Glioblastoma with symptomatic postbiopsy hemorrhage

Case contributed by Dr Francis Deng

Presentation

Right-handed patient with 1-2 weeks of right-leaning gait, left hand incoordination (frequently dropping objects), and left foot clumsiness (losing his flip-flop sandal). Physical examination showed left upper extremity pronator drift and tactile extinction to double simultaneous stimulation.

Patient Data

Age: 60 years
Gender: Male
  • Right deep parietal lobe mass, 5 cm, with surrounding expansile hypodensity (involving the parietal white matter, posterior subinsular region, and posterior superior temporal gyrus white matter, retrolenticular white matter and posterior limb of internal capsule, and dorsolateral thalamus)
  • Mass-effect including 2 mm leftward midline shift and effacement of right parietal sulci, the central sulcus, the posterior ramus of the sylvian fissure, and the posterior body right lateral ventricle
  • Incidental right parotid mass, 1.4 cm

Contrast-enhanced MRI is recommended.

  • Right parietal lobe peripherally enhancing mass, maximal diameter 5 cm, with central necrosis and hemorrhage. The lesion and associated expansile FLAIR abnormality extends deeply, involving the retrolenticular white matter, posterior limb of internal capsule, and dorsolateral thalamus. Mass effect includes 2 mm leftward midline shift. Prominent draining medullary veins lateral to the mass.
  • Two right superficial parotid masses, 1.2 cm and 1.4 cm, likely primary salivary gland neoplasms.
  • Chronic microhemorrhage in the left centrum semiovale underlying the precentral gyrus
  • Mild, scattered T2/FLAIR hyperintensities in the subcortical and periventricular white matter are nonspecific but likely reflect chronic small vessel disease in a patient of this age.

Stereotactic biopsy was performed. Postoperative head CT (not shown) showed no immediate complications.

Frozen section diagnosis: 

Infiltrating glioma without necrosis or vascular proliferation on frozen section.

Final pathologic diagnosis:

Integrated diagnosis: astrocytoma, IDH-mutant, CNS WHO grade 4

Histologic diagnosis: astrocytoma with mitotic activity, necrosis, and microvascular proliferation

CNS WHO grade: 4

Molecular findings:

  • IDH1/2: MUTANT [R132S] (PCR) 
  • ATRX: RETAINED nuclear staining (immunohistochemistry; consistent with
    wild type)
  • p53: scattered weakly positive cells (immunohistochemistry; consistent
    with wild type)
  • MGMT promoter methylation: NEGATIVE (PCR)
  • 1p/19q: NOT co-deleted (FISH)

Note: The tumor demonstrates moderate cellular anaplasia, mitotic activity, focal necrosis with palisading and microvascular proliferation. The presence of retained nuclear staining for ATRX in the face of an astrocytic tumor with a mutation in IDH1 is unusual, and additional molecular studies might be informative about this finding.

NB: See the end of the case for subsequently amended final pathologic diagnosis.

On postoperative day 2, the patient developed worsening left-sided weakness and left-sided neglect.

2 days postbiopsy

ct
  • Multifocal acute intraparenchymal hemorrhage around the right parietal white matter mass. The largest, at the anterior margin extending to the posterior insula, measures 2.6 cm, likely affecting the descending corticospinal tract at the level of the corona radiata. Total hemorrhage volume approximately 7 mL. Increased edema extending to the superior right temporal lobe.
  • Increased mass effect including 7 mm upward midline shift and entrapment of the temporal and occipital horns of the right lateral ventricle.

3 days postbiopsy

mri
  • Compared to the preoperative MRI, the right deep parietal lobe mass is newly associated with multifocal acute to early subacute perilesional hemorrhage, increased surrounding expansile FLAIR hyperintensity, and a small region of diffusion restriction anterior to the enhancing mass
  • Mass effect on adjacent brain parenchyma and right lateral ventricle has increased, with leftward midline shift of 1.2 cm
  • Diffusion tensor imaging delineates white matter regions with reduced fractional anisotropy due to the enhancing mass, surrounding FLAIR abnormality (edema or infiltrative tumor), and/or the new region of diffusion restriction/cytotoxic edema anterior to the mass, including the posterior aspect of the expected path of the corticospinal tracts in the corona radiata and posterior limb of internal capsule.

The patient underwent surgery for tumor resection with intraoperative neuro-electrophysiological functional monitoring due to the location of the tumor. Subtotal resection was achieved. More extensive resection was limited by declining motor evoked potential monitoring.

Following the surgery, the prior biopsy pathology was amended. An orthogonal assay for IDH mutation was performed on a new instrument at this institution and found the previously reported R132S variant to be below the threshold of diagnostic confidence. The amended pathology report is as follows:

Final pathologic diagnosis:

Integrated diagnosis: glioblastoma, IDH-wildtype, CNS WHO grade 4

Histologic diagnosis: astrocytoma with mitotic activity, necrosis, and microvascular proliferation

CNS WHO grade: 4

Molecular findings:

  • IDH1/2: WILD TYPE (PCR, amended) 
  • ATRX: RETAINED nuclear staining (immunohistochemistry; consistent with
    wild type)
  • p53: scattered weakly positive cells (immunohistochemistry; consistent
    with wild type)
  • MGMT promoter methylation: NEGATIVE (PCR)
  • 1p/19q: NOT co-deleted (FISH)

Case Discussion

This case demonstrates the correspondence between brain lesion localization and clinical manifestations; the typical imaging characteristics of glioblastoma; the importance of molecular diagnostics in classifying gliomas; and the potential complications of surgical intervention.

The signs and symptoms of sensory deficits including proprioceptive abnormalities, extinction, and neglect suggest a lesion localization in the contralateral parietal lobe. The addition of contralateral hemiparesis indicates involvement that is slightly more anterior (ie, the posterior frontal lobe) and/or deep (such as internal capsule).

Glioblastomas are the most common primary brain tumor in adults. Patients typically present with subacute neurologic manifestations. The typical MRI appearance reflects the histological findings of necrosis, neovascularity, hemorrhage, and tumoral infiltration. Glioblastomas are wildtype for isocitrate dehydrogenase (IDH), while diffuse gliomas with activating mutations in the IDH1 or IDH2 genes but otherwise similar histologic and molecular features would be characterized instead as grade 4 astrocytoma in the WHO 5th edition classification of central nervous system tumors.

A major goal of surgical management of high-grade glioma is maximal resection of enhancing tumor but some locations place neurologic function at risk with this strategy. Stereotactic biopsy is performed first for tumors in deep-seated locations. Following stereotactic biopsy of intraaxial brain tumors, imaging is indicated to detect bleeding and other complications. Intracranial hemorrhage is the most common complication in this setting but symptomatic hemorrhage occurs in less than 10% of biopsies 1,2. The hemorrhage in this case was multifocal in the periphery of the tumor, away from the biopsy target site. The pathophysiology is not clear but possibly relates to changes in hemodynamics in the perioperative/postoperative setting that cause rupture of friable tumor neovascularity analogous to venous hypertension-related bleeding.

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