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Biopsien gehoren zunehmend zum Standardinstrument, um Nierentumoren abzuklaren. Die Diagnostik per Nadel ist zuverlassig und liefert wichtige Ergebnisse fur die Therapie. Entscheidend ist, ausreichend qualitatives Gewebe zu entnehmen — auch als Basis fur neue diagnostische Ansatze.

Colorectal cancer (CRC) is the second leading cause for cancer-related death in industrialized nations. Nodal involvement has been identified as a relevant prognostic feature in CRC. Extra nodal metastasis (ENM) describes the spread of malignant cells beyond the nodal capsule. ENM is thought to be an independent risk factor for poor survival. This study examined ENM as an independent risk factor for poor overall survival in patients with node-positive CRC. Data from a prospectively maintained CRC database was retrospectively analyzed. Blinded slides of patients with stage III and IV CRC following radical surgical resection were re-examined for the presence of ENM. The effect of ENM on overall survival was examined using Kaplan–Meier curves. One hundred forty-seven cases with node-positive CRC (UICC stages III and IV) including 78 cases with ENM were included for analysis. ENM was seen in 60 patients with colon cancer (58.8%) and in 18 patients with rectal cancer (40%), p = 0.033. ENM-positive patients had a significantly higher odd for cancer-related death compared to ENM-negative patients ratio of [OR 0.44: 0.22–0.88, CI 95%, p = 0.021], p = 0.02. The median overall survival was significantly longer in patients without ENM, 51.0 ± 33 vs. 30.5 ± 42 months, p = 0.02. Extra nodal metastasis is an independent prognostic factor in patients with node-positive colorectal cancer. Extra nodal metastasis is associated with high odds of tumor-related mortality and poor overall survival.

Bei der Nachresektion nach T1-Blasentumoren kann eine exakte Relokalisation des ehemaligen infiltrativen Tumorareals wegen reaktiver Veranderungen, multipler Narben oder wechselnder Operateure erschwert sein. In unserer Untersuchung haben wir die Bedeutung der exakten Tumordokumentation und die Lokalisation und Rate der Residualtumore analysiert. Von Juli 2007 bis Februar 2012 sind an unserer Klinik 167 Nachresektionen nach einem T1 high grade-Blasentumor durchgefuhrt worden. Neben der Residualtumorrate und klinischen Parametern wurde die Lokalisation der Residualtumore untersucht, die anhand unserer standardisierten Blasentumordokumentation evaluiert wurde. Es zeigte sich eine Residualtumorrate von 58,1 % (97 von 167 Patienten). In 85,6 % (83 von 97 Patienten) der Falle war das Residuum im Bereich des ehemaligen Tumorareals: davon 41,2 % (n = 40) ausschlieslich im Areal des ehemaligen Tumors, 44,3 % (n = 43) multifokal im ehemaligen Areal und zusatzlich an neuen Arealen. Bei 11 Patienten (11,3 %) lag ein Residualtumor im Bereich des ehemaligen Tumorareals vor, welches endoskopisch vom Operateur als unauffallig eingeschatzt und erst histologisch bestatigt wurde. T1 high grade-Blasentumore zeigten eine relevante Rate von Residualtumoren in der Nachresektion, was nach unseren Ergebnissen die leitliniengerechte obligate Nachresektion rechtfertigt. In den meisten Fallen ist das ehemalige Tumorareal betroffen. Eine exakte Nachresektion des ehemaligen Tumorareals ist durch die vorgestellte Blasentumordokumentation auch bei multiplen Narben, reaktiven Veranderungen und wechselnden Operateuren gezielt moglich.

