The First Histological Analysis of the Tissues Lining the Fossa Navicularis: Insights to its Etiology.

The fossa navicularis (FN) is an anatomical variant on the ventral surface of the basilar part of the occipital bone that, to date, has only been investigated in bone specimens. We aim to clarify the structure of the fossa navicularis by gross anatomical, radiological, and histological methods. The FN was found in the occipital bone of the Caucasian male cadaver. There was no bony or histological continuity between the FN and posterior cranial fossa. The histological analysis found that the overlying tissue was composed of loose connective tissue with a mixture of collagen and elastic fibers and a vascular matrix including arteries, veins, and capillaries. There was no evidence of lymphoid, glandular, or notochordal tissues. As no previous studies have performed histological analysis of the FN, this report adds to our knowledge of tissues that are involved in its formation

Comprehensive Analysis of MGMT Promoter Methylation: Correlation with MGMT Expression and Clinical Response in GBM

O6-methylguanine DNA-methyltransferase (MGMT) promoter methylation has been identified as a potential prognostic marker for glioblastoma patients. The relationship between the exact site of promoter methylation and its effect on gene silencing, and the patient's subsequent response to therapy, is still being defined. The aim of this study was to comprehensively characterize cytosine-guanine (CpG) dinucleotide methylation across the entire MGMT promoter and to correlate individual CpG site methylation patterns to mRNA expression, protein expression, and progression-free survival. To best identify the specific MGMT promoter region most predictive of gene silencing and response to therapy, we determined the methylation status of all 97 CpG sites in the MGMT promoter in tumor samples from 70 GBM patients using quantitative bisulfite sequencing. We next identified the CpG site specific and regional methylation patterns most predictive of gene silencing and improved progression-free survival. Using this data, we propose a new classification scheme utilizing methylation data from across the entire promoter and show that an analysis based on this approach, which we call 3R classification, is predictive of progression-free survival (HR  = 5.23, 95% CI [2.089–13.097], p<0.0001). To adapt this approach to the clinical setting, we used a methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) test based on the 3R classification and show that this test is both feasible in the clinical setting and predictive of progression free survival (HR  = 3.076, 95% CI [1.301–7.27], p = 0.007). We discuss the potential advantages of a test based on this promoter-wide analysis and compare it to the commonly used methylation-specific PCR test. Further prospective validation of these two methods in a large independent patient cohort will be needed to confirm the added value of promoter wide analysis of MGMT methylation in the clinical setting

A case series of atypical features of patients with biopsy-proven isolated IgG4-related hypophysitis and normal serum IgG4 levels.

BACKGROUND: IgG4-related hypophysitis is a rare clinical entity that forms part of an emerging group of multi-organ IgG4-related fibrosclerotic systemic diseases. The rare prevalence of the disease, presenting features that overlap with other sellar pathologies, and variable imaging features can make preoperative identification challenging. PURPOSE AND METHODS: We report three cases of isolated IgG4-related hypophysitis with atypical clinical and imaging features that mimicked those of pituitary apoplexy and other sellar lesions. Additionally, we review the literature of IgG4-related hypophysitis to provide context for individual patient data described herein. RESULTS: All patients presented with symptoms that mimicked those of pituitary apoplexy and visual disturbance, and MRI findings suggestive of pituitary macroadenoma, Rathke\u27s cleft cyst and craniopharyngioma. The clinical presentation warranted surgical decompression, resulting in rapid symptomatic improvement. Preoperative high-dose followed by postoperative low-dose glucocorticoid replacement therapy was administered in all cases. Histopathology showed dense infiltrate of IgG4 cells. Post-operative follow-up monitoring for 12-26 months revealed normal serum IgG4 levels with no other organ involvement, while endocrinological testing revealed persistent pituitary hormone deficiencies. CONCLUSIONS: Our cases highlight the importance of considering IgG4-related hypophysitis in the differential diagnosis of solid and cystic sellar lesions presenting acutely with pituitary apoplexy symptoms. Existing diagnostic criteria may not be sufficiently precise to permit rapid and reliable identification, or avoidance of surgery in the acute setting. In contrast to other reports of the natural history of this condition, despite the severity of presenting features, the disease in our cases was pituitary-restricted with normal serum IgG4 levels

Autologous Bone Harvest in Anterior Cervical Spine Surgery: A Quantitative and Qualitative In Vitro Analysis of Cadaveric Tissue.

