Low-grade oligodendroglioma of the pineal gland: a case report and review of the literature

<p>Abstract</p> <p>Background</p> <p>Gliomas are a very rare subtype of pineal region tumours, whereas oligodendrogliomas of the pineal region are exceedingly rare, since there have been only 3 cases of anaplastic oligodedrogliomas reported this far.</p> <p>Methods-Results</p> <p>We present a case of a low-grade oligodendroglioma arising in the pineal gland of a 37 year-old woman. The patient presented with diplopia associated with a cystic pineal region mass demonstrated on MRI. Total resection was performed and histological examination showed that the cystic wall consisted of tumour cells with a central nucleus a perinuclear halo and minimal pleomorphism. Immnunohistochemical analysis showed that these cells were diffusely positive for CD57, and negative for GFAP, CD10, CD99, cytokeratins, neurofilaments and synaptophysin. FISH analysis was performed in a small number of neoplastic cells, which were not exhausted after immunohistochemistry and did not reveal deletion of 1p and 19q chromosome arms. However, the diagnosis of a low grade oligodendroglioma of the pineal gland was assigned.</p> <p>Conclusion</p> <p>Although the spectrum of tumours arising in the pineal gland is broad, the reports of oligodendrogliomas confined to this location are exceedingly rare, and to the best of our knowledge there is no report of a low-grade oligodendroglioma. However, they should be added in the long list of tumours arising in the pineal gland.</p

Neuropathology of aging in cats and its similarities to human Alzheimer’s disease

Elderly cats develop age-related behavioral and neuropathological changes that ultimately lead to cognitive dysfunction syndrome (CDS). These neuropathologies share similarities to those seen in the brains of humans with Alzheimer’s disease (AD), including the extracellular accumulation of ß-amyloid (Aβ) and intraneuronal deposits of hyperphosphorylated tau, which are considered to be the two major hallmarks of AD. The present study assessed the presence and distribution of Aβ and tau hyperphosphorylation within the cat brain (n = 55 cats), and how the distribution of these proteins changes with age and the presence of CDS. For this, immunohistochemistry was performed on seven brain regions from cats of various ages, with and without CDS (n = 10 with CDS). Cats accumulate both intracytoplasmic and extracellular deposits of Aβ, as well as intranuclear and intracytoplasmic hyperphosphorylated tau deposits. Large extracellular aggregates of Aβ were found in elderly cats, mainly in the cortical brain areas, with occasional hippocampal aggregates. This may suggest that these aggregates start in cortical areas and later progress to the hippocampus. While Aβ senile plaques in people with AD have a dense core, extracellular Aβ deposits in cats exhibited a diffuse pattern, similar to the early stages of plaque pathogenesis. Intraneuronal Aβ deposits were also observed, occurring predominantly in cortical brain regions of younger cats, while older cats had few to no intraneuronal Aβ deposits, especially when extracellular aggregates were abundant. Intracytoplasmic hyperphosphorylated tau was found within neurons in the brains of elderly cats, particularly in those with CDS. Due to their ultrastructural features, these deposits are considered to be pre-tangles, which are an early stage of the neurofibrillary tangles seen in AD. The largest numbers of pre-tangles are found mainly in the cerebral cortex of elderly cats, whereas lower numbers were found in other regions (i.e., entorhinal cortex and hippocampus). For the first time, intranuclear tau was found in both phosphorylated and non-phosphorylated states within neurons in the cat brain. The highest numbers of intranuclear deposits were found in the cortex of younger cats, and this tended to decrease with age. In contrast, elderly cats with pre-tangles had only occasional or no nuclear labelling

