Original ArticlePleomorphic Xanthoastrocytoma with Anaplastic Features: Retrospective Case Series
Introduction
Pleomorphic xanthoastrocytoma (PXA) was first identified in 1979 by Kepes et al.1 as a unique meningocerebral astrocytoma with a relatively favorable prognosis despite its malignant pathologic features. Composed of spindle cells and multinucleated giant cells, PXAs were also noted to contain large lipid droplets and abundant reticulin fibers that made them resemble fibrous xanthomas.2 Subsequent immunohistochemical staining with glial fibrillary acidic protein made it possible to identify astrocytic components within the tumors and corroborated their standing as a unique neoplasm, with the World Health Organization (WHO) officially recognizing PXA as a distinct central nervous system tumor in 1993.3
Though clinically indolent, PXA can undergo transformation into a true malignant glioma,4 with progression rates between 10% and 38% occurring as late as 15 years after initial diagnosis.4, 5 This observation has underscored the importance of primary therapeutic interventions that minimize tumor recurrence and maximize overall survival (OS). Extent of resection (EOR) has been identified as an important determinant of OS,6, 7, 8, 9 while the utility of adjuvant radiation remains unclear, with most published accounts consisting of case reports.10, 11, 12 Kepes et al.1 initially speculated that tumor features such as lack of necrosis, cystic composition, superficial cortical anatomy, and lymphocytic infiltrate were responsible for the favorable prognosis, and a number of subsequent studies have largely validated this hypothesis, including a series of 71 patients in which OS rates were 81% at 5 years and 70% at 10 years.7
In 2007, the WHO reclassified PXA as a grade II tumor that can also be found “with anaplastic features” (aPXA).13 These latter cases demonstrate variable levels of necrosis and/or ≥5 mitoses per high-power field (hpf). These features are important diagnostic criteria but also appear to hold prognostic value: Mitotic index was found to be independently associated with survival outcomes,7 while necrosis appeared to be significantly associated with earlier mortality in one series6 but not in another.7 Nevertheless, PXA and aPXA are both regarded as grade II neoplasms despite little understanding of the impact of their pathologic differences on clinical outcomes.
With few exceptions, aPXA has not been studied as an independent entity. In an effort to improve understanding of how pathologic features influence outcomes for aPXA, we present our institutional experience in the management of 8 aPXA patients seen at the University of California, San Francisco (UCSF) from 1999–2012.
Section snippets
Patient Population and Data Collection
All consenting patients evaluated by the Department of Neurological Surgery at UCSF have had their names and pathologic diagnoses collected and recorded in an IRB-approved program since 1991 (Committee for Human Research [CHR] H7828-29842-01). We obtained further permission to study patients with aPXA (CHR H41995-35010-01).
Patient records were reviewed to extract data on demographics, presentation and symptomatology, histopathologic features, treatment modality, morbidity and mortality, and
Patient Population and Tumor Characteristics
The UCSF Department of Neurosurgery managed 8 patients with aPXA from 1999–2012 (Table 1). There was a female predominance in our cohort, with 5 female and 3 male patients. Our patients ranged in age from 4–74 years at time of diagnosis, with median and mean ages of 22 and 28, respectively. Tumor volumes averaged 61 cm3, with a diameter ranging from 0.9 cm–6.3 cm. The most common presenting symptoms were seizure (50%) and headaches (25%). The great majority of aPXAs arose from the cerebral
Discussion
Since its identification in 1979 by Kepes et al., PXA remains a challenging tumor to classify. Due to its intrinsically pleomorphic appearance and variably indolent versus malignant clinical course, identification and differentiation from other low-grade gliomas are paramount to planning an effective treatment strategy. Importantly, recent research has been increasingly highlighting the manner in which anaplastic features render aPXA a markedly different neoplastic process.
Similar to other
Conclusion
Accurate initial diagnosis of aPXA—often with the help of multiple experienced neuropathologists—is a critical step in the implementation of aggressive and proactive management strategies. Subtotally resected tumors tend to recur, and adjuvant therapies such as radiation and chemotherapy currently have unclear roles in the prevention of tumor progression or dissemination. Regardless of treatment strategy, anaplastic features are a poor prognostic marker and call into question the inclusion of
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2022, Hematology/Oncology Clinics of North AmericaCitation Excerpt :Although PXAs account for less than 1% of all astrocytomas, there is high prevalence of BRAF V600E mutations in grade 2 (up to 70%), and to a lesser degree in grade 3 (17%–65%), tumors.116,117 Patient outcomes are favorable compared with other gliomas, with 5-year overall survival of greater than 75% for grade 2 and greater than 55% for grade 3 PXA following surgical resection, radiation, and chemotherapy.115,118,119 Forty percent of patients with PXA showed a radiographic response to BRAF inhibitor monotherapy.20
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2021, Annales de PathologieCerebrospinal Fluid Spread in a Child with Pleomorphic Xanthoastrocytoma: Report with Cytopathologic Evidence
2021, World NeurosurgeryCitation Excerpt :Anaplastic PXA resulting from either high-grade transformation of PXA grade II or a de novo origin has been recognized and formally included in the WHO 2016 classification of the central nervous system tumors.4-6 This anaplastic variety portends a poor outcome compared with the grade II PXA.3-5,7 Cerebrospinal fluid (CSF) dissemination of PXA tumors is a rare phenomenon.
Spinal Pleomorphic Xanthoastrocytoma: Case Report and Literature Review
2020, World NeurosurgeryCitation Excerpt :Nonetheless, in rare diseases such as spinal PXA this may present as only a guide for management. Despite the majority of PXA cases having an indolent course, up to 20% of PXA will progress into a higher-grade anaplastic PXA,34 and there are cases where they have transformed to glioblastoma in cranial and spinal PXA.19,38-41 When PXA involves the spinal axis this may potentially lead to a different biological course.
Role of a Promoter Mutation in TERT in Malignant Transformation of Pleomorphic Xanthoastrocytoma
2019, World NeurosurgeryBRAF V600E, TERT, and IDH2 Mutations in Pleomorphic Xanthoastrocytoma: Observations from a Large Case-Series Study
2018, World NeurosurgeryCitation Excerpt :In our study, the frequency of TERT promoter mutation in patients with anaplastic PXA was greater than patients with PXA but not statistically significant (a similar observation was made by Koelsche et al.12). Of the 2 patients with anaplastic PXA and TERT promoter mutation in our study, 1 had a recurrence of glioblastoma 11 months after GTR, concurring with a recent report.32 Also, in their study, Eckel-Passow et al.33 found the TERT promoter mutation only to have worst survival prognosis compared with IDH mutation and 1p/19q codeletion.
Conflict of interest statement: The authors have no financial interests to report. This work was supported by the Reza and Georgianna Khatib Endowed Chair in Skull Base Tumor Surgery at University of California, San Francisco, and the Michael J. Marchese Chair at Northwestern University.