Malignant transformation of pleomorphic xanthoastrocytoma and differential diagnosis: case report

Abstract

Background: Pleomorphic xanthoastrocytoma (PXA) is a rare astrocytic glioma, characterized by large pleomorphic and frequently multinucleated cells, spindle and lipidized cells, a dense pericellular reticulin network, and numerous eosinophilic granular bodies according to the grade II glial tumor standards of the World Health Organization's (WHO) 2016 guidelines. PXA rarely transforms into anaplastic PXA or glioblastoma (GBM) and anaplastic PXA, classified as WHO grade III, has a more aggressive clinical behavior with poorer prognosis than PXA. Case presentation: Here we describe an unusual case of PXA in a 19-year-old woman, first admitted with headache and a mass in the left temporal lobe in 2005 that was removed. Twelve years later, she returned with left temporal headache, diplopia and tinnitus. A local tumor recurrence was found, and a second resection was performed. The specimen showed highly malignant findings, such as necrosis, microvascular proliferation, and multiple mitoses. The integrated diagnosis was made as high grade glioma, probably derived from PXA. Immunohistochemical (IHC) stains were positive for oligo2, and approximately 21% positive for Ki-67, while negative for CD34, IDH1 R132H. INI1 and ATRX were retained. As the histological classification was glioblastoma, the patient received GBM-appropriate chemotherapy and radiation therapy and outpatient follow-ups have demonstrated no obvious symptoms for 1 year after surgery. Additional molecular analyses found BRAF V600E mutations in both resections, supporting the idea that the recurrent tumor had derived from PXA. Conclusions: This case highlights the complexities of differential diagnosis based on the World Health Organization's 2016 guidelines. More integrated criteria to differentiate anaplastic PXA from GBM and epithelioid GBM, combined with genetic screening results, might be needed.

Prevalence of BRAFV600 in glioma and use of BRAF Inhibitors in patients with BRAFV600 mutation-positive glioma: systematic review

“…Case studies have identified eGBM arising from PXA. 40 Our findings are broadly consistent with prevalence estimates presented in the WHO guidelines. 41 WHO categorises DIA and DIG subtypes together; we have found the prevalence of BRAFV600 mutation to be somewhat higher in DIA, compared with DIG.…”

A case series of pediatric survivors of anaplastic pleomorphic xanthoastrocytoma

“…In fact, the existing literature includes both pediatric and adult cases where APXA was either challenging to diagnose or misdiagnosed as either low-grade tumors or WHO grade 4 gliomas. 3 , 12 , 18 , 24–26 …”

“… 4 , 6 , 7 Furthermore, BRAFV600E mutation has also been most commonly described in PXA and APXA. 3 , 8 , 9 …”

Pleomorphic Xanthoastrocytoma, Anaplastic Pleomorphic Xanthoastrocytoma, and Epithelioid Glioblastoma: Case Series With Clinical Characteristics, Molecular Features and Progression Relationship

“…A-PXA and E-GBM are similar in histology, immunohistochemistry, molecular and clinical characteristics. Although PXA rarely transforms into A-PXA or GBM [8], there have been some related studies of PXA transformed into GBM so far, for example, 1) a case of secondary disease with an IDH1 mutation had been reported, which is a common type of molecular feature of secondary GBM secondary to astrocyte tumors [2]. 2) Shingo Tanaka et al described a case of E-GBM developing at the site of a previously resected PXA with the BRAF V600E mutation 13 years after the initial surgery [15].…”

“…However, 5%-20% of patients with PXA have a recurrence with malignant transformation. PXA rarely transforms into anaplastic pleomorphic xanthoastrocytoma (A-PXA) or glioblastoma (GBM) [8].…”