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Page 10 of 15 Dasgupta et al. J Transl Genet Genom 2018;2:15. I https://doi.org/10.20517/jtgg.2018.21

reported extensive contrast enhancement (defined as enhancement in > 75% of tumor volume) to be
significantly correlated with group 3 tumors. They also reported that non-WNT/non-SHH subgroup tumors
[29]
showing extensive contrast enhancement were associated with poor survival. Mata-Mbemba et al. ,
reported good contrast enhancement in 22 of 26 (86%) patients with group 3 medulloblastoma; only 4 (14%)
[31]
patients showed minimal enhancement. Dasgupta et al. , reported good contrast enhancement in 96% of
patients with group 3 medulloblastoma (n = 27); nearly 50% patients showed contrast uptake in > 80% of the
tumor. They described “fluffy” or “cotton-wool” pattern of enhancement (bright contrast uptake admixed
with relatively poor uptake) as a specific marker of group 3 medulloblastoma.

Other imaging features
[22]
Perreault et al. reported 63% of group 3 tumors (n = 25) to be associated with ill-defined tumor margins
[31]
compared to other subgroups (nearly 10%). In the study by Dasgupta et al. , 67% of group 3 medulloblastomas
(n = 27) were classified as having an ill-defined infiltrative margin with no tumor showing a lobulated margin.
[25]
MRS characteristics of group 3 medulloblastoma include high creatinine levels, readily detectable taurine
(generally minimal or absent in SHH) and lower lipid levels (prominent peak in SHH). The sizes of primary
tumors in group 3 were reportedly smaller compared to other subgroups (generally < 3.5 cm), particularly in
the presence of metastases suggestive of an aggressive malignancy with metastatic dissemination as an early
clonal event [29,30] that does not give time to the primary tumor to grow locally and fill the IVth ventricle.
Metastases from group 3 medulloblastoma are more likely to be spinal, typically laminar, often quite large
with “sugar-coating” appearance, and have a matching pattern, i.e., presence of enhancement post-contrast
as well as restricted diffusion [29,30] .

GROUP 4 MEDULLOBLASTOMA
Group 4 tumors are the most prevalent subgroup accounting for 35% of all medulloblastomas and have an
[5,6]
intermediate prognosis . The 5-year overall survival in group 4 tumors can be highly variable, ranging
from ~50% in patients with poor-risk features (subtotal resection, metastases, LCA histology) to > 85%
[3,6]
in patients with favorable prognostic features . Group 4 tumors are commonly seen in childhood and
early adolescence, and much less commonly in extremes of age (infants or adults). There is a striking male
[5,6]
preponderance in this subgroup even reaching beyond 80%. They are mostly associated with classic
histology, although a significant minority (about 25%) does show LCA morphology. Metastatic disease is
reported in 35%-40% of patients at initial diagnosis (second only to group 3 tumors).

Anatomic location
Although not clearly known, it is hypothesized that deregulation of synaptic pruning in the premature
glutamatergic neuronal network resulting in an imbalance between apoptosis, survival and proliferation, is the
[5]
likely underlying mechanism for tumorigenesis in group 4 medulloblastoma . Group 4 tumors are exclusively
[23]
known to be located in the midline in the IVth ventricle. Wefers et al. found 23 of 27 (90%) group 4 tumors
to be located in the midline and having contact with the cochlear and cuneate nucleus. In a study of adult
[28]
medulloblastoma, Zhao et al. reported predominant midline vermian location of group 4 tumors in 39 of 44
(89%) patients and brainstem contact with caudate and cuneate nucleus in 36 (82%) patients. In the study by
[31]
Dasgupta and colleagues , all group 4 tumors (n = 23) were located in the midline on the horizontal axis.
Nearly 39% of these tumors had their epicentre located inferiorly on the vertical axis (some even extending
beyond the foramen magnum), which was highest amongst all subgroups. The authors also reported a very
specific imaging feature of group 4 medulloblastoma, i.e., inferior extension with resultant dilation of the
superior recess of IVth ventricle.

Contrast-enhancement pattern
Weak, minimal, or no enhancement is a characteristic feature of group 4 tumors, which serves as an
[22]
important feature to distinguish from other subgroups. Perreault et al. reported 59% of group 4