An 18th century description of endometriosis : The autopsy of the Countess von Reitzenstein.

Descriptions of endometriosis in 18th century monographs and manuscripts are rare and the recorded macroscopic features of endometriosis seldom support this attribution to the described cases. Recently, we became aware of an anonymous German autopsy report from the 18th century. After transcription, the manuscript was assessed by pathologists with historical expertise. This revealed that the patient died because of a malignant tumor, most probably of a gynecological origin. Furthermore, the described ovarian pathologic findings strongly support the diagnosis endometriotic ovarian cyst. Like Giovanni Battista Morgagni (1668-1772) in his landmark publication De Sedibus et Causis Morborum per Anatomen Indagatis (1761), the author correlated the pathological findings at autopsy with the symptoms of the patient. The identity of the patient could, with high probability, be established as being the Countess of Reitzenstein, the wife of a Prussian general major in the army of Friedrich the Great: Karl Erdmann von Reitzenstein (1722-1789).

Acute dyspnea caused by a giant spindle cell lipoma of the larynx.

BACKGROUND: The spindle cell lipoma (SCL) is a special type of lipoma and this is very rare in the head and neck regions. There are only five reported cases exist, which describes the occurrence of a SCL in the hypopharynx. METHODS: Our case report presents a case of a very large SCL in the larynx. We want to describe that how we treated the patients and compared the situation with other reported cases. RESULTS: Intraoperatively, we found a tumor mass of 7 × 5 cm. It was successfully removed with the carbon dioxide laser. No postoperative complications occurred. CONCLUSIONS: Although SCL is a very rare diagnosis in the larynx/hypopharynx, it should be included in the differential diagnosis of larynx/hypopharynx tumors. Our case is the first report of such a large SCL in the larynx. The clinical symptoms occurred relatively late and ended up in an acute situation of stridor and dyspnea.

[The Malady of Emperor Frederick III. and Virchow's diagnostic role]. / Die Krankheit Kaiser Friedrichs III. und Virchows Rolle.

Crownprince Frederick Wilhelm of Prussia was once the hope of the liberal movement in Germany. He embodied and lived a humanistic ideal based on the spirit of the enlightenment. Starting in January 1887 the passionate pipe smoker suffered on an unusual long hoarseness. A polyp of the vocal cord was diagnosed. Although this diagnosis seemed harmless, an odyssee was launched that made history. Rudolf Virchow-the foremost pathologist of that time-was involved in the following histological diagnosis. His role and that of the sprouting histopathology will be presented in this essay.

Type A dissection and chronic dilatation: tenascin-C as a key factor in destabilization of the aortic wall.

OBJECTIVES: Tenascin-C plays an important role in myocardial and vascular remodelling. We hypothesized that tenascin-C is a key factor in the development of degenerative disease of the ascending aorta, leading to chronic dilatation and acute aortic dissection. METHODS: Ascending aortic wall specimens were obtained during surgery for chronic dilatation (n=52) and acute Type A dissection (n=30). Patients (n=12) undergoing aortic valve replacement served as controls. Tenascin-C expression was evaluated by immunostaining and semi-quantitatively assessed using the ImageJ software. TN-C levels in peripheral blood were determined by enzyme-linked immunosorbent assay. RESULTS: Histological examination showed a clear difference between chronic dilatation and acute dissection. In chronic dilatation, tenascin-C staining was homogenously distributed throughout the media parallel to vascular smooth muscle cells. In acute dissection, a strong staining with a heterogenous and spotty distribution was detected. Control aortas showed no tenascin-C staining. Tenascin-C expression was significantly higher in Type-A dissection compared with chronic dilatation. This was accompanied by a significant elevation of tenascin-C levels in peripheral blood in acute dissection. There was no statistical correlation between the tenascin-C level in peripheral blood and the aortic diameter either in dissection or in dilatation. CONCLUSIONS: Tenascin-C is a marker of progressive destabilization of the aortic wall independent of size in chronic dilatation and acute dissection. Therefore, it might be a valuable tool in guiding intervention strategies in patients with disease of the ascending aorta.

The Austrian Brain Tumour Registry: a cooperative way to establish a population-based brain tumour registry.

