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Home , Astrocytoma, Central neurocytoma, Cyst, Medulloblastoma

Pictorial Essay

Cystic-appearing Intracranial neoplastic lesions

Pablo Sartori1, Nicolás Sgarbi2

1 Diagnóstico Mediter, Ciudad Autónoma de Buenos Aires, Argentina. 2 Clinical Department, Hospital de Clínicas de Montevideo, Montevideo, Uruguay.

Abstract Cystic and cyst-appearing intracranial lesions are common findings of brain neoplastic tumors. This paper intends to re- viewed the origin of this lesion, radiologic appearance and differential diagnosis as guidance for the treating physician. This paper will review the cystic lesions of neoplastic etiology that most frequently occur in the brain.

Keywords Brain, cysts, , tomography, magnetic resonance imaging

Introduction There is a more aggressive variant known as pilomyxoid as- trocytoma.6 A cystic lesion can be defined as an -lined cavity On computed tomography (CT), these tumors appear as iso- that contains fluid or semisolid material.1-3 to hypodense solid/cystic expansive masses; calcifications are Expansive lesions may be entirely cystic or have cavitary areas rare, and there is enhancement of the solid component after and are sub-classified into intra-or extra-axial lesions depend- intravenous (IV) contrast administration.4,6,7 ing on their location. On MRI, the cystic component appears isointense on T1- and The most common intracranial expansive cystic lesions are T2-weighted images compared with (CSF) detailed in Table 1. The purpose of this article is to illustrate the wide spectrum Table 1 of intracranial cystic lesions of neoplastic origin and describe their morphologic characteristics. Location Examples

Pilocytic Intra-axial tumors4,5 Central Differential diagnoses are mentioned in Table 2.

1) This is the most common in children and young Intra-axial adults, usually located near the midline. Two-thirds of lesions occur in the , in the optic chiasma, around the Pleomorphic xanthoastrocytoma third ventricle and in the hypothalamic-pituitary region. In Dysembryoplastic embryonal tumor adults, one-half of tumors are supratentorial.4,6,7 Cerebellar have been reported to be associated multiforme with type I, Ollier’s disease and Turcot and PHACE syndromes.4,6-8 depend on location. In the posterior fossa tumors, there is a mass effect with signs of raised intra- cranial pressure.6 Extra-axial Pituitary macroadenoma These tumors appear as well-circumscribed solid/cystic mass- es of round or oval shape, with a solid mural , occa- 6,7 sionally with a necrotic center. Source: References 4, 5.

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signal intensity, and hyperintense on FLAIR images, and it is 2) Hemangioblastoma associated with a mural nodule that is usually isointense on This is a rare vascular tumor, generally associated with von T1-weighted sequences and hyperintense on T2-weighted / Hippel-Lindau disease, although these tumors may be seen FLAIR images, generally enhancing after the administration sporadically.4,8 occur in young patients in of gadolinium (Fig. 1).4-7 the cerebellum or, less commonly, in the .4,8 Both the cystic and solid components may enhance after On CT, these tumor appear as cystic/solid posterior fossa mass- gadolinium administration.6,7 es, with enhancement of the solid portion after IV contrast a b c d

Fig. 1 Brain MRI. (A) Axial T1-weighted, (B) coronal T2-weighted, (C) axial FLAIR and (D) gadolinium-enhanced axial T1- weighted images. Seven-year-old male patient with headaches and dizziness. The images show an expansive, predominantly cystic lesion on the right cerebellar hemisphere (star) with an eccentric solid mural nodule (arrows). The lesion produces mass effect with midline shift to the left, surrounded by a mild vasogenic edema. The solid portion shows irregular enhancement after gadolinium administration. Considering patient’s age and clinical presentation, the lesion is consistent with pilocytic as- trocytoma (confirmed by biopsy).

Table 2: Differential diagnoses of cystic-appearing intracranial neoplastic lesions.

