BACKGROUND: Gliomatosis cerebri (GC), a radiologically defined diffusely infiltrating glioma, is ... more BACKGROUND: Gliomatosis cerebri (GC), a radiologically defined diffusely infiltrating glioma, is no longer considered a distinct entity since the 2016 WHO classification for tumors of the CNS. Due to its rarity and dismal prognosis treatment recommendations in children remain ambiguous. Using central neuroradiological review, we performed a multi-institutional, retrospective study of GC providing comprehensive radiological, clinical, and (epi)genetic characterization. RESULTS: We included 104 patients between 1-19 years. Within a median follow-up of 15.5 months (range, 2.3-138.8), 93 patients (89.4 %) had died, 4 (3.8 %) were lost to follow-up and 7 (6.8 %) were alive with stable/progressive disease. Median progression-free- (PFS) and overall survival (OS) were 8.6 months (interquartile range, 4.3-14.0) and 15.5 months (10.9-27.7), respectively. Former WHO grading correlated significantly with median OS: WHO °II: 47.8 months (25.2-55.7); WHO °III: 15.9 months (11.4-26.3); WHO °IV: 1...
Lung cancer is the leading cause of cancer‐related death. NSCLC accounts for 80–90% of cases. In ... more Lung cancer is the leading cause of cancer‐related death. NSCLC accounts for 80–90% of cases. In young patients, adenocarcinoma is the most frequent histotype and 3–7% expresses the rearrangement of ALK oncogene, sensitive to TKIs. Crizotinib is the first ALK inhibitor approved by the FDA.
Cerebellar mutism syndrome (CMS) is a common complication following surgical resection of childho... more Cerebellar mutism syndrome (CMS) is a common complication following surgical resection of childhood tumors arising in the posterior fossa. Alteration of linguistic production, up to muteness and emotional lability, generally reported at least 24 h after the intervention, is the hallmark of post-operative CMS. Other associated traits include hypotonia and other cerebellar motor signs, cerebellar cognitive-affective syndrome, motor deficits from the involvement of the long pathways, and cranial neuropathies. Recovery usually takes 6 months, but most children are burdened with long-term residual deficits. The pathogenic mechanism is likely due to the damage occurring to the proximal efferent cerebellar pathway, including the dentate nucleus, the superior cerebellar peduncle, and its decussation in the mesencephalic tegmentum. Proven risk factors include brain stem invasion, diagnosis of medulloblastoma, midline localization, tumor size, invasion of the fourth ventricle, invasion of the...
Medulloblastoma (MB) is the most common malignant brain tumor. It is classified into four subgrou... more Medulloblastoma (MB) is the most common malignant brain tumor. It is classified into four subgroups characterized by distinct mutations, deregulation of specific signaling pathways and different clinical outcomes. A series of pathways and epigenetic mechanisms are deregulated across multiple subtypes, thus representing a window of opportunity for the identification of common targets. A common feature is the presence of stem-like cells (SLCs), a fraction of the tumor bulk which retains the ability to sustain tumor growth and may represent the progenitor giving rise to MB. Recent studies have highlighted the crucial role of microRNAs tumor signaling pathway deregulation. We have previously identified microRNAs deregulated MB and showed that miR-326 is strongly downregulated and represses Hedgehog/Gli signaling. Human and murine MB SLCs were derived and cultured as oncospheres. We investigated the expression levels of miR-326 and its host gene β-arrestin1 in MB specimens and in SLC, the role of the two molecules in MB and the regulation of miR-326/ β-arrestin1 transcriptional unit in SLC. A pharmacological approach was utilized to modulate the expression of miR-326/ β-arrestin1 in MB both in vitro and in vivo. We found that miR-326 cooperates with its host gene β-arrestin1 as tumor suppressor, and is lost in both MB and SLC. Such unit suppresses Hedgehog signaling at multiple levels: β-arrestin1 modulates Gli1-K518 acetylation while miR-326 controls Gli2 and Smo, activatory molecules of the pathway. The analysis of the potential mechanisms involved in the downregulation of this transcriptional unit showed that β-arrestin1/miR-326 are silenced through epigenetic mechanisms at histone levels. Indeed, epigenetic drugs are able to reactivate the miR-326/β- arrestin1 expression and suppress MB and SLC growth in vitro and in vivo. Our study reveals a new microRNA/host gene network in MB and proposes miR-326/β-arrestin1 as tumor suppressors for medulloblastoma patients, susceptible to be re-expressed by epigenetic treatments.