In Austria, registration of malignant brain tumours is legally mandatory, whereas benign and borderline tumours are not reported. The Austrian Brain Tumour Registry (ABTR) was initiated under the auspices of the Austrian Society of Neuropathology for the registration of malignant and non-malignant brain tumours. All Austrian neuropathology units involved in brain tumour diagnostics contribute data on primary brain tumours. Non-microscopically verified cases are added by the Austrian National Cancer Registry to ensure a population-based dataset. In 2005, we registered a total of 1,688 newly diagnosed primary brain tumours in a population of 8.2 million inhabitants with an overall age-adjusted incidence rate of 18.1/100,000 person-years. Non-malignant cases constituted 866 cases (51.3%). The incidence rate was higher in females (18.6/100,000) as compared to males (17.8/100,000), while 95/1,688 (5.6%) cases were diagnosed in children (<18 years). The most common histology was meningioma (n = 504, 29.9%) followed by glioblastoma (n = 340, 20.1%) and pituitary adenoma (n = 151, 8.9%). Comparison with the Central Brain Tumor Registry of the United States (CBTRUS) database showed high congruency of findings. The ABTR model led by neuropathologists in collaboration with epidemiologists and the Austrian National Cancer Registry presents a cooperative way to establish a population-based brain tumour registry with high quality data. This setting links cancer registration to the mission of medical practice and research as defined by the World Medical Association in the Declaration of Helsinki. The continued operation of ABTR will aid in monitoring changes in incidence and in identifying regional disease clusters or geographic variations in brain tumour morbidity/mortality.

Histopathology of columnar-lined esophagus in patients with gastroesophageal reflux disease.

BACKGROUND AND AIMS: The question of whether an endoscopically normal-appearing esophagogastric junction should be biopsied in patients with gastroesophageal reflux disease is controversial. We have addressed this issue using endoscopy and histopathology. METHODS: A total of 114 consecutive patients (58 males) with symptoms of gastroesophageal reflux disease prospectively underwent endoscopy, including biopsy sampling from the esophagogastric junction. Endoscopically visible columnar-lined esophagus was defined by the presence of gastric-type mucosa above the level of the rise of the gastric folds. Histopathology was conducted using the Paull-Chandrasoma classification. RESULTS: Of the 114 patients, 85 (74.6%) had endoscopically visible columnar-lined esophagus of length < or =0.5 cm (n = 82), 1 cm (n = 2) and 7 cm (n = 1); 29 patients (25.4%) had a normal endoscopic junction. All patients had histopathologic columnar-lined esophagus. Intestinal metaplasia and low-grade dysplasia was identified in 26 (22.8%) and 5 (4.4%) individuals, respectively, and was not statistically different in endoscopically normal vs. abnormal junction (P = 0.408 for intestinal metaplasia, P = 0.775 for low grade dysplasia). Intestinal metaplasia was independent from endoscopic esophagitis (P = 0.398) and hiatal hernia (P = 0.405). CONCLUSIONS: Columnar-lined esophagus cannot be excluded by endoscopy. In patients with gastroesophageal reflux disease, biopsy sampling of normal-appearing junction is recommended for histopathologic exclusion of intestinal metaplasia and low-grade dysplasia.

Videoendoscopy and histopathology of the esophagogastric junction in patients with gastroesophageal reflux disease.

BACKGROUND AND AIMS: During endoscopy the stomach is considered to rise at the level of the 'gastric' folds; however, anatomical studies have demonstrated that the proximal gastric folds may in fact be esophageal. This prospective study was designed to assess the histopathology of endoscopically visible proximal gastric folds in patients with gastroesophageal reflux disease. METHODS: 35 consecutive patients (20 males) with gastroesophageal reflux disease underwent video endoscopy, including biopsy sampling from the endoscopically visible esophagogastric junction (0 cm, 0.5 cm and 1.0 cm distal to the rise of gastric folds and 0.5 cm and 1.0 cm proximal to it). Endoscopy was digitally recorded and reviewed for assignment of biopsy level. Columnar-lined esophagus and esophagitis were cataloged according to the Paull-Chandrasoma histopathologic classification and the Los Angeles endoscopic classification. RESULTS: Endoscopy: Normal endoscopic esophagogastric junction was seen in 11 (31%) patients and visible columnar-lined esophagus < or = 0.5 cm in 24 (69%). HISTOLOGY: Columnar-lined esophagus extended 1.0 cm in 22.8% of patients and 0.5 cm in 51.4%, distal to the rise of the gastric folds. In all patients columnar-lined esophagus was interposed between squamous epithelium and gastric oxyntic mucosa. Thus, so-called gastric folds contained mucosa of esophageal origin in all patients. Intestinal metaplasia (Barrett esophagus) was detected in eight (22.9%) patients. CONCLUSIONS: Endoscopy cannot exclude histopathologic columnar-lined esophagus within gastric rugae. Thus, visible 'gastric' folds should not be used for definition of the esophagogastric junction but as a reference landmark for biopsy sampling during endoscopy.

