Presentation
Left-sided headache for several months. The patient presented acutely with intractable nausea and vomiting, falls, agitation, and altered mental status. Initial imaging demonstrated hydrocephalus and a left temporal lobe mass, and an external ventricular drain was placed.
Patient Data
Brain:
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Left anterior temporal lobe enhancing mass, 4.7 x 2.7 cm, with cystic components, small foci of intralesional hemorrhage, and markedly elevated blood volume. The lesion extends to the ependymal surface at the left lateral ventricle temporal horn and to the leptomeningeal surface at the medial part of the left sylvian fissure, abutting middle cerebral artery.
Ventricles:
Right frontal external ventricular drain tip in the third ventricle.
Diffuse moderate ventricular dilation.
Blood layering in the occipital horns of the lateral ventricles.
Ependymal enhancement along the left lateral ventricle temporal and occipital horn and strands of intraventricular enhancement in the atrium.
Extra-axial spaces:
Reactive pachymeningeal enhancement over the right frontal convexity.
Arachnoid cyst over the left frontal convexity.
No abnormal leptomeningeal enhancement.
Bone and extra-cranial soft tissues:
Postoperative changes.
Fiducial markers in place in preparation for surgery.
Impression: Left temporal lobe neoplasm with possible CSF dissemination causing hydrocephalus.
The underwent left temporal craniotomy for tumor resection. Intraoperative findings were of a firm, grey colored lesion abutting the left middle cerebral artery and choroid plexus. Frozen pathology was consistent with astrocytoma.
Pathology:
Tissue sections show a pleomorphic astrocytoma that appears to be based in the superficial cortex with increased mitotic activity (focally reaching 5 mitoses per 10 HPF) and palisading necrosis. Focal perivascular orientation of tumor cells is noted. The main portion of the tumor appears compact with a more moderate component of tumor infiltration at the periphery. No definite eosinophilic granular bodies or Rosenthal fibers are present (PAS). Immunostains show the neoplastic cells are positive for BRAF (V600E mutant protein), CD34 (subset), GFAP, S100, and Olig2, but negative for IDH1 (R132H mutant protein). P53 labels scattered cells. ATRX is retained. There is no increase in pericellular reticulin. A Ki67 proliferation index is increased. MGMT studies were positive for MGMT promoter methylation. NGS studies confirmed the presence of a BRAF V600E mutation and suggested possible homozygous deletion of CDKN2A/2B. No mutations were identified in IDH1, IDH2, or the TERT promoter.
Overall, given the morphologic features, elevated mitotic activity, palisading necrosis, and the molecular findings, the findings are most consistent with anaplastic pleomorphic xanthoastrocytoma (WHO grade 3).
Brain:
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Resection cavity in left temporal lobe with residual masslike enhancement measuring 1.5 cm along the superomedial margin. Linear enhancement elsewhere along the cavity walls and restricted diffusion posterior to the cavity.
Ventricles:
Interval removal of ventricular drain.
Unchanged diffuse ventricular dilation.
Resolution of enhancement within/along the posterior left lateral ventricle.
Extra-axial spaces:
Left cerebral convexity subdural fluid collection and dural enhancement.
Trace epidural fluid collection underlying the craniotomy site.
Bones/extracranial soft tissues:
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Expected postoperative changes.
Impression: Subtotal resection.
The patient underwent radiotherapy with concurrent temozolomide.
Brain:
The left temporal lobe resection cavity has contracted.
Nodular enhancement at the superomedial margin of the cavity persists and has not significantly increase but now has a more encysted/ring-enhancing component. The enhancing component has high relative blood volume (leakage-corrected).
Surrounding FLAIR hyperintensity has slightly increased in extent along the periventricular white matter.
Ventricles:
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Decreased diffuse dilation of the ventricles.
Extra-axial spaces:
Resolved subdural fluid collection but persistent reactive pachymeningeal thickening over the left frontal convexity.
Persistent extradural fluid underlying the craniotomy.
Bones/extracranial soft tissues:
-
Expected postoperative changes.
Impression: Expected evolution of postsurgical/posttreatment changes. No specific evidence of tumor progression. Persistent enhancing nodularity in the resection bed. Hydrocephalus has improved.
The patient underwent adjuvant temozolomide alone for an additional 4 cycles, during which time there was enlargement of the cyst but not the solid enhancing component (interval imaging not shown) and he was asymptomatic. Subsequently, the patient presented with worsening headache, nausea/vomiting, gait instability, and confusion.
