eEdE- 188 A pictorial review of typical and atypical/ bizarre imaging findings, as well as post-treatment changes in Pilocytic Astrocytomas in children.

Authors:Lara A Brandão a

Andrea Rossi MD b

Felippe Mattoso Clinic

Institution:a Felippe Mattoso Clinic- Barra Da Tijuca, Rio De Janeiro-RJ- BrazilFleury Group Diagnostic Medicine

Institution:b Pediatric Neuroradiology Unit, Istituto Giannina Gaslini, 5 Via Gerolamo Gaslini, Genoa 16147, Genova- Italy

Disclosures:Lara A Brandão MD: No disclosures Andrea Rossi MD: No disclosures

Introduction:

Pilocytic astrocytomas (PAs) are low grade (grade I) tumors, most often located in the posterior fossa (60%), with 40% involving the cerebellum and 20% affecting the brainstem.Cerebellar pilocytic astrocytoma (CPA), one of the most common posterior fossa tumors in children (second only to medulloblastoma), has excellent survival after gross total surgical resection. Differential diagnosis between pilocytic astrocytoma (PA) and medulloblastoma (MB) in the posterior fossa is crucial, once the former is a low-grade (grade I) tumor, with excellent prognosis, while MB is a very aggressive tumor, with a dismal prognosis.In the supratentorial compartment PAs represent the most common solid malignancy in the pediatric population, most often located in the hypothalamic region, where these tumors should be distinguished from pilomyxoid astrocytomas (PMXA).

Knowledge of common and apparently bizarre imaging findings of PAs is essential in order to suggest the correct diagnosis and to distinguish these tumors from more aggressive ones.

Purpose:To present the most common imaging findings in pilocytic astrocytomas, to discuss atypical/ bizarre imaging aspects of these brain tumors, as well as to present interesting imaging findings related to treatment.

Methods:We retrospectively reviewed the clinical charts and neuroimaging studies in 108 children diagnosed with pilocytic astrocytomas in the last 19 years. MRI was performed on a 1.5Tesla (T) General Electric (GE) Signa Horizon and 1.5 T GE Excite. Available sequences included sagittal T1 and T1 3D SPGR, axial T1, T2, FLAIR, GRE and DWI, as well as coronal T2. Diffusion tensor imaging (DTI), magnetic resonance spectroscopy (MRS), dynamic susceptibility contrast imaging (DSC) and dynamic contrast enhanced (DCE) studies were obtained in some patients, and gadolinium chelates were administered in all. A neuroradiologist with 19 years experience (BL) evaluated all the images. The diagnosis was confirmed by pathology after surgical resection of the brain tumor.

Findings/ Discussion:Our sample included 68 boys and 40 girls.Age range was between 17 months and 15 years (median 8.2 years).In our series of 108 patients, 65 (64.8%) presented with a posterior fossa PA and 43 (43.2%) with a supratentorial PA. In the posterior fossa, 43 patients (66.15%) had a cerebellar lesion and 22 patients (33.8%) had a midbrain tumor.

The most common neuroimaging features in pilocytic astrocytomas (PAs) were (Figs.1 and 2):

1-Predilection for the posterior fossaAbout 64.8% of PAs were located in the posterior fossa with 43.2% in the cerebellum.In the supratentorial compartment, the most common location was the hypothalamic region, followed by the brain parenchyma.

2- Predilection for the cerebellar hemisphere instead of the cerebellar vermis Among the cerebellar PAs (n=43), 95% (n=40) were located in the cerebellar hemisphere, displacing and compressing the 4th ventricle, as opposed to what is typically demonstrated in MBs that usually compromise the cerebellar vermis, filling the 4th ventricle.

3-Presentation as round, well-circumscribed lesions instead of infiltrativeIn our series, all patients (99%) but one (0.92%), presented with well circumscribed round or oval lesion, that could be entirely resected.

4-Presence of cysts along with solid componentsLarge cysts along with solid components were demonstrated in 102 patients (94.4%).

