S. Dekeyzer J. Huyskens S. Nicolay neuronal and mixed neuronal-glial tumors E. De Smet DNET, ganglioglioma, … C. Venstermans J.W. Van Goethem L. van den Hauwe P. M. Pa rize l B. Goraj AZ KLINA, Brasschaat, Belgium K. Kamphuis-van Ulzen Antwerp University Hospital - University of Antwerp, Antwerp, Belgium (University Medical Center St Radboud, Nijmegen, The Netherlands) overview introduction • introduction neuronal & mixed neuronal-glial tumors • classification • aka glioneuronal tumors • dysplastic cerebellar gangliocytoma • varying morphologic patterns and biological behavior • • ganglioglioma and gangliocytoma less common than pure glial neoplasms, accounting for 0.5%-2% of all primary brain tumors • desmoplastic infantile ganglioglioma • often seizure-associated • dysembryoplastic neuroepithelial tumor (DNET) • less biologically aggressive than most glial tumors • central neurocytoma • have a more favorable prognosis • take home messages • WHO grade I or II Osborn AG. Osborn’s brain classification classification • supratentorial parenchymal, incidentally infratentorial • infratentorial intraventricular – ganglioglioma (GGG), gangliocytoma – rosette-forming glioneuronal tumor of the 4th ventricle – desmoplastic infantile ganglioglioma (DIG) – dysembryoplastic neuroepithelial tumor (DNET) – papillary glioneural tumor • infratentorial parenchymal – dysplastic gangliocytoma of the cerebellum: • supratentorial intraventricular, incidentally extra- = Lhermitte – Duclos disease ventricular – central neurocytoma & extraventricular neurocytoma – cerebellar liponeurocytoma Goraj B. The Neuroradiology Journal 2008 Goraj B. The Neuroradiology Journal 2008 dysplastic cerebellar gangliocytoma Lhermitte-Duclos WHO, grade I dysplastic cerebellar gangliocytoma Cowden syndrome (CS) • aka Lhermitte-Duclos disease (LDD), cerebellar • aka multiple hamartoma-neoplasia syndrome or PTEN hamartoma, granular cell hypertrophy, … hamartoma tumor syndrome • a rare benign cerebellar mass, characterized by • an autosomal dominant phacomatosis overgrowth of the cerebellar cortex • most patients have hamartomatous neoplasms of the • usually involves the cerebellar hemisphere or the vermis skin, and neoplasms and hamartomas of other organs – breast • large lesions may involve both; brainstem is a rarely – thyroid affected – endometrium • probably a hamartoma and not a true neoplasm – gastrointestinal cancers • sporadic vs part of a multiple hamartoma syndrome: – … Cowden syndrome (40%) • when LDD and CS occur together, they are called Cowden-Lhermitte-Duclos or COLD syndrome dysplastic cerebellar gangliocytoma dysplastic cerebellar gangliocytoma imaging imaging • CT: • MRI: – T1-wi: expansile mass with linear hypointense bands – hypodense mass – T2-wi: pathognomonic "tiger stripe" (laminated, striated) pattern of – mass effect with compression of the 4th ventricle, alternating inner hyperintense and outer hypointense layers in enlarged effacement of the CPA cisterns, … cerebellar folia – T2* (GRE, SWI): prominent venous channels surrounding the grossly – obstructive hydrocephalus thickened folia – calcification is rare – T1-Gd: striking linear enhancement of these abnormal veins – necrosis and hemorrhage are absent – DWI: may show restricted diffusion – PWI: increased rCBV, reflecting the prominent enlarged interfolial veins, – no enhancement not malignancy – MRS: normal or slightly reduced NAA and normal Cho:Cr ratios; a lactate doublet may be present • DD: medulloblastoma (desmoplastic variant), subacute cerebellar infarction Spaargaren L et al. Neuroradiology 2003 Spaargaren L et al. Neuroradiology 2003 NCCT dysplastic cerebellar gangliocytoma contrast enhancement in LDD is due to venous proliferation within the lesion in the outer T2-wi portions of the cerebellar cortex and to prominent draining veins striated pattern: alternating bands of high signal intensity and normal signal intensity relative to gray matter Spaargaren L et al. Neuroradiology 2003 Spaargaren L et al. Neuroradiology 2003 classification • supratentorial parenchymal, incidentally infratentorial – ganglioglioma (GGG), gangliocytoma – dysembryoplastic neuroepithelial tumor (DNET) ganglion cell tumors – desmoplastic infantile ganglioglioma (DIG) ganglioglioma - gangliocytoma – papillary glioneural tumor WHO, grade I • supratentorial intraventricular, incidentally extra- WHO, grade II ventricular – central neurocytoma & extraventricular neurocytoma Goraj B. The Neuroradiology Journal 2008 ganglion cell tumors ganglioglioma • well-differentiated neoplasms • contain both ganglion cells and glial elements • contain mature but dysmorphic neurons • immunoreactivity for these 2 cellular populations • most ganglion cell tumors are histologically mixed – glial fibrillary acidic