CASE REPORT
Gliomatose cerebral (GC) é um padrão tumoral glial raro, difusamente infiltrativo, atualmente definido pela classificação de 2021 da Organização Mundial da Saúde (OMS) como um glioma difuso que envolve pelo menos três lobos cerebrais, frequentemente se estendendo para a substância cinzenta profunda e regiões infratentoriais. A apresentação clínica varia dependendo da localização da lesão. A ressonância magnética (RM) tipicamente mostra hiperintensidades T2-FLAIR generalizadas sem realce significativo pelo contraste ou efeito de massa. Um diagnóstico definitivo requer confirmação histopatológica e perfil molecular. Alterações moleculares importantes — incluindo mutações IDH1/2, codeleção 1p/19q, perda de ATRX e metilação do promotor MGMT — são essenciais para classificação, prognóstico e planejamento terapêutico precisos. Quando viável, recomenda-se a ressecção supramáxima segura. Apresentamos três casos ilustrativos: dois gliomas difusos com mutação IDH e um glioma IDH tipo selvagem, cada um exemplificando a complexidade diagnóstica e os desafios terapêuticos associados à GC. Esses casos ressaltam a importância da integração do diagnóstico molecular em uma estrutura multidisciplinar para otimizar a tomada de decisões clínicas. Além disso, destacamos a crescente relevância da incorporação de dados genômicos e metabolômicos na classificação de gliomas para aumentar a precisão diagnóstica e subsidiar estratégias terapêuticas personalizadas. Incentivamos a análise do CG sob uma perspectiva genética e molecular, à luz dos avanços científicos atuais.
Gliomatosis cerebri (GC) is a rare, diffusely infiltrative glial tumor pattern currently defined by the 2021 World Health Organization (WHO) classification as a diffuse glioma involving at least three cerebral lobes, often extending into deep gray matter and infratentorial regions. Clinical presentation varies depending on lesion location. Magnetic resonance imaging (MRI) typically shows widespread T2-FLAIR hyperintensities without significant contrast enhancement or mass effect. A definitive diagnosis requires histopathological confirmation and molecular profiling. Key molecular alterations—including IDH1/2 mutations, 1p/19q codeletion, ATRX loss, and MGMT promoter methylation—are essential for accurate classification, prognosis, and treatment planning. When feasible, safe supramaximal resection is recommended. We present three illustrative cases: two IDH-mutant diffuse gliomas and one IDH–wild-type glioma, each exemplifying the diagnostic complexity and therapeutic challenges associated with GC. These cases underscore the importance of integrating molecular diagnostics within a multidisciplinary framework to optimize clinical decision-making. Furthermore, we highlight the growing relevance of incorporating genomic and metabolomic data into glioma classification to enhance diagnostic accuracy and support personalized therapeutic strategies. This case series encourages the analysis of GC from a genetic and molecular perspective in light of current scientific advances.
2. Herrlinger U, Jones DTW, Glas M, et al. Gliomatosis cerebri: no evidence for a separate brain tumor entity. Acta Neuropathol. 2015;131(2):309-19. http://doi.org/10.1007/s00401-015-1495-z. PMid:26493382.
3. Louis DN, Perry A, Wesseling P, et al. The 2021 WHO classification of tumors of the central nervous system: a summary. Neuro-oncol. 2021;23(8):1231-51. http://doi.org/10.1093/neuonc/noab106. PMid:34185076.
4. Divé I, Weber KJ, Hartung TI, et al. Gliomatosis cerebri (GC) growth pattern: a single-center analysis of clinical, histological, and molecular characteristics of GC and non-GC glioblastoma. Neurooncol Adv. 2023;5(1):vdad131. http://doi.org/10.1093/noajnl/ vdad131. PMid:38024242.
5. Georgakis MK, Spinos D, Pourtsidis A, et al. Incidence and survival of gliomatosis cerebri: a population-based cancer registration study. J Neurooncol. 2018;138(2):341-9. http://doi.org/10.1007/ s11060-018-2802-z. PMid:29464663.
6. Chen S, Tanaka S, Giannini C, et al. Gliomatosis cerebri: clinical characteristics, management, and outcomes. J Neurooncol. 2013;112(2):267-75. http://doi.org/10.1007/s11060-013-1058-x. PMid:23341100.
7. Jennings MT, Frenchman M, Shehab T, et al. Gliomatosis cerebri presenting as intractable epilepsy during early childhood. J Child Neurol. 1995;10(1):37-45. http://doi.org/10.1177/088307389501000111. PMid:7539465.
