Pilocytic astrocytomas (PA) are low-grade (WHO grade I) glial neoplasms [2, 4]. They mainly occur in midline structures including the optic nerves and chiasm, thalamus and hypothalamus, cerebellum, brainstem, and spinal cord. The involvement of the optic pathways by a PA is a frequent finding in patients with Neurofibromatosis type 1. Radiologically, PA are well-circumscribed masses with a cystic component and a mural nodule that shows strong enhancement [5]. PA usually follow a benign course [4].

Histologically, typical PA shows a biphasic architecture. Dense areas of spindle astrocytic cells are interspersed with microcystic areas composed of round cells that exhibit stellate processes [4]. Rosenthal fibers are brightly eosinophilic structures of various shapes that are typically found in the dense areas. These fibers may be round, thick, and elongated, or may exhibit a tadpole-like or corkscrew-like morphology. Eosinophilic granular bodies are globular structures composed of small eosinophilic granules. They are typically found in the microcystic areas. Mitoses are exceptional. Vascular abnormalities are frequent, such as hyalinization, multiple vascular lumens, and glomeruloid vascular proliferation.

On smear preparations, PA are composed of astrocytic cells that exhibit long, bipolar processes resembling hairs (Fig. 10.1), hence the name of the tumor (pilocytic: “hair-like cell” in Greek) [6]. Nuclei are round or oval with a thin chromatin. Cytoplasmic fibrillary processes are usually thin, but may be thicker and show a corkscrew-like appearance (Figs. 10.2 and 10.3). Rosenthal fibers are a common feature (Fig. 10.4). Eosinophilic granular bodies may also be seen (Fig. 10.5). However, they are not pathognomonic of PA, as they may also be encountered in gangliogliomas and pleomorphic xanthoastrocytomas. Microvascular proliferation may be observed (Fig. 10.6). In PA, glomeruloid vessels should not be considered as a sign of malignancy.

Around 70% of PA are characterized by a tandem duplication at 7q34. This duplication results in a fusion between KIAA1549 and BRAF genes that promotes the activation of the mitogen-activated protein kinase (MAPK) signaling pathway [4, 7].

Piloid gliosis . Reactive piloid gliosis may develop around various space-occupying lesions. It closely resembles the dense component of PA. A great abundance of Rosenthal fibers contrasting with a poorly cellular tissue should always raise concerns about the reactive nature of the lesion. Abnormal and proliferative vessels are more evocative of a neoplastic than reactive process. In this situation, neuroradiological data are very useful.

Ganglioglioma . The glial component of gangliogliomas may have a pilocytic appearance (hair-like cells, Rosenthal fibers, eosinophilic granular bodies). However, ganglion cells and lymphocytic perivascular infiltrates, two features of gangliogliomas, are typically not seen in PA.

Diffuse astrocytoma . In diffuse astrocytomas, neoplastic cells usually do not show a hair-like appearance. Their fibrillary processes are not bipolar but irregularly distributed. Cytoplasms and processes may be absent, leaving only “naked” and slightly atypical nuclei. In high-grade astrocytomas (anaplastic WHO grade III, glioblastoma WHO grade IV), nuclei are more atypical. Mitoses may be found. Microvascular proliferation is a key feature of glioblastoma, but may also be observed in some PA, as already mentioned. Necrosis, a characteristic finding in glioblastomas, is not found in PA. In diffuse astrocytomas, Rosenthal fibers and eosinophilic granular bodies are lacking.

Ependymoma. The angiocentric architecture of ependymomas is usually not seen in PA and they lack Rosenthal fibers and eosinophilic granular bodies.

Ganglion cell tumors are WHO grade I, slow-growing neoplasms that mainly affect the temporal lobe [2, 8]. They occur in young patients and are frequently associated with focal epilepsies. Radiologically, ganglion cell tumors are mostly solid-cystic masses that may be calcified. They show variable enhancement and usually do not induce vasogenic edema [9].

Histologically, they are composed of a variable population of dysmorphic ganglion cells. These cells are large neuronal cells that lack the normal stratification of cortical neurons. They show some degree of polymorphism and may be binucleated. The neuronal population may be alone (gangliocytoma) or combined with a glial neoplastic component (ganglioglioma). This glial population usually assumes an astrocytic differentiation (fibrillary or pilocytic). Perivascular lymphocytes cuffing is a frequent finding in these tumors.

Ganglion cells are round neuronal cells harboring an eccentric round nucleus with an eosinophilic prominent nucleolus (Fig. 10.7) [3]. Their cytoplasm is usually abundant and may show margination of the Nissl substance. The neoplastic nature of ganglion cells is suspected when they show some degree of pleomorpism or binucleation. In gangliogliomas, the glial component may resemble pilocytic astrocytoma. Eosinophilic granular bodies are frequently seen, whereas Rosenthal fibers are rarer (Fig. 10.8). In these tumors, vessels are frequently infiltrated by lymphocytes (Fig. 10.9).

Twenty to thirty percent of gangliogliomas exhibit a V600E missense mutation in BRAF gene [7].

Pilocytic astrocytoma . The glial component of gangliogliomas may closely resemble PA. The identification of neoplastic ganglion cells and lymphocytic infiltrates helps in differentiating the two tumors.

