TP53 Mutation, MYCN Amplification, and Large Cell/Anaplastic Histology in Medulloblastoma

Excerpt

To the Editor: A 2.5-y-old girl had headache and vomiting for one month. She was referred following subtotal excision of a posterior fossa mass, with post-operative mutism, hypotonia and hemiparesis. MRI brain demonstrated residual disease (Fig. 1a). Spine showed meningeal enhancement. Cerebrospiral fluid (CSF) demonstrated malignant cells. Histopathology suggested medulloblastoma, large cell/anaplastic (LCA) variant (Fig. 1c). Age < 3 y, residual tumor >1.5cm² and M1 stage classified her as ‘high risk.’ She was started on chemotherapy (vincristine, cisplatin, cyclophosphamide) with plan for radiotherapy once she would complete 3 y of age. Initial clinical improvement was noted in weakness and verbal output. TP53 mutation was detected on Sanger sequencing (Fig. 1f). In-situ hybridization demonstrated cells with deletion of TP53 gene and amplification of MYCN (Fig. 1d, e). After cycle-2 of chemotherapy she had recurrence of headache, irritability and vomiting. MRI was suggestive of progressive disease (Fig. 1b). The family opted for palliative care. The child died a month later.

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