Down syndrome (DS) is the most common chromosome abnormality with a unique cancer predisposition ... more Down syndrome (DS) is the most common chromosome abnormality with a unique cancer predisposition syndrome pattern: a higher risk to develop acute leukemia and a lower incidence of solid tumors. In particular, brain tumors are rarely reported in the DS population, and biological behavior and natural history are not well described and identified. We report a case of a 10-year-old child with DS who presented with a medulloblastoma (MB). Histological examination revealed a classic MB with focal anaplasia and the molecular profile showed the presence of a CTNNB1 variant associated with the wingless (WNT) molecular subgroup with a good prognosis in contrast to our case report that has shown an early metastatic relapse. The nearly seven-fold decreased risk of MB in children with DS suggests the presence of protective biological mechanisms. The cerebellum hypoplasia and the reduced volume of cerebellar granule neuron progenitor cells seem to be a possible favorable condition to prevent MB d...
BackgroundOptic pathway gliomas (OPGs) are rare neoplasms in children with an unpredictable clini... more BackgroundOptic pathway gliomas (OPGs) are rare neoplasms in children with an unpredictable clinical course. Approximately 15% of OPGs occur in patients affected by neurofibromatosis type 1 (NF1): the clinical course of these cases is more indolently than sporadic ones, and NF1 patients less frequently require treatment including surgery. Instead, over 90% of sporadic OPGs require one or more therapeutic approaches. The management of OPG is controversial. They are also characterized by a high risk of morbidity including hypothalamic damage, endocrine deficits, visual deficit and/or neurological impairment.Materials and MethodsIn this paper, we evaluated visual and endocrinological outcomes of a population of OPG followed at our center from 2013 to 2021, with a particular emphasis on the role of surgery.ResultsTwenty-six patients were included in this study (mean age of 40.7 months). Tumor location on imaging was described by the Dodge classification. Five cases had NF 1. Thirteen ca...
Neurotoxicity caused by traditional chemotherapy and radiotherapy is well known and widely descri... more Neurotoxicity caused by traditional chemotherapy and radiotherapy is well known and widely described. New therapies, such as biologic therapy and immunotherapy, are associated with better outcomes in pediatric patients but are also associated with central and peripheral nervous system side effects. Nevertheless, central nervous system (CNS) toxicity is a significant source of morbidity in the treatment of cancer patients. Some CNS complications appear during treatment while others present months or even years later. Radiation, traditional cytotoxic chemotherapy, and novel biologic and targeted therapies have all been recognized to cause CNS side effects; additionally, the risks of neurotoxicity can increase with combination therapy. Symptoms and complications can be varied such as edema, seizures, fatigue, psychiatric disorders, and venous thromboembolism, all of which can seriously influence the quality of life. Neurologic complications were seen in 33% of children with non-CNS sol...
Supplemental File 1: Yield and quality of RNA extracted following the Protocols A, D and E. Data ... more Supplemental File 1: Yield and quality of RNA extracted following the Protocols A, D and E. Data are mean±SD for RNA samples extracted from HSJD-DIPG007 cell lines. T-test was performed for the comparison of the RNAs concentration from Bioanalyzer measurements between the protocols: For Total RNA, Protocol A vs Protocol D p-value=0,00284; Protocol A vs Protocol E p-value= 0,01463; Protocol D vs Protocol E p-value= 0,59438; for Small RNA, Protocol A vs Protocol D p-value=0,01039; Protocol A vs Protocol E p-value= 0,01486; Protocol D vs Protocol E p-value=0,00518. <br>
High-grade gliomas (HGG) represent about 15% of all pediatric brain tumors, with a dismal prognos... more High-grade gliomas (HGG) represent about 15% of all pediatric brain tumors, with a dismal prognosis and survival rates ranging from 15 to 35%. Approximately 10–12% of pediatric HGGs (pHGG) occur in children younger than five years of age at diagnosis, specifically infants (iHGG), with an unexpected overall survival rate (OS) in 60–70% of cases. In the literature, iHGGs include a large variety of heterogeneous lesions with different molecular profiles that likely explain their different outcomes. We report our single-institution experience of iHGG including 11 children under five years of age with newly diagnosed HGG between 2011 and 2021. All patients received surgery and adjuvant chemotherapy; only two patients received radiotherapy because their age at diagnosis was more than four years-old. Molecular investigations, including next generation sequencing (NGS) and DNA methylation, detected three NTRK-fusions, one ROS1-fusions, one MN1-rearrangement, and two PATZ1-fusions. According...
