Pathological Study
Glioneuronal tumours in neurofibromatosis type 1: MRI-pathological study

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Abstract

Neurofibromatosis type 1 (NF1) is an inherited disorder in which affected individuals develop both benign and malignant tumours at an increased frequency. Glioneuronal tumours, such as ganglioglioma and dysembryoplastic neuroepithelial tumour, have been previously reported in patients with NF1. We describe two patients with glioneuronal tumours and typical clinical features of NF1. Molecular analysis of these tumours did not demonstrate loss of the NF1 gene by fluorescence in situ hybridization (FISH) or immunohistochemistry analysis, suggesting they might not be causally associated with gross defects in NF1 expression. Because of the excellent prognosis following the resection of these tumours, it is important to distinguish them from other NF1-associated tumours.

Introduction

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder with a high penetrance and mutation rate, caused by a single gene abnormality.1 This gene maps to chromosome 17q11.2, and codes for a protein, neurofibromin, that acts as a tumour suppressor.[1], [2] As a consequence, individuals with NF1 develop tumours at increased frequency, including neurofibromas, malignant nerve sheath tumours, and pilocytic astrocytomas.[1], [3] Other clinical manifestations include pigmented lesions of the skin, hamartomas of the iris of the eye, skeletal abnormalities and learning disabilities.[1], [2] Increased expression of neurofibromin has been observed during embryonic development suggesting that the NF1 gene may be important in the differentiation and maturation of cells in the CNS.3 Abnormalities of this gene may therefore be related to the occurrence of developmental malformations both in animal models of NF1 and in humans.[2], [3] Partially or completely differentiated glioneuronal tumours such as gangliogliomas and dysembryoplastic neuroepithelial tumours (DNTs) have rarely been reported in NF1.[4], [5], [6], [7] We describe the radiological and pathological features of these low-grade lesions in two patients with NF1.

Section snippets

Case 1

A 23-year-old woman had a three-year history of seizures consisting of right arm dystonic posturing with no loss of awareness, drop attacks, or episodic loss of consciousness. The seizures came on without warning and were associated with prominent gestural and orobuccal automatisms. Secondarily generalized seizures occurred rarely. NF1 stigmata were subsequently noted in the patient's brother and mother. Examination of the patient revealed typical features of NF1, including café-au-lait spots,

Discussion

We report two patients with NF1 who presented with seizures associated with glioneuronal tumours, in whom the diagnosis of NF1 was not previously suspected. The imaging features in both cases suggested low-grade neoplasia with cortical involvement, but the presence of multiple lesions suggested underlying NF1. The pathological features met the criteria for ganglioglioma and DNT, respectively.

Ganglioglioma and DNT share many clinical, radiological and pathological features. Clinically, both are

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