Project description:Rosette-forming glioneuronal tumour (RGNT) of the IV ventricle is a very recent entity, recognized in the latest WHO classification of Central Nervous System Tumors. It is composed by two distinct features: a glial component, with typical characteristics of pilocytic astrocytoma, and a component forming neurocytic rosettes, with eosinophilic regions positive for synaptofisin and/or perivascular rosettes. Herein, we describe a 33-year-old man with RGNT arising in a peculiar location, namely the spinal cord. We further performed an extensive immunohistochemistry and molecular analysis, using array-CGH (aCGH), whole exome and cancer-related hotspot sequencing, in order to better understand its underlying biology. The histology revealed a WHO grade I RGNT typically found in the fourth-ventricle. Immunoreactivity for synaptophysin and neurofilament protein was noted in the neurocytic component, whereas the glial component exhibited positivity for GFAP and S-100. Neurocytic component was found negative for GFAP. Mitoses were rare, and there was no necrosis present. Across all mutational analyses, there were detected somatic mutations in 4 genes: MLL2, CNNM3, PCDHGC4 and SCN1A. The tumor exhibited a microsatellite stable (MSS) phenotype. Array-CGH (aCGH) showed loss in 1p and gain of 1q, as well as gain of the whole chromosomes 7, 9 and 16. Moreover, we observed focal gains/losses in the chromosomes 1, 2, 3, 6, 7, 11, 14, 17, 22 and 23. Local amplifications in 9q34.2 (region with no genes mapped) and 19p13.3 (region encompassing the gene SBNO2) were identified. Additionally, we verified the KIAA1549-BRAF fusion, typically found in pilocytic astrocytomas, through aCGH, RT-PCR and FISH. Our comprehensive molecular profiling of a RGNT case suggests the existence of a unique genetic pathway for the development of these tumors: KIAA1549-BRAF fusion is a possible driver by constitutively activating MAPK pathway, and MLL2 mutation may lead to profound changes in the methylome. Taken together, these mechanisms may increase survival and/or tumorigenic capacity of cells, leading to the development of this rare entity.

Project description:Rosette-forming glioneuronal tumour (RGNT) of the IV ventricle is a very recent entity, recognized in the latest WHO classification of Central Nervous System Tumors. It is composed by two distinct features: a glial component, with typical characteristics of pilocytic astrocytoma, and a component forming neurocytic rosettes, with eosinophilic regions positive for synaptofisin and/or perivascular rosettes. Herein, we describe a 33-year-old man with RGNT arising in a peculiar location, namely the spinal cord. We further performed an extensive immunohistochemistry and molecular analysis, using array-CGH (aCGH), whole exome and cancer-related hotspot sequencing, in order to better understand its underlying biology. The histology revealed a WHO grade I RGNT typically found in the fourth-ventricle. Immunoreactivity for synaptophysin and neurofilament protein was noted in the neurocytic component, whereas the glial component exhibited positivity for GFAP and S-100. Neurocytic component was found negative for GFAP. Mitoses were rare, and there was no necrosis present. Across all mutational analyses, there were detected somatic mutations in 4 genes: MLL2, CNNM3, PCDHGC4 and SCN1A. The tumor exhibited a microsatellite stable (MSS) phenotype. Array-CGH (aCGH) showed loss in 1p and gain of 1q, as well as gain of the whole chromosomes 7, 9 and 16. Moreover, we observed focal gains/losses in the chromosomes 1, 2, 3, 6, 7, 11, 14, 17, 22 and 23. Local amplifications in 9q34.2 (region with no genes mapped) and 19p13.3 (region encompassing the gene SBNO2) were identified. Additionally, we verified the KIAA1549-BRAF fusion, typically found in pilocytic astrocytomas, through aCGH, RT-PCR and FISH. Our comprehensive molecular profiling of a RGNT case suggests the existence of a unique genetic pathway for the development of these tumors: KIAA1549-BRAF fusion is a possible driver by constitutively activating MAPK pathway, and MLL2 mutation may lead to profound changes in the methylome. Taken together, these mechanisms may increase survival and/or tumorigenic capacity of cells, leading to the development of this rare entity. Two-color Agilent 8x60K array CGH (aCGH) was performed in the rosette-forming glioneuronal tumour (CY3) and reference DNA (CY5 - DNA extracted from leucocytes of the patient).

Project description:BackgroundPallister-Hall syndrome (OMIM #146510) is a rare autosomal dominant condition caused by a mutation in the GLI3 gene. The cardinal feature of Pallister-Hall syndrome is the presence of hypothalamic hamartomas, which may manifest with seizures, panhypopituitarism and visual impairment. In Pallister-Hall syndrome, dysplastic histogenetic processes responsible for hypothalamic hamartomas are thought to disrupt early craniofacial development. The clinical presentation of Pallister-Hall syndrome may include: characteristic facies (low-set and posteriorly angulated ears, short nose with flat nasal bridge), cleft palate and uvula, bifid epiglottis and laryngotracheal cleft, limb anomalies (e.g., polysyndactyly, short limbs and nail dysplasia), anal atresia, genitourinary abnormalities and congenital heart defects.Case presentationWe report the case of two monochorionic diamniotic twins diagnosed with Pallister-Hall syndrome during the neonatal period, after the identification of a hypothalamic hamartoma on day 1 by cerebral ultrasound scan, later confirmed by brain magnetic resonance imaging. Cerebral ultrasound and magnetic resonance imaging presentations were identical in both twins.Discussion and conclusionsWe review previously published cases (four reports) of hypothalamic hamartomas identified via cerebral ultrasound and compare reported ultrasonographic features. Main differential diagnoses based on cerebral ultrasound findings are discussed. Full description of typical magnetic resonance imaging appearance is also provided. This is the first case reported in the literature of monochorionic diamniotic twins affected by genetically confirmed Pallister-Hall syndrome with identical hypothalamic hamartomas at cerebral ultrasound and magnetic resonance imaging. Moreover, this paper adds to the existing literature on the sonographic appearance of hypothalamic hamartomas. Considering the consistency in hypothalamic hamartomas' sonographic appearance, we support the use of cerebral ultrasound as a first-line neuroimaging modality in case of clinical suspicion of Pallister-Hall syndrome.

Dataset Information

Pallister-Hall syndrome with orofacial narrowing and tethered cord: a case report.

Publications

Pallister-Hall syndrome with orofacial narrowing and tethered cord: a case report.

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