Pediatric brain tumors represent the most common types of childhood cancer and novel diagnostic a... more Pediatric brain tumors represent the most common types of childhood cancer and novel diagnostic and therapeutic solutions are urgently needed. The gold standard treatment option for brain cancers in children, as in adults, is tumor resection followed by radio- and chemotherapy, but with discouraging therapeutic results. In particular, the last two treatments are often associated to significant neurotoxicity in the developing brain of a child, with resulting disabilities such as cognitive problems, neuroendocrine, and neurosensory dysfunctions/deficits. Nanoparticles have been increasingly and thoroughly investigated as they show great promises as diagnostic tools and vectors for gene/drug therapy for pediatric brain cancer due to their ability to cross the blood–brain barrier. In this review we will discuss the developments of nanoparticle-based strategies as novel precision nanomedicine tools for diagnosis and therapy in pediatric brain cancers, with a particular focus on targeting...
3D models are increasingly used to study mechanisms driving tumor progression and mimicking in vi... more 3D models are increasingly used to study mechanisms driving tumor progression and mimicking in vitro processes such as invasion and migration. However, there is a need to establish more protocols based on 3D culture systems that allow for downstream molecular biology investigations. Materials & methods: Here we present a method for optimal RNA extraction from highly aggressive primary glioma cells invading into Matrigel. The method has been established by comparing previously reported protocols, available commercial kits and optimizing specific steps for matrix dissociation, RNA separation and purification. Results and conclusion: The protocol allows RNA extraction from cells embedded into Matrigel, with optimal yield, purity and integrity suitable for subsequent sequencing analysis of both high and low molecular weight RNA.
Surgical treatment of lesions involving the postero-medial occipito-temporal region is challengin... more Surgical treatment of lesions involving the postero-medial occipito-temporal region is challenging because of high risk of morbidity due to damage or excessive retraction of critical neuro-vascular structures, especially within the dominant hemisphere.1-3 Here, we describe the case of a 17-yr-old patient who underwent resection of an epileptogenic low-grade tumor located within the left-dominant lingual gyrus. Seizures were characterized, as a first symptom, by right-sided simple visual hallucination that pointed to the left pericalcarine region, corresponding to the lesion location. No signs of primary involvement of anterior temporo-mesial structures (hippocampus/amygdala) were found. As the anatomo-electroclinical correlation was concordant, direct tumor removal was indicated through an infra-occipital supratentorial approach. This route allowed direct access to the target through a safe extra-axial corridor, which limits intraparenchymal dissection until the tumor margin is identified and avoids critical vascular structures, such as the vein of Labbé.4,5 An external cerebrospinal fluid (CSF) drainage was used to facilitate brain relaxation, minimizing brain and venous retraction and, consequently, reducing the risk of postoperative neurological complications, especially for vision. Postoperative magnetic resonance imaging (MRI) demonstrated no surgical complications. Pathological examination revealed a ganglioglioma. At 9-mo follow-up, the neurological examination was normal, antiepileptic therapy was stopped, and the patient was seizure-free. The video describes the main surgical steps, using both intraoperative videos and advanced 3-dimensional modeling of neuroimaging pictures. Informed consent was obtained for surgery and video recording.