Brain:
Interval enlargement of the peripherally contrast-enhancing cystic lesion at the left anterior temporal lobe resection site. The anterior part of the enhancing rim has high relative blood volume (leakage-corrected).
Interval enlargement of surrounding FLAIR hyperintensity.
Ventricles:
Interval recurrent dilation of the ventricular system diffusely.
New 3 mm enhancing focus at the obex of the fourth ventricle.
Extra-axial spaces:
No abnormal leptomeningeal enhancement.
Persistent reactive left frontal convexity pachymeningeal thickening and extradural fluid underlying the craniotomy.
Bones/extracranial soft tissues:
Expected postoperative changes.
Fiducial markers in place in preparation for surgery.
Impression: Continued enlargement of left temporal lobe cystic mass, suspected to represent tumor progression. Recurrent communicating hydrocephalus suspected to be due to CSF tumor dissemination on the basis of a new enhancing deposit at the obex.
The patient underwent left craniotomy for fenestration of the left temporal cyst into the ventricular system. Dissection of the tumor was limited by adherence of tumor to the middle cerebral artery. Resection of the cyst wall showed tumor.
Pathology:
Recurrent High Grade Astrocytoma, BRAF V600E-mutant, in a background of treatment-related changes.
Note: Sections show a cellular glial neoplasm composed of atypical and pleomorphic cells in a background of treatment related changes including calcifications, vascular hyalinization, and hemosiderin deposition. Immunohistochemical stain for BRAF V600E mutant protein is positive. Ki-67 immunostain shows that a considerable proportion of tumor nuclei are proliferative. Overall, the amount of viable tumor present and the degree of proliferation suggest a moderately active glioma.
Follow-up
The patient presented within 2 weeks of surgery with urinary retention and leg weakness. A high-volume lumbar puncture was performed for diagnostic and therapeutic purposes. 25 mL of xanthochromic cerebrospinal fluid was sent for cytopathology. No malignant cells were identified. The clinical condition improved slightly but the patient returned within a few days for worsening gait and urinary retention.
Case Discussion
Pleomorphic xanthoastrocytoma is a rare tumor in adults. The typical appearance is that of a supratentorial nodulocystic tumor, most often in the temporal lobe, centered superficially and often involving leptomeninges. Anaplastic pleomorphic xanthoastrocytoma (WHO CNS grade 3) tends to have heterogeneous contrast enhancement of the solid components, obvious peritumoral edema, and high relative cerebral blood volume on dynamic susceptibility contrast perfusion weighted imaging 1. Although considered a circumscribed as opposed to diffusely infiltrating astrocytoma, pleomorphic xanthoastrocytoma carries a distinct possibility for leptomeningeal/CSF dissemination including to the spine (drop metastases) 2-4.
In this case, the patient had possible CSF dissemination at presentation, as suggested by intraventricular and ependymal surface enhancement and the presence of hydrocephalus. However, malignant cells were not found on cytological analysis of the ventricular fluid obtained via the temporary external ventricular drain. The patient was planned for spinal imaging as part of initial staging but was not able to complete the exam due to their condition. Therefore, CSF dissemination was not proven initially.
The patient underwent resection, which on imaging appeared to be a subtotal rather than gross total resection, which increases the risk of recurrence. The intraventricular enhancement had, curiously, resolved on the postoperative exam. The patient underwent adjuvant treatment with chemoradiotherapy, and, reassuringly, the hydrocephalus resolved. During adjuvant therapy with temozolomide alone, however, imaging showed progressive enlargement of the residual mostly-cystic enhancing lesion at the resection site, suspicious for tumor progression. Upon symptom development, the patient underwent re-resection, which proved the presence of active recurrent tumor. There was not able to be a gross total resection and the cyst was fenestrated into the ventricle to reduce the mass effect.
Following re-resection, the patient presented with lower extremity weakness and urinary retention, raising concern for myelopathy. Spinal MRI demonstrated several intradural lesions indicative of drop metastases causing cord edema by compression and/or invasion.
The patient was started on a course of steroids and, because of the tumor BRAF mutation status, targeted molecular therapy with dabrafenib and trametinib (BRAF and MEK inhibitors). On 6-month follow-up, there was a decrease in spinal tumor size but not complete resolution, as well as improvement in symptoms (able to walk independently again).
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