Ectopic Cerebellar Tissue in the Occipital Bone: A Case Report.

Ectopic cerebellar tissue has only been described in isolated case reports, with only two reported cases in adult patients. We report the case of a 63-year-old woman with progressive, medically refractory headaches. A scan showed an intraosseous lesion of the midline occipital bone.

Histology of the vertebral artery-dural junction: relevance to posterolateral approaches to the skull base.

Objective: The far-lateral and extreme-lateral infrajugular transcondylar-transtubercular exposure (ELITE) and extreme-lateral transcondylar transodontoid (ELTO) approaches provide access to lesions of the foramen magnum, inferolateral to mid-clivus, and ventral pons and medulla. A subset of pathologies in this region require manipulation of the vertebral artery (VA)-dural interface. Although a cuff of dura is commonly left on the VA to avoid vessel injury during these approaches, there are varying descriptions of the degree of VA-dural separation that is safely achievable.

Correction: Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Structural Variation Detection by Proximity Ligation from Formalin-Fixed, Paraffin-Embedded Tumor Tissue.

The clinical management and therapy of many solid tumor malignancies depends on detection of medically actionable or diagnostically relevant genetic variation. However, a principal challenge for genetic assays from tumors is the fragmented and chemically damaged state of DNA in formalin-fixed, paraffin-embedded (FFPE) samples. From highly fragmented DNA and RNA there is no current technology for generating long-range DNA sequence data as is required to detect genomic structural variation or long-range genotype phasing.

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

PurposeThe 2015 American College of Medical Genetics and Genomics-Association for Molecular Pathology (ACMG-AMP) guidelines were a major step toward establishing a common framework for variant classification. In practice, however, several aspects of the guidelines lack specificity, are subject to varied interpretations, or fail to capture relevant aspects of clinical molecular genetics. A simple implementation of the guidelines in their current form is insufficient for consistent and comprehensive variant classification.

Novel interstitial 2.6 Mb deletion on 9q21 associated with multiple congenital anomalies.

Array comparative genomic hybridization (aCGH) is now commonly used to identify copy number changes in individuals with developmental delay, intellectual disabilities, autism spectrum disorders, and/or multiple congenital anomalies. We report on an infant with multiple congenital anomalies and a novel 2.6 Mb interstitial deletion within 9q21.

Functional screening in Drosophila identifies Alzheimer's disease susceptibility genes and implicates Tau-mediated mechanisms.

Using a Drosophila model of Alzheimer's disease (AD), we systematically evaluated 67 candidate genes based on AD-associated genomic loci (P < 10(-4)) from published human genome-wide association studies (GWAS). Genetic manipulation of 87 homologous fly genes was tested for modulation of neurotoxicity caused by human Tau, which forms neurofibrillary tangle pathology in AD. RNA interference (RNAi) targeting 9 genes enhanced Tau neurotoxicity, and in most cases reciprocal activation of gene expression suppressed Tau toxicity.

Gliosarcoma arising from an oligodendroglioma (oligosarcoma).

Gliosarcoma, a biphasic tumor with both mesenchymal and glial elements, is typically considered a variant of astrocytoma (glioblastoma), WHO Grade IV. A 57-year-old man presented with altered mental status and was found to have a large right frontal mass. Biopsy and subsequent subtotal resection revealed a WHO Grade II oligodendroglioma with classic histological features, expression of IDH1 R132H mutant protein, and chromosome 1p19q co-deletion.

A common 8q (MYC) amplification detected in a multifocal anaplastic astrocytoma by SNP array karyotyping.

The distinction of multifocal versus multicentric gliomas can conceivably have important therapeutic implications. We present a 27-year-old man with two radiologically distinct non-enhancing infiltrative masses in the anterior frontal lobe and the posterior temporoparietal region. No intervening disease was evident on MRI modalities; the lesions were stable over a period of many months.

Myxoid liposarcoma: a case report of a sentinel metastasis to the parotid gland with molecular confirmation.

