Lymphomas in patients with neurofibromatosis type 1 (NF1): another malignancy in the NF1 syndrome?

Neurofibromatosis type 1 (NF1) is an autosomal dominant multisystem syndrome caused by mutations in the neurofibromin 1 (NF1) gene that encodes for the protein neurofibromin acting as a tumour suppressor. Neurofibromin functions primarily as a GTPase-activating protein for the Ras family of oncogenes, which activates many signalling pathways for cell proliferation and differentiation; without neurofibromin, Ras is constitutively activated, thereby turning on many downstream signalling pathways related to oncogenesis. Patients with NF1 have a well known predisposition for certain types of malignancies including malignant peripheral nerve sheath tumours, gliomas, and breast cancers, as well as a potential association of NF1 with lymphoproliferative disorders such as lymphomas. In this article, we review the pathophysiology and tumourigenesis of NF1, previously reported cases of cutaneous lymphomas in NF1 patients along with our case demonstration of a NF1-associated scalp B-cell lymphoma, and NF1-associated extra cutaneous lymphomas. The diagnosis of lymphomas particularly cutaneous lymphomas may be difficult in NF1 patients as they often have skin lesions and/or cutaneous/subcutaneous nodules or tumours like neurofibromas, which raises the possibility of underdiagnosed cutaneous lymphomas in NF1 patients. We also comprehensively discuss the association between NF1 and lymphomas. In summary, most studies support a potential association between NF1 and lymphomas. Further investigation is needed to clarify the association between NF1 and lymphomas in order to bring clinical awareness of possibly underdiagnosed NF1-associated lymphomas and individualised management of NF1 patients to practice.

Immunohistochemical Markers in the Diagnosis of Calcifying Pseudoneoplasm of the Neuraxis.

BACKGROUND: Calcifying pseudoneoplasm of the neuraxis (CAPNON) is a rare tumor-like lesion with unknown pathogenesis. It is likely under-reported due to diagnostic challenges including the nonspecific radiographic features, lack of diagnostic markers, and often asymptomatic nature of the lesions. METHODS: We performed detailed examination of 11 CAPNON specimens diagnosed by histopathology, with the help of electron microscopy and immunohistochemistry. RESULTS: Electron microscopy revealed the presence of fibrillary materials consistent with neurofilaments. In addition to some entrapped axons at the periphery of CAPNONs, we discovered that all specimens stained positive for neurofilament-light (NF-L) within the granular amorphous cores, but not neurofilament-phosphorylated (NF-p). CAPNONs also showed variable infiltration of CD8+ T-cells and a decreased ratio of CD4/CD8+ T-cells, suggesting an immune-mediated process in the pathogenesis of CAPNON. CONCLUSION: NF-L and CD4/CD8 immunostains may serve as diagnostic markers for CAPNON and shed light on its pathogenesis.

Incidentally Found Double Aortic Arch While Treating Posterior Inferior Cerebellar Artery Aneurysm: Conversion from Femoral to Radial Artery Access.

BACKGROUND: Asymptomatic double aortic arches are a unique occurrence. CASE DESCRIPTION: An incidental finding of a double aortic arch in an elderly male was discovered during workup of a transient ischemic attack. The following case presentation details an effective treatment approach in cerebrovascular stenting in a patient with variant aortic arch anatomy. The initial diagnostic cerebral angiogram was performed via transfemoral approach and was quite challenging. CONCLUSIONS: Faced with challenging anatomy, the radial artery approach is a viable option when navigating into the cerebrovascular anatomy for stenting when proximal variants such as a double aortic arch are identified.

A systematic characterization of the factors influencing polymerization and dynamic behavior of n-butyl cyanoacrylate.