Tumors with cystic components Differential diagnoses

Ependymoma and medulloblastoma (children in the posterior fossa) Metastases or hemangioblas- Pilocytic astrocytoma toma (adults)

Hemangioblastoma Pilocytic astrocytoma , Pilocytic astrocytoma, subependymal giant astrocytoma, ependymoma, Pituitary , hypothalamic or optic pathway , Rathke cleft cyst, , throm- Craniopharyngioma bosed aneurysms

Supratentorial intraparenchymal: Pilocytic astrocytoma, Pleomorphic xanthoastrocytoma, primitive Ependymoma neuroectodermal tumor, ganglioglioma/gangliocytoma and oligodendroglioma

Medulloblastoma Pilocytic astrocytoma, atypical teratoid/rhabdoid tumor and ependymoma

Ganglioglioma Ependymoma

Pleomorphic xanthoastrocytoma Meningioma, glioblastoma, DNET, oligodendroglioma, metastasis

Dysembryoplastic neuroepithelial tumor (DNET) Gangliocytoma, Pilocytic xanthoastrocytoma

Glioblastoma Metastasis,

Metastasis Abscesses, glioblastoma, astrocytoma, Pleomorphic xanthoastrocytoma

Meningiomas

Schwannomas Meningiomas

Pituitary macroadenoma / Craniopharyngioma Craniopharyngioma /pituitary macroadenoma

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Fig. 2 Brain MRI. (A) Axial T1-weighted, (B) T2-weighted images, (C) Axial and (D) coronal T1-weighted images with gado- linium. Images show a cystic expansive lesion on the left cerebellar hemisphere (star), with internal septa and a peripheral mural nodule. The solid portion strongly enhances after gadolinium administration (arrows). The diagnosis of Hemangioblastoma was confirmed by . a b c d

Fig. 3 Brain MRI. (A) Axial T1-weighted image, (B) axial T2-weighted image (C) coronal T2-weighted image and (D) gadolinium- enhanced axial T1-weighted image. A solid expansive lesion originates near the foramen of Monro, containing multiple cysts (arrows) and causing midline shift and left supratentorial obstructive , heterogeneously enhancing after gado- linium administration. Central neurocytoma was diagnosed by biopsy. administration.8 On MRI, these tumors appear as iso- to hy- Central neurocytomas present with symptoms of increased in- pointense lesions on T1-weighted sequences and hyperintense tracranial pressure secondary to obstructive hydrocephalus.9-11 on T2-weighted sequences, with a strongly enhancing solid These tumors appear as heterogeneous, well-demarcated, mural nodule (Fig. 2).8 lobulated lesions with a solid/cystic component, with an at- On T2-weighted sequences, signal voids occur because of the tachment to the septum pellucidum.4,9-11 high vascularity of these tumors.8 Calcifications are rare and Central neurocytomas appear heterogeneous on CT; on MRI, the presence of spontaneous hyperintensity on T1-weighted they have a “bubbly” appearance due to the presence of sequences is suggestive of recent .8 cysts. These tumors appear isointense on T1-weighted se- Digital angiography is a diagnostic tool that may be consid- quences, iso- to hyperintense on T2-weighted sequences, ered, given the high vascularity of these tumors. with associated calcifications in 50% of cases (Fig. 3).4,9,11

3) Central neurocytoma 4) Ependymoma This is a , formerly known as “ependymoma of the These tumors may be either supratentorial (40%) or in- foramen of Monro” or “intraventricular oligodendroglioma”.9 fratentorial (60%) in location. The former may affect the Typically intraventricular, located in the close brain parenchyma or ventricular cavities, being more com- to the foramen of Monro, although it may have other loca- mon in young patients. Those arising in the posterior fossa tions (gray nuclei, , intramedullary location, occur in children.12,13 etc.), this tumor usually affects young adults and has a favor- Symptoms vary and depend on tumor location (supra/infraten- able prognosis.4,9-11 torial), with possible manifestations of increased intracranial

