Pilocytic astrocytoma. Pilocytic astrocytomas are relatively well-circumscribed, common, low-grade astrocytic tumors. They are strongly associated with MAPK pathway alterations (frequently with a KIAA1549::BRAF fusion, BRAF V600E, or NF1 mutation) (15; 21). Classic histologic findings are those of fine hair-like cellular processes (giving the name “piloid”) in a loose background. They can be found throughout the central nervous system but most often in the cerebellum. They are most common before 20 years of age (18). They are usually sporadic but can occur in neurofibromatosis type 1 (germline NF1 mutation), Noonan syndrome (germline PTPN11 or RAF1 mutation) (23), and encephalocraniocutaneous lipomatosis (germline FGFR1 mutation) (02). They have an excellent prognosis if completely surgically resected (09). The extent of resection depends on anatomic location. They may also respond to MAPK pathway inhibitors. A related entity, pilomyxoid astrocytomas, are tumors of infancy that occupy the optic pathway or hypothalamus and are more aggressive, which is partially due to their sensitive anatomic location and propensity for recurrence and dissemination (25).
High-grade astrocytoma with piloid features. High-grade astrocytoma with piloid features is a rare, DNA methylation-defined entity showing recurrent molecular alterations in one of the following: MAPK pathway alteration, homozygous loss of CDKN2A or CDKN2B, amplification of CDK4, or ATRX mutation (20). The only consistent morphologic finding is astrocytic differentiation, but the differential diagnosis includes infiltrating gliomas, pleomorphic xanthoastrocytoma, and pilocytic astrocytoma. They also show variable localization, overlapping with these same entities. Sufficient data are not available for formal CNS WHO grade designation; however, the current data suggest these tumors have a clinical behavior roughly corresponding to CNS WHO grade 3 (20).
Pleomorphic xanthoastrocytoma. Pleomorphic xanthoastrocytoma is a tumor of intermediate grade (WHO grade 2 or 3), typically localized superficially to the temporal lobe and often extending to the pial surface; they occur in young adults (14). They show morphologic heterogeneity but frequently show large, atypical giant cells (11). Though generally circumscribed, they may show an invading pattern at the periphery of the tumor. Molecularly, they are notable for recurrent MAPK pathway alterations (most frequently BRAF V600E) with concomitant homozygous loss of CDKN2A or CDKN2B (08; 22). Mutations in TERT promoter are reported and more frequently encountered in higher-grade (WHO grade 3) pleomorphic xanthoastrocytomas (19). They show frequent recurrence, including with cerebrospinal fluid dissemination, and higher grade portends a worse overall survival (14).
Subependymal giant cell astrocytoma. Subependymal giant cell astrocytomas are tumors associated with the lateral ventricle and interventricular foramen of Monro. They are strongly associated with tuberous sclerosis, being the most common tumor of the central nervous system in tuberous sclerosis (12; 17). They typically arise before 25 years of age. Molecularly, they show biallelic inactivation of either TSC1 or TSC2 (03). Histomorphologically, they follow their name closely; they are subependymal in the above-described regions and show large astrocytic cells with a ganglion-cell-like appearance (24). They show a generally favorable prognosis and are amenable to mTOR inhibitor therapy (06; 10).
Chordoid glioma. Chordoid gliomas are glial neoplasms that arise in the third ventricle. The neoplastic cells are glial in differentiation (expression of glial fibrillary acid protein or GFAP) and are clustered in a mucinous background. Molecular features include a recurrent mutation in the PRKCA gene (specifically p.D463H) (13). Given their rarity, outcome data are limited, but surgical resection is the mainstay of therapy (04; 07; 01).
Astroblastoma, MN1-altered. Astroblastomas, MN1-altered, are rare hemispheric tumors typically affecting patients under 40 years of age and are more common in females. They are characterized by alterations in MN1, often as a fusion with BEND2 (05). They have a striking morphologic appearance, showing “astroblastic pseudorosettes” that consist of perivascular tumor cells arranged radially with cytoplasmic processes pointed toward the core vessel. This can give rise to a pseudopapillary appearance (16). Given the rarity of the lesion, outcome data are limited but suggest that the degree of surgical resection impacts prognosis. Recurrence and aggressive behavior have been reported in some cases.
