Monday Article #13: Medulloblastoma- A rare childhood brain tumour

Medulloblastoma (MB) is a rare childhood brain cancer that have the incident rate of 1.5-2 cases per 100,000 population. Even though it is a rare cancer, it accounts for 64.3% of all embryonal tumours in paediatric patients which makes it the most common malignant childhood brain cancer. MB mostly occurs in children aged 0-16 years old but there are some cases where adults can develop MB too. MB arises from the cerebellum or posterior fossa of the brain as shown in figure 1. In some cases, the tumour can be found in the fourth ventricle (an area with cerebrospinal fluid) which can cause blockage to the flow of the cerebrospinal fluid. This causes symptoms such as headaches and nausea. The cerebellum is essential for balance and posture, therefore, if a tumour is located in the cerebellum, it can cause the patient to have poor balance, movement instability and pointing tremor.


Figure 1 show the brain highlighting the cerebellum and fourth ventricle where MB is most likely to arise from. (Taken from Nature Reviews)


MB Classification

MB can be classified into histological and molecular subgroups. Histologically, there are classic (CLA), large cell anaplastic (LCA), medulloblastoma with extensive nodularity (MBEN) and desmoplastic/nodular (DN).


CLA

Classic MB is the most common MB case in clinical practice with around 72% of patients having the classic variant. Under the microscope, it is characterised by its round nuclei with high nucleus to cytoplasm ratio as well as the absence of increased cell size.


LCA

The term anaplasia in LCA indicates that there is an increased in cell size compared to others. LCA also have increased cytologic pleomorphism and higher rate of mitotic and apoptotic activity. Patients with LCA often have poor prognosis.


DN and MBEN

DN and MBEN are very similar in terms of histology which is characterised by round nodules of neurocytic differentiation with pericellular collagen deposition that can be detected by reticulin staining. MBEN, as its name suggest, have larger nodules compared to DN and the nodules tends to be more irregular in shape.


Molecular Classification

Due to recent advancements in transcriptomics and the ability to monitor transcription across the genome, scientist have been able to classify MB via its molecular profile. These classifications are wingless (WNT), sonic hedgehog (SHH), group 3 (G3) and group 4 (G4). WNT and SHH, as they are named, have activated WNT and SHH pathway respectively while G3 and G4 do not have a specific pathway activated. The 4 molecular subgroups are summarised in figure 2. WNT and SHH often have CTNNB1 and PTCH1/SUFU mutation respectively while G3 and G4 have isochromosome 17q mutation. These classifications can be used to stratify patients into high risk and low risk groups and the intensity of the treatment can be based on the risk stratification. Low risk patients such as patients with WNT can be given lower dosage to minimise the side effect but with the highest chance of curing the patient. The order of the molecular classification from good prognosis to bad prognosis are as follow: WNT, G4, SHH and G3


Figure 2 shows a summary of the 4 molecular subgroups WNT, SHH, G3 and G4. (taken from Ramaswamy et al., 2017)


MB Treatment

Currently, the treatment to patients with MB are first, to undergo surgery for tumour resection and followed by chemotherapy and radiotherapy which should start no longer than 28 days after the surgery. This is to ensure that the best outcome is achieved from the treatment after surgery. Example of chemotherapy drugs given are cisplatin, cyclophosphamide, vincristine, etoposide, methotrexate and procarbazine. In terms of radiotherapy, a total of between 24-39Gy are given over a period of several weeks depending on the patient being in a low risk or high-risk group. However, radiotherapy to patients under the age of 3 are avoided as it can cause some serious side effects such as long-term cognitive impairment as their cognitive function is not fully developed yet.


References

1. Orr BA. Pathology, diagnostics, and classification of medulloblastoma. Brain Pathol. 2020 May;30(3):664-678. doi: 10.1111/bpa.12837. PMID: 32239782; PMCID: PMC7317787.

2. Taylor MD, Northcott PA, Korshunov A, et al. Molecular subgroups of medulloblastoma: the current consensus. Acta Neuropathol. 2012;123(4):465-472. doi:10.1007/s00401-011-0922-z

3. Ramaswamy V, Taylor MD. Medulloblastoma: From Myth to Molecular. J Clin Oncol. 2017 Jul 20;35(21):2355-2363. doi: 10.1200/JCO.2017.72.7842. Epub 2017 Jun 22. PMID: 28640708.

4. https://www.cancerresearchuk.org/about-cancer/childrens-cancer/brain-tumours/types/medulloblastoma

 

This article was prepared by Jennifer Chang

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