Glioblastoma

From Dog
Gross postmortem appearance of a canine glioblastoma[1]

Glioblastoma, a form of astrocytoma, are an aggressive brain tumor and spinal cord neoplasia of dogs which carries a poor prognosis.

They are classified as a World Health Organization grade IV astrocytoma[1] and represent only about 5% of all astrocytomas[2][3].

These primary tumors, which are powerfully expressive of tyrosine kinase, are among the most common primary neural tumours traditionally associated with older brachycephalic breeds such as the Boston Terrier and Boxer[4][5][6]. They usually present without clinical or histological evidence of a less malignant precursor lesion[7].

Secondary glioblastomas progress from low-grade diffuse astrocytoma or anaplastic astrocytoma[8].

Dogs with cerebral glioblastomas usually present with central nervous disorders such as anorexia, ataxia, circling, generalized proprioceptive deficits, behavioral changes and seizures[9].

With peripheral spinal cord glioblastomas, a visible mass is often evident associated with the spinal column, which is often painful upon palpation[10].

Routine blood count, serum chemistry profile, urinalysis, thoracic radiographs, and abdominal ultrasound are usually unrewarding. However, imaging studies such as CT or MRI usually elucidate a mass lesion within the brain or associated with the spinal cord[11].

Definitive diagnosis requires histopathological analysis of neoplastic tissue. Glioblastomas produce a mass effect and peritumoral edema causing midline shifts of neuronal tissue with the cardinal features of necrosis or microvascular proliferation.

These tumors appear histologically as highly vascular and pleomorphic astrocytic tumor cell populations interspersed with areas of serpentine necrosis bordered by pseudopalisading glial cells. Numerous bizarre, multinucleated giant cells may also be observed.

Immunohistochemically, these tumors uniformly express vimentin and glial fibrillary acid protein.

A differential diagnosis would include meningioma, metastatic lymphoma, choroid plexus tumor and pituitary adenoma.

Treatment with surgical excision is rarely curative although radiation therapy or chemotherapy may prolong survival in younger dogs.

Chemotherapy drugs include hydroxyurea (30 - 50 mg/kg orally 3 times a week), lomustine[12], temozolomide[13] and cediranib (tyrosine kinase inhibitor)[14].

The use of COX-2 inhibitors, though beneficial with human glioblastomas, has been shown to be ineffective against the canine counterpart[15].

References

  1. 1.0 1.1 Lipsitz D et al (2003) Glioblastoma multiforme: clinical findings, magnetic resonance imaging, and pathology in five dogs. Vet Pathol 40(6):659-669
  2. Koestner A & Higgins RJ (2002) Tumors of the nervous system. In: Tumors of Domestic Animals, ed. Meuten DJ, pp:697–738. Iowa State University Press, Ames, IA
  3. Candolfi M et al (2007) Optimization of adenoviral vector-mediated transgene expression in the canine brain in vivo, and in canine glioma cells in vitro. Neuro Oncol 9(3):245-258
  4. Heidner GL et al (1991) Analysis of survival in a retrospective study of 86 dogs with brain tumors. J Vet Intern Med 5:219–226
  5. Foster ES et al (1988) Clinical signs of tumors affecting the rostral cerebrum in 43 dogs. J Vet Intern Med 2:71–74
  6. LeCouteur RA (1999) Current concepts in the diagnosis and treatment of brain tumours in dogs and cats. J Small Anim Pract 40:411–416
  7. Stoica G et al (2009) Identification of cancer stem cells in dog glioblastoma. Vet Pathol 46(3):391-406
  8. Ohgaki H & Kleihues P (2012) The Definition of Primary and Secondary Glioblastoma. Clin Cancer Res Dec 3
  9. Giri DK et al (2011) Giant cell glioblastoma in the cerebrum of a pembroke welsh corgi. J Comp Pathol 144(4):324-327
  10. Röthlisberger A et al (2012) Suspected primary glioblastoma multiforme in the canine spinal cord. J Small Anim Pract 53(10):604-607
  11. Sutherland-Smith J et al (2011) Magnetic resonance imaging apparent diffusion coefficients for histologically confirmed intracranial lesions in dogs. Vet Radiol Ultrasound 52(2):142-148
  12. Gori JL et al (2012) In vivo selection of autologous MGMT gene-modified cells following reduced-intensity conditioning with BCNU and temozolomide in the dog model. Cancer Gene Ther 19(8):523-529
  13. Hegi ME et al (2005) MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352:997–1003
  14. Schulz-Utermoehl T et al (2010) In vitro hepatic metabolism of cediranib, a potent vascular endothelial growth factor tyrosine kinase inhibitor: interspecies comparison and human enzymology. Drug Metab Dispos 38(10):1688-1697
  15. Jankovsky JM et al (2011) COX-2 and c-kit expression in canine gliomas. Vet Comp Oncol Nov 23