Coexisting cancer stem cells with heterogeneous gene amplifications, transcriptional profiles, and malignancy are isolated from single glioblastomas.

Glioblastoma (GBM) is known as an intractable, highly heterogeneous tumor encompassing multiple subclones, each supported by a distinct glioblastoma stem cell (GSC). The contribution of GSC genetic and transcriptional heterogeneity to tumor subclonal properties is debated. In this study, we describe the systematic derivation, propagation, and characterization of multiple distinct GSCs from single, treatment-naive GBMs (GSC families).

Medulloblastoma in adults: an analysis of clinico-pathological, molecular and treatment factors.

Background: Medulloblastoma is a highly malignant, embryonal tumor, which is rare in adults, and shows distinct clinical, histopathological, molecular and treatment response features.

Methods: We retrospectively investigated 44 adults (age 17-48 years) with a histological diagnosis of medulloblastoma, and in 23 immunohistochemistry was used to identify the molecular subgroups. We analyzed demographic, diagnostic, therapeutic and cognitive data, and correlated with PFS (progression-free-survival) and OS (overall survival).

Second series by the Italian Association of Pediatric Hematology and Oncology of children and adolescents with intracranial ependymoma: an integrated molecular and clinical characterization with a long-term follow-up.

Background: A prospective 2002-2014 study stratified 160 patients by resection extent and histological grade, reporting results in 2016. We re-analyzed the series after a median of 119 months, adding retrospectively patients' molecular features.

Methods: Follow-up of all patients was updated.

Infantile Abdominal and Pelvic Lipoblastomas: A Case Series.

Lipoblastomas are rare benign mesenchymal tumors that arise from embryonal fat cells. They are usually discovered in infants and children under 3 years of age, and mostly occur in the trunk (from 10 to 60%, depending on the study) and extremities (from 40 to 45%), while head and neck localizations are rare, with only five cases described to date. We report on three cases of lipoblastomas in infants younger than 4 years, with unusual localizations: one intra-abdominal, discovered during a laparotomy for an intussusception; one pelvic, misdiagnosed as an ovarian mass; and one gluteal with a pelvic extension.

Severe arterial hypertension and hyperandrogenism in a boy: a rare case of catecholamine- and β-HCG-secreting pheochromocytoma.

Background Pheochromocytomas (PCCs) and paragangliomas (PGLs) are known to physicians as the "great mimickers" because of their variable presentation, especially in the pediatric population. Rarely, they co-secrete other hormones. Case presentation An 11-year-old boy presented with severe hypertension (HTN) with cardiac target organ damage.

Prognostic Characterization of Higher-Grade Meningiomas: A Histopathological Score to Predict Progression and Outcome.

Higher-grade meningiomas (WHO grade II and III) represent a diagnostic and prognostic challenge. We assessed the pathological and molecular characteristics of 94 higher-grade meningiomas (85 grade II, 9 grade III) to identify novel prognostic parameters. Higher mitotic count (p = 0.

Integrated DNA methylation analysis identifies topographical and tumoral biomarkers in pilocytic astrocytomas.

Pilocytic astrocytoma (PA) is the most common glioma in pediatric patients and occurs in different locations. Chromosomal alterations are mostly located at chromosome 7q34 comprising the oncogene with consequent activation of the mitogen-activated protein kinase pathway. Although genetic and epigenetic alterations characterizing PA from different localizations have been reported, the role of epigenetic alterations in PA development is still not clear.

Role of Immunohistochemistry in the Identification of Supratentorial C11ORF95-RELA Fused Ependymoma in Routine Neuropathology.

Ependymomas (EPs) are tumors of the brain and spinal cord constituting ∼10% of the childhood central nervous system neoplasms and about 30% in children aged <3 years. Their anatomic distribution varies according to the age, with those arising in the supratentorial (ST) compartment, spinal cord being more common in older children and adults, and those at the infratentorial location are more common and occurring more frequently in infants and children. Recently, molecular classification of EP subgroups has been proposed and a supratentorial ependymoma subgroup characterized by RELA-fusion genes (ST-EP-RELA) has been established.

Androgen receptor status predicts development of brain metastases in ovarian cancers.

Brain metastases are uncommon localizations in epithelial ovarian cancer (EOC), their reported incidence is increasing and no predictive biomarkers have been identified yet. Goals of this study were: i) to define a possible association between Estrogen Receptor (ER), Progesterone Receptor (PR), Androgen Receptor (AR),human EGF receptor 2 (HER2) and brain progression in EOC patients, and ii) to identify differences in ER, PR, AR and HER2 protein expression from primary EOC and its matched resected brain metastasis. A retrospective series of 11 EOC with matched brain metastasis surgically removed was collected.

Gastrointestinal Autonomic Nerve Tumor of the Colon: A Rare Cause of Persistent Abdominal Pain in a Child.

Gastrointestinal autonomic nerve tumor (GANT) is extremely rare and considered a variant of gastrointestinal stromal tumors (GISTs). GANT originates from the intestinal autonomic nervous system mostly of small intestine or the stomach. We report a colonic GANT diagnosed in a 5-year-old child who presented with abdominal pain and fever for a long period.