Progressive up-regulation of genes encoding DNA methyltransferases in the colorectal adenoma-carcinoma sequence.

Epigenetic silencing is a prominent feature of cancer. Here, we investigated the expression of DNA demethylase and three DNA methyltransferases during colorectal tumorigenesis comparing the genes encoding DNA methyltransferases 1 (DNMT1), 3A, and 3B (DNMT3A and DNMT3B) with methyl-CpG binding domain protein 2 (MBD2), recently described as the only active DNA demethylase. Total RNA isolated from normal colonic mucosa (n = 24), benign adenomas (n = 18), and malignant colorectal carcinomas (n = 32) was analyzed by reverse transcriptase-PCR with subsequent quantification by capillary gel electrophoresis. In contrast to MBD2, expression of DNMT1 and DNMT3A increased in parallel to the degree of dysplasia, with significant overexpression in the malignant lesion when compared with mucosa or with benign lesions (DNMT1). Pairwise comparisons between tumors and matched, adjacent healthy mucosa tissue (n = 13) revealed that expression of all three genes encoding DNA methyltransferases increased by two- to three-fold. Our data suggest a relevant role of the DNA methyltransferases during colorectal tumorigenesis. This increase is not counterbalanced by enhanced expression of the demethylating component MBD2. As a consequence, epigenetic regulation in the adenoma-carcinoma sequence may be driven by increased methylating activity rather than suppressed demethylation.

Osteoclast-like giant cell tumor in mucinous cystadenocarcinoma of the pancreas: an immunohistochemical and molecular analysis.

Osteoclast-like giant cell tumors (OLGT) are rare neoplasms of the pancreas and mostly associated with ductal adenocarcinomas. In this report, we present the rare case of OLGT associated with mucinous cystadenocarcinoma (MCC). We investigated the expression profile of both tumors by methods of molecular biology and immunohistochemistry. The panel of markers included osteopontin, her2/neu, mismatch repair genes, K-ras, p53, E-cadherin, VEGF-C, and podoplanin. Osteopontin was expressed by the osteoclast-like giant cells but not by the mononuclear tumor cells of the OLGT. We detected an amplification and overexpression of her2/neu in the MCC but not in the OLGT. Although we observed an immunohistochemical expression of hMSH2 and hMLH1 in the OLGT, we were not able to confirm this result by western blot analysis. We also did not find any microsatellite instability (D2S123, BAT26). While mutation of K-ras codon 12 was found in both tumor components, there was wild-type DNA of p53. E-cadherin was expressed in MCC but not in OLGT. VEGF-C was only positive in osteoclast-like giant cells and some of the mononuclear cells of OLGT. The vessel-rich stroma of OLGT did not present any podoplanin-positive lymphatic vessel. The observation of our case and others in the published literature may indicate separating OLGT with undifferentiated carcinoma from OLGT with MCC for the better clinical outcome of the latter.

[Rokitansky's first description of a spondylocostal dysplasia, dysostosis]. / Rokitanskys Erstbeschreibung einer spondylokostalen Dysplasie.

The bicentenary of Carl Rokitansky's birth prompted us to evaluate his less well-known work related to osteopathology. Of various articles containing humoropathological interpretations of osseous diseases, one work should be highlighted. It is, to the best of our knowledge, the first description of a spondylocostal dysplasia, re-discovered many years later, precisely described and accompanied by an excellent illustration.