Alpha-methylacyl-CoA racemase (AMACR, p504S), an enzyme involved in cellular energy metabolism by the oxidation of branched-chain fatty acids, is a biomarker that is known to be overexpressed in prostatic and colorectal carcinoma as well as in papillary renal cell carcinoma. We aimed to correlate its immunohistochemically detected expression with histopathological grading in noninvasive bladder cancer in order to hint at a so far unknown role of AMACR in the pathobiology of this tumor entity. Therefore, a cohort of 163 patients (mean age 65.3 years) diagnosed with noninvasive bladder cancer was immunohistochemically investigated in terms of AMACR expression. There was variable positive AMACR staining in 52 (31.9%) of the cases investigated. All tumors were graded by three independent clinical histopathologists according to the 1973 World Health Organization (WHO) and the 1998 WHO/International Society of Urological Pathology (ISUP) system. We found a significant positive correlation between AMACR expression and higher tumor grades using both histopathologic grading schemes. These novel findings clearly allow including high-grade noninvasive bladder carcinomas in the group of AMACR-positive neoplasms and might reflect a so far unknown role of AMACR racemase in the pathobiology and tumor cell energy metabolism of the latter tumor entity.

Renal cell carcinomas (RCCs) of the clear cell type are associated with alteration of the von Hippel-Lindau (VHL) tumor suppressor gene, the subsequent stabilization and overexpression of hypoxia inducible factor (HIF), which causes upregulation of transforming growth factor-alpha (TGFα), thereby generating an autocrine loop via the epidermal growth factor receptor (EGFR). So far, there is only limited information available about the differential expression of the EGFR and TGFα in clinical samples of RCCs harboring VHL alterations. In this study, we report comparative analyses of the EGFR and TGFα protein and messenger RNA (mRNA) expression in 99 RCCs of the clear cell type including 54 tumors with known VHL status and show that in comparison to their VHL wild type (wt) counterparts, TGFα and EGFR are more frequently expressed in RCCs harboring VHL alterations. Furthermore, upregulation of EGFR but not TGFα protein expression correlated to higher tumor stage. We speculate that EGFR expression is associated with the VHL status of RCCs and discuss the findings with respect to their potential impact on novel targeted therapeutic approaches to RCC.

Neurofibromatosis 1 (NF1) is one of the most common autosomal dominant diseases. Although there is a considerable variability in clinical expression, NF1 is almost fully penetrant in adult patients and may be associated with a variety of skeletal anomalies. Spinal deformities are the most common skeletal manifestation, with an incidence estimated from 10-25% in various studies. Some NF1 patients have a dystrophic form of scoliosis, which is characterized by early age at onset and rapid progression. Complications have been reported during spinal instrumentation of dystrophic curves due to soft, non-resistant vertebral bony tissue, suggesting that an alteration of bone quality may occur in NF1 patients. Recent studies have suggested that decreased bone mineral density (BMD) may occur among patients with NF1. We performed a cross-sectional study on 104 adults with NF1, using quantitative ultrasonometry (QUS) to investigate whether decreased BMD is a general phenomenon in NF1 patients. The data reveal that BMD, as measured by age- and gender- adjusted Z-scores, is significantly lower in NF1 patients than in the normal reference population. The decrease in BMD appears to be even more marked among NF1 patients with scoliosis that requires surgical treatment. The findings indicate that NF1 produces a generalized alteration of bone in addition to the focal osseous dysplasias of the vertebrae, tibia, and sphenoid wing that characterize this condition. The pathological mechanism underlying these bony changes remains to be elucidated.

Neuroblastoma is the most frequent extracranial solid tumor of early childhood. Histologically and genetically, neuroblastoma represents a heterogeneous group of tumors with significant differences in clinical behavior. In the past, several different characteristic chromosomal aberrations of neuroblastoma have been described, of which a deletion on chromosome 1p and N-myc amplification have been shown to be of major prognostic significance. However, the role of various other nonrandom DNA imbalances in tumor development and progression needs to be clarified. Taking advantage of the recently established comparative genomic hybridization (CGH), we show that this method is able to accurately detect chromosomal imbalances of known prognostic impact. As CGH gives a comprehensive picture of genetic imbalances in just one experiment, it additionally sheds light on other abnormalities of possible prognostic relevance. We therefore recommend further use of this method not only in the field of research but also for the purpose of genetic routine diagnostics in neuroblastoma.