We present a case demonstrating the performance of different radiographical imaging modalities in... more We present a case demonstrating the performance of different radiographical imaging modalities in the diagnostic work-up of a patient with neurofibromatosis type 1 (NF1) and plexiform neurofibroma (PN). The newborn boy showed an expansive-infiltrative cervical and facial mass presented with macrocrania, craniofacial disfigurement, exophthalmos and glaucoma. A computer tomography (CT) and a magnetic resonance imaging (MRI) were performed. The CT was fundamental to evaluate the bone dysmorphisms and the MRI was crucial to estimate the mass extension. The biopsy of the lesion confirmed the suspicion of PN, thus allowing the diagnosis of NF1. PN is a variant of neurofibromas, a peripheral nerves sheath tumor typically associated with NF1. Even through currently available improved detection techniques, NF1 diagnosis at birth remains a challenge due to a lack of pathognomonic signs; therefore congenital PN are recognized in 20% of cases. This case highlights the importance of using differ...
Bi‐allelic inactivation of XPD protein, a nucleotide excision repair (NER) signaling pathway comp... more Bi‐allelic inactivation of XPD protein, a nucleotide excision repair (NER) signaling pathway component encoded by ERCC2 gene, has been associated with several defective DNA repair phenotypes, including xeroderma pigmentosum, photosensitive trichothiodystrophy, and cerebro‐oculo‐facio‐skeletal syndrome. We report a pediatric patient harboring two compound heterozygous variants in ERCC2 gene, c.361‐1G>A and c.2125A>C (p.Thr709Pro), affected by severe postnatal growth deficiency, microcephaly, facial dysmorphisms and pilocytic astrocytoma of the brainstem. Some of these features point to a DNA repair syndrome, and altogether delineate a phenotype differentiating from disorders known to be associated with ERCC2 mutations. The DNA repair efficiency following UV irradiation in the proband's skin fibroblasts was defective indicating that the new set of ERCC2 alleles impacts on NER efficiency. Sequencing analysis on tumor DNA did not reveal any somatic deleterious point variant in cancer‐related genes, while SNP‐array analysis disclosed a 2 Mb microduplication involving the 7q34 region, spanning from KIAA1549 to BRAF, and resulting in the KIAA1549:BRAF fusion protein, a marker of pilocytic astrocytoma. In conclusion, this report expands the clinical and mutational spectrum of ERCC2‐related disorders.
BACKGROUND: Gliomatosis cerebri (GC), a radiologically defined diffusely infiltrating glioma, is ... more BACKGROUND: Gliomatosis cerebri (GC), a radiologically defined diffusely infiltrating glioma, is no longer considered a distinct entity since the 2016 WHO classification for tumors of the CNS. Due to its rarity and dismal prognosis treatment recommendations in children remain ambiguous. Using central neuroradiological review, we performed a multi-institutional, retrospective study of GC providing comprehensive radiological, clinical, and (epi)genetic characterization. RESULTS: We included 104 patients between 1-19 years. Within a median follow-up of 15.5 months (range, 2.3-138.8), 93 patients (89.4 %) had died, 4 (3.8 %) were lost to follow-up and 7 (6.8 %) were alive with stable/progressive disease. Median progression-free- (PFS) and overall survival (OS) were 8.6 months (interquartile range, 4.3-14.0) and 15.5 months (10.9-27.7), respectively. Former WHO grading correlated significantly with median OS: WHO °II: 47.8 months (25.2-55.7); WHO °III: 15.9 months (11.4-26.3); WHO °IV: 1...
Lung cancer is the leading cause of cancer‐related death. NSCLC accounts for 80–90% of cases. In ... more Lung cancer is the leading cause of cancer‐related death. NSCLC accounts for 80–90% of cases. In young patients, adenocarcinoma is the most frequent histotype and 3–7% expresses the rearrangement of ALK oncogene, sensitive to TKIs. Crizotinib is the first ALK inhibitor approved by the FDA.
Cerebellar mutism syndrome (CMS) is a common complication following surgical resection of childho... more Cerebellar mutism syndrome (CMS) is a common complication following surgical resection of childhood tumors arising in the posterior fossa. Alteration of linguistic production, up to muteness and emotional lability, generally reported at least 24 h after the intervention, is the hallmark of post-operative CMS. Other associated traits include hypotonia and other cerebellar motor signs, cerebellar cognitive-affective syndrome, motor deficits from the involvement of the long pathways, and cranial neuropathies. Recovery usually takes 6 months, but most children are burdened with long-term residual deficits. The pathogenic mechanism is likely due to the damage occurring to the proximal efferent cerebellar pathway, including the dentate nucleus, the superior cerebellar peduncle, and its decussation in the mesencephalic tegmentum. Proven risk factors include brain stem invasion, diagnosis of medulloblastoma, midline localization, tumor size, invasion of the fourth ventricle, invasion of the...
