General
- Pilocytic means "hair-like," due to long, bipolar processes
Definition
- Essential:
- Classic histological features of pilocytic astrocytoma, such as OR
- Biphasic
- Compact growth patterns (compact bipolar cells with rosenthal fibres)
- Loose growth patterns (loose, textured multipolar cells with micro cyst)
- Piloid cytology
- Low proliferative activity
- With or without Rosenthal fibres
- And/or eosinophilic granular bodies
- A low-grade piloid astrocytic neoplasm with a solitary МАРК alteration, such as KIAA1549-BRAF fusion
Numbers
- Most common CNS neoplasm of childhood
- Peak age 8 - 13 years
- May arise in adults but very rare
- Male:Female ratio: same
- Better prognosis than diffuse types, particularly if resectable (such as cerebellar tumours)
- 5 yrs and 10 yrs survival >95% after surgical resection
Genetics
- Mitogen- activated protein kinase (MAPK) pathway alterations
Genetic alteration | % of tumours | Prevalence |
KIAA1549::BRAF fusion | >60% | Common, particularly cerebellar; rare in other tumour forms except diffuse leptomeningeal glioneuronal tumour |
Other BRAF fusions | <5% | Occasional; very rare in other entities |
BRAF mutations (especially p.V600E) | ~5–10% | Occasional, mainly supratentorial; also in many other glial and glioneuronal tumours |
NF1 mutation | ~10–15% | Typically germline; common with optic pathway tumours |
FGFR1 mutation | <5% | Found mainly in midline tumours; also observed in other low-grade gliomas |
FGFR1 fusions (especially FGFR1::TACC1) | <5% | FGFR1::TACC1 fusion more common; also observed in other low-grade gliomas |
NTRK family fusions | ~2% | Rare; also observed in other glial/glioneuronal tumours |
KRAS mutation | Single cases | Very rare in pilocytic astrocytoma; extremely rare in other entities |
RAF1 fusion | Single cases | Very rare in pilocytic astrocytoma; extremely rare in other entities (with the possible exception of pleomorphic xanthoastrocytoma) |
ROS1 fusions | Single cases | Very rare in pilocytic astrocytoma; more common in infantile hemispheric glioma; extremely rare in other entities |
Other alterations (of MET, RET, etc.) | Single cases | Very rare in pilocytic astrocytoma; frequency in other entities not determined (probably extremely rare) |
- BRAF mutation forming
- Fusion protein (KIAA1549:BRAF)
- Most common in 70% esp in infratentorial pilocytic astrocytomas
- Associated with more diffuse pattern but not inc in clinical aggressive behaviour
- Might actually have improved prognosis
- BRAF V600E
- Associated with noonan syndrome (neuro-cardio-facial-cutaneous syndrome)
- Germline mutation in MAPK pathway genes (most common is PTPN11 mutation in >50% pts)
- Associated with NF1
- NF1 gene on chr 17 → encodes neurofibromin protein → acts in the MAPK pathway as GAP for RAS
CNS WHO grading
- Grade I
Locations
- Usually involves midline structures
- Posterior fossa
- Cerebellum
- 3rd ventricle
- Thalamus
- Basal ganglia
- Hypothalamus
- Neurohypophysis
- Optic nerve/chiasm(optic nerve glioma)
- Cerebral hemispheres, cerebellum (cerebellar astrocytoma), brain stem (dorsal exophytic brain stem glioma), spinal cord, may occupy the ventricles
- Paeds: infra-tentorial region
Clinical features
- Less seizures as they do not involve cerebral cortex that often
- Hypo-pituitary
- Visual loss
- Affect optic pathway
Radiological
- Well circumscribed
- Large tumour cyst with a contrast enhancing wall and mural nodules.
