Implications of Tumor Location on Subtypes of Medulloblastoma

Teo, Wan Yee; Shen, Jianhe; Su, Jack M.; Yu, Alexander; Wang, Jian; Chow, Wing Yuk; Li, Xiaonan; Jones, Jeremy; Dauser, Robert C.; Whitehead, William E.; Adesina, Adekunle M.; Chintagumpala, Murali; Man, Tsz-Kwong; Lau, Ching C.

doi:10.1002/pbc.24511

Cited by 54 publications

(47 citation statements)

References 34 publications

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“…However, our results of WNT tumors differ from those of Teo et al 26 in that while midline location was described for all 5/5 WNT tumors in that study, most of the WNT tumors in our study involved the CP/CPA (8/14). In another study, Gibson et al 22 reported 6/6 WNT tumors to be midline but infiltrating the dorsal brain stem.…”

Section: Discussioncontrasting

confidence: 99%

“…23,24 While studies have also suggested that SHH tumors could arise from the cochlear nucleus in the brain stem in younger patients, 25 we did not observe a difference in SHH tumor location between infants and older patients. Our results are also consistent with a study by Teo et al, 26 which reported cerebellar hemispheric involvement in 9 of 17 (53%) SHH medulloblastomas regardless of age at diagnosis. In our study, SHH rarely invaded the brain stem, consistent with a prior study that reported brain stem infiltration by WNT but not SHH tumors.…”

Section: Discussionsupporting

confidence: 93%

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MRI Surrogates for Molecular Subgroups of Medulloblastoma

Perreault

Ramaswamy

Achrol³

et al. 2014

AJNR Am J Neuroradiol

278

205

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BACKGROUND AND PURPOSE Recently identified molecular subgroups of medulloblastoma have shown potential for improved risk stratification. We hypothesized that distinct MR imaging features can predict these subgroups. MATERIALS AND METHODS All patients with a diagnosis of medulloblastoma at one institution, with both pretherapy MR imaging and surgical tissue, served as the discovery cohort (n = 47). MR imaging features were assessed by 3 blinded neuroradiologists. NanoString-based assay of tumor tissues was conducted to classify the tumors into the 4 established molecular subgroups (wingless, sonic hedgehog, group 3, and group 4). A second pediatric medulloblastoma cohort (n = 52) from an independent institution was used for validation of the MR imaging features predictive of the molecular subtypes. RESULTS Logistic regression analysis within the discovery cohort revealed tumor location (P < .001) and enhancement pattern (P = .001) to be significant predictors of medulloblastoma subgroups. Stereospecific computational analyses confirmed that group 3 and 4 tumors predominated within the midline fourth ventricle (100%, P = .007), wingless tumors were localized to the cerebellar peduncle/cerebellopontine angle cistern with a positive predictive value of 100% (95% CI, 30%–100%), and sonic hedgehog tumors arose in the cerebellar hemispheres with a positive predictive value of 100% (95% CI, 59%–100%). Midline group 4 tumors presented with minimal/no enhancement with a positive predictive value of 91% (95% CI, 59%–98%). When we used the MR imaging feature–based regression model, 66% of medulloblastomas were correctly predicted in the discovery cohort, and 65%, in the validation cohort. CONCLUSIONS Tumor location and enhancement pattern were predictive of molecular subgroups of pediatric medulloblastoma and may potentially serve as a surrogate for genomic testing.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionsupporting

confidence: 93%

MRI Surrogates for Molecular Subgroups of Medulloblastoma

Perreault

Ramaswamy

Achrol³

et al. 2014

AJNR Am J Neuroradiol

278

205

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“…It accounts for 25% -30% of the MBs and has a bimodal age distribution. On imaging, the tumor is typically located in the body of the cerebellum, lateralizing to the sides of the organ (4,12,13). Raleigh et al also described the tumor as typically isointense on T2-FLAIR sequence (14).…”

Section: Discussionmentioning

confidence: 99%

“…The other three molecular subtypes of MB are typically situated in the midline (13). Wnt MB is the smallest subgroup (10%) and typically arises from the dorsal brainstem and fourth ventricle as a result of activation of the WNT pathway, vital in tumor growth.…”