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pressure occurring most frequently with infratentorial tumors creased secondary to obstructive hydro- due to their intraventricular location. Patients with supratento- cephalus being common.14 rial Ependymoma may experience headache, or neu- These tumors are often associated with Turcot syndrome type rologic deficit.12,13 2, Gorlin-Goltz syndrome, Li Fraumeni syndrome, Rubinstein- These tumors appear as masses with cystic areas and chunky Taybi syndrome, Fanconi anemia and Nijmegen syndrome.14 calcification, and may occasionally bleed.12 are frequently located at the poste- Supratentorial are larger in size (owing to rior fossa midline, involving the vermis, extending into the their typically intra-parenchymal location) and tend to con- fourth ventricle, with leptomeningeal dissemination; there- tain a cystic component, while infratentorial ependymomas fore a complete evaluation of the neuroaxis should be per- commonly have an intraventricular location and therefore are formed.14,15 smaller in size.13 In adults and older children, these tumors may be located On CT, solid areas are iso-to hypointense. On MRI, they are in the cerebellar hemispheres and present cystic degenera- iso- to hypointense on T1-weighted images and iso- to hyper- tion.14,15 intense on T2-weighted images.12,13 On CT, medulloblastomas appear hyperdense (due to their The cystic component is similar in signal intensity to the CSF highly cellular nature), with variable peripheral edema, and on T1- and T2-weighted images, with no complete suppres- calcifications may occur in about 20% of cases.14,15 sion on FLAIR due to its high protein content.12 Enhancement is variable.14 Enhancement is heterogeneous and irregular with associated On MRI, these tumors appear hypo- to isointense on T2- areas of necrosis (Fig. 4).12,13 weighted images, being predominantly homogeneous with On gradient echo sequences (GRE), blooming may be seen in little necrotic, hemorrhagic or calcic component. calcifications or foci of hemorrhage, with restricted diffusion Heterogeneity on T2-weighted sequences associated with a on diffusion-weighted imaging.12,13 “honeycomb” pattern of enhancement allows identification Some intraparenchymal supratentorial ependymomas may of the anaplastic variant of medulloblastoma with a sensitiv- manifest as expansive solid/cystic lesions with mural nodule ity of 100% (Fig. 5).14,15 and associated calcification.12,13 Intraventricular ependymomas may extend into the adjacent 6) Ganglioglioma brain parenchyma and cause vasogenic edema. Ependymo- This is a well differentiated neuroepithelial tumor that occurs mas located in the fourth ventricle tend to fill it as a “plaster in children and young adults, with a predilection for the tem- cast” and may extend through the foramen of Luschka and poral lobe, being a common cause of epilepsy.5,16,17 Magendie, causing dissemination of the disease.12 This tumor may also occur in the parietal and frontal lobes.16 It is a solid-cystic enhancing mass, partially located in the pe- 5) Medulloblastoma riphery of a cerebral hemisphere.16 This is the most common malignant tumor of the central ner- Calcifications are common and may be surrounded by vaso- vous system (CNS) in pediatric age.14,15 genic edema.5,16 Symptoms depend on tumor location, with symptoms of in- On CT, gangligliomas have a variable appearance. The most a b c d

Fig. 4 Brain MRI. (A) Axial T1-weighted (b) T2-weighted (C) DWI, (D) gadolinium-enhanced T1-weighted images. Expansive solid/cystic lesion seen at the left temporoparietal level, with mass effect pushing on the ipsilateral lateral ventricle. There is poor and irregular enhancement after gadolinium administration (arrow). Ependymoma was diagnosed by pathology.

