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 medically refractory epilepsy WHO, grade I – 2nd most common tumor-associated TLE • grows slowly, surgery usually curative • often associated with cortical dysplasia • a congenital malformation rather than a true neoplastic lesion? Koeller KK and Henry JM. RadioGraphics 2001 Barkovich AJ and Raybaud C. Pediatric Neuroimaging, 5th ed. dysembryoplastic neuroepithelial tumor : DNET imaging • wedge-shaped cortical mass, “points" toward ventricle

• multicystic/septated "bubbly" appearance T1-wi T2-wi FLAIR • hyperintense on T2-wi • rim of hyperintensity on FLAIR • no enhancement; 1/3 enhance • no surrounding vasogenic edema • remodelling the inner table of the skull

Koeller KK and Henry JM. RadioGraphics 2001 Osborn AG. Osborn’s brain T1-wi + Gd

a 22-year-old woman

seizures

GRE T2* rCBV

T1-wi T2-wi FLAIR T1-wi + Gd

T1-wi + Gd DWI ADC DD

• other LGG: – diffuse astrocytoma – oligodendroglioma a 41-year-old man – pleomorphic xanthoastrocytoma – ganglioglioma ER: generalized seizures, loss of consciousness

rCBV = 1.2 T1-wi T2-wi FLAIR

T1-wi + Gd DWI ADC

a 15-year-old girl

seizures oligodendroglioma, WHO, grade II IDH status unknown, 1p/19q codeleted T1-wi T2-wi FLAIR T1-wi + Gd

T1-wi + Gd

a 15-year-old girl

a 50-year-old man

headache

T2-wi T1-wi + Gd Pathology: – histology: oligodendroglioma vs DNET – FISH 1p/19q: no codeletion DNET

FLAIR T2-wi T1-wi + Gd

T1-wi T2-wi a 31-year-old man

infectious, meningeal signs, headaches family history: father with brain tumour no seizures

classification

• supratentorial parenchymal, incidentally infratentorial – ganglioglioma (GGG), gangliocytoma – desmoplastic infantile ganglioglioma (DIG)

FLAIR T2-wi T1-wi + Gd – dysembryoplastic neuroepithelial tumor (DNET) – papillary glioneural tumor

• supratentorial intraventricular, incidentally extra- ventricular – central neurocytoma & extraventricular neurocytoma

Goraj B. The Neuroradiology Journal 2008 T1-wi T2-wi

central neurocytoma, WHO grade II

• young adults • 3rd and lateral ventricles central neurocytoma – may arise extraventricular • attached to the septum pellucidum • calcification is common • previously called (can be confused with) intraventricular oligodendroglioma central neurocytoma

NECT NECT

• WHO, grade II lesions • body of lateral ventricles • lesion attached to septum pellucidum, extending through foramen of Monro in contralateral ventricle

FLAIR T2 • young and middle-aged adults (< 40 years of age)

• CT: - mixed density, heterogeneous cystic appearance - hydrocephalus common - calcification in 50-70%, hemorrhage rare T1 + gd T1 + gd - moderate heterogeneous enhancement

• MRI: - heterogeneous mass, isointense on T1-wi - bubbly appearance on T2-wi - heterogenously hyperintense on FLAIR

FLAIR T2-wi T1-wi T2-wi T1-wi + Gd

T1-wi + Gd

causes of temporal lobe epilepsy cortical based tumors with ‘cyst + nodule aspect’ common • ganglioglioma • most common = mesial temporal sclerosis • metastasis • tumor-associated temporal lobe epilepsy less common – ganglioglioma (40%) – DNET (20%) • pilocytic astrocytoma • pleomorphic xanthoastrocytoma – diffuse low-grade astrocytoma (20%) • glioblastoma – other (20%) rare • pilocytic astrocytoma • hemangioblastoma • pleomorphic xanthoastrocytoma • desmoplastic infantile tumors (astrocytoma/ganglioglioma) • oligodendroglioma • papillary glioneuronal tumor • schwannoma

Osborn AG. Osborn’s brain Osborn AG. Osborn’s brain From: Smirniotopoulos JG et al. RadioGraphics 2007 Smirniotopoulos JG et al. RadioGraphics 2007