Pleomorphic xanthoastrocytomas (PXA) are rare grade2, occasionally grade 3 astrocytic tumors according to the current WHO classification. PXAs account for less than 1% of all astrocytomas. PXAs are categorized as circumscribed astrocytic tumors, suggesting benign behavior, but can transform into highly malignant tumors and even spread via the cerebrospinal fluid (CSF).

We present 3 recent cases highlighting the clinical and differential diagnostic difficulties related to PXA. Patient #1 harboring BRAF mutant right parietal PXA (WHO gr 2) recurred 6 months following gross total resection (GTR) as a tumor which met the diagnostic criteria of epitheloid glioblastoma (WHO gr 4). The recurrent tumor was treated according to Stupp regimen following GTR. No progression has been detected 16 month following the second surgery. Patient #2 was operated with a temporal tumor which fulfilled the criteria of PXA (WHO grade 3). Surgery was followed by radiotherapy and adjuvant temozomolid. However, the patient showed multifocal recurrence and underwent repeated surgery and histology. Due the lack of BRAF mutation and CDKN2A/B deletion as well as the aberrant p53 staining the recuuernce was more suggestive of a giant cell glioblastoma (WHO gr 4) and retrospectively the primer histology was reconsidered to be the same glioblastoma. The tumor showed only poor and transient response to salvage bevazicumab therapy. Patient #3 presented with precuneal tumor and signs of elevated intracranial pressure (ICP). The patient underwent VP shunt implantation and stereotactic biopsy. The histology and the combined presence of BRAF mutation and CDKN2A/B deletion suggested the diagnosis of PXA (WHO gr 2). Therefore, GTR was planned following the stabilization of the patient’s medical condition. Follow-up MRI revealed no progression in the tumor site, but new leptomeningeal enhancement was detected. Repeated CSF sampling confirmed CSF dissemination. Retrospectively, tumor was disseminated at the initial diagnosis and this might have caused the ICP elevation. Due to rapid deterioration no oncotherapy could be initiated.

In conclusion, even low-grade PXAs can show aggressive clinical behavior. Therefore, detailed histological and molecular diagnosis and very strict follow up is needed even after GTR. In case of unexpected ICP elevation in PXA patient CFS spread should be considered.