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Fig. 5 Medulloblastoma. MRI (A) Axial T2-weighted image; (B) sagittal T1-weighted image and (C) gadolinium-enhanced axial T1-weighted image. Expansive, heterogeneous infratentorial midline mass distorting the fourth ventricle and irregularly en- hancing after gadolinium administration (arrows). The T2-weighted sequence shows a cystic component (star). a b c d

Fig. 6 Brain MRI. (A) Axial T1-weighted image, (B) Axial T2-weighted image, (C) coronal T2-weighted image and (D) gadolini- um-enhanced axial T1-weighted image. Multicystic lesion with septa (arrows) on the right temporal lobe, at the level of the hip- pocampus, surrounded by vasogenic edema. The lesion partially compresses the temporal horn of the ipsilateral lateral ventricle and heterogeneously enhances after gadolinium administration. Ganglioglioma was diagnosed. frequent presentation is a hypodense mass with irregular/het- On MRI, the solid portion is hypo- to isointense on T1- and erogeneous enhancement.16,17 T2-weighted images, while the cystic portion is hypointense On MRI, the appearance of these tumors is variable and on T1-weighted images and hyperintense on T2-weighted nonspecific: they may have a cystic component, be hipo- to images (Fig. 7).16 isointense on T1-weighted images with associated cortical The solid portion shows irregular enhancement and, in 70% , and be hyperintense on T2-weighted images.5,16,17 of cases, there is an associated enhancement of adjacent lep- tomeninges, with the appearance of a “dural tail”.5,16 7) Pleomorphic xanthoastrocytoma This is a superficial cortical supratentorial tumor, occurring 8) Dysembrioplastic neuroepithelial tumor (DNET) most often in the temporal lobe, followed by the frontal and DENTs occur in children and adolescents, often with a history occipital lobes.5,16,18 It predominantly affects young patients of epilepsy.19,20 with a history of seizures and it is associated with cortical These are supratentorial cortical tumors commonly located in dysplasia.18 the temporal lobe, of multinodular solid/microcystic “bubbly” This tumor appears as a frequently cystic supratentorial mass appearance, without peripheral edema or mass effect.19-21 containing a solid mural nodule that is adjacent to the lep- On CT, DNETs appear as well-demarcated hypodense masses.21 tomeninges.16 On MRI, these tumors appear as “bubbly” lesions due to their On CT, the tumor is seen as a hypo- to isoattenuating mass.16 solid/cystic appearance, with these portions being slightly more Calcification is rare.16 hyperintense than the CSF, while solid components appear

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Fig. 6 Brain MRI. (A) Axial T1-weighted image, (B) Axial T2-weighted image, (C) coronal T2-weighted image and (D) gadolini- um-enhanced axial T1-weighted image. Multicystic lesion with septa (arrows) on the right temporal lobe, at the level of the hip- pocampus, surrounded by vasogenic edema. The lesion partially compresses the temporal horn of the ipsilateral lateral ventricle and heterogeneously enhances after gadolinium administration. Ganglioglioma was diagnosed. a b c d

Fig. 7 Brain MRI. (A) Sagittal T1-weighted image, (B) axial T2-weighted image, (C) axial FLAIR and (D) gadolinium-enhanced T1-weighted image. Expansive cystic lesion of left frontal lobe location, surrounded by vasogenic edema, containing an ec- centric solid mural nodule with thin septa inside (arrows). After gadolinium administration, there is strong enhancement of the peripheral mural nodule as well as of the above-mentioned septa. The lesion crosses the midline, partially compressing the frontal horns of the lateral ventricles. Pleomorphic xanthoastrocytoma was diagnosed by pathology. hypointense on T1-weighted images and hyperintense on T2- glioblastoma NOS (not otherwise specified; the presence or weighted images.20,21 absence of is not specified).22 DNETs are wedge-shaped, contain multiple internal septa Glioblastoma is the most common primary malignant brain and may cause remodeling of the inner table (60%) (a find- tumor in adults, accounting for 12%-15% of all intracranial ing that may be seen in other cortical tumors) and develop neoplasms.23,24 calcification, with no or faint enhancement after gadolinium This tumor is more prevalent in males (3:2) between 45 and administration (Fig. 8).19-21 70 years of age, with the cerebral hemispheres being its DNETs are characterized by the “FLAIR hyperintense ring more common location. Infratentorial or spinal cord location sign”: this is a well-defined thin ring of hyperintensity on is rare.24,25 FLAIR at the borders of the tumor, separating it from healthy Prognosis is often unfavorable owing to the high degree of brain parenchyma.19 malignancy, and survival is variable, depending on the type (secondary or de novo), estimated at 14 months.25,26 9) Glioblastoma (formerly glioblastoma multiforme) may arise de novo (>90%) or progress from an In 2016, the World Health Organization (WHO) updated the existing low-grade tumor (<10%).24,27 classification of CNS tumors (Table 3), replacing the old des- On MRI, this tumor appears as an expansive heterogeneous ignation of glioblastoma multiforme with IDH-wild type glio- lesion of poorly defined borders, located in the cerebral hemi- blastoma (without mutation), IDH-mutant glioblastoma and spheres, with portions of cystic appearance due to large areas