Intracellular fibrillar congophilic inclusions are well known as neurofibrillary tangles in neurons and as Biondi bodies in choroid plexus epithelial cells. Recently similar amyloid-like inclusions in adrenal cortical cells were described (Eriksson and Westermark 1990). This study on 150 adrenal glands confirms these observations. In our material the age-related accumulation of congophilic inclusions starts earlier (in the sixth decade) and reaches a higher incidence (42.7%). We found similar intracellular inclusions in other endocrine organs, for example in the anterior lobe of the pituitary, in the cells of parathyroid glands and in Sertoli cells. The age-related incidence of these fibrillar inclusions in the pituitary was 68%: the co-incidence with interstitial amyloid deposits was 49.5%. Thus the intracellular accumulation of congophilic fibrils in old age is a wide-spread phenomenon and occurs not only in neurons but also in endocrine cells (adrenal, pituitary and parathyroid glands) and in active secretory cells (choroid plexus and Sertoli cells).

Fibro-osteo-cemental lesions of the jaw bones are a heterogeneous group of diseases which present problems in classification. Psammous desmo-osteoblastoma is one of four newly proposed entities (Makek 1983) and has until now been characterized by its light microscopic, clinical and radiological features. On electron microscopy this tumour exhibits fibroblastic (preosteoblastic), osteoblastic and osteocytic cells and a globular mineralization unlike the mineralization of the psammoma bodies. Immunohistological investigations with anti-osteonectin, a bone specific protein linking mineral to collagen, showed positive intracellular staining in all tumour cells and extracellular staining in the osteoid. The psammoma bodies were, however, not stained. These results confirm the view of the osteogenic histogenesis of psammous desmo-osteoblastoma, with an osteogenic differentiation of the tumour cells, bone formation and association of psammoma bodies which are not of bone origin. This combination of findings supports the view that psammous desmo-osteoblastoma represents a new and distinct entity occurring in desmal preformed cranio-facial bones which should be incorporated in a revised WHO-classification.

Using light and electron microscopy, 65 cases of amyloid deposits in the heart were examined. Five different groups were distinguished: I. isolated atrial amyloidosis, II. senile cardiac amyloidosis, III. cardiac amyloid accompanying chronic infections and tumors, IV. cardiac amyloid accompanying plasma cell dyscrasia, V. idiopathic cardiac amyloidosis. Seen structurally, no principal differences in the precise localization of the amyloid deposits were found in any of the groups investigated. Amyloid is always deposited in the vicinity of cells with myocytic cell differentiation (i.e. the heart muscle cells, non-striated muscle cells of the vessels), whereby the relevant basement membranes serve as conductors. A systematic relationship between amyloid and the collagenous fibers of the interstitium or the tunica adventitia of the vessels could not be demonstrated, which shows the concept "pericollagen" to be inadequate for the morphological characterization of amyloid deposits in the heart. Whereas for group I a localized mechanism for the production of amyloid must be considered, in the case of groups II-V a vascular principle expression of a generalized amyloidosis seems to be the major factor. The question of the differing concentration of amyloid deposits in the heart suggests that localized factors (e.g. changes in the myocytic basement membranes) and quantitative changes of the amyloid-building proteins may also be important.

140 biopsies from 108 patients afflicted with the carpal tunnel syndrome were studied, 27 of whom showed deposition of amyloid, in 6 of them to such an extent that the amyloid was considered significant in the pathogenesis of the carpal tunnel syndrome. Morphologically, vessels and ligaments were affected and especially the peritendinous structures. As it was always part of generalized amyloidosis, the amyloid in the carpal tunnel consisted immunohistologically of amyloid A in three cases (including one case with simultaneous amyloid deposition of the AA- and the AB-type), of amyloid A kappa in one case, of amyloid of prealbumin origin in seventeen cases and of AB-amyloid in eight cases. We also described for the first time the manifestation of generalized senile amyloidosis (ASs) in the carpal tunnel. Deposition of amyloid of beta-2-microglobulin type (AB) in the carpal tunnel was particularly frequent and massive.