You are here

Article Text

Article menu

Download PDFPDF

Lobar haemorrhagic mass in a young girl with neurofibromatosis type 1
Free
  1. Rita Ceponiene1,
  2. Michael L Levy2,
  3. John Ross Crawford3
  1. 1Department of Neurosciences, University of California San Diego, La Jolla, California, USA
  2. 2Department of Neurosurgery, University of California San Diego, San Diego, California, USA
  3. 3Department of Neurosciences and Pediatrics, University of California San Diego, San Diego, California, USA
  1. Correspondence to Dr John Ross Crawford, jrcrawford{at}ucsd.edu

https://doi.org/10.1136/bcr-2013-200565

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    Description

    A 9-year-old girl with neurofibromatosis type 1 (NF-1) presented with sudden onset neurological deterioration following a 2-day history of headache. She was comatose on arrival with right third nerve palsy and contralateral hemiparesis. A head CT revealed a large right frontal acute haemorrhagic lesion with midline shift and uncal herniation (figure 1). The patient underwent emergent decompressive craniotomy and resection of the mass lesion where, the pathology demonstrated a highly cellular glial tumour with extensive nuclear pleomorphism and increased mitotic index consistent with a diagnosis of high-grade glioma (figure 2).

    Figure 1
    Figure 1

    Preoperative head CT demonstrating a large right frontal lobar heterogeneous haemorrhage with acute and subacute components without oedema, an 8 mm midline shift and uncal herniation (right).

    Figure 2
    Figure 2

    H&E-stained biopsy specimen demonstrates a glial tumour with extensive nuclear pleomorphism and brisk mitotic activity in a microcystic background consistent with diagnosis of a high-grade glioma.

    The differential diagnosis of an acute non-traumatic cortical haemorrhage in a child with NF1 includes aneurysm, haemorrhagic transformation of an ischaemic stroke and tumour. While majority of parenchymal tumours in NF-1 are low-grade astrocytomas, the rapid progression of symptoms in association with cerebral haemorrhage supported the diagnosis of a high-grade neoplasm.

    NF-1 is a genetic tumour syndrome in which the neurofibromin, one of the main Ras-GAP proteins, is silenced on chr 17q11.2. Ras-GAP proteins activate Ras-GTP-hydrolase, inactivating the Ras signalling pathway that promotes cell proliferation. While low-grade astrocytomas are most commonly associated with NF-1, they are generally not haemorrhagic. Malignant gliomas have been rarely reported in children with NF-1.1 ,2 Experiments in animal models suggest that early inactivation of the P53 tumour suppressor gene may act in synergy with downstream Ras pathways to promote high grade transformation.3 Our case demonstrates the rare association of high-grade tumours with NF-1 and expands the differential diagnosis of haemorrhagic lesions in the patient population.

    Learning points

    • Brain tumours in children may present with intracranial haemorrhage.

    • High-grade glioma is a rare tumour in association with neurofibromatosis type 1 and should be included in the differential diagnosis

    References

    1. ↵
      1. Huttner AJ,
      2. Kieran MW,
      3. Yao X,
      4. et al
      . Clinicopathologic study of glioblastoma in children with neurofibromatosis type 1. Pediatr Blood Cancer 2010;2013:890–6.
      OpenUrl
    2. ↵
      1. Distelmaier F,
      2. Fahsold R,
      3. Reifenberger G,
      4. et al
      . Fatal glioblastoma multiforme in a patient with neurofibromatosis type 1: the dilemma of systematic medical follow-up. Childs Nerv Syst 2007;2013:343–7.
      OpenUrl
    3. ↵
      1. Zhu Y,
      2. Guignard F,
      3. Zhao D,
      4. et al
      . Early inactivation of p53 tumor suppressor gene cooperating with NF1 loss induces malignant astrocytoma. Cancer Cell 2005;2013:119–30.
      OpenUrl
    View Abstract

    Footnotes

    • Competing interests None.

    • Patient consent Obtained.

    • Provenance and peer review Not commissioned; externally peer reviewed.