Medulloblastoma, SHH-activated

Medulloblastoma - sonic, sonic hedgehog (SHH) subgroupactivated tumours are malignant tumours of the central nervous system. They are the second most common medulloblastoma subgroup (after group 4) group, divided according to TP53  mutation status into TP53-wildtype and TP53-mutant that are approximately as common as group 3distinct entities differing in their molecular, epidemiological and histological characteristics. They

Overall, they are found most commonly in adults and infants, but infrequently also in children. Although they can arise from the vermis of the cerebellum, as is typical for group 3 and 4, (especially in infants) they are most frequently located laterally within the cerebellar hemispheres. 

Epidemiology

SHH subgroup tumours-activated TP53-wildtype medulloblastomas are twice as common as those with TP53-mutations and account for approximately 2720% of all medulloblastomas, and, unlike group 3 and 4,medulloblastoma. They have no particular predilection for males, with a ~1:1 male to femaleM:F ratio ^{of 1-2,4}:1. 

They are most frequently encountered in adults (>16 years) and infants (<4 years) but^1-2,4,5. 

SHH-activated TP53-mutant medulloblastomas are uncommonaccount for only 10% of all medulloblastoma, occur primarily in children and have a predilection of males (M:F 3:1) ^1-2,45. 

Pathology

SHH medulloblastomas-activated tumours are currently divided into two groups based on TP53 status and four subgroups on the basis of DNA methylation or transcriptome profiling ⁵. 

The SHH-3 subgroup is only seen in tumours with TP53 mutations, whereas all four subgroups can be encountered in tumorus without TP53 mutations ⁵. 

In parallel with molecular subgroups, SHH-activated tumours can demonstrate various histologies, with classic, large cell/anaplastic and desmoplastic/nodular/medulloblastoma with extensive nodularity (MBEN) allprimarily seen in TP53-wildtype tumours, whereas classic, large cell/anaplastic encountered in TP53 mutant tumours ^2,5. 

Importantly, almost all desmoplastic/nodular/medulloblastoma with extensive nodularity (MBEN) tumours are SHH subtype ². 

Radiographic features

The radiographic features of SHH subgroup tumours are variable, to a degree depending on histological subtype. 

When they are of classic or large cell/anaplastic histology and located in the midline, they are essentially indistinguishable from non-WHT/non-SHH group 3 and group 4 tumours ³. 

The desmoplastic/nodular/medulloblastoma with extensive nodularity (MBEN) tumours, on the other hand, tend to occur in the lateral parts of the cerebellar hemispheres ³. 

For more details on radiographic features, please refer to the general article on medulloblastoma. 

Treatment and prognosis

Surgery is the first line of therapy (as is the case in all subgroups) with the aim being histological proof, molecular subtyping and maximal tumour resection, with adjuvant therapy depending on an overall risk profile (see general article on medulloblastoma) ². 

The incidence of CNS metastatic disease in the SHH subgroup at diagnosis is relatively common in infants (17%) and children (22%) but is uncommon in adults ¹. 

SHH tumours have an intermediate prognosis compared to other subtypes of medulloblastoma; that is, better than group 3 tumours, but significantly worse than WNT subtypes. Prognosis is also strongly influenced by age ^1,4:

• 77% 10-year overall survival in infants
• 51% 10-year overall survival in children
• 35% 10-year overall survival in adults

Prognosis is also influenced by histological subtype, with extensive desmoplastic and nodular subtype - dominating SHH medulloblastomas in infants - probably accounting for the improved survival ⁴.