8. Sanson M, Cartalat-Carel S, Taillibert S, et al. Initial chemotherapy in gliomatosis cerebri. Neurology. 2004;63(2):270-5. http:// doi.org/10.1212/01.WNL.0000129985.39973.E4. PMid:15277619.
9. Taillibert S, Chodkiewicz C, Laigle-Donadey F, Napolitano M, Cartalat-Carel S, Sanson M. Gliomatosis cerebri: a review of 296 cases from the ANOCEF database and the literature. J Neurooncol. 2005;76(2):201-5. http://doi.org/10.1007/s11060-005-5263-0. PMid:16200347.
10. Mallick S, Giridhar P, Rath GK. Evidence-based practice in neuro-oncology. Cham: Springer; 2022.
11. NATIONAL CANCER INSTITUTE. Gliomatosis cerebri diagnosis and treatment. 2018. Available from: https://www.cancer.gov. Accessed: 7/20/2025.
12. Doig D, Thorne L, Rees J, et al. Clinical, imaging and neurogenetic features of patients with gliomatosis cerebri referred to a tertiary neuro-oncology centre. J Pers Med. 2023;13(2):222. http:// doi.org/10.3390/jpm13020222. PMid:36836456.
Neuro-oncol. 2014;16(1):81-91. http://doi.org/10.1093/neuonc/ not159. PMid:24305719.
15. Sanson M, Marie Y, Paris S, et al. Isocitrate dehydrogenase 1 codon 132 mutation is an important prognostic biomarker in gliomas. J Clin Oncol. 2009;27(25):4150-4. http://doi.org/10.1200/ JCO.2009.21.9832. PMid:19636000.
16. Lasocki A, Gaillard F. Gliomatosis cerebri: radiological review. J Med Imaging Radiat Oncol. 2013;57(6):689-93. http:// doi.org/10.1111/1754-9485.12097.
17. Takahashi H, Matsutani M. Gliomatosis cerebri: an entity or a pattern? Review of the literature. J Neurooncol. 2006;76(3):241-4.
18. Brat DJ, Aldape K, Bridge JA, Canoll P, Colman H, Hameed MR, et al. Molecular Biomarker Testing for the Diagnosis of Diffuse Gliomas. Arch Pathol Lab Med. 2022 May 1;146(5):547-574. doi:10.5858/ arpa.2021-0295-CP.
19. Aibaidula A, Chan AKY, Shi Z, Li Y, Zhang R, Yang R, et al. Adult IDH wild-type lower-grade gliomas should be further stratified. Neuro Oncol. 2017 Oct 1;19(10):1327-1337. doi:10.1093/neuonc/ nox078
20. Mellinghoff IK, Ellingson BM, Touat M, et al. Ivosidenib in IDH1-mutant, chemotherapy-refractory glioma: a phase 1 trial. Nat Med. 2023;29(2):250-7.
21. Wesseling P, Capper D. WHO 2021 classification of gliomas. Neuropathol Appl Neurobiol. 2022;48(3):e12704. http://doi.org/10.1111/ nan.12704.
22. Esteller M, Garcia-Foncillas J, Andion E, et al. Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents. N Engl J Med. 2000;343(19):1350-4. http:// doi.org/10.1056/NEJM200011093431901. PMid:11070098.
23. Bonosi L, Marrone S, Benigno UE, et al. Maximal safe resection in glioblastoma surgery: a systematic review of advanced intraoperative image-guided techniques. Brain Sci. 2023;13(2):216. http:// doi.org/10.3390/brainsci13020216. PMid:36831759.
24. Wu A, Qiu X, An Y, et al. Association of the Neurologic Assessment in Neuro-Oncology (NANO) scale with survival outcomes in patients with gliomas: a systematic review and meta-analysis. Front Oncol. 2022;12:836998. http://doi.org/10.3389/fonc.2022.836998.
1Neurosurgery Residency, Hospital Universitário São Francisco – HUSF, Bragança Paulista, SP, Brazil.
2Department of Neurosurgery, Hospital Universitário São Francisco – HUSF, Bragança Paulista, SP, Brazil.
3Laboratory of Cell and Molecular Tumor Biology and Bioactive Com-pounds, Universidade São Francisco, Bragança Paulista, SP, Brazil.
Received Jul 20, 2025
Accepted Jul 29, 2025