Cortical neurons . On smear preparations, cortical neurons mostly appear as “naked,” round-to-oval, nuclei with a distinct nucleolus. The abundant cytoplasm and polymorphism of neoplastic ganglion cells are usually lacking. Lymphocytic infiltrates are absent.

Subependymal giant cell astrocytoma (SEGA) . Unlike ganglion cell tumors, this neoplasm is typically located in the lateral ventricle, near the foramen of Monro. Cytologically, the neoplastic cells of SEGA may resemble the ganglion cells of ganglion cell tumors. In SEGA, eosinophilic granular bodies and lymphocytic infiltrates are not seen.

Pleomorphic xanthoastrocytoma (PXA) is a rare superficial epileptogenic tumor that occurs in children and young adults and especially affects the temporal lobe [10]. Most of the cases are low-grade neoplasms (WHO grade II). However, a minority is more aggressive and presents anaplastic features (WHO grade III) [2]. Radiologically, PXA are cystic masses that contain a mural nodule typically “attached” to the underlying leptomeninges [9].

Histologically, PXA shows a frequent involvement of leptomeninges and a reticulin-rich background [10]. Neoplastic cells have a glial appearance and their shape varies from round to spindle. In some cells, cytoplasm may contain lipid vacuoles (“xanthic cells”). Multinucleation is common. Nuclear pleomorphism is usually striking, and some nuclei may contain inclusions. Eosinophilic granular bodies and lymphocytic infiltrates are frequent. Rosenthal fibers are more rarely encountered.

In typical low-grade PXA, smear preparations usually show clusters of glial tumoral cells [11]. The neoplastic cells are mostly intermediate in size and accompanied by a minority of large multinucleated bizarre cells (Fig. 10.10). By definition, the nuclear pleomorphism is striking (Fig. 10.11). The neoplastic cells often show a spindle cytoplasm with glial fibrillary processes (Fig. 10.12). Xanthic cells may be found. As in ganglion cell tumors, eosinophilic granular bodies and perivascular lymphocytic infiltrates are encountered.

BRAF V600E mutation is found in approximately 60 % of PXA. Homozygous deletion of CDKN2A/B is a frequent finding [7].

Giant cell glioblastoma . Low-grade PXA (WHO grade II) does not exhibit necrosis or vascular proliferation. However, the cytological differentiation from anaplastic PXA (WHO grade III) is difficult.

Ganglion cell tumors. See Sect. 10.3.2.4.

Subependymal giant cell astrocytoma (SEGA) is a tumor of the anterior part of the lateral ventricles, typically near the foramen of Monro. SEGA are found in 6–14% of patients with Tuberous Sclerosis complex (TSC) [12]. TSC is a dominantly inherited disorder that affects multiple organs including the brain. Besides SEGA, the neurological manifestations of TSC include cortical tubers, subependymal nodules, epilepsy, cognitive impairment, and autism.

On smear preparations, SEGA are characterized by clusters of neoplastic cells with a glial appearance (Fig. 10.13) [13]. They usually are round with an abundant eosinophilic cytoplasm and fibrillary processes. The nuclei are eccentric with a single prominent nucleolus. Binucleated or multinucleated cells may be observed.

If the neuropathologist is aware of the location of the tumor (lateral ventricle) and of the underlying condition of the patient (TSC), the intraoperative diagnosis is not difficult.

For differential diagnosis between SEGA and ganglion cell tumors, see Sect. 10.3.2.4.

High-grade gliomas are less frequent in children than in adults, accounting for approximately 10% of all CNS tumors [14]. One subtype, called diffuse midline glioma, is characterized by the involvement of midline structures such as the pons and the thalami, and is molecularly defined by a mutated H3 histone [15]. This tumor is associated with a very poor prognosis and is classified as grade IV in the 2016 WHO classification. IDH1/2-mutated diffuse gliomas are usually not found in children. In this section, only diffuse intrinsic pontine glioma (DIPG) will be discussed.

On smear preparations, these tumors show a glial fibrillary background. The cells have an astrocytic morphology with hyperchromatic nuclei (Fig. 10.14). Nuclear atypia are variable. Mitoses and microvascular proliferation are characteristic but may be lacking.

Sixty-five percent of DIPG are characterized by a mutation in the H3F3A gene coding histone variant H3.3 [15]. K27M mutations in H3F3A gene result in the substitution of a lysine by a methionine and disrupt global methylation at this residue.

In this situation, the neuroimaging data are critical [16]. DIPG are infiltrative lesions with ill-defined margins that enlarge the pons and engulf the basilar artery. In contrast, brainstem PA are exophytic masses. On smears as in histological sections, DIPG may show various patterns: diffuse astrocytoma (WHO grade II), anaplastic astrocytoma (WHO grade III), or glioblastoma (WHO grade IV). Even lesions that appear to be low-grade are associated with a dismal prognosis.

Ependymomas (EP) account for 6–12% of all CNS pediatric tumors [17]. Pediatric EP are mostly intracranial (2/3 infratentorial and 1/3 supratentorial). Unlike in adults, spinal ependymomas are rare in children. According to the WHO 2016 classification, EP are divided into: subependymoma and myxopapillary EPs (grade I), classic EP (grade II), and anaplastic EP (grade III) [2]. Subependymoma mainly occurs in adults and is not described here. The myxopapillary variant is a tumor of the cauda equina that rarely affects children.