Meninges Outside the Meninges: Ectopic Meningiomas and Meningothlelial Proliferations

Extracranial meningiomas have been reported for decades now and have been described in the head and neck; calvarial, nasal cavity, paranasal sinuses, nasopharynx, parotid gland and in various remote anatomical locations systemically. The presence of microanatomical structures for all intents and purposes resembling and having the histopathological characteristics of meninges outside of the central nervous system meninges is uncommon but well-documented. Typically, these lesions are found in the lung or part of hamartomatous/choristomatous lesions and frequently occur in the head and neck anatomical region. The lesion first described by Suster and Rosai termed "hamartoma of the scalp with ectopic meningothelial elements" is the prototypical example of lesions with meningothelial elements. We have described recently a similar hamartomatous lesion with meningothelial elements occurring in the tongue. In this chapter, we will review the clinicopathological features of ectopic meningiomas and lesions that contain meningothelial elements and their possible pathogenesis

A General System for Automatic Biomedical Image Segmentation Using Intensity Neighborhoods

Image segmentation is important with applications to several problems in biology and medicine. While extensively researched, generally, current segmentation methods perform adequately in the applications for which they were designed, but often require extensive modifications or calibrations before being used in a different application. We describe an approach that, with few modifications, can be used in a variety of image segmentation problems. The approach is based on a supervised learning strategy that utilizes intensity neighborhoods to assign each pixel in a test image its correct class based on training data. We describe methods for modeling rotations and variations in scales as well as a subset selection for training the classifiers. We show that the performance of our approach in tissue segmentation tasks in magnetic resonance and histopathology microscopy images, as well as nuclei segmentation from fluorescence microscopy images, is similar to or better than several algorithms specifically designed for each of these applications

Discovery and Validation of a New Class of Small Molecule Toll-Like Receptor 4 (TLR4) Inhibitors

Many inflammatory diseases may be linked to pathologically elevated signaling via the receptor for lipopolysaccharide (LPS), toll-like receptor 4 (TLR4). There has thus been great interest in the discovery of TLR4 inhibitors as potential anti-inflammatory agents. Recently, the structure of TLR4 bound to the inhibitor E5564 was solved, raising the possibility that novel TLR4 inhibitors that target the E5564-binding domain could be designed. We utilized a similarity search algorithm in conjunction with a limited screening approach of small molecule libraries to identify compounds that bind to the E5564 site and inhibit TLR4. Our lead compound, C34, is a 2-acetamidopyranoside (MW 389) with the formula C17H27NO9, which inhibited TLR4 in enterocytes and macrophages in vitro, and reduced systemic inflammation in mouse models of endotoxemia and necrotizing enterocolitis. Molecular docking of C34 to the hydrophobic internal pocket of the TLR4 co-receptor MD-2 demonstrated a tight fit, embedding the pyran ring deep inside the pocket. Strikingly, C34 inhibited LPS signaling ex-vivo in human ileum that was resected from infants with necrotizing enterocolitis. These findings identify C34 and the β-anomeric cyclohexyl analog C35 as novel leads for small molecule TLR4 inhibitors that have potential therapeutic benefit for TLR4-mediated inflammatory diseases. © 2013 Neal et al

Multiresolution identification of germ layer components in teratomas derived from human and nonhuman primate embryonic stem cells

We propose a system for identification of germ layer components in teratomas derived from human and nonhuman primate embryonic stem cells. Tissue regeneration and repair, drug testing and discov-ery, the cure of genetic and developmental syndromes all may rest on the understanding of the biology and behavior of embryonic stem (ES) cells. Within the field of stem cell biology, an ES cell is not con-sidered an ES cell until it can produce a teratoma tumor (the ”gold” standard test); a seemingly disorganized mass of tissue derived from all three embryonic germ layers; ectoderm, mesoderm, and endo-derm. Identification and quantification of tissue types within ter-atomas derived from ES cells may expand our knowledge of abnor-mal and normal developmental programming and the response of ES cells to genetic manipulation and/or toxic exposures. In addition, because of the tissue complexity, identifying and quantifying the tis-sue is tedious and time consuming, but in turn the teratoma provides an excellent biological platform to test robust image analysis algo-rithms. We use a multiresolution (MR) classification system with texture features, as well as develop novel nuclear texture features to recognize germ layer components. With redundant MR transform, we achieve a classification accuracy of approximately 88%. Index Terms — Stem cell biology, multiresolution, classifica-tion, feature extractio

