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Astrocytes are multipolar, star-like cells of the CNS with an eosinophilic cytoplasm and cytoplasmic processes. The term “astrocytoma” widely applies to tumors that exhibit astrocytic differentiation. Microscopically these lesions appear as hypercellular area of neoplastic cells with irregular, elongated hyperchromatic nuclei, a high degree of fibrillarity, intermixture with normal brain elements, and the frequent formation of secondary structures around neurons, blood vessels and beneath the pia mater [13, 14]. Nuclear hyperchromasia and enlargement as well as cellular crowding and clustering may distinguish neoplastic and reactive astrocytes [14]. On IHC, glial fibrillary acidic protein (GFAP) is a hallmark of astrocytic differentiation; however, it is obviously not neoplasm-specific and is less expressed in undifferentiated examples.

Fig. 1. Nomenclature for gliomas according to the updated WHO classification of CNS tumors (2016) [11]. NOS, not otherwise specified (no genetic testing done). Italic, provisional entities; blue, new genetic-based nomenclatures; red, new entities or variants. * A variant.

The group of astrocytomas includes both circumscribed and infiltrating lowgrade (LGG) and high-grade (HGG) gliomas. Circumscribed lesions correspond to unique tumor types, such as pilocytic astrocytoma (PA; WHO grade I), subependymal giant cell astrocytoma (SEGA; WHO grade I), and pleomorphic xanthoastrocytoma (PXA; WHO grade II), which mainly occur in children and young adults and are generally associated with a more or less indolent clinical course. Diffusely infiltrating astrocytomas are divided into 3 main types, namely diffuse astrocytoma (DA; WHO grade II), anaplastic astrocytoma (AA; WHO grade III) and glioblastoma multiforme (GBM; WHO grade IV). Although the majority of infiltrating astrocytomas show fibrillary structure, there is a large morphological heterogeneity, including gemistocytic, small cell, granular cell, giant cell and epithelioid subtypes. With few exceptions these variants do not pose a unique genetic background, but some may behave in a distinct manner. For instance, small cell astrocytoma and granular cell astrocytoma appear to have a more aggressive clinical course despite their relatively indolent appearance.

The updated WHO classification of CNS tumors (2016) [11] put diffusely infiltrating astrocytic and oligodendroglial neoplasms into the same combined category, which is distinct from “other astrocytic tumors.” It reflects that diffuse gliomas sharing driven IDH1/IDH2 mutations are nosologically more similar than, for example, DA and PA. Such an approach provides dynamic classification based on both phenotype and genotype, groups tumors with similar prognostic markers, and guides use of therapies for biologically and genetically similar entities. Additionally, anaplastic PXA (WHO grade III) was added as a distinct tumor entity (instead of using the descriptive name “PXA with anaplastic features”), grading of pilomyxoid astrocytomas (previously WHO grade II) was suppressed (it is now considered as a variant of PA), and variants of DA (protoplasmic astrocytoma, fibrillary astrocytoma) have been abandoned [11].

GBM and its variants (e.g., gliosarcoma) is the most aggressive neoplasm of the astrocytic lineage and most common primary brain tumor in adults, making up approximately 50% of all gliomas. It is composed of poorly differentiated, often pleomorphic neoplastic cells with marked nuclear atypia and brisk mitotic activity, whereas microvascular proliferation and/or necrosis are essential diagnostic features [5]. In general, the histological variants of GBM carry similar dismal prognosis [15, 16]. A vast majority (approximately 95%) of these tumors are considered as arising de novo and are designated as “primary glioblastomas” (pGBM). Of note, pediatric GBM nearly always arise de novo [17]. In contrast, “secondary glioblastomas” (sGBM) result from transformation of DA and AA into higher grade neoplasms [18], which is referred to as “malignant progression.” The updated WHO classification of CNS tumors (2016) [11] separates GBM into IDH1/IDH2 wild-type and mutant tumors, corresponding approximately to 90 and 10% of cases, respectively. Additionally, the new tumor variant “epithelioid GBM” was added, as well as the new pattern “GBM with primitive neuronal component” (previously referred as “GBM with PNET-like component”), which may have an increased tendency for craniospinal dissemination [11].