5- High T2 signal intensity in the solid portionThe enhancing solid component of PA was typically hyperintense on the T2 images compared with the normal cerebellar /brain parenchyma in all (98.14%), but two patients (1.85%).This is a very typical imaging finding. It is related to low cell density and high water content in this tumor, also known as “watery tumor”.

6- Absence of restricted diffusion in the solid portion Absence of restricted diffusion was demonstrated in all (99%) but one (0.92%) patient.The solid component of PAs has greater ADC values than do other cerebellar tumors such as MB and atypical teratoid rhabdoid tumors.PAs are typically iso- to hypointense to the cerebellar parenchyma on the diffusion weighted images (DWI) and hyperintense on the apparent diffusion coefficient map (ADC map). DWI is considered the single most useful sequence for differentiating among pediatric posterior fossa tumors.

The most common neuroimaging features in pilocytic astrocytomas (PAs) were (Figs.1 and 2):

7- Striking enhancement in the solid portion Despite being low-grade (grade I) tumors, striking enhancement is characteristic and was demonstrated in all patients on our series. The extent of gadolinium enhancement matches the T2 abnormality.

8-Displacement of adjacent white matter tracts on the DTIThe adjacent white matter tracts were typically displaced by the tumor. No infiltration or interruption of adjacent white matter tracts was demonstrated.

The typical imaging features described above may be very useful to suggest the precise diagnosis of a pilocytic astrocytoma and to distinguish this tumor from more aggressive ones, such as medulloblastomas.

Fig.1: PA- Typical imaging findings9 year old girl. 4 months ago she started presenting with headaches, neck pain and vomiting. Now presenting with ataxia, nystagmus, incoordination, and papilledema. (A-sagittal T1, B-axial T and C-axial FLAIR).There is a round well-circumscribed lesion located in the left cerebellar hemisphere (A,B), compressing and displacing the fourth ventricle (arrow in B), with secondary obstructive hydrocephalus, as well as CSF extravasation (C).The solid component is bright on the T2 (B), which is very typical, and related to low cell density and high water content in this tumor. There is a large cyst (A,B) associated with the solid component, which is also very typical.Note is made of secondary tonsillar herniation to the cervical canal (A).

Fig.1: PA - Typical imaging findingsWhile PA is most often located in the cerebellar hemisphere, compressing and displacing the 4th ventricle (D-axial T2), MB is typically located in the midline, filling the 4th ventricle (E,F-axial T2).The solid portion of PA is typically hyperintense to the cerbellar cortex on T2, (D) whereas the solid component of MB is usually isointense to the cerebellar cortex on T2 (E), due to high cell content. However some MBs may present with high signal intensity on T2 (F), resembling a PA.Hence, diagnosis of a brain tumor should not rely on one single imaging characteristic of a lesion.

Fig.1: PA- Typical imaging findingsThere is no restricted diffusion in the solid component of the PA (G-axial T2, H-DWI and I-ADC map), which helps distinguish PAs from MBs, which typically presents with restricted diffusion due to high cell density (J-axial T2, K-DWI and L-ADC map).

Fig.1: PA- Typical imaging findingsThe T2 signal abnormality (M-coronal T2) matches the extent of gadolinium enhancement (N,O- coronal and axial T1 with contrast), which is typically marked.

Fig.2: PA- Typical imaging findingsFifteen-year old boy presenting with right-sided hemiparesis.There is a PA with cystic and solid components involving the basal ganglia, thalamus and internal capsule on the left (A-axial T1 with contrast), displacing the corticospinal tract medially (B,C: tractography before surgery).After drainage of the cystic component (D-tractography), the pyramidal tract is back to a more anatomic location (compare to C).

