Presentation
Sudden onset right upper limb and face paresthesia.
Patient Data
CT brain (non-contrast): There is a small, uniformly hyperdense, regularly-shaped ovoid hematoma within the left midbrain/left cerebral peduncle measuring 16 mm (ap) x 8.5mm (trans) x 11mm (cc), estimated volume using the ABC/2 rule about 1cc. There is a surrounding rim of hypoattenuation in keeping with vasogenic edema that extends as inferiorly as the left side of the pons and superiorly as the posterior limb of the left internal capsule, compatible with evolving vasogenic edema no additional focus of intracranial hemorrhage is identified. No evidence of acute ischemia. Ventricles, cisterns and sulci are within normal limits for age. No hydrocephalus or midline shift. No calvarial fracture suspicious bony abnormality seen. Opacification of several ethmoid air cells. Other paranasal sinuses and mastoid air cells are clear.
CTA Circle of Willis (not shown): No vascular abnormality is identified in the region of the left midbrain hemorrhage. There is no evidence of the CT angiographic 'spot sign' to suggest dynamic hemorrhage at the time of examination.
Conclusions:
Small left midbrain intracerebral hemorrhage with surrounding halo of vasogenic edema, with no hydrocephalus. An underlying lesion is suspected (e.g. cavernoma or tumor)
There is a ~1.5cm lesion extending from the left through a peduncle and in the left midbrain and pons. This demonstrates nodular peripheral enhancement.
On T2 and FLAIR sequences this lesion is predominantly hyperintense with heterogenous areas of hypointensity. There is a small amount of surrounding T2 and FLAIR hyperintensity.
At the medial and posterior aspects of this lesion there is low T2 and FLAIR signal and corresponding blooming susceptibility weighted sequences indicating the location of resolving hematoma demonstrated on previous CT.
No convincing abnormal diffusion restriction.
The brain parenchyma is otherwise unremarkable. No other signal abnormality or abnormal enhancement.
Intracranial arteries (MRA not shown) are unremarkable. No abnormal vessel, aneurysm, or early draining vein is demonstrated.
Conclusion:
Resolving hematoma in the left cerebral peduncle, left midbrain, and left pons. Adjacent lesion with nodular peripheral enhancement and central necrosis. Appearance is very suspicious for high grade glioma.
The patient went on to have a stereotactically guided biopsy.
Histology
MICROSCOPIC DESCRIPTION: Paraffin sections show small fragments of a moderately hypercellular glial tumor. This is composed of a mixture of oligodendroglial and astrocytic cells. Both show mild nuclear pleomorphism. Scattered gliofibrillary oligodendrocytes are also noted. Several mitotic figures are identified and there is microvascular proliferation with multilayering of atypical cell around vessel lumena. No necrosis is seen. Several incorporated neurons containing melanin pigment are also noted.
IMMUNOHISTOCHEMISTRY:
- GFAP positive in tumor and reactive astrocytes and in gliofibrillary oligodendrocytes.
- NogoA positive in tumor oligodendrocytes.
- IDH-1 R132H negative (not mutated / wild-type)
- ATRX positive (not mutated)
- MGMT negative (likely methylated)
- p53 positive in tumor astrocytes p16 negative
- Topopisomerase labeling index: Approximately 20%.
FINAL DIAGNOSIS: IDH-1 wild-type anaplastic oligoastrocytoma - WHO Grade III
NOTE: This case predates the 2016 WHO classification of CNS tumor revision. As no 1p19q co-deletion status is available a formal diagnosis cannot be reached and the NOS is therefore used (not otherwise specified) - which is recognized in the current classification for cases where molecular information is unavailable. It should also be noted, that under the new classification both an astrocytic and oligodendroglial component needs to be identified, each with its own molecular markers. True oligoastrocytomas are therefore going to be rare, and this case would most likely be classified as either an astrocytoma or an oligodendroglioma.
MRI obtained 3 months after biopsy and at the end of combined chemoradiotherapy (Stupp protocol) demonstrates a left front burr hole with biopsy tract. Ring-enhancing mass within the left pons/midbrain extending into the left cerebral peduncle, which measures 24 x 19 x 35 mm in maximal dimensions, previously measures 17 x 11 x 27 mm. There is increased central low signal indicative of increased necrosis. Blooming surround this mass indicates surrounding blood product.
Surrounding more extensive high FLAIR signal, which tracts inferiorly to the medulla (new) and posteriorly to the left cerebellar hemisphere via the left cerebellar peduncle (new). It also newly crosses the midline into the right pons and midbrain, as well as increased FLAIR signal within the inferior left frontal lobe, left temporal lobe, extending into the left internal capsule / corona radiata and along the biopsy tract.
MRS demonstrated increased lactate peak with preserved NAA and mildly elevated choline. There is possibly some minor increase in CBV that corresponds with the enhancing margins of the mass, but this is minimal. There is also high DWI / low ADC signal indicating restricted diffusion within the enhancing margins of the mass but blood product in the region limits reliability.
Conclusion
Left midbrain/pons mass has increased in size with increased central necrosis. There is marked increase in surrounding FLAIR signal. At this time (3 months post biopsy, end of Stupp protocol) the absence of convincing elevation of CBV, and relatively mild MRS changes, favor a significant component of pseudoprogression.
The peripherally enhancing lesion in the left cerebral peduncle is stable, with a focus of enhancement demonstrated extending into the left thalamus is again noted, but since the previous study, there has been decrease in extent of FLAIR hyperintensity, particularly adjacent to the trigone of the left lateral ventricle and in the left middle cerebellar peduncle extending into the anterior left cerebellar hemisphere.
Hemosiderin staining is again demonstrated, consistent with previous hemorrhage. There is a probable focus of elevated CBV within the left thalamus, corresponding to the focus of enhancement. Elsewhere, no convincing CBV elevation. MRS again demonstrates elevated choline and a lactate peak.Elevated T2 signal in the left inferior olivary nucleus probably represents non-enhancing tumor. Alternatively it may represent hypertrophic olivary degeneration.
Conclusion
Slight decrease in size of bulkiness of FLAIR hyperintensity suggests evolution of pseudoprogression seen on the prior study, although no doubt residual tumor is present and some co-existing tumor growth may be present.
Case Discussion
The diagnosis of pseudoprogression can be difficult and knowledge of timing of the scan relative to chemoradiotherapy is crucial (typically ~3 months post end of chemoradiotherapy, but commonly seen within 0 - 6 months).
This patient was also more likely to demonstrate pseudoprogression as their tumor is MGMT methylated (and thus alkylating agents e.g. temozolomide will have greater efficacy).
It is also crucial to realize that it is not a question of pseudoprogression OR persistence presence of tumor (or even probably tumor growth); both can be occurring simultaneously. It is really a question of determining which process is dominant and accounts for the imaging features.
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