Myxoid liposarcoma is a subtype of liposarcoma with a predilection for the deep soft tissues of the extremities that accounts approximately for 10% of all adult soft tissue sarcomas. We report a case of a metastatic myxoid liposarcoma to the parotid gland, with fine-needle aspiration cytology correlation and molecular characterization. The lesion was diagnosed in a 53-year-old Hispanic male who presented with a left posterior thigh mass.

The molecular pathology of sarcomas.

Sarcomas are rare malignancies of mesenchymal lineage with more than 100 specific types and many benign potential mimics. In situ and precursor lesions are generally not described and thus much of molecular pathology in this field concentrates on molecular diagnosis, prognosis and determination of therapeutic targets. This chapter discusses the applications of molecular methodologies that provide insight into pathogenesis of sarcoma, and of molecular methods which are currently applied to, or will likely soon influence, the clinical management of this complex array of tumors.

KRAS mutation detection in colorectal cancer by a commercially available gene chip array compares well with Sanger sequencing.

Background: Binding of a ligand to the epidermal growth factor receptor (EGFR) stimulates various intracellular signaling pathways resulting in cell cycle progression, proliferation, angiogenesis and apoptosis inhibition. KRAS is involved in signaling pathways including RAF/MAPK and PI3K and mutations in this gene result in constitutive activation of these pathways, independent of EGFR activation. Seven mutations in codons 12 and 13 of KRAS comprise around 95% of the observed human mutations, rendering monoclonal antibodies against EGFR (e.

Sarcoma arising as a distinct nodule within glioblastoma: a morphological and molecular perspective on gliosarcoma.

Gliosarcoma is a variant of glioblastoma and is characterized by distinct glial and sarcomatous components. Typically, there is no macroscopic boundary between the components and special stains are often required to distinguish the glial and sarcomatous elements. Some studies suggest similar genetic alterations in both components pointing to a common origin.

Molecular classification of adult renal epithelial neoplasms using microRNA expression and virtual karyotyping.

Oncocytoma, chromophobe renal cell carcinoma (chRCC), and the eosinophilic variant of clear cell RCC (ccRCC) are morphologically similar tumors with significantly different clinical courses. These renal tumor subtypes show characteristic structural genetic changes; however, the mRNA expression patterns of oncocytoma and chRCC are strikingly similar. MicroRNAs (miRNA) are small RNA molecules that regulate the expression of many genes and have been shown to be useful for tumor classification and identification.

Detection of myxoid liposarcoma-associated FUS-DDIT3 rearrangement variants including a newly identified breakpoint using an optimized RT-PCR assay.

Myxoid/round cell liposarcoma is characterized by the recurrent translocations t(12;16)(q13;p11) and, less commonly, t(12;22)(q13;q12), which fuse FUS or EWSR1, respectively, to DDIT3 on chromosome 12. Although a number of different variant breakpoints have been described, greater than 90% of all cases have one of the three different FUS-DDIT3 fusions, which may have clinical significance. To identify the individual breakpoints, a sequence-specific assay such as reverse transcription-PCR (RT-PCR) is needed.

Mast cell burden and reticulin fibrosis in the myeloproliferative neoplasms: a computer-assisted image analysis study.

The mast cell has been associated with fibrosis in many different tissues, organs, and different disease processes including hematopoietic malignancies. Mast cells are often increased in the bone marrow of patients with primary bone marrow disorders, and patients with systemic mastocytosis often have a second concomitant neoplastic disease of the bone marrow. The goals of the current study were to determine the role the mast cell has in the pathogenesis of myeloproliferative neoplasms (MPN) and to correlate the mast cell burden with the degree of reticulin fibrosis.

Polymorphisms in TGFbeta and TNFalpha are associated with the myelodysplastic syndrome phenotype.

Context: Myelodysplastic syndromes (MDSs) are characterized by ineffective hematopoiesis, excessive apoptosis, and the aberrant expression of a number of cytokines. The genes encoding these cytokines are significantly polymorphic. It is unknown whether these cytokine polymorphisms are associated with, and may therefore be playing a role in the pathogenesis of, MDS.