2-Imaging findings that could be considered atypical or bizarre were:

2.1- Presentation as a transmantle lesion 2.2- Infiltrative, rather than well circumscribed2.3- Presence of blood products 2.4- Restricted diffusion 2.5- Very high choline peak along with presence of lipids and lactate in the MRS 2.6- High blood volume in the DSC studies 2.7- Cerebrospinal fluid (CSF) spread

Pilocytic tumors may present as transmantle lesions, extending from the cortex through the brain parechyma, to the ventricular margins (Fig.3). Not every lesion that extends from the cortex to the ventricles will be a transmantle dysplasia (Fig.4 A,B). If the lesion presents with non homogeneous signal intensity, cystic components, or if there is enhancement, a brain tumor should be considered the most likely diagnosis.Other lesions that may present as transmantle lesions are cavernous angiomas (Fig.4 C,D).

2.1-Presentation as a transmantle lesion (Fig.3)

2- Imaging findings that could be considered atypical or bizarre were:

Fig.3: Transmantle PASeventeen month old boy presenting with seizures on the right. Axial T2 (A and B) and FLAIR (C-E) demonstrate a non homogeneous high signal intensity lesion that extends from the surface of the brain to the left ventricular margin, consistent with a transmantle lesion. There is suggestion of cystic components in the periphery of the lesion (E).

Fig.3: Transmantle PAThe lesion has a triangular shape in the coronal plane (F- coronal STIR) and a faint enhancement is demonstrated in the axial T1 with contrast (arrow, G).Based on the topography, a diagnosis of transmantle dysplasia was suggested and the patient was followed clinically. He remained with well controlled seizures until the age of 10 years , when he came to the neurologist presenting with right side hemiparesis. Another MRI was done.

Fig.3: Transmantle PAComparing the first MRI (H- axial T2) with the second one 10 years later(I-axial T2, J,K- axial T1 with contrast) the lesion has grown significantly.Surgical resection was performed and pathology (L and M) was consistent with pilocytic astrocytoma presenting with some areas of anaplastic degeneration.

Fig.4: Other transmantle lesionsFocal cortical dysplasia presenting with high signal intensity on the T2 (A,B) extending from the surface of the brain on the right to the ventricular margin.(C-axial T2 and D-axial gradient echo): Transmantle cavernous hemangioma extending from the cortex to the left ventricular margin, presenting with high signal intensity on the axial T2 (C) and very low signal intensity on the gradient echo (D).

Pilocytic astrocytomas are typically well circumscribed, localized lesions. However, sometimes the tumor may be infiltrative, presenting with ill-defined margins, and hence complete surgical resection will be very difficult.

2.2- Infiltrative, rather than well circumscribed lesion (Fig.5)

2- Imaging findings that could be considered atypical or bizarre were:

Fig.5: Infiltrative rather than well circumscribed PA23 month old boy with developmental delay, low stature and low weight for his age.There is a PA infiltrating the left cerebellar hemisphere and vermis, extending anteriorly to the left cerebellar pontine angle, compressing the 4th ventricle. (A-coronal T2, B-D- axial T2.). There is an associated cystic component in the right cerebellar hemisphere.

Fig.5: Infiltrative rather than well circumscribed PAThere is striking enhancement in the solid component. (E-sagittal, F-coronal and G-H- axial T1 with contrast).

Fig.5: Infiltrative rather than well circumscribed PAThere is no restricted diffusion (A-ADC map). MRS (J-K) demonstates a huge choline peak, along with reduced NAA and Cr peaks, as well as lipids, very consistent with the diagnosis of PA.

Pilocytic astrocytomas, depite being grade I (low grade) tumors may bleed. In some patients, a large amount of blood may be demonstrated in these tumors. Knowledge of this “unexpected” finding is essential in order not to change the diagnosis in these cases.

2.3- Presence of blood products (Fig.6)

2- Imaging findings that could be considered atypical or bizarre were:

Fig.6: Hemorrhagic PA10 year old girl, presenting with headache and dizziness.There is a PA within the cerebellar vermis (A-sagittal T1)- (which is not the most common location for PA in the cerebellum), presenting with solid and cystic components (A-sagittal T1, B,C- axial T2).The solid portion is hyperintense to the cerebellar parenchyma on T2 (B and C), as usual, and there is no restricted diffusion (D- ADC map), which is also very characteristic.

