_{Published September 30, 2022}

Primary brain tumors are the most common solid tumors in children, second only to leukemia in terms of cancer incidence, and are the leading cause of childhood cancer-related mortality [1, 2]. Tumors may present across all pediatric age groups, including infants, children, adolescents, and young adults, with the majority of cases presenting in the first decade of life. Clinical presentations vary, based upon the type of tumor, location, and patient age; however, the most common presenting symptoms include headaches, nausea and vomiting, and gait abnormalities [3]. In infants and very young children, obstructive hydrocephalus results in macrocephaly with bulging fontanelle [4]. Brainstem tumors commonly have symptoms associated with involved tracts and cranial nerves.

Imaging plays a crucial role in the initial workup, management, and post-treatment follow-up of primary pediatric posterior fossa tumors. Treatment options vary, based upon the tumor type, location, and patient age, and are beyond the scope of this InPractice review. The most common primary posterior fossa tumors in children that we will discuss and illustrate during our 2023 ARRS Annual Meeting Categorical Course session include (in descending order of frequency): medulloblastoma, pilocytic astrocytoma, ependymoma, diffuse midline glioma, and atypical teratoid-rhabdoid tumor.

Medulloblastoma

Medulloblastomas are high-grade (WHO grade 4) embryonal tumors and represent the most common malignant and the most common primary posterior fossa brain tumors in children [5]. Various subcategories of medulloblastomas have been described and used in the past; however, the latest molecular classification lists the following subtypes: wingless/integrated (WNT)—activated, sonic hedgehog (SHH)—activated, and non-WNT/non-SHH (also known as groups 3 and group 4), with additional subcategories for SHH-activated and non-WNT/non-SHH variants [6]. Classically, medulloblastomas were thought of as midline cerebellar tumors, but certain subtypes have a propensity for off-midline presentations.

General Imaging Features

Imaging characteristics for the various subtypes of medulloblastoma are overall similar, reflecting that of densely packed, highly cellular tumors. Masses tend to be spherical in shape and displace adjacent structures, as opposed to the more pliable appearance of ependymomas. Increased density on CT and diffusion restriction on MRI are characteristic of medulloblastomas, reflective of their high cellularity. T2 signal intensity is variable, typically having areas of both increased and decreased T2 signal compared to cerebellar parenchyma. Small intralesional cysts are common, while intralesional hemorrhage and calcification are uncommon, though may occasionally be seen. Enhancement ranges from patchy to more robust solid enhancement [7, 8] (Fig. 1).

On MR spectroscopy, a high-grade tumoral spectrum is evident with increased choline and decreased N-acetyl aspartate peaks. A taurine peak just to the left of the choline peak may be a specific marker for medulloblastoma in the posterior fossa [9].

The frequency of metastatic disease varies depending upon the molecular subtype, ranging from approximately 10% to up to 45% at the time of initial presentation [5]. It is therefore important to image the spine prior to surgical resection and with subsequent surveillance imaging to evaluate for disseminated disease.

WNT-Activated Medulloblastoma

WNT-activated medulloblastomas are the least common subset and have the best overall prognosis. These tumors commonly present in older children and adolescents and may occur midline or laterally around the foramen of Luschka, cerebellar peduncle, and cerebellopontine angle [6, 7, 10].

SHH-Activated Medulloblastoma

SHH-activated medulloblastomas are a more heterogeneous subset than WNT-activated, with an overall intermediate prognosis. Tumors tend to be located laterally in the cerebellar hemispheres, since they are thought to arise from precursors in the external granule-cell layer of the cerebellum, but they may occur in the midline as well [6, 11]. There is a bimodal presentation, occurring most commonly in infants and then young adults, though they may also occur in children. The infantile variant tends to have extensive nodularity on histology and more frequently metastasizes [11, 12]. Nearly all nodular or desmoplastic variants fall into this category. SHH-activated medulloblastomas are stratified based on their TP53 status as either TP53-wildtype or TP53-mutant, with TP53-mutant portending a worse prognosis [6].

Non-WNT/Non-SHH Medulloblastoma, Groups 3 and 4

Non-WNT/non-SHH medulloblastomas are the most common molecular subsets, have an increased incidence in boys, present as midline vermian tumors, and often have classic or large cell anaplastic features on histology. Group 3 tumors tend to occur in infants and young children, have a higher incidence of metastases, and have the worst overall prognosis of any medulloblastoma tumor subset. Group 4 tumors are the most common subset, occur in older children and adolescents, and have an intermediate prognosis [6, 11]. In terms of distinguishing imaging features, group 3 tumors often have avid enhancement, while hypoenhancement is preferentially seen with group 4 tumors [13].

Pilocytic Astrocytoma

Pilocytic astrocytomas are the most common primary brain tumor in children, accounting for approximately one-third of all gliomas, and the second most common primary posterior fossa tumor in children after medulloblastomas. They are low-grade, WHO grade 1, tumors with an excellent prognosis in the setting of gross total surgical resection. Pilocytic astrocytomas result from MAPK pathway alterations, often with BRAF fusion or BRAF V600E point mutations. BRAF fusion is common in posterior fossa pilocytic astrocytomas and is associated with improved outcomes [14]. BRAF V600E point mutations, on the other hand, tend to be associated with poorer outcomes [15]. Increased frequency of pilocytic astrocytomas is seen in patients with neurofibromatosis type 1 (NF1), most commonly involving the optic pathways, though they may occur nearly anywhere with NF1 [16].

