Definition
- Essential:
- An astrocytoma with pleomorphic tumour cells, including large multinucleated cells, spindle cells, xanthomatous (lipldized) cells, and eosinophilic granular bodies
- Desirable:
- Reticulin deposition
- BRAF mutation or other МАРК pathway gene alterations, combined with homozygous deletion of CDKN2A and/or CDKN2B
- A DNA methylome profile of pleomorphic xanthoastrocytoma
Numbers
- Rare 1 % of all primary brain tumours
- 25 yrs mean
- Male: Female = 1:1
- PXA may comprise more than 5% of tumours in epilepsy surgery series
Localisation
- Superficial meningocerebral location (leptomeninges and cerebrum)
- 98% arise supratentorially
- Preferential temporal lobe involvement
- May arise in cerebellum, spinal cord and rarely in retina
CNS WHO grading
- Grade 2 unless there is high mitotic index or necrosis then becomes Grade 3: PXA with anaplastic features
- 15 - 20% progress to malignancy
Origin
- Subpial astrocytes
- May be a developmental neuroglial tumour with prominent glioproliferative changes associated with focal cortical dysplasia
Pathological
- Pleiomorphic(Greek many forms): variable histological appearance of tumour
- Spindled cells are intermingled with mononucleated or multinucleated giant astrocytes
- Nuclei show variation in size and staining
- Can be closely (epithelioid pattern) pack or arranged in sheets of fusiform cells
- Xanthoastrocytoma
- Presence of large often multi nucleated xanthomatous cells that have intracellular accumulation of lipids (droplets) → pushes cytoplasmic organelles and glial filaments to periphery
- Presence of reticulin fibre (best seen with silver impregnation) from
- Reactive change s in the meninges
- Tumour cells surrounded by basement membrane stains positive for reticulin
- Granular features: intranuclear inclusions
- No necrosis and no mitotic activity, except in tumours "with anaplastic features"
- Positive stain:
- GFAP and S100
- Reticulin, class III beta tubulin (73%)
- Variable expression of neuronal markers including synaptophysin
Genetic profile
- BRAF V600E point mutation
- Constitutionally activated BRAF → MAPK signaling
- More frequent in grade II than in anaplastic tumours
- Correlate with a temporal tumour location and possibly younger age.
- No IDH mutation
Clinical presentation
- Associated with intractable seizures → superficial tumours
- HCP less common
Radiology
- General
- Cystic with a frequent cyst mural nodule architecture
- Strong contrast enhancing
- CT
- Well-defined
- Solid
- Enhances
- Isodense to gray matter
- Calcification may be present
- Cystic
- Partially cystic masses of various sizes
- MRI
- Predominately superficial, cortical
- Partially cystic masses which are
- Hypo- to isointense to gray matter on unenhanced T1-weighted images
- Mildly hyperintense on T2-weighted
- Solid
- Enhances
- Peripheral location of the tumor,
- Leptomeningeal contact of the tumor
Management
- Surgery
- Is the treatment of choice for PXAs and PXA associated epilepsy.
- Because
- Superficial location,
- Relative circumscription
- Cyst/mural nodule architecture of the tumor.
- Chemotherapy
- Alkylating chemotherapy
- BRAF inhibitor vemurafenib
- Used in a few cases with otherwise treatment resistant PXA
- Radiotherapy and treatment with alkylating chemotherapy for anaplastic PXA.
Outcome
- Gross total resection usually eliminates seizures
- 5 yr overall survival 90.4%
Prognosis
- Luyken et al., 2003
- None of the five PXA cases in the epilepsy surgery series recurred after a median follow- up of 8 years in the overall cohort .
- The prognosis in unselected cohorts (i.e. including cases without long- term epilepsy) is worse:
- PXA grade 2
- 5 yr PFS 71%
- OS: 90%
- Grade 3 anaplastic PXA
- 5 yr PFS 49%
- OS: 57%
- Ida et al., 2014
- A gross total resection seems to confer a significant survival benefit when compared to STR/ biopsy cases
Differential diagnosis
- Diffuse astrocytomas
- No IDH mutation in PX
- Mesenchymal tumours:
- Refuted by positive GFAP stain
- Pilocystic astrocytoma
- Similarities
- Eosinophilic grandular bodies and spindle shaped cells
- Cystic tumours
- BRAF V600E in PXA vs BRAF KIAA 1549 and BRAF V600E in PA
- Pilocytic astrocytoma
Feature | ||
WHO Grade | Grade 1 | Grade 2 or 3 |
Common Appearance | Large cystic lesion with a brightly enhancing mural nodule | Cortical tumors with a cystic component and vivid contrast enhancement |
Calcification | Present in around 20% of cases | Rare |
Common Location | Cerebellum (sporadic) or optic chiasm and pathway (NF1) | Temporal lobe |
Growth Characteristics | - | Slow growth, no surrounding edema, scalloping of the overlying bone |
Dural Involvement | - | Reactive dural involvement (dural tail sign) can be found |
Cystic Component | - | Frequently with a peripheral eccentric cystic component (50-60%) |
- Ganglioglioma
- Meningioma
- Meningiosarcoma
- Fibrous xanthoma
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