Fig.6: Hemorrhagic PAStriking enhancement is demonstrated in the solid component (E-sagittal T1, F,G- axial T1 with contrast), and low signal intensity foci are noted within the solid portion in the gradient echo images (H,I) related to the presence of blood products, as confirmed on surgical resection.

Diffusion is typically not restricted in pilocytic astrocytomas, since these are low cell density lesions. However around 7% of these tumors may present with restricted diffusion. Diagnosis of a brain tumor should not rely on one single imaging aspect of the lesion.

2.4-Restricted diffusion (Fig.7)

2- Imaging findings that could be considered atypical or bizarre were:

Fig.7: Restricted diffusion in PA9-year old boy presenting with well controlled seizures in the last 3 years.Recently developed right-sided hemiparesis.There is a large lesion compromising most of the left cerebral hemisphere, presenting with solid component associated with calcification, as well as cystic components (A- axial CT). The solid component presents with striking enhancement (B-axial CT and C- axial T1 with contrast.)

Fig.7: Restricted diffusion in PAThe solid and cystic components are clearly visible on the T2 (D). The solid portion of the pilocytic tumor is isointense on T2, which is not common in these lesions. Another very uncommon finding in this case is restricted diffusion, characterized by high signal intensity on the DWI (E), not related to T2 shine through, since the lesion is dark on T2.F- axial CT after surgical resection- diagnosis of PA was confirmed.

Choline (Cho) is typically related to tumor cell density and hence, higher Cho/creatine and Cho/N-acetyl-aspartate (Cho/NAA) ratios are typically demonstrated in higher grade (grade III) than in lower grade (grade II) gliomas. However, total Cho (tCho) is not an effective or accurate biomarker for grade I PAs. Choline is typically very high in pilocytic tumors, despite their benign clinical course (Fig. 8). Lipids and lactate are also usually demonstrated in the spectra of PA.

The spectral pattern of PAs may be used to distinguish between these tumors and grade II ependymomas (Fig.9).However, the spectral pattern of PAs may overlap with that of MB (Fig.10) as well as with that of multiforme (GBM) (Fig.11).

2.5- Very high choline peak along with presence of lipids and lactate in the MRS (Figs.8 and 9)

2- Imaging findings that could be considered atypical or bizarre were:

Fig.8: Very high choline along with lipids and lactate in PASame patient as figure 1.Sspectra from the lesion (A-B) demonstrates very high Cho peak, reduced NAA and Cr peaks, along with presence fo lipids and lactate, very typical of PA.

Fig.9: EpendymomaWhile PAs are characterized by a very high Cho peak in the spectra, grade II ependymomas typically present with a very high myo-inositol peak in the curve.

Fig.10: MedulloblastomaSpectra from MB may look very similar to that from PA, with a very high Cho peak, along with reduced NAA and Cr peaks and presence of lipids and lactate.Taurine (Tau) peak (arrow in B), is considered very characteristic of MB, but it is not easily detected.

Fig.11: Very high choline in PA and GBMSpectra from a hypothalamic PA (A) and from a GBM (B).Findings are very smilar including very high choline peak, reduced NAA and Cr peaks. along with presence of lipids.

Despite being low grade (grade I tumors) PAs may present with very high blood volumes in the dynamic susceptibility contrast studies (DSC). This finding is not related to aggressiveness in these lesions, and should not dismiss one to make the correct diagnosis.

2.6- High blood volumes in the DSC studies (Fig.12)

2- Imaging findings that could be considered atypical or bizarre were:

Fig.12: PA presenting with very high blood volumesSame patient as in Fig.1.There is a cerebellar pilocytic astrocytoma presenting with striking enhancement in the solid component (A-axial T1 with contrast) and very high blood volumes in the cerebral blood volume maps (CBV maps) (B-CBV map from GRE EPI study and C-CBV map from SE EPI sequence).