protein (GFAP) + tumors that contain both ganglion cell and glial – synaptophysin and neurofilament protein + elements: gangliogliomas • glial component: – the most common glioneuronal neoplasm in the CNS – astrocytes in varying states of differentiation – are the most common cause of tumor-related temporal lobe epilepsy, accounting for 40% of all cases – affects the biologic behavior of the tumor • tumors that demonstrate exclusive ganglion cell – usually has histologic features of pilocytic astrocytoma composition are very rare: gangliocytomas – if less differentiated (as in HGG), more aggressive behavior – malignant degeneration • glial component is absent in gangliocytoma Osborn AG. Osborn’s brain Koeller KK and Henry JM. RadioGraphics 2001 ganglioglioma, WHO grade I or II ganglioglioma: GG • 0.4%-0.9% of all intracranial tumors imaging: • young patients: 80% < 30 years; peak age 10-20 years • CT: • predilection for cerebral hemispheres: – well-circumscribed mass of low density – – temporal lobe 75% located in the cortical gray matter – little mass effect or edema – frontal lobe – solid portions: • superficial location • isodense, hypodense, mixed • expansive growth; well-defined margins • variable contrast enhancement • calcification: 35% of cases – peritumoral edema is rare – erosion of the inner table of the calvarium Barkovich AJ and Raybaud C. Pediatric Neuroimaging, 5th ed. Koeller KK and Henry JM. RadioGraphics 2001 NCCT ganglioglioma: GG ganglioglioma: GG imaging: • MRI: variable appearance – peripheral location within the cerebral hemispheres – sharply or poorly defined margins – solid, cystic, ‘cyst with a mural nodule’, cluster of small cysts – variable SI on T1-wi (mixed), hyperintense ĨŽĐƵƐь calcification – hyperintense on T2-wi – variable enhancement of solid portions Barkovich AJ and Raybaud C. Pediatric Neuroimaging, 5th ed. From: Koeller KK and Henry JM. RadioGraphics 2001 a 7-year-old girl T1-wi T2-wi FLAIR seizures T1-wi + Gd DWI ADC a 11-year-old girl T1-wi complex partial seizures FLAIR T1-wi + Gd T1-wi T2-wi FLAIR pathology: ganglioglioma vs pilocytic astrocytoma T1-wi + Gd DWI ADC a 16-year-old boy • previous medical history: CO intoxication • complex partial seizures for 3 months • clinical neurological examination: normal • EEG: normal T2-wi T1-wi + Gd • R/depakine 500-1000mg/day • MRI T1-wi T1-wi + Gd T2-wi FLAIR T1-wi + Gd T2-wi FLAIR T1-wi + Gd • DD: – ganglioglioma – pleomorphic xanthoastrocytoma (PXA) – (pilocytic astrocytoma) GRE T2* Neurosurgery neuropathology • fMRI: Broca: OK differential diagnostic problem: • histological features of both • partial resection – pleomorphic xanthoastrocytoma (PXA) – ingrowth insula and lentiform nucleus – ganglioglioma • presence of ganglion cells • strong GFAP immunoreactivity: +++ • absence of reticuline network • increased proliferative activity: grade II • final diagnosis: ganglioglioma, grade II a 9-year-old boy T1-wi T2-wi FLAIR seizures T1-wi + Gd DWI ADC a 2-year-old girl T2-wi T1-wi + Gd posterior fossa mass T1-wi + Gd fMRI-motor T1-wi T2-wi FLAIR T1-wi T1-wi + Gd T1-wi + Gd DWI ADC T1-wi + Gd a 52-year-old man SiljadeSiljade CACA • walking difficulties • problems right leg (‘stuurloos’) apraxia gangliocytoma • MRI: cerebellar mass since 6 years T1-wi T2-wi FLAIR T1-wi + Gd gangliocytoma • 0.1%-0.5% of all brain tumors • purely neuronal variant of ganglioglioma – without any glial (astrocytic) component desmoplastic infantile tumors • uncommon (astrocytoma/ganglioglioma • often seen in older children and young adults • floor of 3rd ventricle, temporal lobe, cerebellum, … WHO, grade I • often calcified • absence of mass effect • no perilesional edema Koeller KK and Henry JM. RadioGraphics 2001 Raybaud C et al. Childs Nerv Syst 2006 desmoplastic infantile ganglioglioma: DIG • 1st described by Vandenberg et al. in 1987: 11 cases • very large brain tumor in the 1st year of life – frontal and parietal lobes a 1-day-old baby – both cystic and solid portions – intense desmoplastic reaction at the periphery of the mass with attachment to the dura macrocephaly • M:F = 2:1 tense bulging fontanelles • rapid growth • surgery • overall good prognosis Koeller KK and Henry JM. RadioGraphics 2001 T1-wi T2-wi T1-wi T1-wi T2-wi FLAIR T2-wi T1-wi T1-wi + Gd T1-wi + Gd DD • variety of more malignant tumors: – teratomas – choroid plexus papilloma – primitive neuroectodermal tumors (PNET) – atypical teratoid/rhabdoid tumors (AT/RT) – … dysembryoplastic neuroepithelial tumor : DNET • benign masses of the cerebral cortex or deep gray matter: temporal lobe (62%) and frontal lobe (31%) dysembryoplastic neuroepithelial • children and young adults: majority of patients < 20 y • man > woman tumor • patients present with partial complex seizures – in 20% of cases of