[Orchiectomy due to early syphilis]. / Frühsyphilis als Ursache einer Orchiektomie.

Granulomatous and abscessing testicular inflammations are important differential diagnoses of testicular tumors. Infectious orchitis should always be considered in unclear testicular masses with negative tumor markers. We report the case of a 45-year-old man with abscessing orchitis due to early syphilis diagnosed after orchiectomy with the suspicion of a seminoma.

Beyond the BRAFV600E hotspot: biology and clinical implications of rare BRAF gene mutations in melanoma patients.

BRAF gene mutations can be found in approximately 50% of melanomas, but the most common BRAF mutation leads to substitution at residue 600 of the protein, from valine to glutamic acid. BRAFV600E occurs in up to 95% of all melanoma cases and can be successfully blocked by using a combination of BRAF- and MEK inhibitors. The wider availability of next-generation sequencing is revealing more non-V600 BRAF mutations, and the clinical implications of these mutations are widely unknown. In this review, we will discuss the biology of the MAPK pathway and the different types of BRAF mutations as well as their effect on MEK activation. Current literature will be reviewed including in vitro data, case reports and case series.

Direct comparison of regulators of calcification between bone and vessels in humans.

Calcification is not only physiologically present in bone but is a main pathophysiological process in vasculature, favouring cardiovascular diseases. Our aim was to investigate changes in the expression of calcification regulators during vascular calcification in bone and vasculature. Levels of gene expression of osteoprotegerin (OPG), receptor activator of NF-κB ligand (RANKL), osteopontin (OPN), matrix gla protein (MGP), bone sialoprotein (BSP), SMAD6, and runt-related transcription factor 2 (RUNX2) were determined in bone, aorta, and external iliac artery tissue samples of transplant donors. Histological stages of atherosclerosis (AS) in vessels are defined as "no changes", "intima thickening", or "intima calcification". Patients' bone samples were subgrouped accordingly. We demonstrate that in vessels BSP and OPN expression significantly increased during intima thickening and decreased during intima calcification, whereas the expression of regulators of calcification did not significantly change in bone during intima thickening and intima calcification. At the stage of intima thickening, MGP, OPG, and SMAD6 expression and at stage of intima calcification only MGP expression was lower in bone than in vessel. The expression of BSP and RANKL was regulated in opposite ways in bone and vessels, whereas the expression of MGP, OC, RUNX2, and OPN was regulated in a tissue-specific manner. Our study is the first direct comparison of gene expression changes during AS progression in bone and vessels. Our results indicate that changes in the expression of regulators of calcification in the vessel wall as well as in bone occur early in the calcification process, even prior to deposition of calcium/phosphate precipitation.

Low expression of the putative tumour suppressor spinophilin is associated with higher proliferative activity and poor prognosis in patients with hepatocellular carcinoma.

BACKGROUND: Spinophilin, a multifunctional intracellular scaffold protein, is reduced in certain types of cancer and is regarded as a novel putative tumour suppressor protein. However, the role of spinophilin in hepatocellular carcinoma (HCC) has never been explored before. METHODS: In this study, we determined for the first time the expression pattern of spinophilin in human HCC by immunohistochemistry and quantitative reverse transcriptase-PCR analysis. In addition, we performed immunohistochemical analysis of p53, p14(ARF) and the proliferation marker Ki-67. Kaplan-Meier curves and multivariate Cox proportional models were used to study the impact on clinical outcome. Small interfering RNA (siRNA) was used to silence spinophilin and to explore the effects of reduced spinophilin expression on cellular growth. RESULTS: In our study, complete loss of spinophilin immunoreactivity was found in 44 of 104 HCCs (42.3%) and reduced levels were found in an additional 37 (35.6%) cases. After adjusting for other prognostic factors, multivariate Cox regression analysis identified low expression of spinophilin as an independent prognostic factor with respect to disease-free (hazard ratio (HR)=1.8; 95% confidence interval (CI)=1.04-3.40; P=0.043) and cancer-specific survival (HR=2.0; CI=1.1-3.8; P=0.025). Reduced spinophilin expression significantly correlated with higher Ki-67 index in HCC (P=0.014). Reducing spinophilin levels by siRNA induced a higher cellular growth rate and increased cyclin D2 expression in tumour cells (P<0.05). CONCLUSION: This is the first study of the expression pattern and distribution of spinophilin in HCC. According to our data, the loss of spinophilin is associated with higher proliferation and might be useful as a prognostic marker in patients with HCC.

Prolactin receptor is a negative prognostic factor in patients with squamous cell carcinoma of the head and neck.