INTRODUCTION: Brain arteriovenous malformations are abnormal connections between arteries and veins without an intervening capillary bed. Endovascular glue embolization with N-butyl cyanoacrylate (NBCA) is an accepted form of treatment. The reported complication rates vary widely from 2% to 15%, and timing of polymerization appears to play a major role. Additionally, the interaction between NBCA and vessel surface as well as the presence of biological catalysts are poorly understood. METHODS: Polymerization time was measured for mixtures of Lipiodol/NBCA of 50/50, 70/30, and 60/40. The influence of pH, temperature, and the presence of biological catalysts on polymerization time was investigated. Contact angles were measured on polyvinyl alcohol cryogel (PVA-C), silicone, and endothelial surfaces in a submerged aqueous environment to assess physical surface interactions. High speed video analysis of glue injection through a microcatheter was performed to characterize simulated coaxial flow. RESULTS: NBCA polymerization rate increased with pH and temperature. A hydrophilic surface such as PVA-C was better than silicone at mimicking the physical properties of endothelium. Live endothelium provided a catalytic surface that at least doubled the rate of polymerization. Blood products further increased the polymerization rate in the following order (slowest to fastest): plasma, platelets, red blood cells (RBCs), and lysed RBCs. These factors could explain the discrepancy between in vitro and in vivo results reported in the current literature. High speed video analysis of NBCA injection showed dripping to jetting transition with significant wall effect which deviated from previous ideal assumptions. CONCLUSIONS: The determinants of NBCA polymerization rate are multifactorial and dependent mainly on the presence of biological catalysts coupled with flow related wall interaction.

Left Internal Carotid Artery Arising from the Right Cavernous Internal Carotid Artery: A Case Report.

Anatomical variations involving the internal carotid artery are uncommon. Herein, we present a very rare origin of the internal carotid artery. An adult female presented to the emergency department after falling. Imaging revealed that the left internal carotid artery arose from the contralateral cavernous segment of the internal carotid artery. Such a variation should be kept in mind by radiologists and surgeons who interpret and operate in this area, respectively.

A rare case of atlantooccipital dissociation in the context of occipitalization of the atlas, with a 2-year follow-up: case report.

Atlantooccipital dislocation (AOD) is a rare and often fatal injury. In cases of survival, residual deficits are severe and often include cranial nerve palsy, quadriplegia, or respiratory issues. Occipitalization is defined as partial or complete congenital fusion of the occiput to the atlas and is exceptionally rare. The authors present a rare case of AOD superimposed on a congenital occipitalization of the atlas. This 39-year-old man had AOD following a motor vehicle collision. On examination, his overall motor score on the American Spinal Injury Association scale was 5/100, and his rectal tone was absent. Computed tomography demonstrated AOD in an area of occipitalization. Magnetic resonance imaging revealed ligamentous injury leading to C1-2 instability. Intervention included occipital cervical instrumentation fusion from the occiput to C-3. Six months postoperatively, imaging revealed fusion of the graft and consolidation of the fractured occipitalization. At the 2-year follow-up, the patient's strength was 3/5 for wrist extension and handgrip on the right side and full strength in the rest of the myotomes. Bladder and bowel function was also normalized. A high-velocity collision led to disruption of the atlantooccipital ligaments and fracture of the occipitalized lateral masses in this patient. Internal fixation and fusion led to good fusion postoperatively. Occipitalization probably led to abnormal joint mechanics at the C1-occiput junction, which might have altered the amount of force required to fracture the occipitalization and produce AOD. This difference may partially account for the favorable neurological outcome in the featured patient compared with traditional cases of AOD.

Individual cell movement, asymmetric colony expansion, rho-associated kinase, and E-cadherin impact the clonogenicity of human embryonic stem cells.

Clonality is, at present, the only means by which the self-renewal potential of a given stem cell can be determined. To assess the clonality of human embryonic stem cells (hESC), a protocol involving seeding wells at low cell densities is commonly used to surmount poor cloning efficiencies. However, factors influencing the accuracy of such an assay have not been fully elucidated. Using clonogenic assays together with time-lapse microscopy, numerical analyses, and regulated gene expression strategies, we found that individual and collective cell movements are inherent properties of hESCs and that they markedly impact the accuracy of clonogenic assays. Analyses of cell motility using mean-square displacement and paired migration correlation indicated that cell movements become more straight-line or ballistic and less random-walk as separation distance decreases. Such motility-induced reaggregation (rather than a true clone) occurs approximately 70% of the time if the distance between two hESCs is <6.4 mum, and is not observed if the distance is >150 mum. Furthermore, newly formed small hESC colonies have a predisposition toward the formation of larger colonies through asymmetric colony expansion and movement, which would not accurately reflect self-renewal and proliferative activity of a true hESC clone. Notably, inhibition of Rho-associated kinase markedly upregulated hESC migration and reaggregation, producing considerable numbers of false-positive colonies. Conversely, E-cadherin upregulation significantly augmented hESC clonogenicity via improved survival of single hESCs without influencing cell motility. This work reveals that individual cell movement, asymmetric colony expansion, Rho-associated kinase, and E-cadherin all work together to influence hESC clonogenicity, and provides additional guidance for improvement of clonogenic assays in the analysis of hESC self-renewal.