Pediatric Medulloblastoma â€“ Update on Molecular Classification Driving Targeted Therapies

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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“…It typically arises from the fourth ventricle. It is associated with minimal to no enhancement (4,11,14,15).…”

Section: Discussionmentioning

confidence: 99%

“…In contrast to SHH MBs, few drugs are developed to target the wingless (WNT) pathway. With standard therapy, Wnt MBs has the best prognosis (11,15).…”

Section: Discussionmentioning

confidence: 99%

Medulloblastoma with Suprasellar Extension and Atypical Presentation

et al. 2017

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“…It is still motivating to find further prognostic markers [3,6,11,23,25,27,34]. Nowadays, an exact diagnosis of pediatric brain tumors can be established based on the methylation profile of dif- [18,21,35].…”

Section: Discussionmentioning

confidence: 99%

“…There are non-overlapping histological (classic, desmoplastic, extensive nodular, large cell/anaplastic) and molecular classifications (SHH, WNT, Group 3 and 4) for medulloblastoma [3,6,11,23,25,27,34]. Despite multimodal therapies, the 70-75% long-term survival rate has not been exceeded yet in high-risk patients [13,29,34].…”

Section: Introductionmentioning

confidence: 99%

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High expression of DNA methyltransferases in primary human medulloblastoma

Pócza

Krenács

Turányi

et al. 2016

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Medulloblastoma in children and adolescents: a systematic review of contemporary phase I and II clinical trials and biology update

et al. 2017

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Survival rates for patients with medulloblastoma have improved in the last decades but for those who relapse outcome is dismal and new approaches are needed. Emerging drugs have been tested in the last two decades within the context of phase I/II trials. In parallel, advances in genetic profiling have permitted to identify key molecular alterations for which new strategies are being developed. We performed a systematic review focused on the design and outcome of early‐phase trials evaluating new agents in patients with relapsed medulloblastoma. PubMed, clinicaltrials.gov, and references from selected studies were screened to identify phase I/II studies with reported results between 2000 and 2015 including patients with medulloblastoma aged <18 years. A total of 718 studies were reviewed and 78 satisfied eligibility criteria. Of those, 69% were phase I; 31% phase II. Half evaluated conventional chemotherapeutics and 35% targeted agents. Overall, 662 patients with medulloblastoma/primitive neuroectodermal tumors were included. The study designs and the response assessments were heterogeneous, limiting the comparisons among trials and the correct identification of active drugs. Median (range) objective response rate (ORR) for patients with medulloblastoma in phase I/II studies was 0% (0–100) and 6.5% (0–50), respectively. Temozolomide containing regimens had a median ORR of 16.5% (0–100). Smoothened inhibitors trials had a median ORR of 8% (3–8). Novel drugs have shown limited activity against relapsed medulloblastoma. Temozolomide might serve as backbone for new combinations. Novel and more homogenous trial designs might facilitate the development of new drugs.

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Pediatric Medulloblastoma â€“ Update on Molecular Classification Driving Targeted Therapies

Cited by 76 publications

References 50 publications

Medulloblastoma with Suprasellar Extension and Atypical Presentation

Medulloblastoma with Suprasellar Extension and Atypical Presentation

High expression of DNA methyltransferases in primary human medulloblastoma

Medulloblastoma in children and adolescents: a systematic review of contemporary phase I and II clinical trials and biology update

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