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of necrosis and hemorrhage, heterogeneously enhancing after proliferation, a marked decrease in N-acetyl aspartate levels gadolinium administration and surrounded by extensive perile- due to neuronal cell death and an elevated lipid/lactate peak sional edema (Fig. 9).24,25 associated with the cystic-necrotic component, findings that Glioblastomas often extend into the corpus callosum crossing are suggestive of a neoplastic lesion.24 the midline, involving the contralateral cerebral hemisphere At perfusion MRI, an increased relative cerebral blood volume (“butterfly” ).24 (rCBV) is a marker of neovascularization in a high-grade glial These tumors show areas of restricted diffusion because of lesion.24,27 their high cellularity and MRI tractography demonstrates de- struction or infiltration of fiber tracts.24,27 10) Metastasis MR spectroscopy can provide valuable information for char- A brain lesion in a patient with known malignant tumor sug- acterizing both the lesion and the surrounding parenchyma. gests the possible presence of metastasis.28 There is elevation of choline due to abundant cell membrane The sources of brain metastases are usually the lung, breast,

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Fig. 8 Brain MRI. (A) Axial T2-weighted image, (B) sagittal T1-weighted image and (C) axial FLAIR. A multinodular microcystic lesion is seen on the left temporal lobe, without peripheral edema or mass effect (arrows). The FLAIR sequence shows a faintly hyperintense peripheral ring. DNET was confirmed.

Table 3: 2016 WHO Classification adjusted for cystic-appearing tumors.

Tumor Molecular marker Tumor Grade

Pilocytic astrocytoma BRAF alteration I

Hemangioblastoma — I

Central neurocytoma — II

Ependymoma RELA fusion positive II/III WNT-activated SHH-activated (TP53-mutated) SHH-activated (TP53-wild- Medulloblastoma IV (all subtypes) type) Group 3 Group 4 Ganglioglioma — I

Pleomorphic xanthoastrocytoma BRAF alteration II

DNET — I

Glioblastoma IDH-wild type IDH-mutated NOS IV (all subtypes)