Medulloblastoma (MB) is the most common malignant brain tumor. It is classified into four subgrou... more Medulloblastoma (MB) is the most common malignant brain tumor. It is classified into four subgroups characterized by distinct mutations, deregulation of specific signaling pathways and different clinical outcomes. A series of pathways and epigenetic mechanisms are deregulated across multiple subtypes, thus representing a window of opportunity for the identification of common targets. A common feature is the presence of stem-like cells (SLCs), a fraction of the tumor bulk which retains the ability to sustain tumor growth and may represent the progenitor giving rise to MB. Recent studies have highlighted the crucial role of microRNAs tumor signaling pathway deregulation. We have previously identified microRNAs deregulated MB and showed that miR-326 is strongly downregulated and represses Hedgehog/Gli signaling. Human and murine MB SLCs were derived and cultured as oncospheres. We investigated the expression levels of miR-326 and its host gene β-arrestin1 in MB specimens and in SLC, the role of the two molecules in MB and the regulation of miR-326/ β-arrestin1 transcriptional unit in SLC. A pharmacological approach was utilized to modulate the expression of miR-326/ β-arrestin1 in MB both in vitro and in vivo. We found that miR-326 cooperates with its host gene β-arrestin1 as tumor suppressor, and is lost in both MB and SLC. Such unit suppresses Hedgehog signaling at multiple levels: β-arrestin1 modulates Gli1-K518 acetylation while miR-326 controls Gli2 and Smo, activatory molecules of the pathway. The analysis of the potential mechanisms involved in the downregulation of this transcriptional unit showed that β-arrestin1/miR-326 are silenced through epigenetic mechanisms at histone levels. Indeed, epigenetic drugs are able to reactivate the miR-326/β- arrestin1 expression and suppress MB and SLC growth in vitro and in vivo. Our study reveals a new microRNA/host gene network in MB and proposes miR-326/β-arrestin1 as tumor suppressors for medulloblastoma patients, susceptible to be re-expressed by epigenetic treatments.
Down syndrome (DS) is the most common chromosome abnormality with a unique cancer predisposition ... more Down syndrome (DS) is the most common chromosome abnormality with a unique cancer predisposition syndrome pattern: a higher risk to develop acute leukemia and a lower incidence of solid tumors. In particular, brain tumors are rarely reported in the DS population, and biological behavior and natural history are not well described and identified. We report a case of a 10-year-old child with DS who presented with a medulloblastoma (MB). Histological examination revealed a classic MB with focal anaplasia and the molecular profile showed the presence of a CTNNB1 variant associated with the wingless (WNT) molecular subgroup with a good prognosis in contrast to our case report that has shown an early metastatic relapse. The nearly seven-fold decreased risk of MB in children with DS suggests the presence of protective biological mechanisms. The cerebellum hypoplasia and the reduced volume of cerebellar granule neuron progenitor cells seem to be a possible favorable condition to prevent MB d...
BackgroundOptic pathway gliomas (OPGs) are rare neoplasms in children with an unpredictable clini... more BackgroundOptic pathway gliomas (OPGs) are rare neoplasms in children with an unpredictable clinical course. Approximately 15% of OPGs occur in patients affected by neurofibromatosis type 1 (NF1): the clinical course of these cases is more indolently than sporadic ones, and NF1 patients less frequently require treatment including surgery. Instead, over 90% of sporadic OPGs require one or more therapeutic approaches. The management of OPG is controversial. They are also characterized by a high risk of morbidity including hypothalamic damage, endocrine deficits, visual deficit and/or neurological impairment.Materials and MethodsIn this paper, we evaluated visual and endocrinological outcomes of a population of OPG followed at our center from 2013 to 2021, with a particular emphasis on the role of surgery.ResultsTwenty-six patients were included in this study (mean age of 40.7 months). Tumor location on imaging was described by the Dodge classification. Five cases had NF 1. Thirteen ca...