BACKGROUND: The influence of human prolactin (hPRL) on the development of breast and other types of cancer is well established. Little information, however, exists on the effects of hPRL on squamous cell carcinomas of the head and neck (SCCHNs). METHODS: In this study, we evaluated prolactin receptor (PRLR) expression in SCCHN cell lines and assessed by immunohistochemistry the expression in 89 patients with SCCHNs. The PRLR expression was correlated with clinicopathological characteristics as well as clinical outcome. The effect of hPRL treatment on tumour cell growth was evaluated in vitro. RESULTS: Immunoreactivity for PRLR was observed in 85 out of 89 (95%) tumours. Multivariate COX regression analysis confirmed high levels of PRLR expression (>25% of tumour cells) to be an independent prognostic factor with respect to overall survival (HR=3.70, 95% CI: 1.14-12.01; P=0.029) and disease-free survival (P=0.017). Growth of PRLR-positive cancer cells increased in response to hPRL treatment. CONCLUSION: Our data indicate that hPRL is an important growth factor for SCCHN. Because of PRLR expression in a vast majority of tumour specimens and its negative impact on overall survival, the receptor represents a novel prognosticator and a promising drug target for patients with SCCHNs.

Distinct signatures of B-cell homeostatic and activation-dependent chemokine receptors in the development and progression of extragastric MALT lymphomas.

Chemokine receptors mediate migration and activation of lymphocytes through binding of their ligands. Recent studies have revealed important contributions of chemokine receptors to the development, progression, and dissemination of haematopoietic neoplasms. Because the chemokine receptor expression profile in extragastric MALT lymphoma is unknown, we performed a comprehensive study on tissue samples of parotid glands, parotid glands affected by Sjögren syndrome, extragastric MALT lymphoma, and extranodal diffuse large B-cell lymphoma (eDLBCL) originating from MALT lymphoma (transformed MALT lymphoma). By investigating the expression of 19 chemokine receptors by real-time PCR using a semi-quantitative approach and of four chemokine receptors (CCR1, CCR5, CXCR6, and XCR1) by immunohistochemistry, we show that the chemokine receptor expression profiles of extragastric MALT lymphomas differ substantially from those of extranodal DBLCL, with lower expression of CCR1, CCR8, and CXCR3, and the absence of expression of CX3CR1 and XCR1 in eDLBCL. Expression of CCR6, CCR7, CXCR3, CXCR4, and CXCR5, responsible for B-cell homing to secondary lymphoid tissue, was detected in both B-cell malignancies. Expression of CCR4 was just detected in trisomy 3-positive MALT lymphoma cases. Comparing gastric with extragastric MALT lymphomas, up-regulation of CXCR1 and CXCR2 accompanied by down-regulation of CCR8 and CX3CR1 and loss of XCR1 expression in extragastric MALT lymphomas appear to be key determinants for the site of origin of MALT lymphomagenesis. Our results support a model of stepwise progression of extragastric MALT lymphoma from a non-neoplastic event to Sjögren syndrome, to MALT lymphoma, and finally to overt eDLBCL, guided by differentially expressed B-cell homeostatic and activation-dependent chemokine receptors and their ligands.

How a cell deals with abnormal proteins. Pathogenetic mechanisms in protein aggregation diseases.

Defective protein folding is responsible for many diseases. Although these diseases seem to be quite diverse at the first glance, there is evidence for common pathogenetic principles. The basis of the pathological changes is the cell's inability to prevent protein misfolding, to revert misfolded proteins to normal or to eliminate misfolded proteins by degradation. This could result in deposition of potentially cytotoxic protein aggregates (protein aggregation diseases). Chronic degenerative diseases of the central nervous system (e.g. Alzheimer's and Parkinson's disease), the amyloidoses, but also chronic liver diseases, for example alcoholic and nonalcoholic steatohepatitis, belong to this category of disorders. This review highlights general pathogenic principles of protein aggregation diseases based on immunohistochemical and biochemical studies as well as observations in a mouse model for protein aggregation in the context of alcoholic and nonalcoholic steatohepatitis. The cellular defense mechanisms involved in protein quality control as well as the pathogenesis of protein aggregation diseases will be discussed.

Successful antibiotic treatment of Borreliosis associated pseudolymphomatous systemic infiltrates.

The clinical management of late stage Borreliosis can be difficult due to various associated symptoms and signs and cumbersome microbiological tests. We report a case of successful antibiotic treatment of Borreliosis-associated pseudolymphomatous infiltrates in bone marrow and lymph nodes, which were diagnosed by bone marrow trephine biopsy and positron emission tomography.