Multidisciplinary approach to anaplastic and metastatic meningioma: A case report and review of the literature.

Background: Meningiomas are slow-growing neoplasms, accounting for 20% of all primary intracranial neoplasms and 25% of all intraspinal tumors. Atypical and anaplastic meningiomas are infrequent, representing fewer than 5% of all meningiomas. Unusually, they can show aggressive behavior, and extracranial metastases are extremely rare, representing approximately 0.1% of all reported cases. Case Description: Fifty-six-year-old male patient diagnosed with atypical basal frontal meningioma with multiple resections, both endoscopic endonasal and transcranial. After hypofractionated radiosurgery, the patient showed new tumor recurrence associated to right cervical level II ganglionic metastasis. We opted for complete resection of the meningioma and reconstruction with anterior rectus abdominis muscle flap, as well as selective cervical ganglionectomy. Anatomical pathology showed neoplastic proliferation of meningothelial cells in syncytial cytoplasm, oval or spherical nuclei with slight anisocariosis and hyperchromasia, and intranuclear vacuoles, all compatible with anaplastic meningioma. Conclusion: Due to a lack of consensus on how to treat a metastatic malignant meningioma, this pathology requires a multidisciplinary approach, and treatment needs to be adapted to each particular case. Complete resection of the lesion is the primary goal, and this requires complex procedures involving endocranial as well as extracranial surgeries, which result in composite defects difficult to resolve. Microvascular free flaps are considered the gold standard in reconstructions of large skull base defects, with high success rates and few complications.

Ganoderic acid A/DM-induced NDRG2 over-expression suppresses high-grade meningioma growth.

PURPOSE: N-myc downstream-regulated gene 2 (NDRG2) is down-regulated in grade-III meningioma [anaplastic meningioma (AM)] and associated with clinically aggressive behavior. Current therapies in the treatment of high-grade meningioma are lacking with limited success. This study aims to validate the effect of NDRG2-targeted therapy using structurally related bioactive triterpene compounds derived from the edible mushroom Ganoderma lucidum (ganoderic acid A:GA-A/ganoderic acid DM:GA-DM) in human AM in relevant pre-clinical models. METHODS: Tissue samples from the AM tumor regions of three human patients and control non-tumor samples were used to analyze the expression pattern of NDRG2. In vitro cell culture and in vivo cell-line-derived orthotopic xenograft animal models of AM were utilized to assess efficacy of treatment with GA-A/DM. RESULTS: Downregulation of NDRG2 expression was observed in surgically resected high-grade meningiomas compared to normal brain. These results prompt us to use NDRG2-targeting agents GA-A/DM. In vitro results showed that 72-h treatments of 25 µM GA-A/DM induced AM cell death, upregulate NDRG2 protein expression, downregulate NDRG2 promoter methylation in meningioma cells as compared to azacitidine and decitabine, the most commonly used demethylating agents. Our results also demonstrated that GA-A/DM does not have any detrimental effect on normal human neurons and arachnoid cells. GA-A/DM promoted apoptotic factors (Bax) while suppressing MMP-9, p-P13K, p-AKT, p-mTOR, and Wnt-2 protein expression. RNAi-mediated knockdown of NDRG2 protein expression increased tumor proliferation, while forced expression of wt-NDRG2 decreased proliferation in an in vitro model. Magnetic resonance (MR) imaging and Hematoxylin (H&E) staining demonstrated gross reduction of tumor volume in GA-A/DM treated mice at 5 weeks when compared with saline-treated orthotopic AM xenografted controls. There was an overall decrease in tumor cell proliferation with increased survival in GA-A/DM-treated animals. Enzyme assays showed that GA-A/DM did not negatively impact hepatic function. CONCLUSION: GA-A/DM may be a promising natural therapeutic reagent in the treatment of AM by suppressing growth via NDRG2 modulation and altering of intracellular signal pathways. We have shown it could potentially be an effective treatment for AM with decreased cellular proliferation in vitro, decreased tumor volume and increased survival in vivo.

Meningioma anaplásico / Anaplastic meningioma

Se presenta el caso clínico de un paciente que comenzó a presentar cefalea, vértigos, trastornos visuales y pérdida del equilibrio. Mediante la resonancia magnética se visualizó una imagen tumoral parietal izquierda de 3 cm diámetro, de localización extraaxial y contornos lobulados bien definidos, con gran captación no homogénea de contraste, rodeada de extenso edema perilesional. Se realizó angiotomografía, previa a la cirugía, en busca de irrigación y daño vascular. Se logró la resección de 95% de la lesión (grado II de Simpson), que incluyó duramadre adyacente infiltrada y respetó el seno longitudinal superior. Los resultados anatomopatológicos confirmaron que se trataba de un meningioma anaplásico de grado III, con criterio de tratamiento coadyuvante.

The case report of a patient who began presenting headache, vertigos, visual disorders and loss of balance is presented. By means of the magnetic resonance a left tumoral parietal image of 3 cm diameter was visualized, of extra-axial localization and well defined lobulated contours, with great non-homogeneous zones of contrast, surrounded by extensive perilesional edema. An angiotomography was carried out, previous to the surgery, looking for irrigation and vascular compromise. The resection of 95% of the lesion was achieved (grade II of Simpson) which included adjacent infiltrated dura madre and preserving the superior longitudinal sinus. Pathological results confirmed that it was an anaplastic meningioma grade III, with criterium for adyuvant treatment.