Tumor Suppressor Gene Alterations in Respiratory Epithelial Adenomatoid Hamartoma (REAH): Comparison to Sinonasal Adenocarcinoma and Inflamed Sinonasal Mucosa.

Respiratory epithelial adenomatoid hamartoma (REAH) is an unusual benign sinonasal glandular proliferation. REAH is not considered a neoplasm, although, no molecular evidence exists to support or refute this possibility. Microdissection of 10 cases of REAH, 9 cases of sinonasal adenocarcinoma (SNAC) and 10 cases of chronic sinusitis was performed. DNA was extracted and polymerase chain reaction performed using fluorescently labeled primers flanking known tumor suppressor genes on chromosomes 9p (CDKN2/p16), 11p (H-ras), 17p (p53), and 18q (DCC/DPC4). Polymerase chain reaction products were analyzed semiquantitatively by capillary electrophoresis. Allele ratios were calculated using the peak height from the shorter allele divided by the peak height from the longer allele. The loss of heterozygosity (LOH) ratio was calculated as the allele ratio from tumor tissue divided by the allele ratio from normal tissue. The fractional allelic loss (FAL) was calculated as the percentage of loci that harbored LOH divided by the number of loci that were informative. REAH demonstrated an intermediate FAL of 31% compared with SNAC (64%) and chronic sinusitis (2%). REAH and SNAC had the highest LOH for multiple loci located on 9p (p16) and 18q (DCC/DPC4). The molecular profile of REAH shows a mean FAL of 31%, which would be considered unusually high for a non-neoplastic entity. Appreciable allelic loss within REAH suggests the possibility that REAH may be a benign neoplasm rather than a hamartoma

Pathology Case Study: Abdominal Bloating and Discomfort

This is a case study presented by the University of Pittsburgh Department of Pathology, which describes a 64-year-old woman initially diagnosed with acute myelogenous leukemia. Visitors are given an extensive patient history, radiology findings, and both gross and microscopic descriptions, including images. They are also given an opportunity to diagnose the patient using the findings before clicking on the "Final Diagnosis" section, which provides a discussion of the findings as well as references. This is an excellent resource for students in the health sciences to familiarize themselves with using patient history and laboratory results to diagnose disease. It is also a helpful site for educators to use to introduce or test student learning in autopsy pathology

THE "-OMAS" and "-OPIAS": Targeted and Philosophical Considerations Regarding Hamartomas, Choristomas, Teratomas, Ectopias, and Heterotopias in Pediatric Otorhinolaryngologic Pathology

The spectrum of "developmental" lesions that occur in the head and neck predominantly congenital in origin and arising at birth and/or discovered in childhood is broad and fascinating. These have been grouped into categories such as "ectopias", "heterotopias", "hamartomas", and "choristomas". On a philosophical and consequently systematic level, these lesions, mostly benign tumors seem to lack a true understanding of the pathogenetic foundation on which to base a more unified taxonomic designation. In this review, we will consider some of these select tumors as they represent syndromic associations (nasal chondromesenchymal hamartoma and DICER1 syndrome), the lingual choristoma from the perspective of its nomenclature and classification, lesions with ectopic meningothelial elements, and teratomas and the enigmatic "hairy polyp" in reference to a broader discussion of pathogenesis and pluripotent cells in the head and neck. A consistent thread will be how these lesions are designated with some final thoughts on future directions regarding the investigation of their pathogenesis and taxonomic nomenclature