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Dasgupta et al. J Transl Genet Genom 2018;2:15. I https://doi.org/10.20517/jtgg.2018.21 Page 9 of 15

enhancement in 94% of patients with SHH-subgroup medulloblastoma, with approximately half of them
showing enhancement involving > 80% of the tumor. Over 50% of SHH-subgroup tumors demonstrated
heterogeneous intensity of contrast uptake within the tumor.

Peri-tumoral edema
SHH-pathway tumors are more frequently associated with peri-tumoral edema, appreciated as hyperintensity
on T2/FLAIR images beyond the tumor margin, compared to other molecular subgroups. In a study of adult
[27]
medulloblastoma, Keil et al. reported the median volume of edema for SHH-subgroup tumors as 5.1 cm 3
[28]
3
compared to 1.2 cm for group 4 medulloblastoma. Zhao et al. also reported very frequent presence of
peri-tumoral edema in adult SHH-subgroup medulloblastoma, which was seen in 52 of 64 (81%) patients. In
[31]
another study , 91% of SHH-subgroup medulloblastoma (n = 44) were associated with edema as compared
to 26%-41% for the other three subgroups. More importantly, moderate to severe peri-tumoral edema (defined
as edema beyond 1.5 cm from the tumor edge) was almost exclusively seen in this subgroup (39% in SHH vs.
6% in WNT-subgroup vs. none in non-WNT/non-SHH tumors).

Other imaging features
SHH-subgroup medulloblastomas are often associated with the presence of both microcyst (≤ 1 cm) as well as
[28]
macrocysts (> 1 cm). In a study involving adult SHH-subgroup patients , intra-tumoral cyst/cavity was seen
in 44 of 64 (68%) patients, second only to WNT-pathway medulloblastoma. Although not classical for SHH-
[31]
pathway, intra-tumoral macrocysts were more commonly seen in infantile SHH-subgroup medulloblastoma .
The spectral pattern of SHH-subgroup medulloblastoma differs markedly from group 3 and group 4
tumors. SHH-subgroup medulloblastoma are characterized by prominent choline and lipid peaks with low
[25]
creatine levels and near or complete absence of taurine . Using a 5-metabolite signature from magnetic
[25]
resonance spectroscopy (MRS), Bluml et al. could reliably discriminate the SHH-subgroup from non-SHH
medulloblastoma. A proportion of patients with SHH-subgroup medulloblastoma present with enhancing
nodular deposits within the cerebellar cortex outside the primary site [29,30] ; these are now believed to represent
multi-centric disease rather than metastases and can identify SHH-subgroup with high specificity.

GROUP 3 MEDULLOBLASTOMA
Group 3 tumors comprising about 25% of all medulloblastomas are generally aggressive tumors and have
[3-6]
the worst prognosis amongst all subgroups with a 5-year survival rarely exceeding 50% . Although most
group 3 tumors exhibit classic morphology, LCA histology is overrepresented in this subgroup (nearly 40%),
whereas desmoplastic histology is almost never seen. They have a male preponderance (twice as common in
boys compared to girls), occur mostly in younger children (almost never in adults) and have a high incidence
[5,6]
of leptomeningeal metastases (40%-50%) at initial diagnosis .

Anatomic location
Unlike WNT and SHH-subgroup medulloblastoma, there is limited understanding of the tumorigenesis in
[33]
group 3 and 4 tumors . It is hypothesized that group 3 medulloblastomas arise from prominin1+/CD133+
[5]
lineage neural stem cell following decoupling of proliferation and differentiation . Nonetheless, group 3
medulloblastomas have been uniformly reported to be in the midline within the IVth ventricle and vermis.
[23]
Wefers et al. , reported that 73% of group 3 tumors (n = 15) grew within the vermis and 80% were in
[31]
contact with cochlear and cuneate nucleus. Dasgupta and colleagues , reported that even on the vertical
axis, majority (70%) of these tumors (n = 27) were central in location, with only 30% having the epicentre
somewhat inferiorly.

Contrast-enhancement pattern
While most of the other conventional imaging features are non-specific for group 3 tumors, contrast
[24]
enhancement assumes significance in differentiating them from other subgroups. Lastowska et al. ,