Neurotoxicity caused by traditional chemotherapy and radiotherapy is well known and widely descri... more Neurotoxicity caused by traditional chemotherapy and radiotherapy is well known and widely described. New therapies, such as biologic therapy and immunotherapy, are associated with better outcomes in pediatric patients but are also associated with central and peripheral nervous system side effects. Nevertheless, central nervous system (CNS) toxicity is a significant source of morbidity in the treatment of cancer patients. Some CNS complications appear during treatment while others present months or even years later. Radiation, traditional cytotoxic chemotherapy, and novel biologic and targeted therapies have all been recognized to cause CNS side effects; additionally, the risks of neurotoxicity can increase with combination therapy. Symptoms and complications can be varied such as edema, seizures, fatigue, psychiatric disorders, and venous thromboembolism, all of which can seriously influence the quality of life. Neurologic complications were seen in 33% of children with non-CNS sol...
Supplemental File 1: Yield and quality of RNA extracted following the Protocols A, D and E. Data ... more Supplemental File 1: Yield and quality of RNA extracted following the Protocols A, D and E. Data are mean±SD for RNA samples extracted from HSJD-DIPG007 cell lines. T-test was performed for the comparison of the RNAs concentration from Bioanalyzer measurements between the protocols: For Total RNA, Protocol A vs Protocol D p-value=0,00284; Protocol A vs Protocol E p-value= 0,01463; Protocol D vs Protocol E p-value= 0,59438; for Small RNA, Protocol A vs Protocol D p-value=0,01039; Protocol A vs Protocol E p-value= 0,01486; Protocol D vs Protocol E p-value=0,00518. <br>
High-grade gliomas (HGG) represent about 15% of all pediatric brain tumors, with a dismal prognos... more High-grade gliomas (HGG) represent about 15% of all pediatric brain tumors, with a dismal prognosis and survival rates ranging from 15 to 35%. Approximately 10–12% of pediatric HGGs (pHGG) occur in children younger than five years of age at diagnosis, specifically infants (iHGG), with an unexpected overall survival rate (OS) in 60–70% of cases. In the literature, iHGGs include a large variety of heterogeneous lesions with different molecular profiles that likely explain their different outcomes. We report our single-institution experience of iHGG including 11 children under five years of age with newly diagnosed HGG between 2011 and 2021. All patients received surgery and adjuvant chemotherapy; only two patients received radiotherapy because their age at diagnosis was more than four years-old. Molecular investigations, including next generation sequencing (NGS) and DNA methylation, detected three NTRK-fusions, one ROS1-fusions, one MN1-rearrangement, and two PATZ1-fusions. According...
Pediatric brain tumors represent the most common types of childhood cancer and novel diagnostic a... more Pediatric brain tumors represent the most common types of childhood cancer and novel diagnostic and therapeutic solutions are urgently needed. The gold standard treatment option for brain cancers in children, as in adults, is tumor resection followed by radio- and chemotherapy, but with discouraging therapeutic results. In particular, the last two treatments are often associated to significant neurotoxicity in the developing brain of a child, with resulting disabilities such as cognitive problems, neuroendocrine, and neurosensory dysfunctions/deficits. Nanoparticles have been increasingly and thoroughly investigated as they show great promises as diagnostic tools and vectors for gene/drug therapy for pediatric brain cancer due to their ability to cross the blood–brain barrier. In this review we will discuss the developments of nanoparticle-based strategies as novel precision nanomedicine tools for diagnosis and therapy in pediatric brain cancers, with a particular focus on targeting...
3D models are increasingly used to study mechanisms driving tumor progression and mimicking in vi... more 3D models are increasingly used to study mechanisms driving tumor progression and mimicking in vitro processes such as invasion and migration. However, there is a need to establish more protocols based on 3D culture systems that allow for downstream molecular biology investigations. Materials & methods: Here we present a method for optimal RNA extraction from highly aggressive primary glioma cells invading into Matrigel. The method has been established by comparing previously reported protocols, available commercial kits and optimizing specific steps for matrix dissociation, RNA separation and purification. Results and conclusion: The protocol allows RNA extraction from cells embedded into Matrigel, with optimal yield, purity and integrity suitable for subsequent sequencing analysis of both high and low molecular weight RNA.