- Contrast enhancement is variable
- Some assume cyst mural nodule architecture
- Optic tumours
- Form a fusiform enhancing mass
- Brain stem tumours
- Are relatively discrete
- Often exophytic and variably contrast enhancing
- There are three radiological patterns of pilocytic astrocytoma:
- Classic:
- A cystic lesion with an enhancing mural nodule in 2/3 of cases.
- Cyst wall sometimes does enhance (46% of case) and sometimes does not (in 21% of cases).
- False cystic astrocytoma:
- A cystic (central nonenhancing zone because Of the necrosis) component within the tumor mass (in 16% of cases).
- Solid:
- No cystic component (in 17% of cases)
- Of note, a wall thicker than 2 to 3 mm and enhancing is considered neoplastic.
- CT:
- It appears as a hypodense mass lesion in almost three-fourths of the cases and is isodense to the white matter in the rest.
- This is a helpful differentiating feature from medulloblastomas that are hyperdense on a nonenhanced CT scan.
Histopathology
- Macroscopic
- Microscopic
- Characterized by a biphasic pattern with varying proportions of piloid areas alternating with spongy areas
- Piloid areas are formed of compacted strongly GFAP+ bipolar cells (with hair-like bipolar processes) associated with Rosenthal fibers
- Spongy areas are loosely textured and formed of weakly GFAP+ multipolar cells (protoplasmic astrocytes) associated with microcysts and eosinophilic granular bodies (brightly eosinophilic PAS+ globular aggregates)
- Bipolar neoplastic cells with elongated hair-like processes that are arranged in parallel bundles and resemble mats of hair (knotted hair)
- Rosenthal fibers (tapered corkscrew shaped, brightly eosinophilic, hyaline masses), often associated with eosinophilic protein droplets (resembling foamy macrophages); may have microscopically infiltrative margin; mural nodule may be highly vascular; often calcifications
- Leptomeningeal extension is not a sign of malignancy
- Some cerebellar tumours show a diffuse growth pattern
G: Spongy areas
- Positive stains: GFAP (strong), PTAH, PAS (protein droplets), alpha-1-antichymotrypsin (protein droplets)
Differential diagnosis
- Diffuse astrocytoma:
- Grades II - IV; a prognostically important distinction
- Gliosis
- Hemangioblastoma:
- Cells appear fibrillar on frozen section
- Other cystic tumors:
- Especially those with a cyst mural nodule architecture (pleomorphic xanthoastrocytoma and ganglioglioma)
- Pleomorphic Xanthoastrocytoma
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%) |
- Piloid gliosis:
- Hypocellular, no spongy areas, numerous Rosenthal fibers
DNET | PXA |
Arise embryological from the secondary germinal layer • Subependymal layer • Cerebellar external granular layer • Hippocampal dentate fascia • Subpial granular layer | From subpial astrocyte → superficial with leptomeningeal involvement (67%) |
Frontal and temporal | Temporal (50%) |
Bubly (septations) on T2WI | Mural nodule with cystic component (multiloculated or single cystic) 67% have dural tail (leptomeningeal involvement) Isointense nodule and hyperintense cystic on T2WI |
Grade 1 Mucinous cells | Grade 2 |
<20 yrs | <20 yrs |
3% of all primary brain Ca | 1% of all astrocytomas |
Management
- Surgery
Prognosis
- Stuer et al., 2007
- 5 yrs.
- PFS 72%
- OS 87%
- 14% of cases displayed atypical and 6% anaplastic features.
- Patients benefited from a complete vs. a subtotal resection/biopsy
- Some evidence in favour of radio- and chemotherapy for aggressive tumours
- Rate of tumor recurrence in children after radiological complete tumor resection
- Less than 10%
- Which location of benign childhood pilocytic astrocytoma has the highest incidence of leptomeningeal spread?
- The optic-hypothalamic pathway
- Poor prognostic factor
- Sub total resection
- Esp: invasion to the brainstem
- A total resection is associated with overall a 5-year survival of 90%.
- A subtotal resection is associated with 5-year survival of about 48.5%.
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