Presentation
Nausea and vomiting. Known NF1.
Patient Data
Irregularly-shaped cystic mass within the left cerebellar hemisphere demonstrates homogeneous T1 signal, high T2 signal and sharply delimited rim enhancement with a vividly enhancing superior nodule. The mass exerts positive mass effect upon the fourth ventricle, displaced to the right, with evidence of ambient cistern effacement mild symmetrical temporal horn dilatation in keeping with mild hydrocephalus. The mass is separate from the left tentorium cerebelli.
There is associated mild diffusion restriction with ADC depression (not shown) in the periphery of the lesion. No additional intracranial lesion is seen. Minimal surrounding edematous change.
Screening T2 sagittal images of the whole spine were obtained, with no evidence of mass lesion and normal cord signal. Capacious spinal canal. (not shown).
Left suboccipital craniectomy-related skull defects demonstrated. Expected postsurgical change is noted within the left cerebellar surgical bed with locules of post-operative pneumocephalus and foci of circumferential blood product deposition. Postsurgical leptomeningeal enhancement is demonstrated along the left cerebellar folia and along the left tentorium cerebelli. No definite residual enhancing tumor mass noted in the left cerebellar hemisphere. There is a shallow ( 3 mm ) subdural hematoma along the dorsolateral aspect of the left cerebellar hemisphere as well as shallow left cerebellar subarachnoid hemorrhage. No interval remote intra-or extra-axial mass lesions. No acute infarcts.
Conclusion:
Expected left cerebellar post-surgical change with no definite large volume tumor residual.
Paraffin sections show a glial tumor of varying tumor cell density. Tumor cells are a mixture of piloid cells arranged in loose fasciculi and small protoplasmic and fibrillary astrocytes arranged in diffuse sheets. Scattered Rosenthal fibers and granular eosinophilic bodies are noted and areas with a myxomatous/mucinous stroma are also seen. There is prominent microvascular proliferation with endothelial cell hyperplasia. Scattered foci of bland infarct-like necrosis are also seen. No mitotic figures are identified.
IMMUNOHISTOCHEMISTRY:
- GFAP: positive
- IDH-1: negative
- nestin: positive
- p53: negative
- MGMT: negative
Epithelial membrane antigen (EMA) negative
Topoisomerase labeling index is approximately 5%
FINAL DIAGNOSIS: Pilocytic astrocytoma (WHO Grade I)
There has been marked disease progression since the previous scan (which demonstrated minor enhancement in the surgical bed) with a large peripherally enhancing mass with multiple regions of nodular enhancement having developed at the site of the previous resection, now almost the same size as the lesion was prior to the initial surgery. There has been a commensurate increase in T2 signal hyperintensity and mass-effect, although the 4th ventricle remains open and there is no evidence of hydrocephalus. Cerebral blood volume (CBV) is elevated in parts of the enhancing tumor and MR spectroscopy demonstrates elevation of choline and a small lactate peak with a mostly preserved NAA peak. The supratentorial brain is unremarkable.
Histology - re-resection
The sections show a variably hypercellular glial tumor within the cerebellar white matter. This shows a biphasic architecture.
One component consists of cells with pilocytic features. These have elongated hyperchromatic nuclei and bipolar processes which vary in thickness and are arranged in loose fasciculi. Rosenthal fibers are noted within this component.
The second component consists of cells with moderately pleomorphic round and oval vesicular nuclei. These are arranged in diffuse sheets. No mitotic figures are identified. Foci of vascular endothelial cell hyperplasia are identified. There is no necrosis. Tumor is sharply demarcated from the adjacent cerebellar cortex but merges gradually with cerebellar white matter.
Immunohistochemistry shows strong staining in tumor cells for GFAP and nestin. A small number of tumor cells show nuclear staining for p16. Nuclear staining for MGMT is seen in <15% of tumor cells indicating probable methylation. No staining for IDH-1 or BRAF-V600E is seen. The features are of pilocytic astrocytoma and, except for the absence of necrosis, are similar to those seen in the previous biopsies.
The topoisomerase labeling index shows regional variation - approximately 4-6%.
FINAL DIAGNOSIS: NF-1 associated pilocytic astrocytoma (WHO Grade I)
Case Discussion
This case demonstrates aggressive behavior of an astrocytic tumor with piloid features in a patient with known NF1.
At the time this was reported, it was determined to be a pilocytic astrocytoma. Although generally considered low-grade tumors (WHO grade 1) they can behave more aggressively, as is the case here.
More recently high-grade astrocytoma with piloid features has been described and is defined by its DNA-methylation profile - and as such whether this case is definitely an example of not is uncertain.
The histology images were reviewed (in 2022) by a neuropathologist who said:
"Given that this entity is defined by methylation profile, I can't be completely certain that this entity is high-grade astrocytoma with piloid feature.
It certainly has a piloid appearance. It's also in the most common location. The microvascular proliferation and necrosis is hard to interpret because you can get that pilocytic astrocytomas also. But necrosis is generally present in HGAPF. The lack of mitotic figures is unusual, and that was the case in both resections. The topoisomerase and cellularity are also low. But ultimately, you can also get HGAPFs that are histologically low grade, so all this could still fit."
The patient had rapid recurrence and was deemed inoperable and died from the tumor three years after initial diagnosis.
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