Variante amelanótica en melanoma cerebral primario: a propósito de un caso / Primary intracranial melanoma, amelanotic variant: Case report

El melanoma cerebral primario es un tumor muy infrecuente (0,07% de las neoplasias primarias del SNC). Generalmente muestra un abundante contenido en melanina, y solo en contadas ocasiones se han descrito variantes hipoamelanóticas. Presentamos el caso de una paciente con clínica de cefalea, paresia braquial izquierda y síndrome lobar frontal. La RM mostró una masa frontal derecha con captación homogénea de contraste. Como tratamiento, se realizó una resección quirúrgica completa. El estudio anatomopatológico fue diagnóstico para melanoma, con muy escaso contenido en melanina y alto índice proliferativo. Se realizó un estudio de extensión exhaustivo para descartar otra localización primaria. Debido a varias complicaciones intercurrentes, la paciente evolucionó desfavorablemente, sin llegar a recibir otros tratamientos. La variante amelanótica de los melanomas cerebrales primarios no ha sido descrita con detalle previamente. Repasamos la literatura al respecto y discutimos los detalles de manejo y diagnóstico de esta entidad clínica (AU)

Primary brain melanoma is a very rare tumour (only 0.07% of primary CNS neoplasms) which usually shows with abundant melanin content; whereas hypo/melanotic variants have been scarcely described. We introduce the case of a female patient with headache, left brachial paresis and frontal lobar syndrome. The MRI image showed a right frontal mass with homogeneous contrast uptake. As treatment, a complete surgical resection was performed. Pathology was diagnostic for melanoma, with very low melanin content and a high proliferative index. A thorough extension study was performed to rule out an extracranial primary origin. Due to several intercurrent complications, the patient evolved unfavorably, not being able to receive further treatment. The amelanotic variant of primary intracranial malignant melanomas has not been described in detail previously. We will review the literature, focusing on the particularities of management and diagnosis of this clinical entity (AU)

Primary intracranial melanoma, amelanotic variant: Case report.

Primary brain melanoma is a very rare tumour (only 0.07% of primary CNS neoplasms) which usually shows with abundant melanin content; whereas hypo/melanotic variants have been scarcely described. We introduce the case of a female patient with headache, left brachial paresis and frontallobar syndrome. The MRI image showed a right frontal mass with homogeneous contrast uptake. As treatment, a complete surgical resection was performed. Pathology was diagnostic for melanoma, with very low melanin content and a high proliferative index. A thorough extension study was performed to rule out an extracranial primary origin. Due to several intercurrent complications, the patient evolved unfavorably, not being able to receive further treatment. The amelanotic variant of primary intracranial malignant melanomas has not been described in detail previously. We will review the literature, focusing on the particularities of management and diagnosis of this clinical entity.

Safeness and efficacy of 2-µm handheld thulium laser during microsurgical resection of supratentorial and infratentorial meningiomas: Experience of a single center.

Aims: We performed a retrospective nonrandomized study to analyze the results of a microsurgery of intracranial meningiomas using 2-µm thulium flexible handheld laser fiber (Revolix jr). Methods: From February 2014 to December 2021, 75 nonconsecutive patients suffering from intracranial meningiomas, admitted in our department, have been operated on with microsurgical technique assisted by 2-µm thulium flexible handheld laser. We have reviewed demographic and clinical data to evaluate safety and efficacy of the technique. Results: There were no complications related to the use of the 2-µm thulium laser. We operated on a high percentage of cranial base and tentorial and posterior fossa meningioma in our series. The neurological outcome and degree of resection did not differ from previous series. The neurosurgical team found the laser easy to use and practical for avoiding bleeding and traction. Conclusion: The use of 2-µm thulium fiber handheld flexible laser in microsurgery of intracranial meningiomas seems to be safe and to facilitate tumor resection, especially in "difficult" conditions (e.g., deep seated, highly vascularized, and hard tumors). Even if in this limited retrospective trial the good functional outcome following conventional microsurgery had not further improved, nor the surgical time was reduced by laser, focusing its use on "difficult" (large and vascularized) cases may lead to different results in the future.

Molecular Characterization of New FBXL4 Mutations in Patients With mtDNA Depletion Syndrome.

Encephalomyopathic mitochondrial DNA (mtDNA) depletion syndrome 13 (MTDPS13) is a rare genetic disorder caused by defects in F-box leucine-rich repeat protein 4 (FBXL4). Although FBXL4 is essential for the bioenergetic homeostasis of the cell, the precise role of the protein remains unknown. In this study, we report two cases of unrelated patients presenting in the neonatal period with hyperlactacidemia and generalized hypotonia. Severe mtDNA depletion was detected in muscle biopsy in both patients. Genetic analysis showed one patient as having in compound heterozygosis a splice site variant c.858+5G>C and a missense variant c.1510T>C (p.Cys504Arg) in FBXL4. The second patient harbored a frameshift novel variant c.851delC (p.Pro284LeufsTer7) in homozygosis. To validate the pathogenicity of these variants, molecular and biochemical analyses were performed using skin-derived fibroblasts. We observed that the mtDNA depletion was less severe in fibroblasts than in muscle. Interestingly, the cells harboring a nonsense variant in homozygosis showed normal mtDNA copy number. Both patient fibroblasts, however, demonstrated reduced mitochondrial transcript quantity leading to diminished steady state levels of respiratory complex subunits, decreased respiratory complex IV (CIV) activity, and finally, low mitochondrial ATP levels. Both patients also revealed citrate synthase deficiency. Genetic complementation assays established that the deficient phenotype was rescued by the canonical version of FBXL4, confirming the pathological nature of the variants. Further analysis of fibroblasts allowed to establish that increased mitochondrial mass, mitochondrial fragmentation, and augmented autophagy are associated with FBXL4 deficiency in cells, but are probably secondary to a primary metabolic defect affecting oxidative phosphorylation.