P11.13 Metachronous spinal primitive neuroectodermal tumor after treatment of a hemispheric anaplastic oligodendroglioma through p53 germline mutation

Abstract

INTRODUCTION: Acquired mutations in the p53 tumor-suppressor gene have been detected in several human cancers, including sarcoma, colon, breast, and lung cancer. Li-Fraumeni syndrome (LFS) is a rare familial association of malignant neoplasms in children and young adults, transmitted through germline mutations of this gene. On the other hand, some families having a germ-line mutation in p53 display some, but not all features of LFS. Tumors with p53 mutation are associated with decreased survival rate, increased resistance to chemotherapy and radiation and an elevated risk to relapse. MATERIALS AND METHODS: We report a case of a 17-years-old male patient with no family history of malignancy, who presented with confusion, speech disorder, weakness and mood disorders. A MRI showed a large brain tumor located in the left temporo-parietal lobe. Following the debulking the histologic examination showed an anaplastic oligodendroglioma (WHO-grade III). The patient underwent radiotherapy for a total dose of 60 Gy (2 Gy/fractions, 5 fractions per week) and sequential chemiotherapy with Procarbazina, Lomustine and Vincristine according to EORTC schedule. Seven months after the end of treatmentthe boy developed leg weakness and difficulty walking. Brain MRI was negative. Because of clinical worsening, the patient underwent to spine MRI that showed the presence of intradural extramedullary spinal solid masses with contrast enhancement. The boy underwent to decompressive laminectomy (T5-T6) and partial resection of the lesion. The histopathologic evaluation of the resected tissue revealed malignant small round blue cells, such as a primitive neuroectodermal tumor. The clinical conditions deteriorated rapidly and he died within few months. RESULTS: We performed a p53 gene analysis in the two metachronous primary lesions of our patient A novel germline p53 splicing mutation was identified.. Both tumors underwent PCR amplification of three segments that included exons 6-7-9 of the TP53 gene. Direct DNA sequencing of the amplified segment identified heterozygous C>T mutation in codon 742 in exon 7. Genomic DNA from the second tumor showed the same mutation and loss of heterozygosity at the p53 locus. Familial p53 testing revealed homozygous wild-type alleles. CONCLUSION: We detected a rare, de novo, germline p53 mutation in a patient with no family history of malignancies presenting with methachronous tumors and exhibiting a more fulminant course than typical cases of Li-Fraumeni. This case emphasizes the importance of a genetic evaluation in the setting of multiple malignancies, synchronous or methachronous, even in the absence of family history.