Patients diagnosed with PA should be searched for CSF spread. Despite the low malignancy grade, PA may spread via CSF.CSF spread is more common in pilomyxoid astrocytomas but may also be demonstrated in PA.

2.7- Cerebrospinal fluid (CSF) spread (Fig.13).

2- Imaging findings that could be considered atypical or bizarre were:

Fig.13: PA with CSF spreadSix-year old boy diagnosed with hypothalamic PA. A residual solid lesion is demonstrated after surgical resection (A-sagittal, B- coronal and C,D- axial high resolution T2).

Fig.13: PA with CSF spreadSmall enhancing nodules consistent with CSF spread are demonstrated on the surface of the spinal cord (E,F-sagittal T1 with contrast and fat suppression), as well as on the surface of the conus medullaris (G-sagittal T1 with contrast and fat suppression).

3-Interesting imaging findings during/ after chemotherapy/radiation therapy were: 3.1- Development of enhancement in a previously non-enhancing tumor; 3.2- Transient enlargement of the lesion related to pseudoprogression; 3.3- Development of cavernous angioma.

Some PAs that do not enhance may develop enhancement only after CT. This is probably due to an inflammatory reaction induced by the drug (Fig.14).

3.1- Development of enhancement in a previously non-enhancing tumor;

3- Interesting imaging findings during/ after chemotherapy (CT)/radiation therap (RT)

Fig.14: Appearence of enhancement after CT2-year old girl presenting with ataxia. There is a solid hypothalamic PA, with no enhancement on the sagittal (A) and coronal (B) T1 with contrast. One month after chemotherapy, significant enhancement is demonstrated in the lesion (C,D- sagittal and coronal T1 with contrast).

Transient enlargement of a PA may be demonstrated after initiation of chemotherapy as well as radiation therapy (Fig.15). This transient enlargement is probably related to an inflammatory response to therapy, and sometimes necrosis will be demonstrated within the lesion.Knowledge of this treatment-related change is crucial in order not to consider it as treatment failure. If enlargement of a PA is demonstrated in the first weeks after initiation of treatment, a follow-up MRI should be done in order to diagnose pseudoprogression (tumor response).

3.2- Transient enlargement of the lesion related to pseudoprogression

3- Interesting imaging findings during/ after chemotherapy (CT)/radiation therap (RT)

Fig.15: Transient enlargement of the tumor after treatmentThere is a PA in the hypothalamic/third ventricle region (A-axial T2 before chemotherapy-CT). One month after initiation of CT the lesion is larger (B- axial T2, C-axial T1 with contrast). Three months later (D-axial T2, E-axial T1 with contrast) the external diameter of the lesion is even larger but there is necrotic degeneration (area with high signal on T2 and no enhancement on the contrast enhanced study), which means less viable tumor and hence therapeutic response.

3- Interesting imaging findings during/ after chemotherapy/radiation therapy

3.3- Development of cavernous angioma.

Vascular malformations such as cavernous angiomas, capillary telangectasias and venous angiomas may develop during/ after radiation therapy (Fig.16). Vascular malformations should be included in the differential diagnosis of lesions that develop in or around irradiated areas.

Fig.16: Development of cavernous angioma after RTFourteen year old boy after surgical resection of a PA adjacent to the left ventricle. A residual enhancing nodule is demonstrated in the axial T1 with contrast (A). Blood volume is not elevated in the lesion (B-cerebral volume map-CBV map).Fourteen months later the lesion is much larger and has a larger enhancing component (C-axial T1 with contrast) that presents with very high blood volume (D-CBV map).Neurosurgeon was concerned about anaplastic transformation or a new tumor induced by radiation therapy. Surgical resection was done and pathology was consistent with cavernous angioma (E).

Summary/ Conclusion:

Pilocytic astrocytomas are a very common brain tumor in children.Since these are grade I tumors with very good prognosis after complete surgical resection,precise diagnosis is essential.The radiologist should be familiar not only with the most common neuroimaging aspects of these lesions but also with atypical/ bizarre imaging findings, as well as possible changes after treatment.

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