Dissecting progressive stages of 5-fluorouracil resistance in vitro using RNA expression profiling.

Resistance to anticancer drugs such as the widely used antimetabolite 5-fluorouracil (FU) is one of the most important obstacles to cancer chemotherapy. Using GeneChip arrays, we compared the expression profile of different stages of FU resistance in colon cancer cells after in vitro selection of low-, intermediate- and high-resistance phenotypes. Drug resistance was associated with significant changes in expression of 330 genes, mainly during early or intermediate stage. Functional annotation revealed a majority of genes involved in signal transduction, cell adhesion and cytoskeleton with subsequent alterations in apoptotic response, cell cycle control, drug transport, fluoropyrimidine metabolism and DNA repair. A set of 33 genes distinguished all resistant subclones from sensitive progenitor cells. In the early stage, downregulation of collagens and keratins, together with upregulation of profilin 2 and ICAM-2, suggested cytoskeletal changes and cell adhesion remodeling. Interestingly, 6 members of the S100 calcium-binding protein family were suppressed. Acquisition of the intermediate-resistance phenotype included upregulation of the well-known drug resistance gene ABCC6 (ATP-binding cassette subfamily C member 6). The very small number of genes affected during transition to high resistance included the primary FU target thymidylate synthase. Although limited to an in vitro model, our data suggest that resistance to FU cannot be explained by known mechanisms alone and substantially involves a wide molecular repertoire. This study emphasizes the understanding of resistance as a time-depending process: the cell is particularly challenged at the beginning of this process, while acquisition of the high-resistance phenotype seems to be less demanding.

Expression of heat shock proteins in human hepatocellular carcinoma after radiofrequency ablation in an animal model.

Since tumor cells are known to express heat shock proteins (HSPs) as a response to cellular stress, such as heat, our goal was to determine the expression of HSPs in human hepatocellular carcinoma (HCC) before and after percutaneous radiofrequency (RF) ablation using a rat model. In 12 nude rats, human HCC cells (SK-HEP-1) were inoculated subcutaneously. A total of 21 tumors were grown in the bilateral flanks of the rats. Of those, 19 were treated with percutaneous RF ablation (diameter of RF electrode, 18 gauge; RF ablation energy, 60-600 W; duration, 20-100 sec). To determine the extent of necrosis, and the cellular expression of HSP 70 and HSP 90, the tumors were excised within 6, 12 and 24 h after RF ablation, respectively. The extent of the coagulation necrosis and the expression of HSP 70 and 90 were evaluated. Linear regression analysis showed a significant correlation between the volume of coagulation necrosis and the RF energy applied. Before RF ablation, expression of HSP 70 and 90 was 0% and 0-30%, respectively. Following RF ablation, the maximum level of HSP 70 expression was 60%, and the maximum level of HSP 90 expression was 100%. The expression of HSP 70 and 90 in HCC is significantly increased by RF ablation. These findings are of particular importance in the host-tumor immune response and might be useful in forthcoming immunotherapeutical strategies.

Podocyte flattening and disorder of glomerular basement membrane are associated with splitting of dystroglycan-matrix interaction.

The transmembrane component of the dystroglycan complex, a heterodimer of alpha- and beta-dystroglycan, was recently localized at the basal cell membrane domain of podocytes, and it was speculated that it serves as a device of the podocyte for maintaining the complex podocyte foot process architecture, and for regulating the exact position of its ligands, the matrix proteins laminin and agrin, in the glomerular basement membrane (GBM). The redistribution of dystroglycan in two experimental rat models of foot process flattening and proteinuria-i.e., podocyte damage induced by polycationic protamine sulfate perfusion, and reactive oxygen species (ROS)-associated puromycin aminonucleoside nephrosis-was examined. In both experimental diseases, aggregation and reduced density of alpha-dystroglycan by endocytosis by podocytes was observed. In in vitro solid-phase binding assays, protamine and ROS competed with the binding of alpha-dystroglycan with purified laminin and a recombinant C-terminal fragment of agrin that contains the dystroglycan-binding domain. These changes were associated with disorder of the fibrillar components of the lamina rara externa of the GBM, as confirmed quantitatively by fractal analysis. These results indicate that both polycation and ROS induce similar changes in the distribution of podocyte alpha-dystroglycan that involve competitive disruption of alpha-dystroglycan/matrix protein complexes, endocytosis of the liberated receptor by podocytes, and disorganization of the matrix protein arrangement in the lamina rara externa. This links functional damage of the dystroglycan complex with structural changes in the GBM.