Pyogenic Granuloma of the Sigmoid Colon causing Intussusception in an Infant.

Pyogenic granuloma is a benign vascular tumor that may affect the gastrointestinal tract. This report describes a rare case of sigmoid-colon pyogenic granuloma in a 4-month-old boy causing intussusception. Resection and anastomosis were curative.

Correction: the complex surgical management of the first case of severe combined immunodeficiency and multiple intestinal atresias surviving after the fourth year of life.

[This corrects the article on p. 257 in vol. 17, PMID: 25587526.

A comprehensive characterization of mitochondrial DNA mutations in glioblastoma multiforme.

Glioblastoma multiforme (GBM) is the most malignant brain cancer in adults, with a poor prognosis, whose molecular stratification still represents a challenge in pathology and clinics. On the other hand, mitochondrial DNA (mtDNA) mutations have been found in most tumors as modifiers of the bioenergetics state, albeit in GBM a characterization of the mtDNA status is lacking to date. Here, a characterization of the burden of mtDNA mutations in GBM samples was performed.

The complex surgical management of the first case of severe combined immunodeficiency and multiple intestinal atresias surviving after the fourth year of life.

Severe combined immunodeficiency (SCID) is a life-threatening syndrome of recurrent infections and gastrointestinal alterations due to severe compromise of T cells and B cells. Clinically, most patients present symptoms before the age of 3 months and without intervention SCID usually results in severe infections and death by the age of 2 years. Its association with intestinal anomalies as multiple intestinal atresias (MIA) is rare and worsens the prognosis, resulting lethal.

Heterotopic pancreas in Meckel's diverticulum in a 7-year-old child with intussusception and recurrent gastrointestinal bleeding: case report and literature review focusing on diagnostic controversies.

Meckel's diverticulum, the most common congenital abnormality of the small intestine, may be associated to heterotopic pancreas, often diagnosed incidentally on histopathological examination. Intussusception affects infants between the ages of 5 and 9 months, but it may also occur in older children, teenagers and adults, and in some cases can be derived by a Meckel's diverticulum resulting in acute abdomen. We analyse the management and the recent literature on similar cases, describing diagnostic options.

Bevacizumab and fotemustine for recurrent glioblastoma: a phase II study of AINO (Italian Association of Neuro-Oncology).

The optimal combination of bevacizumab with cytotoxic or cytostatic drugs in recurrent glioblastoma is unknown. We performed a phase 2 trial of combined bevacizumab and fotemustine for patients with glioblastoma at first relapse after radiotherapy and temozolomide. The primary endpoint was 6-month progression-free survival (PFS), while secondary endpoints were overall survival (OS), response rate based on RANO criteria and toxicity.

Heterogeneous phenotype of human glioblastoma: in vitro study.

Glioblastomas (GBMs) are the most lethal primary brain tumours. Increasing evidence shows that brain tumours contain the population of stem cells, so-called cancer stem cells (CSCs). Stem cell marker CD133 was reported to identify CSC population in GBM.

Predictors of outcome in an AIEOP series of childhood ependymomas: a multifactorial analysis.

Several molecular biomarkers have been suggested as predictors of outcome for pediatric ependymomas but deserve further validation in independent case series. We analyzed intracranial ependymomas belonging to a series of 60 patients prospectively treated according to the protocol sponsored by the Italian Association of Pediatric Hematology-Oncology. We used a tissue microarray to analyze nucleolin (NCL), cyclin-dependent kinase inhibitor 2A (CDKN2A), tumor protein 53 (TP53), and epidermal growth factor receptor (EGFR) by immunohistochemistry and by 1q gain by fluorescent in situ hybridization.

Somatic complex I disruptive mitochondrial DNA mutations are modifiers of tumorigenesis that correlate with low genomic instability in pituitary adenomas.

Mitochondrial DNA (mtDNA) mutations leading to the disruption of respiratory complex I (CI) have been shown to exhibit anti-tumorigenic effects, at variance with those impairing only the function but not the assembly of the complex, which appear to contribute positively to cancer development. Owing to the challenges in the analysis of the multi-copy mitochondrial genome, it is yet to be determined whether tumour-associated mtDNA lesions occur as somatic modifying factors or as germ-line predisposing elements. Here we investigated the whole mitochondrial genome sequence of 20 pituitary adenomas with oncocytic phenotype and identified pathogenic and/or novel mtDNA mutations in 60% of the cases.

Different aquaporin-4 expression in glioblastoma multiforme patients with and without seizures.

Aquaporin-4 (AQP-4), the most important water channel in the brain, is expressed by astrocyte end feet abutting microvessels. Altered expression levels of AQP-4 and redistribution of the protein throughout the membranes of cells found in glioblastoma multiforme (GBM) lead to development of the edema often found surrounding the tumor mass. Dysregulation of AQP-4 also occurs in hippocampal sclerosis and cortical dysplasia in patients with refractory partial epilepsy.