Angiogenic Gene Signature Derived from Subtype Specific Cell Models Segregate Proneural and Mesenchymal Glioblastoma

Intertumoral molecular heterogeneity in glioblastoma identifies four major subtypes based on expression of molecular markers. Among them, the two clinically interrelated subtypes, proneural and mesenchymal, are the most aggressive with proneural liable for conversion to mesenchymal upon therapy. Using two patient-derived novel primary cell culture models (MTA10 and KW10), we developed a minimal but unique four-gene signature comprising genes vascular endothelial growth factor A (VEGF-A), vascular endothelial growth factor B (VEGF-B) and angiopoietin 1 (ANG1), angiopoietin 2 (ANG2) that effectively segregated the proneural (MTA10) and mesenchymal (KW10) glioblastoma subtypes. The cell culture preclassified as mesenchymal showed elevated expression of genes VEGF-A, VEGF-B and ANG1, ANG2 as compared to the other cell culture model that mimicked the proneural subtype. The differentially expressed genes in these two cell culture models were confirmed by us using TCGA and Verhaak databases and we refer to it as a minimal multigene signature (MMS). We validated this MMS on human glioblastoma tissue sections with the use of immunohistochemistry on preclassified (YKL-40 high or mesenchymal glioblastoma and OLIG2 high or proneural glioblastoma) tumor samples (n = 30). MMS segregated mesenchymal and proneural subtypes with 83% efficiency using a simple histopathology scoring approach (p = 0.008 for ANG2 and p = 0.01 for ANG1). Furthermore, MMS expression negatively correlated with patient survival. Importantly, MMS staining demonstrated spatiotemporal heterogeneity within each subclass, adding further complexity to subtype identification in glioblastoma. In conclusion, we report a novel and simple sequencing-independent histopathology-based biomarker signature comprising genes VEGF-A, VEGF-B and ANG1, ANG2 for subtyping of proneural and mesenchymal glioblastoma

Primary paraganglioma of the spine: A clinicopathological study of eight cases

Context: Spinal paragangliomas are rare neuroendocrine tumors of the extra-adrenal paraganglionic system. Aims: This study describes the clinicopathological features of eight cases of spinal paraganglioma and highlights the significance of important morphological features and immunohistochemistry in the diagnosis of paraganglioma at this unusual site. Material and Methods: All the cases of primary spinal paragangliomas diagnosed during the last six years (2008-2013) in the Department of Pathology at our hospital were reviewed. Results: There were six males and two females. The mean age at diagnosis was 50.4 years. All patients presented with low back pain. All tumors were located in the cauda equina or conus medullaris region. Magnetic Resonance Imaging and intraoperative appearance were that of a vascular, well-circumscribed intradural, extramedullary tumor suggestive of either schwannoma or ependymoma. All the patients underwent gross total resection of the tumor. Histopathology in five of the cases showed ′ependymoma-like histology′ while only three cases had a predominant classic ′zellballen′ pattern. Two cases had prominent ′gangliocytic differentiation′. In the five cases with ′ependymoma-like histology′, the diagnosis was confirmed on Immunohistochemistry (IHC). Conclusions: Even though relatively rare, paraganglioma should be considered in the differential diagnosis of spinal tumors and due to their clinical, radiological and histopathological similarity to schwannoma and ependymoma, the diagnosis should be based on close examination of the clinical, radiological and pathological findings

Massive primary cerebellopontine angle melanocytoma in an 11 year old child: A case report and review of literature

A rare case of meningeal melanocytoma in an 11 year-old girl is reported. The tumor was sub-totally resected. She received no adjuvant treatment and is symptom-free at the follow-up of 8 months

Cerebellar Liponeurocytoma: Report of a Rare Entity

Cerebellar liponeurocytoma is a rare clinicopathological entity, included in the 2000 World Health Organization (WHO) classification of tumors of the central nervous system in the category of glioneuronal tumors. These are WHO Grade II, slow-growing tumors in adults with known recurrences. To date, about 70 cases of liponeurocytomas have been reported. This tumor needs to be differentiated from oligodendroglioma as well as medulloblastoma which are more common and aggressive, requiring postoperative chemoradiation. A high index of suspicion is thus advocated for the diagnosis. We present one such case of this rare entity reported in our institute. A 42-year-old female presented with a 4-month history of headache, neck pain, reduced vision, and cerebellar signs. Imaging showed a midline lesion involving the cerebellar vermis and left lobe suggestive of anaplastic ependymoma/hemangioblastoma. The final diagnosis of cerebellar liponeurocytoma was rendered on routine histopathological examination supported by immunohistochemical analysis

Intramedullary conus metastasis from carcinoma lung

A 46-year-old male presented with progressive paraparesis and sensory impairment in both lower limbs since 2 months. He had urinary and bowel incontinence. On examination he had flaccid paraplegia with a sensory level at 11 th dorsal vertebral level. Magnetic resonance imaging (MRI) scans of the lumbosacral spine showed an enhancing intramedullary lesion in the conus. The patient underwent excision of the conus mass. Histopathology confirmed the tumor to represent a poorly differentiated metastatic carcinoma from an unknown primary. A positron emission tomography-computed tomography (PET-CT) scan of the whole body revealed hypermetabolic activity in the hilum of the right lung confirmed to be a lung carcinoma on a CT-guided biopsy. The patient was undergoing chemoradiation at 1 month follow-up. The author′s literature search has yielded only four other case reports of conus metastasis of which only one is in English literature. The present case report and review of literature are presented

Microbiome mediated tolerance to biotic stressors: a case study of the interaction between a toxic cyanobacterium and an oomycete-like infection in Daphnia magna

Organisms are increasingly facing multiple, potentially interacting stressors in natural populations. The ability of populations coping with combined stressors depends on their tolerance to individual stressors and how stressors interact, which may not be correctly captured in controlled laboratory settings. One largely unexplored reason for this is that the microbial communities in laboratory settings often differ from the natural environment, which could result in different stressor responses and interaction patterns. In this study, we investigated the impact of single and combined exposure to a toxic cyanobacterium and an oomycete-like parasite on the performance of three Daphnia magna genotypes. Daphnia individuals were first sterilized and then experimentally given a natural or a laboratory-derived microbial inoculum. Survival, reproduction and body size were monitored for three weeks and gut microbiomes were sampled and characterized at the end of the experiment. Our study confirmed that natural and laboratory microbial inocula and gut microbiomes are differently structured with natural microbiomes being more diverse than laboratory microbiomes. Our results showed that exposure to the stressors reduced D. magna performance compared to the control. An antagonistic interaction between the two biotic stressors was revealed with respect to D. magna survival, when Daphnia individuals were exposed to the laboratory microbial inoculum. This effect was consistent across all three genotypes. In Daphnia exposed to a natural microbial inoculum this antagonistic interaction could not be detected and the genotype x exposure interaction was genotype dependent. Our results indicate that host-stressor interactions depend on the microbial inoculum and that the gut microbiome has potentially a strong role in this, thereby providing an unexplored dimension to multiple-stressor research

A child with neurological deficits, electrolyte imbalance, and arrhythmia

A child presented with an acute febrile illness associated with neurological symptoms. The differential diagnoses of such a presentation with effects of prolonged hospitalization is discussed