Non-traumatic aortic dissection or rupture as cause of cardiac arrest: presentation and outcome.

OBJECTIVE: To evaluate the frequency, presentation and outcome of non-traumatic aortic dissection/rupture as a cause of cardiac arrest. DESIGN: Retrospective analysis of a cardiac arrest registry in a tertiary care hospital emergency department. RESULTS: Over 11.5 years, aortic dissection/rupture was identified as the immediate cause of cardiac arrest in 46 (2,3%) out of 1990 patients with sudden cardiac arrest, primarily affecting the abdominal aorta in 25 and the thoracic aorta in 21 cases. The characteristics of the 46 patients were as follows: male gender (74%), median age 71 years (IQR 59-76), high co-morbidity (89%), previously known aortic aneurysm (33%), pulseless electric activity (70%) as initial cardiac rhythm. When performed, bedside abdominal sonography or echocardiography was almost always diagnostic. Patients with abdominal aortic dissection/rupture had abdominal (52%) and/or flank pain (32%). Patients with thoracic aortic dissection/rupture complained of chest pain (48%) or dyspnoea (19%). Return of spontaneous circulation occurred in 12 (26%) of 46 patients, emergency surgery was performed in eight of these patients, 2 (4%) survived to discharge in good neurological condition. CONCLUSIONS: Cardiac arrest caused by aortic dissection/rupture is rare, and mortality remains very high, even when circulation can be restored initially. Common features such as previously known aortic aneurysm, old age, male gender and pulseless electrical activity as initial cardiac rhythm should increase suspicion of the condition.

Heat shock protein expression induced by percutaneous radiofrequency ablation of hepatocellular carcinoma in vivo.

Heat shock proteins (HSPs) are known to be of crucial importance in host-tumor interactions. The goal of this study was to determine whether there was an increase in HSP expression in a patient suffering from unresectable hepatocellular carcinoma treated with percutaneous radiofrequency (RF) ablation. Immediately before RF ablation, a computed tomography (CT)-guided core needle biopsy (diameter, 18 gauge) was obtained from the tumor. The RF ablation was then performed using a saline-perfused RF ablation system (diameter of RF electrode, 15 gauge; ablation time, 10 min). Twenty-four hours after tumor ablation, core needle biopsy was repeated, and biopsy specimens were obtained from the residual tumor margin visible on contrast-enhanced CT. For both procedures, no side effects or clinically relevant complications were observed. The specimens were mapped by immunohistochemistry, determining the cellular expression of HSP 70 and HSP 90. After RF ablation, in the cytoplasm and at the tumor cell surface, an 8-fold increase in HSP 70 and a 1.2-fold increase in HSP 90 was observed, respectively. In the cell nucleus, the HSP 90 expression before RF ablation was 10%, and decreased to 0% after RF ablation. We have demonstrated that, following RF ablation, cellular expression of HSP 70 and HSP 90 in hepatocellular carcinoma is increased. We further suggest that routing of HSP 90 from the nucleus to the cell surface occurred after RF ablation. This may be of relevance in further therapeutic anti-tumor strategies.

Myxoma valvulae arteriae pulmonalis described by Rokitansky: medicohistorical and clinicopathological aspects.

The bicentenary of the birth of Rokitansky, the first true descriptive pathologist, was celebrated in February 2004. Rokitansky gathered many and important specimens that are now displayed in the Federal Museum of Pathological Anatomy in Vienna. On examining Rokitansky's collection we found a myxoma of the pulmonary valve of a 70-year-old woman who died in 1833. Cardiac myxomas are rare but are the most frequent primary heart tumors, appearing even less frequently on cardiac valves. Modern histology has confirmed Rokitansky's diagnosis on gross pathology. The good condition of this 171-year-old specimen was surprising. Thus, Rokitansky described the myxoma 75 years before Ribbert's first description of a myxoma in this rare localization.