The involvement of tau in nucleolar transcription and the stress response

Tau is known for its pathological role in neurodegenerative diseases, including Alzheimer’s disease (AD) and other tauopathies. Tau is found in many subcellular compartments such as the cytosol and the nucleus. Although its normal role in microtubule binding is well established, its nuclear role is still unclear. Here, we reveal that tau localises to the nucleolus in undifferentiated and differentiated neuroblastoma cells (SHSY5Y), where it associates with TIP5, a key player in heterochromatin stability and ribosomal DNA (rDNA) transcriptional repression. Immunogold labelling on human brain sample confirms the physiological relevance of this finding by showing tau within the nucleolus colocalises with TIP5. Depletion of tau results in an increase in rDNA transcription with an associated decrease in heterochromatin and DNA methylation, suggesting that under normal conditions tau is involved in silencing of the rDNA. Cellular stress induced by glutamate causes nucleolar stress associated with the redistribution of nucleolar non-phosphorylated tau, in a similar manner to fibrillarin, and nuclear upsurge of phosphorylated tau (Thr231) which doesn’t colocalise with fibrillarin or nucleolar tau. This suggests that stress may impact on different nuclear tau species. In addition to involvement in rDNA transcription, nucleolar non-phosphorylated tau also undergoes stress-induced redistribution similar to many nucleolar protein

Υπερδομική χαρτογράφηση της πρωτεΐνης Fras1 στον εξωκυττάριο χώρο

Basement membranes are thin, sheet like arrangements of extracellular matrix proteins that serve a variety of functions including the physical separation of cell layers and tissues, molecular ultrafiltration and tissue morphogenesis. Electronmicroscopically, typical basement membranes display two distinct zones, the lamina lucida and lamina densa. The lamina lucida contains anchoring filaments that extend to the hemidesmosomes and mediate the attachment of the epithelial cells to the basement membrane. The anchoring of the basement membrane to the mesenchyme is ensured by anchoring fibrils that are associated with the lamina densa and transverse the underlying zone termed sub-lamina densa. Fras1 gene, encodes a putative extracellular matrix multidomain protein (4010 amino acids) expressed from various epithelia of the developing embryo. Fras1 is a putative extracellular matrix protein which has been implicated in the structural adhesion of embryonic epidermis to dermis. Moreover, mutations in Fras1/FRAS1 have been associated with the mouse blebbed phenotype and the human rare genetic disorder Fraser syndrome, respectively. Loss of Fras1 function results in the formation of subepidermal hemorrhagic blisters as well as unilateral or bilateral renal agenesis during mouse embryogenesis. Previous reports demonstrated that dermal-epidermal separation upon blister formation in Fras1-/- mutants occurs below the lamina densa, implying a role for Fras1 at the level of basement membranemesenchymal adherence. In accordance with the previous, other reports indicate that Fras1 is detected underneath the lamina densa of embryonic lung epithelia and exerts its function below the lamina densa. Yet, so far few data exist on the ultrastructual localization of Fras1 within the extracellular space. We therefore performed immunogold labeling experiments in order to study the expression pattern of Fras1 within extracellular space. The aim of the present study was to investigate the ultrastructual immunolocalization of Fras1 within the basement membrane of the developing mouse skin epithelium and to compare with that of a different epithelium such as the esophagus. The epithelium of skin and esophagus that we studied is described as stratified squamous. We used a specific antibody against Fras1 in free floating sections of E14.5 mouse embryos. The protein was subsequently visualized on ultrathin sections as silver intensified gold particles. Ultrastructual immunogold labeling using antibodies raised against the central NG2-like domain of Fras1 detected the protein underneath the lamina densa of embryonic skin and esophagus. This finding is in accordance with the reported indications that Fras1 exerts its function below the lamina densa and is detected within sub-lamina densa of embryonic lung epithelia. Ultrastructual immunogold labeling experiments revealed identical expression pattern of Fras1 in both embryonic skin and esophagus. Notably, the deposition of the protein was also identical to the reported detection of Fras1 in embryonic lung epithelia. The above imply that Fras1 could be an indisputable component of embryonic basement membranes. Fras1 detected in several ultra-thin sections to be anchored on amorphous electron dense structures located underneath lamina densa. The origin and molecular composition of these structures has to be studied in order to evaluate the importance of these finding. We propose that the Fras1 localization may be connected to a well studied component of basal membranes, anchoring fibrils. Recently, Shimizu et al. suggested that 90% of the anchoring fibrils originated and terminated in the lamina densa. Our data suggest that Fras1 is detected in the lower part of anchoring fibrils within sub-lamina densa. Whether there is a potential colocalization between Fras1 and Collagen VII which is the major structural component of the anchoring fibrils, remains to be determined. In conclusion, we demonstrate that Fras1 is an indisputable component of embryonic sub-lamina densa of basal membranes of stratified squamous epithelia