nested-variant urothelial carcinoma. Case report and molecular aspects]. / Die Nested-Variante des Urothelkarzinoms. Fallbericht und molekulare Aspekte.

The nested variant of urothelial carcinoma is a rare urothelial neoplasia which is characterized by relatively bland morphology and early muscle-invasive growth. We report on a 65-year-old male patient with a non-invasive high-grade urothelial lesion (carcinoma in situ and pTa G3). After treatment with BCG an invasive urothelial carcinoma was discovered whereas the carcinoma in situ had disappeared. Examination of the bladder specimen showed a nested-variant urothelial carcinoma. Molecular analyses indicated a de-novo genesis of the invasive urothelial carcinoma.

[Histopathology of urothelial carcinomas: crucial for patient management]. / Histopathologie des Harnblasenkarzinoms: Entscheidend für das Management der betroffenen Patienten.

Urothelial carcinomas include tumors with very different clinical outcomes: 70-80% of urothelial carcinomas are genetically stable and are associated with a favorable prognosis, but 20-30% are genetically unstable and have a high progression rate. Therefore, the current World Health Organization classification (2004) differentiates the histologic grade as low grade (LG) or high grade (HG). Unequivocal language is mandatory to optimize therapy and assess prognosis. In addition to TNM classification and histologic grade, genetic factors such as mutations of p53, fibroblast growth factor receptor 3 (FGFR3), and phosphatidylinositol-3-kinase (PIK(3)CA) are relevant in patients' prognoses.