Keywords

1 Introduction [1,2,3,4]

  • Pleomorphic xanthoastrocytoma (PXA) is a low-grade glial tumor constituting 1% brain tumors.

  • Kepes et al. described it for the first time in 1993.

  • Arises from subpial astrocytes.

  • Most commonly affects second and third decade of life (10–30 years); Median age—33 years (Range 4.5–75).

  • No gender predilection.

  • Associated with seizure in young adults and considered a part of epileptogenic tumors spectrum.

  • Nearly 50% of patients present with seizure and one-third present with headache.

  • These tumors commonly arise from the temporal lobe (nearly 50%). Frontal, multi-lobar, and spinal location has also been described.

  • Mostly localized but isolated reports of leptomeningeal dissemination.

  • Most of the tumors are supratentorial, less than 10% are infratentorial.

  • Tumor is superficial, proximal to dura but without involvement.

2 Classification

  • Pleomorphic xanthoastrocytoma—WHO grade II tumors (80%)

  • Anaplastic pleomorphic xanthoastrocytoma (APXA)—WHO grade III tumor (Anaplastic may be de novo or as progression from grade II)

  • Criteria

    • >5 mitoses per 10 high-power fields and increased cellularity

    • Presence of necrosis

    • MIB-1 labeling index >4%

3 Investigation

Anaplastic cases appear as high-grade glioma.

3.1 Appearance on CT Scan

  • Solid and cystic component

  • Appears hypodense or isodense

  • Calcification rare

  • With little or no surrounding edema

  • Cause scalloping of the overlying bone

3.2 MRI

  • Appears solid-cystic tumor with homogenous to heterogeneous contrast enhancement

  • Peripheral eccentric cystic component (50–60%)

  • Exhibit dural tail which is mostly reactive

  • T1: Solid component iso to hypointense

  • T1 post contrast: enhancement

  • T2: Solid component iso- to hyperintense

  • T2 FLAIR: Cystic areas show hyperintensity

4 Pathology

  • Tumors are moderately cellular, predominantly pleomorphic and show foci of lymphoplasmacytic infiltration.

  • Necrosis and mitoses rare.

  • The tumor has been named pleomorphic as there is variable histological feature including spindle cells, polygonal cells, and multinucleated cells.

  • Pathogenesis is driven by MAPK pathway.

  • Nearly 60–70% patients harbor BRAF mutations; less common in anaplastic PXA.

  • Mutation of BRAF confers better survival compared with wild variant.

  • Immunohistochemistry

    • GFAP: Positive

    • S100: Positive

    • Vimentin: Positive

    • Reticulin: Positive

    • PAS: Positive

    • Synaptophysin, MAP2 and neurofilament: variable

    • Ki-67 proliferation index: <1%

5 Treatment

5.1 Surgical Excision [5]

  • Surgical excision standard of care and a maximal safe resection is aim of surgery.

  • Nearly 60% patients can undergo GTR.

  • 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]

  • Data on adjuvant radiation is limited.

  • Conflicting data about survival advantage in PXA.

  • Radiation has been utilized more in salvage setting (76%).

  • In APXA radiation may be more effective as these patients experience early failure.

5.2.1 Indications for Adjuvant RT

  • PXA with GTR: Not required.

  • PXA with STR or recurrence: RT should be considered.

  • APXA: adjuvant radiation may be considered upfront even after GTR.

5.2.2 Target Volume

  • In adjuvant or salvage setting:

    • 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)

  • 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

  • Role of chemotherapy controversial.

  • V600E BRAF mutation in nearly 70% patients which constitutively activates RAS/RAF/MEK/ERK signaling pathway.

  • BRAF inhibitor monotherapy or BRAF+MEK inhibitor are used in recurrent tumors.

  • BRAF inhibitors, Vemurafenib and Dabrafenib showed promising result.

6 Results [2, 3]

Median OS of 183 months; PFS of 38 months.

 

PFS (5 year)

OS (5 year)

PXA

Nearly 60%

Nearly 75%

APXA

Nearly 49%

Nearly 60%

6.1 Prognostic Factors (Favorable)

  • Patients younger than 20 years

  • GTR

  • Grade II [PFS: (48 vs 11.7 months) and OS: (209 vs 68 months)]

  • Adjuvant treatment

7 Follow-up

  • Nearly 50% patients experience progression within 3 years.

  • Local recurrence is most common pattern of recurrence. Leptomeningeal spread seen in 7% patients.

  • Follow-up should be done with clinical examination and CEMRI of brain every 3 months for first 3 years and thereafter every 6 months.

  • Re-surgery followed by radiation or chemotherapy may be used to salvage.

8 Treatment Algorithm

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