2018 NPB-09

This case was originally published in 2019. The information provided in this case was accurate and correct at the time of initial program release. Any changes in terminology since the time of initial publication may not be reflected in this case.

A previously healthy 7-year-old boy with unremarkable past medical history was brought to his primary care physician with complaints of headaches that did not improve with over-the-counter analgesics. MRI revealed a heterogeneously-enhancing solid and cystic mass in the left occipital region. He underwent craniotomy and tumor resection.

Tissue Site
Brain, left occipital lobe

The whole slide image provided is an H&E stained slide of the left occipital lobe of the brain from a craniotomy.

The diagnosis is a pleomorphic xanthoastrocytoma (PXA), a relatively rare cortical, well-circumscribed astrocytic tumor currently classified as WHO grade II or grade III (anaplastic).The etiology of this tumor remains unknown; however, reported cases have demonstrated an association with cortical dysplasia. This association, along with occasional neuronal differentiation in a subset of tumors, suggests this neoplasm could result from impaired migration of multipotent precursor cells.

PXA occurs predominantly in children and adolescents, less frequently in older individuals, and affects men and women equally. These neoplasms have a predilection for the temporal lobe and are commonly associated with epilepsy. Exceptional cases of cerebellar, spinal cord, and retinal locations, among others, have been reported. PXA has a relatively favorable prognosis. The 5- to10-year overall survival rate has been estimated at 70% on average. The survival rate is 90% for grade II lesions, while the survival rate for anaplastic PXA is significantly less. The most critical predictive factor for recurrence is the extent of resection. Gross total resection usually eliminates seizures and is the preferred treatment modality.

PXAs are typically located on the cortical surface of the cerebral hemispheres, abutting the leptomeninges, and are almost always supratentorial. The tumors are well-demarcated, commonly with a cystic component, and sometimes with an associated mural nodule. On MRI (Image A), PXA appears as a well-circumscribed, partially cystic mass, hypo/isointense on T1, hyperintense on T2, with contrast enhancement, and involving the adjacent leptomeninges. When tumors lack a cystic component, they present as solid, contrast-enhancing masses.

Microscopically, as the name implies, the neoplastic astrocytes exhibit variable cytomorphology ranging from irregular spindled cells to polygonal and epithelioid cells arranged in cords and fascicles (Image B). The presence of multinucleated and bizarre nuclear forms is a common feature, as are intranuclear pseudoinclusions and prominent nucleoli. Some tumor cells are lipid-laden, hence the name xanthoastrocytoma (Image C). Additional histopathologic features useful for the diagnosis include patchy perivascular lymphocytic infiltrates and eosinophilic granular bodies (EGBs) (Image D), highlighted with PAS. Ganglion cells are occasionally seen. Despite the degree of pleomorphism, mitotic figures are generally scarce. The designation of anaplastic PXA, currently recognized as a grade III neoplasm, is reserved for those tumors presenting with ≥5 mitosis/10 high power fields (HPFs). The presence or absence of necrosis remains indeterminate for grading purposes.

IHC stains can be helpful in confirming the morphologic impression and establishing the diagnosis. GFAP staining (Image E) varies from focal to diffuse in neoplastic astrocytes. CD34 IHC (Image F) highlights vasculature and the fine ramified processes of some neoplastic cells. Focal staining with neuronal markers (synaptophysin, neurofilament, and MAP2) is also expected. Individual tumor cells are invested by basement membrane material highlighted with histochemistry for reticulin (Image G) or IHC for collagen IV (Image H).

The most common genetic abnormality, seen in approximately 65% of all PXAs, is BRAF V600E mutation that can be detected by IHC with BRAF VE1 (Image I). Homozygous deletion of 9p21.3, a region coding for CDKN2A/B has been detected in 60% of these tumors. BRAF fusions/duplications, as seen in other low-grade gliomas, have not been consistently found in PXA. Mutations of TP53 are seen in about 5% of PXA. The Ki67 labeling index is low and estimated at less than 3% in the majority of grade II cases but can be slightly elevated in anaplastic examples. Due to the degree of pleomorphism and presence of multinucleated giant cells, the most significant differential diagnoses are giant cell glioblastoma (GBM), gliosarcoma, pleomorphic sarcoma, and ganglioglioma. Features favoring PXA over GBM include the presence of EGBs, low mitotic rate, and an intercellular reticulin network. Ganglioglioma is less cellular, less pleomorphic, and contains more abnormal ganglion cells than PXA. CD34-positive stellate cells are a feature commonly shared between PXA and ganglioglioma. Mesenchymal tumors could also enter into the differential; however, the nonglial nature of soft tissue neoplasms can be easily demonstrated by lack of GFAP positivity.

• PXA is categorized as a grade II tumor with <5 mitoses/10 HPFs or as a grade III tumor (anaplastic PXA) with ≥5 mitosis/10 HPFs. The presence or absence of necrosis is indeterminate for grading purposes.
• PXA is an uncommon tumor predominantly affecting children and adolescents. A common clinical presentation is intractable epilepsy for tumors located in the temporal lobe.
• The most common genetic abnormality in PXA is BRAF V600E mutation.

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