Medulloblastoma, non-WNT/non-SHH, group 4

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Medulloblastoma, non-WNT/non-SHH

Definition

• An embryonal tumour of the cerebellum consisting of poorly differentiated cells and without WNT-activated and SHH-activated

• Has KDM6A and SNCAIP over expression

Numbers

• 40% of all medulloblastoma

• All age groups
• Peak incidence 5-15 yrs

• M:F=2:1

CNS WHO grading

• Grade

Origin

• Non-WNT/SHH Group 4

Localisation

• Non-WNT/SHH Group 4

Histological subtype

• Classic
• Standard-risk tumour; classic morphology found in almost all group 4 tumours

• Large cell / anaplastic (very rare)
• Tumour of uncertain clinicopathological significance

Genetic profile

• Group 4 tumours are characterized by recurrent alterations in
• KDM6A (13%)
• SNCAIP (10.4%)
• Other rare
• SNCAIP (in 10.4%),
• MYCN (in 6.3%),
• KMT2C (in 5.3%),
• CDK6 (in 4.7%),
• ZMYM3 (in 3.7%)

• -80% of group 4 tumours involve copy number alterations on chromosome 17:
• 17p deletion,
• 17q gain, or
• A combination of these in the form of an isodicentric 17q
• Aka: Isochromosome 17q (that is, i17q)
• An abnormal chromosome in which both chromosome arms are identical.
• Isochromosome 17q is one of the most frequent somatic copy- number alterations in Group 3 and Group 4 medulloblastoma

Immunophenotype

• Same for all medulloblastoma

Radiology

CT

• 90% hyperdense

• 50% Cysts formation/necrosis (especially in older patients)

• 20% Calcification is seen

• Enhancement is present in over 90% of cases and is usually prominent

MRI

• T1
• Hypointense to grey matter

• T1 C+ (Gd)
• Overall 90% enhance, often heterogeneously
• Seen as solid, avidly enhancing masses with perilesional oedema
• Group 4 tumours tend to enhance less

• T2/FLAIR
• Overall are iso-hyperintense to grey matter
• Heterogeneous due to calcification, necrosis and cyst formation
• Surrounding oedema is common
• MBs with extensive nodularity (which align with the SHH group) have demonstrated multiple small T2w cystic areas within the tumour in a ‘grapelike’ morphology on MRI

• DWI/ADC (hypercellular)
• High DWI signal ("restricted diffusion")
• Low ADC values (lower than normal cerebellum e.g. ~550 x 10-6 mm2/s)

• MR spectroscopy
• Elevated choline
• Decreased NAA

• MRI is able to delineate the fourth ventricle and subarachnoid space to a much greater degree than CT.
• Although medulloblastomas project into the fourth ventricle, unlike ependymomas they do not usually extend into the basal cisterns.

Imaging

 

Predicting molecular subgroup from imaging

• Cerebellar peduncle
• Very likely WNT subgroup and therefore best prognosis

• Cerebellar hemisphere
• Very likely SHH subgroup and therefore intermediate prognosis
• Likely desmoplastic/nodular/medulloblastoma with extensive nodularity (MBEN)

• Midline
• Maybe group 3, group 4 or SHH
• Typically infants with a tumour with ill-defined margins but prominent enhancement: likely group 3 (or SHH) and therefore worst prognosis
• Typically children with a tumour with well-defined margins but mild or no enhancement: likely group 4 and therefore slightly better prognosis
• Adults with variably defined and variably enhancing tumours: most likely SHH; haemorrhage raises the probability of group

• MR spectroscopy may also be distinctive:
• Group 3 or 4
• Taurine peak
• High creatine
• SHH
• Little or no taurine
• Low creatine

Prognosis

• 30–40% of patients are metastatic at diagnosis

• Hill et al
• Group 3 MB had significantly reduced times to relapse, while those with group 4 MB had a prolonged time to relapse
• Group 4 MB need for extended surveillance

• Groups 3 and 4 had distant relapses of disease