Elsevier

World Neurosurgery

Volume 95, November 2016, Pages 368-374
World Neurosurgery

Original Article
Pleomorphic Xanthoastrocytoma with Anaplastic Features: Retrospective Case Series

https://doi.org/10.1016/j.wneu.2016.07.068Get rights and content

Objective

Pleomorphic xanthoastrocytoma (PXA) is a unique meningocerebral glioma with a relatively favorable prognosis. PXA also possesses a variant with anaplastic features (aPXA), which is associated with poor outcomes. To date, few studies have examined the clinicopathologic importance of these anaplastic features.

Methods

From 1999–2012, 8 patients with aPXA were treated at the University of California, San Francisco, California, United States. Cases were reconfirmed by neuropathology, and clinical information regarding patient demographics, tumor characteristics, and treatment outcomes was assembled. Tumors were classified as aPXA according to the World Health Organization diagnostic criteria established in 2007.

Results

There were 5 female and 3 male patients in our cohort, ranging in age from 4–74 years at initial diagnosis. Seizure was the most common presenting symptom (50%), and the majority of tumors arose in the frontal or temporal lobes (88%). Six patients received subtotal resection (STR), and all suffered from progression despite adjuvant radiotherapy and chemotherapy. Median time to progression was 20 months, with a 1-year progression-free survival rate of 57%. Three aPXA patients expired with a median survival of 87 months. Four patients developed disseminated disease. Three of 8 (38%) showed BRAFv600 mutation.

Conclusion

aPXA is associated with poorer clinical outcomes compared with PXA. Gross total resection should be the goal of initial treatment. It remains unclear whether adjuvant radiation and chemotherapy are able to prevent progression or dissemination. Long-term monitoring of all patients is a critical step in management due to the potential for tumors to transform into higher-grade lesions.

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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    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.

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