Surgical treatment of lesions involving the postero-medial occipito-temporal region is challengin... more Surgical treatment of lesions involving the postero-medial occipito-temporal region is challenging because of high risk of morbidity due to damage or excessive retraction of critical neuro-vascular structures, especially within the dominant hemisphere.1-3 Here, we describe the case of a 17-yr-old patient who underwent resection of an epileptogenic low-grade tumor located within the left-dominant lingual gyrus. Seizures were characterized, as a first symptom, by right-sided simple visual hallucination that pointed to the left pericalcarine region, corresponding to the lesion location. No signs of primary involvement of anterior temporo-mesial structures (hippocampus/amygdala) were found. As the anatomo-electroclinical correlation was concordant, direct tumor removal was indicated through an infra-occipital supratentorial approach. This route allowed direct access to the target through a safe extra-axial corridor, which limits intraparenchymal dissection until the tumor margin is identified and avoids critical vascular structures, such as the vein of Labbé.4,5 An external cerebrospinal fluid (CSF) drainage was used to facilitate brain relaxation, minimizing brain and venous retraction and, consequently, reducing the risk of postoperative neurological complications, especially for vision. Postoperative magnetic resonance imaging (MRI) demonstrated no surgical complications. Pathological examination revealed a ganglioglioma. At 9-mo follow-up, the neurological examination was normal, antiepileptic therapy was stopped, and the patient was seizure-free. The video describes the main surgical steps, using both intraoperative videos and advanced 3-dimensional modeling of neuroimaging pictures. Informed consent was obtained for surgery and video recording.
We present a case demonstrating the performance of different radiographical imaging modalities in... more We present a case demonstrating the performance of different radiographical imaging modalities in the diagnostic work-up of a patient with neurofibromatosis type 1 (NF1) and plexiform neurofibroma (PN). The newborn boy showed an expansive-infiltrative cervical and facial mass presented with macrocrania, craniofacial disfigurement, exophthalmos and glaucoma. A computer tomography (CT) and a magnetic resonance imaging (MRI) were performed. The CT was fundamental to evaluate the bone dysmorphisms and the MRI was crucial to estimate the mass extension. The biopsy of the lesion confirmed the suspicion of PN, thus allowing the diagnosis of NF1. PN is a variant of neurofibromas, a peripheral nerves sheath tumor typically associated with NF1. Even through currently available improved detection techniques, NF1 diagnosis at birth remains a challenge due to a lack of pathognomonic signs; therefore congenital PN are recognized in 20% of cases. This case highlights the importance of using differ...
Bi‐allelic inactivation of XPD protein, a nucleotide excision repair (NER) signaling pathway comp... more Bi‐allelic inactivation of XPD protein, a nucleotide excision repair (NER) signaling pathway component encoded by ERCC2 gene, has been associated with several defective DNA repair phenotypes, including xeroderma pigmentosum, photosensitive trichothiodystrophy, and cerebro‐oculo‐facio‐skeletal syndrome. We report a pediatric patient harboring two compound heterozygous variants in ERCC2 gene, c.361‐1G>A and c.2125A>C (p.Thr709Pro), affected by severe postnatal growth deficiency, microcephaly, facial dysmorphisms and pilocytic astrocytoma of the brainstem. Some of these features point to a DNA repair syndrome, and altogether delineate a phenotype differentiating from disorders known to be associated with ERCC2 mutations. The DNA repair efficiency following UV irradiation in the proband's skin fibroblasts was defective indicating that the new set of ERCC2 alleles impacts on NER efficiency. Sequencing analysis on tumor DNA did not reveal any somatic deleterious point variant in cancer‐related genes, while SNP‐array analysis disclosed a 2 Mb microduplication involving the 7q34 region, spanning from KIAA1549 to BRAF, and resulting in the KIAA1549:BRAF fusion protein, a marker of pilocytic astrocytoma. In conclusion, this report expands the clinical and mutational spectrum of ERCC2‐related disorders.
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