Abstract
Pleomorphic xanthoastrocytoma is a rare glial tumor that often arises from the temporal lobe of young adults. This is considered a low-grade tumor but has an aggressive variant which may arise de novo or after progression from grade II tumors. Surgery is the cornerstone of therapy and confers survival advantage when a GTR is accomplished. Adjuvant radiation therapy is advocated in higher grade tumor or in salvage setting. Recent molecular studies have identified BRAF mutation in nearly 60% patients and BRAF inhibitors are in use with promising results in a subset of patients.
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1 Introduction [1,2,3,4]
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Pleomorphic xanthoastrocytoma (PXA) is a low-grade glial tumor constituting 1% brain tumors.
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Kepes et al. described it for the first time in 1993.
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Arises from subpial astrocytes.
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Most commonly affects second and third decade of life (10–30 years); Median age—33 years (Range 4.5–75).
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No gender predilection.
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Associated with seizure in young adults and considered a part of epileptogenic tumors spectrum.
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Nearly 50% of patients present with seizure and one-third present with headache.
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These tumors commonly arise from the temporal lobe (nearly 50%). Frontal, multi-lobar, and spinal location has also been described.
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Mostly localized but isolated reports of leptomeningeal dissemination.
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Most of the tumors are supratentorial, less than 10% are infratentorial.
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Tumor is superficial, proximal to dura but without involvement.
2 Classification
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Pleomorphic xanthoastrocytoma—WHO grade II tumors (80%)
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Anaplastic pleomorphic xanthoastrocytoma (APXA)—WHO grade III tumor (Anaplastic may be de novo or as progression from grade II)
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Criteria
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>5 mitoses per 10 high-power fields and increased cellularity
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Presence of necrosis
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MIB-1 labeling index >4%
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3 Investigation
Anaplastic cases appear as high-grade glioma.
3.1 Appearance on CT Scan
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Solid and cystic component
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Appears hypodense or isodense
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Calcification rare
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With little or no surrounding edema
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Cause scalloping of the overlying bone
3.2 MRI
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Appears solid-cystic tumor with homogenous to heterogeneous contrast enhancement
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Peripheral eccentric cystic component (50–60%)
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Exhibit dural tail which is mostly reactive
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T1: Solid component iso to hypointense
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T1 post contrast: enhancement
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T2: Solid component iso- to hyperintense
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T2 FLAIR: Cystic areas show hyperintensity
4 Pathology
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Tumors are moderately cellular, predominantly pleomorphic and show foci of lymphoplasmacytic infiltration.
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Necrosis and mitoses rare.
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The tumor has been named pleomorphic as there is variable histological feature including spindle cells, polygonal cells, and multinucleated cells.
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Pathogenesis is driven by MAPK pathway.
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Nearly 60–70% patients harbor BRAF mutations; less common in anaplastic PXA.
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Mutation of BRAF confers better survival compared with wild variant.
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Immunohistochemistry
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GFAP: Positive
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S100: Positive
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Vimentin: Positive
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Reticulin: Positive
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PAS: Positive
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Synaptophysin, MAP2 and neurofilament: variable
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Ki-67 proliferation index: <1%
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5 Treatment
5.1 Surgical Excision [5]
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Surgical excision standard of care and a maximal safe resection is aim of surgery.
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Nearly 60% patients can undergo GTR.
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Patients with a GTR have good long-term survival.
GTR (months) | STR (months) | |
---|---|---|
PFS | 48 | 14 |
OS | NR | 62 |
5.2 Radiation [2, 3, 6,7,8,9,10]
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Data on adjuvant radiation is limited.
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Conflicting data about survival advantage in PXA.
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Radiation has been utilized more in salvage setting (76%).
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In APXA radiation may be more effective as these patients experience early failure.
5.2.1 Indications for Adjuvant RT
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PXA with GTR: Not required.
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PXA with STR or recurrence: RT should be considered.
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APXA: adjuvant radiation may be considered upfront even after GTR.
5.2.2 Target Volume
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In adjuvant or salvage setting:
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Local radiation only (post-operative cavity plus any residual enhancing mass with 1 cm isotropic expansion as CTV and 3–5 mm additional as PTV)
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In CSF positive cases: CSI should be considered.
5.2.3 Dose
Local radiation: 54–60 Gy in conventional fractionation
CSI dose 30 Gy to the entire cranio-spinal axis followed by boost to the primary up to 56–60 Gy
5.3 Chemotherapy
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Role of chemotherapy controversial.
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V600E BRAF mutation in nearly 70% patients which constitutively activates RAS/RAF/MEK/ERK signaling pathway.
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BRAF inhibitor monotherapy or BRAF+MEK inhibitor are used in recurrent tumors.
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BRAF inhibitors, Vemurafenib and Dabrafenib showed promising result.
7 Follow-up
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Nearly 50% patients experience progression within 3 years.
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Local recurrence is most common pattern of recurrence. Leptomeningeal spread seen in 7% patients.
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Follow-up should be done with clinical examination and CEMRI of brain every 3 months for first 3 years and thereafter every 6 months.
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Re-surgery followed by radiation or chemotherapy may be used to salvage.
8 Treatment Algorithm
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Mallick, S., Anjali, V.R. (2021). Pleomorphic Xanthoastrocytoma. In: Mallick, S., Giridhar, P., Rath, G.K. (eds) Evidence based practice in Neuro-oncology. Springer, Singapore. https://doi.org/10.1007/978-981-16-2659-3_19
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DOI: https://doi.org/10.1007/978-981-16-2659-3_19
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