Meningioma — I

Schwannoma — I

Craniopharyngioma — I

Source: Reference No. 22

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melanoma, and tumors of the gastrointestinal tract.28 meningiomas, schwannomas, or pitu- Brain metastases are generally located in the white matter/ itary macroadenomas (Figs. 11-13).31 gray matter junction of the cerebral hemispheres, in the per- Ten to twenty per cent of meningiomas may have cystic de- fusion territory of cerebral arteries.29 generation, showing a density or signal intensity similar to On CT, metastases appear iso- to hypodense, surrounded by that of CSF.4,31 vasogenic edema, and may not be detected without IV con- Calcifications can be better assessed by CT.4 trast administration.23 Peritumoral cysts occurring adjacent to schwannoma may be On MRI, these lesions generally appear hypointense on T1- arachnoid cysts; meningiomas may trap CSF between the tu- weighted images and hyperintense on T2-weighted images, mor and the cerebral cortex.31 may show restricted diffusion on DWI, and (completely or Craniopharyngiomas or pituitary macroadenomas with su- irregularly) enhance after gadolinium administration, appear- prasellar extension may obstruct and enlarge perivascular ing as ring, punctuate or nodular.28-30 spaces.31,32 Large or highly aggressive lesions may have central necrosis Peritumoral cysts and enlarged perivascular spaces do not en- and/or cavitation (Fig. 10).28,29 hance, and thus can be distinguished from tumors.31 The characterization of a cystic-appearing lesion in the CNS Extra-axial tumors enables a proper specific diagnostic approach. This shortens Some extra-axial tumors may undergo cystic degeneration or the diagnostic time and provides a therapeutic approach spe- be associated with non-neoplastic cysts. Examples include: cific to each pathology (Table 1).

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Fig. 9 Glioblastoma. Brain MRI. (A) Axial T1-weighted, (B) T2-weighted images, and (C) axial and (D) coronal T1-weighted im- ages with gadolinium enhancement. Expansive solid-cystic mass (star) on the left frontal lobe with associated necrotic areas. Presence of vasogenic edema causing mass effect, with midline shift to the right (arrows) and compression of the frontal horn of the ipsilateral lateral ventricle.

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Fig. 10 Cystic metastasis from lung . Brain MRI. (A) Axial T1-weighted, (B) T2-weighted images, (C) DWI and (D) appar- ent diffusion coefficient (ADC) map. Cystic lesion (arrows) in the right parietal lobe, with focal wall thickening in the posterior region, showing incomplete peripheral restriction on DWI. Metastasis from primary disease was confirmed by pathology.

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Fig. 11 MRI of the petrous temporal bone. (A) Axial T1-weighted image, (B) axial T2-weighted image, gadolinium-enhanced axial (C) and coronal (D) T1-weighted images. Heterogeneous lesion with a cystic component (arrows) located in the right cer- ebellopontine angle; the medial border abuts the pons and the lateral border widens the porus acusticus, extending into the internal auditory canal (IAC) involving the IAC funds. The lesion shows irregular enhancement after gadolinium administration. Cranial nerve VIII schwannoma with a cystic component was confirmed.

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Fig. 12 MRI of the pituitary gland. (A) Coronal T1-weighted image, (B) coronal T2-weighted image, (C) gadolinium-enhanced sagittal T1-weighted image and (D) gadolinium-enhanced coronal T1-weighted image. Altered morphology of the pituitary gland due to the presence of a cystic-appearing lesion (star), not enhancing after gadolinium administration. The lesion extends upwards abutting and displacing the optic chiasm. Cystic macroadenoma was confirmed.

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Fig. 13 MR of the sellar region. (A) Coronal T1-weighted image, (B) coronal T2-weighted image and (C) sagittal and (D) coronal T1-weighted images with gadolinium enhancement. Sellar morphology alteration (arrow) resulting from an expansive solid-cystic lesion with spontaneously hyperintense areas on T1-weighted images because of its high protein/blood content, associated with heterogeneous content. The lesion shows irregular enhancement after gadolinium administration. The mass invades laterally the cavernous sinuses and, caudally, the sphenoidal sinus. It extends upwards, abutting and displacing the optic chiasm, invading the third ventricle and the lateral ventricles. Craniopharyngioma was confirmed.

Ethical responsibilities Right to privacy and informed consent. The authors de- Protection of human subjects and animals. The authors clare that no patient data appear in this article. declare that no experiments were performed on humans or animals for this investigation. Conflicts of interest Confidentiality of data. The authors declare that they have Pablo Sartori declares a possible conflict of interest as a mem- followed the protocols of their work center on the publica- ber of Capítulo de Neurorradiología de la Sociedad Argentina tion of patient data. de Radiología (SAR, Argentine Society of Radiology).

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