Section: Discussionmentioning

confidence: 99%

Medulloblastoma with Suprasellar Extension and Atypical Presentation

et al. 2017

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A 6-year-old boy was referred with symptoms of right partial ptosis, blurred vision and a two-week history of poor coordination and frequent falls. No symptoms of raised intracranial pressure were demonstrated. Imaging showed a large sella mass with extension into the posterior fossa and suprasellar region, suggestive of a craniopharyngioma. Histopathological examination of the postsurgical resection specimen revealed a small blue cell tumor consistent with a medulloblastoma. This case aims to highlight a posterior fossa tumor with an unusual spread and thus clinical presentation.Keywords: Medulloblastoma, Pediatrics Case PresentationA 6-year-old boy was referred to our ophthalmology unit from a district hospital for further investigation on his symptoms of blurred vision and right partial ptosis of two weeks duration. He initially presented to the district hospital following a fall from a staircase. Further history from the child's father revealed that the child seemed uncoordinated. He had fallen several times in the previous two weeks. He dragged his left foot when walking suggesting a left lower limb weakness. He denied any headache or vomiting.On examination, there was a relative afferent pupillary defect over the right eye with partial ptosis and the eyeball turned outward and downward. There was pallor of the optic disc suggestive of compression of the optic nerve. The left fundus examination was normal.Extra ocular muscle movement examination of the right eye showed superior, medial, and recti as well as inferior oblique muscle paresis suggestive of a right cranial nerve (CN) III involvement. There was also a right CN VII palsy evidenced by lagopthalmus and facial asymmetry. General neurological examination revealed a left foot drop with the power reduced to 4/5. The reflexes were brisk. All other neurological examinations were normal.Our working diagnosis at that point was an intracranial bleed causing the third and seventh cranial nerve palsies, as well as the motor deficit (foot drop) secondary to the fall. Intracranial space occupying lesion was also on the list of differential diagnosis. CT brain performed on the patient showed an illdefined, minimally enhancing suprasellar mass with specks of calcification within. The mass extended to the posterior fossa, causing mass effect onto the brainstem and obstructive hydrocephalus (Figure 1).The contrasted MRI brain showed an extra-axial lesion at the base of the skull with an epicenter at the sella region. It measured 7.2 × 4.1 × 3.7 cm. The lesion extended postero-inferiorly towards the right pons and midbrain compressing these structures as well as the fourth ventricle. However, no mass was identified within the fourth ventricle itself. It also extended superiorly into the suprasellar region invading the cavernous sinus. It was predominantly solid with several intratumoural cysts seen, largest of which was within the suprasellar component. The lesion was hypointense on T1W and slightly hyperintense on T2W and FLAIR and demonstrated mild restrict...

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“…Expression profiles of 60 primary human MBs were generated using Affymetrix HG-U133plus2.0 gene chips (Affymetrix Inc. Santa Barbara, USA) according to manufacturer's protocol, as part of a larger study [26]. Primary human MBs were classified into molecular subtypes, Sonic-hedgehog (SHH) activated, Wingless (WNT) activated and non Sonic-hedgehog/ Wingless (non-SHH/WNT) activated tumors, using methods previously described [26].…”

Section: Primary Medulloblastoma Tumor Specimensmentioning

confidence: 99%

Therapeutic implications of CD1d expression and tumor-infiltrating macrophages in pediatric medulloblastomas

et al. 2014

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Immunobiology of medulloblastoma (MB), the most common malignant brain tumor in children, is poorly understood. Although tumor cells in some MBs were recently shown to express CD1d and be susceptible to Vα24-invariant natural killer T (NKT)-cell cytotoxicity, the clinical relevance of CD1d expression in MB patients remains unknown. We investigated the expression of CD1d in pediatric MBs and correlated with molecular and clinical characteristics. Specifically, we explored if NKT cell therapy can be targeted at a subset of pediatric MBs with poorer prognosis. Particularly, infantile MBs have a worse outcome because radiotherapy is delayed to avoid neurocognitive sequelae. Immunohistochemistry for CD1d was performed on a screening set of 38 primary pediatric MBs. Gene expression of the membrane form of M2 macrophage marker, CD163, was studied in an expanded cohort of 60 tumors. Outcome data was collected prospectively. Thirteen of 38 MBs (34.2 %) expressed CD1d on immunohistochemistry. CD1d was expressed mainly on MB tumor cells, and on some tumor-associated macrophages. Majority (18/22, 82 %) of non sonic-hedgehog/Wingless-activated MBs (group 3 and 4) were CD1d-negative (p = 0.05). A subset of infantile MBs (4/9, 44.4 %) expressed CD1d. Macrophages infiltrating MB expressed CD163 apart from CD1d. Molecular subtypes demonstrated statistical differences in CD163 expression, SHH-tumors were the most enriched (p = 0.006). Molecular and clinical subtypes of pediatric MB exhibit distinct differences in CD1d expression, which have important therapeutic implications. High CD1d expression in infantile MBs offers potential new immunotherapeutic treatment with NKT cell therapy in infants, where treatment is suboptimal due delayed radiotherapy.

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Implications of Tumor Location on Subtypes of Medulloblastoma

Cited by 54 publications

References 34 publications

MRI Surrogates for Molecular Subgroups of Medulloblastoma

MRI Surrogates for Molecular Subgroups of Medulloblastoma

Medulloblastoma with Suprasellar Extension and Atypical Presentation

Therapeutic implications of CD1d expression and tumor-infiltrating macrophages in pediatric medulloblastomas

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