Posterior fossa pilocytic astrocytomas most often arise within the cerebellar hemispheres and are therefore lateral in location. Less commonly, they may be midline, arising from the cerebellar vermis. The classic imaging appearance is a large cystic mass with a peripheral solid nodule. More heterogeneous presentations, including a multicystic mass, predominantly solid mass with central cystic changes, or partially hemorrhagic mass, are less common [7, 17].

On MRI, the cystic component of the tumor is often similar to CSF signal intensity on T1 and T2 sequences, with the T2-FLAIR signal being more variable, based upon internal proteinaceous content. Solid portions of the mass avidly enhance, and there may also be enhancement along the margins of the cyst wall. A helpful distinguishing feature of a pilocytic astrocytoma, compared to other posterior fossa tumors, is the lack of diffusion restriction within the solid components of the tumor [18, 19] (Fig. 2).

Ependymoma

Ependymomas are the third most common primary posterior brain tumors, after medulloblastomas and pilocytic astrocytomas. The majority are classic, WHO grade 2, ependymomas, with more aggressive anaplastic ependymomas being WHO grade 3. Ependymomas are soft, pliable tumors that originate in or near the fourth ventricle and squeeze through the outlet foramina into adjacent spaces and cisterns. Because of their pliability, they often surround or encase neurovascular structures.

There are two subgroups of posterior fossa ependymomas: posterior fossa group A (PFA) and posterior fossa group B (PFB) [20]. PFA variants occur most often in infants, are lateral in location, and have a relatively poor prognosis. Because of the lateral location and common extension into the prepontine cistern, gross total resection is often difficult, and radiation therapy is typically avoided in infants because of the potential for morbidity. PFB variants occur in older children and adolescents, tend to arise from the floor of the fourth ventricle, and have a better overall prognosis than PFA variants [16, 21].

On MRI, ependymomas tend to be heterogeneously T2 hyperintense with variable enhancement. Cystic change and calcifications are common, with calcifications occurring in up to 50% of cases, much more common than is seen with medulloblastomas [7]. Given the relative pliability of the tumor, extension through fourth ventricular outlet foramina is characteristic. The presence of reduced or restricted diffusion is variable, but typically less than is seen with highly cellular medulloblastomas. The exception is with anaplastic ependymomas, which may have areas of restricted diffusion that are similar to medulloblastomas. Anaplastic ependymomas tend to have a higher frequency of disseminated metastatic disease and disease recurrence, with a poorer prognosis compared to lower-grade ependymomas [22]. The frequency of disseminated metastatic disease for ependymomas is less than that for medulloblastomas.

Diffuse Midline Glioma

Diffuse midline gliomas (DMGs) “H3K27-altered” are highly aggressive pediatric brain tumors (WHO grade 4) that encompass the majority of lesions previously referred to as diffuse intrinsic pontine gliomas (DIPGs). Prognosis is dismal with a median survival of approximately 11 months from diagnosis [23]. Given the brainstem location, the most common clinical presentations include cranial nerve palsies, pyramidal tract signs (paresis, hyperreflexia, or positive Babinski reflex), and cerebellar signs (dysmetria, ataxia, dysarthria, or nystagmus) [23]. DMGs tend to occur in younger children, with median age at presentation around 6 years [24].

On MR imaging, DMGs present as a diffuse, ill-defined, T2 hyperintense, expansile masses centered within the pons. The degree of enhancement is variable, often absent at initial presentation and typically patchy when present (Fig. 3).

Peripheral enhancement commonly occurs along margins of central necrosis, which occurs more frequently after radiation therapy [25]. Intralesional hemorrhage is uncommon, but areas of hemosiderin deposition may be seen on susceptibility-weighted sequences. Focal areas of restricted diffusion develop in the majority of cases. The presence of central necrosis, diffusion restriction, or enhancement at the time of initial diagnosis has been shown to portend a worse prognosis [24].

Extrapontine spread is common throughout the brainstem, into the thalami and adjacent structures, through the cerebellar peduncles, and into the cerebellar hemispheres. Exophytic components engulf the basilar artery anteriorly and efface the fourth ventricle posteriorly. Disseminated metastatic disease is uncommon, though may be seen occasionally.

Historically, DMGs have been treated presumptively when characteristic imaging features are present, reserving biopsy for cases with nonclassic imaging features or when tissue sampling is required for a clinical trial eligibility. However, more centers are now performing biopsies prior to treatment to confirm molecular classification and histology, shed light on potential prognosis, and help advance investigation of future adjuvant therapies. When biopsy is performed, the posterolateral portion of signal abnormality is typically targeted to minimize potential morbidity. If focal areas of diffusion restriction are present, these areas tend to have the highest diagnostic yield, if they can be safely accessed and sampled [26].

Atypical Teratoid-Rhabdoid Tumor

Atypical teratoid-rhabdoid tumors (ATRTs) are rare and highly aggressive (WHO grade 4) embryonal tumors that tend to occur in infants and young children, with the majority of cases presenting under 3 years of age. As with medulloblastomas, posterior fossa ATRTs may be midline or off-midline and are highly cellular with areas of diffusion restriction. Imaging features significantly overlap with medulloblastoma; therefore, patient age is one of the key features in suggesting ATRT versus medulloblastoma. Compared to medulloblastomas, ATRTs tends to have a more heterogeneous imaging appearance, with a higher incidence of intralesional hemorrhage and calcification, as well as a higher incidence of disease dissemination at the time of presentation [27, 28].

For most cases of primary posterior fossa tumors in children, the correct diagnosis can be suggested based upon distinguishing imaging features, with remaining cases requiring a thoughtful differential diagnosis in the setting of overlapping or nonspecific imaging findings. Our Categorical Course session will focus on recognizing characteristic imaging features for the most common primary pediatric posterior fossa tumors.

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