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IS IT MULTICENTRIC OR MULTIFOCAL GLIOBLASTOMA ?

DR AMIT KUMAR GHOSH

GLOBAL HOSPITAL, CHENNAI

Clinical Profile48 years, female, history of headache and few episodes of vomiting with few episodes of vacant look off and on over 10 days.

On examination, no neurological deficit.

SURGICAL MANAGEMENTShe underwent 1. RIGHT FRONTO PARIETAL PARASAGGITAL CRANIOTOMY, INTERHEMISPHERIC APPROACH, TRANSCALLOSAL EXCISION OF TUMOUR Intra-operative frozen section was reported as a Low Grade lesion, so 2nd tumour has been operated.

2. LEFT FRONTAL SUPRAORBITAL CRANIOTOMY AND EXCISION OF LESION on 29.05.2015

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Interhemispheric approachCorpus callosum

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Foramen of MonroIntraventricular view

POST-OPERATIVE CT

POST-OPERATIVE CT

PATHOLOGICAL DIAGNOSISHistopathological examinationIntraventricular lesion- Glioblastoma WHO grade IV

Left basifrontal lesion- Glioblastoma WHO grade IV

Immunohistochemistry

Intraventricular lesion-

GFAP strong diffuse positiveEMA Patchy positive paranuclear dot likeSynaptophysin NegativeChromogranin Negativep53- 10%

Left Basifrontal lesion-

GFAP Strong diffuse positiveSynaptophysin Negativep53 10%G67 30%

NECROSISENDOTHELIAL PROLIFERATION

ABNORMAL MITOSIS

ABNORMAL MITOSIS

MICRO VACUOLATION

GFAP POSITIVE

Ki67 > 20

Post operative period was uneventful,.She was covered with pre and post operative anticonvulsants and corticosteroids. EVD and surgical drain removed on POD 3 , Sutures removed on POD10Advised Radiotherapy after 2 weeks

DEFINITION OF MULTICENTRIC / MULTIFOCALMultifocal glioma consists of tumours separated by white matter tracts within the same hemisphere.

Multicentric glioma consists of tumors in opposite hemispheres or separated by the tentorium.

MULTIFOCAL / MULTICENTRIC GBMBatzdorf et al. (1963) distinguish between "Multicentric" and "Multifocal"Showalter et al. (2007) suggests that "the clinical utility of this... may be scant."Lim et al. (2007) hypothesize that multifocal GBM is a subtype of GBM arising from Subventricular zone (SVZ) stem cells

-The incidence of solitary, multiple, and multicentric gliomas a series of 209 gliomas was 72.2%, 25.4%, and 2.4%, respectively

U. Batzdorf and N. Malamud, The problem of multicentric gliomas, Journal of Neurosurgery, vol. 20, pp. 122136, 1963.

TYPES OF GBMTYPE1: SVZ+, CTX +TYPE 2: SVZ +, CTX TYPE 3: SVZ -, CTX +TYPE 4: SVZ -, CTX -

MULTICENTRIC / MULTIFOCAL: INCIDENCEMultiple glioma in the form of multifocal or multicentric is uncommon entity.

Incidence in literature varies from 0.15% to 25.4%

Even more uncommon is the Intraventricular GBM as one of the tumors

PATHOLOGYStill there is no unified theory regarding the pathogenesis of multifocal and multicentric GBM, several hypotheses have been developed.The traditionally held view of the pathogenesis of multifocal/multicentric GBM is by three possible pathways. 1) First, a previously known primary high-grade glioma spreads through the cerebrospinal fluid or white matter tracts to other locations. 2) Second, multiple areas of high-grade glioma arisede novofrom initially non-neoplastic cells that are influenced by genetic defect. 3) Third and last, initially diffuse low-grade glioma develops separate from separate areas of malignant transformation within itself, hence giving rise to multifocal/multicentric GBM.

.Some literature proposes that the pathogenesis of multiple and multicentric GBM may involve neural stem cells within the subventricular zone or could result from tumor dissemination along established CNS routes, such as white matter tracts and CSF pathways. Neural stem cells have been found to express matrix metalloproteinases, which are proteolytic enzymes implicated in tumor spread . Furthermore, the SVZ is thought to be a highly permissive environment for tumor growth and cellular migration.

Currently there is no clear guidelinesregarding the optimal management of MF/MC GBM, role of surgery for MF/MC remains controversial.Aggressive resection of one tumor focus, biopsy alone followed by chemotherapy and radiation treatment, and multiple craniotomies during a single operation have all been described with no clear indication of which modality is superior

TREATMENT MODALITIES

REFERENCESAndrea Arcos b, Lorena Romero b,, Ramn Serramito a, Jos M. Santna, Antonio Prieto a, Miguel Gelabert a, Miguel ngel Arrez b: Multicentric glioblastoma multiforme. Report of 3 cases, clinical and pathological study and literature review: neuroc i rugia. 2 0 1 2;23(5):211215Zamponi N1,Rychlicki F,Ducati A,Regnicolo L,Salvolini U,Ricciuti RA.: Multicentric glioma with unusual clinical presentation.: Childs Nerv Syst.2001 Jan;17(1-2):101-5.

Sophia F. Shakur,1Esther Bit-Ivan,2William G. Watkin,2Ryan T. Merrell,3andHamad I. Farhat: Multifocal and Multicentric Glioblastoma with Leptomeningeal Gliomatosis: A Case Report and Review of the Literature: Case Reports in MedicineVolume2013(2013), Article ID132679, 8 pageshttp://dx.doi.org/10.1155/2013/132679Yusuf ZC, Doa GRKANLAR, Erdener TMURKAYNAK: Multicentric Gliomas: Still Remains a Controversial Issue: Turkish Neurosurgery 2005, Vol: 15, No: 2, 71-75

Thank you