Journal List > Brain Tumor Res Treat > v.2(1) > 1059632

Brain Tumor Res Treat. 2014 Apr;2(1):36-38. English.
Published online April 29, 2014.  https://doi.org/10.14791/btrt.2014.2.1.36
Copyright © 2014 The Korean Brain Tumor Society and The Korean Society for Neuro-Oncology
Glioblastoma in a Patient with Neurofibromatosis Type 1: A Case Report and Review of the Literature
Tae-Seok Jeong and Gi-Taek Yee
Department of Neurosurgery, Gil Medical Center, Gachon University, Incheon, Korea.

Correspondence: Gi-Taek Yee. Department of Neurosurgery, Gil Medical Center, Gachon University, 21 Namdong-daero 774beon-gil, Namdong-gu, Incheon 405-760, Korea. Tel: +82-32-460-3304, Fax: +82-32-460-3899, Email: gtyee@gilhospital.com
Received August 08, 2013; Revised November 08, 2013; Accepted March 07, 2014.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


Abstract

Neurofibromatosis type 1 (NF1) is an autosomal dominantly inherited familial tumor syndrome. Benign tumors such as pilocytic astrocytoma, optic glioma make up the majority of intracranial neoplasms in patients with NF1. There have only been a handful of cases in which adult glioblastoma presented with NF1. A 32-year-old male presented with headache and radiological studies showing a high grade intra-axial tumor. The patient underwent gross total surgical excision and the pathology revealed glioblastoma. After the surgery, he received concomitant chemo-radiotherapy with temozolomide and adjuvant temozolomide chemotherapy. We report a NF1 patient who developed glioblastoma and reviewed related articles.

Keywords: Glioblastoma; Neurofibromatosis type 1; CCRT; Temozolomide

INTRODUCTION

Neurofibromatosis type 1 (NF1) is an autosomal dominantly inherited familial tumor syndrome. The incidence of NF1 is about 1 in 3500 individuals [1]. Benign brain tumors such as pilocytic astrocytomas, optic-hypothalamic gliomas are the majority of intracranial neoplasms found in patient with NF1. However, there is an increased risk of developing malignant tumors in the central and peripheral nervous system [2, 3]. Glioblastoma is a common malignant brain tumor in adults but glioblastoma in patients with NF1 is rare. Huttner et al. [4] reported that children with NF1 may be at risk of glioblastoma and that the prognosis of glioblastoma in children with NF1 might be better than those without NF1. We present rare occurrence of glioblastoma with NF1 in a 32-year-old man and its treatment.

CASE REPORT

A 32-year-old man presented with progressive headache. His neurologic examination was normal. He had multiple soft masses on his body including the scalp, and also had multiple café-au-lait spots over his chest, abdomen, back, and arms. The patient had no family history of neurofibromatosis. The magnetic resonance imaging (MRI) showed a huge well enhancing mass with peri-tumoral edema in the right frontal lobe and the apparent diffusion coefficient maps demonstrated iso or slightly low signal intensity compared to the brain parenchyme (Fig. 1). The patient underwent a right frontal craniotomy and gross total tumor removal was performed. We removed some of the scalp masses as we made the scalp incision for the craniotomy. The pathological examination of the intracranial and scalp mass revealed glioblastoma and plexiform neurofibroma respectively (Fig. 2). On immunohistochemistry, the intracranial specimen was strongly positive for glial fibrillary acidic protein (GFAP), and negative for epidermal growth factor receptor (EGFR). The proliferation marker Ki-67 was 10% and the methylguanine methyltransferase (MGMT) gene was unmethylated on methylation-specific polymerase chain reaction. The patient underwent standard concomitant chemo-radiotherapy followed by adjuvant chemotherapy with temozolomide. After finishing 6-cycles of adjuvant chemotherapy, the patient showed no remarkable symptoms and follow-up MRI obtained 9 months after surgery showed no evidence of recurrence (Fig. 3).


Fig. 1
Preoperative magnetic resonance imaging (MRI) reveals large mass in the frontal lobe cross the midline and compress both frontal horns of ventricle. A: T1-weighted image shows large tumor with peripheral cyst component. B: Gd-contrast enhanced MRI shows well enhancement. C: Apparent diffusion coefficient maps demonstrates iso or slight low signal intensity.
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Fig. 2
Histologic examination. A: H&E stain (×100) shows characteristic features of glioblastoma. B: Scalp mass is revealed plexiform neurofibroma (H&E stain, ×200).
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Fig. 3
Post-adjuvant chemotherapy with temozolomide, 9 months after surgery. Gd-enhanced axial (A) and coronal (B) T1-weighted MR images reveal no evidence of tumor recurrence.
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DISCUSSION

NF1, also known as von Recklinghausen disease, is characterized by multiple skin lesions (café-au-lait spots, axillary and/or inguinal freckling), Lisch nodules, and various tumors including optic glioma, brain tumors, soft-tissue sarcomas, carcinomas (breast, lungs, gastrointestinal tract, thyroid, pharynx, ovaries), malignant melanoma, pheochromocytomas [5, 6, 7]. The majority of intracranial tumors with NF1 are pilocytic astrocytomas and optic gliomas which are thought to be pathologically low grade. Up to the year 2010, 12 patients with NF1 associated with glioblastoma had been reported [4]. Among them four occurred in adults. One patient was clinically represented with progressive multiple sclerosis and neurofibromatosis but glioblastoma remained silent during the patient's life. The pathology of glioblastoma was revealed by autopsy [8]. Table 1 shows the characteristics of the glioblastomas with NF1 in adults [8, 9, 10, 11]. Huttner et al. [4] reviewed five glioblastoma patients in children with NF1 and reported their clinicopathologic features. This study suggested that pathological features such as increased p53 expression, increased EGFR amplification, and increased proliferative indices might have predicted a worse overall outcome. They also provided that the survival of glioblastoma patient with NF1 was better than those without NF1. The median overall survival of patients with and without NF1 was 9.25 and 1.08 years respectively. However, because of the limited number of patients, further investigation is needed. In adults, glioblastoma is the most common and aggressive primary brain tumor. The methylation status of the MGMT gene promoter is currently a promising molecular prognostic marker. There is a significant association between MGMT promoter methylation and the outcome of glioblastoma patients treated with temozolomide. Molecular analysis of glioblastomas arising in NF1 patients showed the presence of genetic alterations such as p16INK4A/ARF deletion and p53 mutations [12]. Some studies have reported the cooperation of mutations in NF1 and p53 in the development astrocytomas in transgenic mice [13, 14]. In our case, the promoter methylation of MGMT gene was not observed. Immunohistochemical findings were positive for GFAP, and negative for EGFR. Preliminary studies reported that the prognosis of glioblastoma with NF1 in children may differ from patient without NF1 [4]. In adults, there is limited information about glioblastoma with NF1 cases. In this present case, the patient was treated using surgical excision and chemoradiotherapy with temozolomide. Further investigation for the glioblastoma patients with NF1 in adults would be necessary.


Table 1
The characteristics of previous cases of Glioblastoma with NF1 in adults
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Notes

The authors have no financial conflicts of interest.

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