BACKGROUND: The cervical spine may be used as a harvesting site of local autograft material during anterior cervical discectomy and fusion procedures. We analyzed the quality and composition of bone grafts obtained from different parts of the cervical vertebrae in a cadaveric model. METHODS: Five fresh adult human cadavers with intact cervical spines were used. Using a Smith-Robinson anterior approach to expose C4-5 and C5-6 vertebrae, samples from 4 vertebral sites were harvested under a microscope. Anterior osteophytes were removed piecemeal by a Leksell rongeur (sample A). A high-speed burr was used to drill the endplates of C4-5 and C5-6 (sample C) and uncovertebral joints of C4-5 (sample B) and C5-6 (sample D). Then 20 slides (4 per cadaver) were prepared and analyzed. RESULTS: Tissue fragmentation was associated with use of the high-speed burr. Sample A had minimal tissue fragmentation. Samples B-D showed moderate to high fragmentation. Cartilage was found in all samples. Of the 20 slides, 6 contained soft tissues (sample A in 4, sample D in 2). Disc material was identified in 6 slides (sample A in 1, sample B in 4, sample D in 1). Sample A had the greatest number of intact osteocytes and chondrocytes, and sample B had the least. CONCLUSIONS: Anterior osteophytes provide the highest number of osteocytes, with the highest osteocyte/chondrocyte ratio. Osteocyte viability is a function of vertebral body site and collection technique, with fragmentation caused by use of a high-speed burr decreasing the number of viable osteocytes

A case series of atypical features of patients with biopsy-proven isolated IgG4-related hypophysitis and normal serum IgG4 levels

Background IgG4-related hypophysitis is a rare clinical entity that forms part of an emerging group of multi-organ IgG4-related fibrosclerotic systemic diseases. The rare prevalence of the disease, presenting features that overlap with other sellar pathologies, and variable imaging features can make preoperative identification challenging. Purpose and methods We report three cases of isolated IgG4-related hypophysitis with atypical clinical and imaging features that mimicked those of pituitary apoplexy and other sellar lesions. Additionally, we review the literature of IgG4-related hypophysitis to provide context for individual patient data described herein. Results All patients presented with symptoms that mimicked those of pituitary apoplexy and visual disturbance, and MRI findings suggestive of pituitary macroadenoma, Rathke's cleft cyst and craniopharyngioma. The clinical presentation warranted surgical decompression, resulting in rapid symptomatic improvement. Preoperative high-dose followed by postoperative low-dose glucocorticoid replacement therapy was administered in all cases. Histopathology showed dense infiltrate of IgG4 cells. Post-operative follow-up monitoring for 12-26 months revealed normal serum IgG4 levels with no other organ involvement, while endocrinological testing revealed persistent pituitary hormone deficiencies. Conclusions Our cases highlight the importance of considering IgG4-related hypophysitis in the differential diagnosis of solid and cystic sellar lesions presenting acutely with pituitary apoplexy symptoms. Existing diagnostic criteria may not be sufficiently precise to permit rapid and reliable identification, or avoidance of surgery in the acute setting. In contrast to other reports of the natural history of this condition, despite the severity of presenting features, the disease in our cases was pituitary-restricted with normal serum IgG4 levels.12 month embargo; published online: 16 December 2017This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Adult Apical Ligament of the Dens Lacks Notochordal Tissue: Application to Better Understanding the Origins of Skull Base Chordomas.

INTRODUCTION: The apical ligament has long been reported to contain notochord remnants and thus might serve as a site of origin of chordoma formation at the skull base. However, to our knowledge, the histologic study of the apical ligament using histologic staining specific for notochordal tissue has not been previously performed. Therefore the current study was undertaken. METHODS: Fifteen apical ligament samples underwent histologic examination with specific markers for notochordal differentiation. RESULTS: Across all samples, there was no indication of any notochordal remnants. CONCLUSIONS: On the basis of our cadaveric study, the apical ligament does not contain notochord tissue and in adults should not be considered a remnant of this structure. Moreover, it is unlikely that the apical ligament gives rise to chordomas at the craniocervical junction under normal circumstances