A piloid neoplasm, closely related to pilocytic astrocytoma that has a prominent mucoid matrix and angiocentric arrangement of monomorphous, bipolar tumor cells typically without Rosenthal fibers or eosinophilic granular bodies/hyaline droplets [4].

Earlier reports refer to tumors with similar features as “infantile” pilocytic astrocytoma, and the occasional phenotypical conversion of a pilomyxoid astrocytoma to a typical pilocytic astrocytoma supports a common origin for these two tumors [4].

The incidence of pilomyxoid astrocytomas is not known. They present in the very young (median 10 months) but can occur in older children without gender predilection [4]. Although mostly located in the hypothalamic/chiasmatic region, they can occur in the cerebellum [7]. Two patients with pilomyxoid astrocytomas and neurofibromatosis 1 (NF1) have been reported [8].

Pilomyxoid astrocytomas present as solid gelatinous masses partly infiltrating parenchyma; thus a clear surgical plane may not be identified [9].

Pilomyxoid astrocytomas show a markedly mucoid matrix, monomorphous bipolar cells, and a predominantly angiocentric cell arrangement (Fig. 28.2). The tumor typically has a compact, rather solid architecture while others are more infiltrative. The lesion is composed of relatively monomorphous, medium-sized bipolar cells, the processes of which may radiate from vessels in a pseudorosette fashion; cells may also be aligned along the long axis of vessels. When strictly defined, the tumor does not contain Rosenthal fibers or eosinophilic granular bodies/hyaline droplets. Mitotic figures and vascular proliferation may be present, and rare examples may be focally necrotic.

Immunohistologically, tumors are positive for GFAP, S-100 protein, and vimentin and may show expression for synaptophysin but are negative for neurofilament protein and chromogranin. MIB-1/Ki-67 labelling indices were found to vary substantially between 2 and 20 % [4].

An astrocytic neoplasm with a relatively favorable prognosis typically encountered in children and young adults; characteristic histological features include pleomorphic and lipidized cells expressing GFAP and often surrounded by a reticulin network as well as eosinophilic granular bodies. Lesions with significant mitotic activity (five or more mitoses per 10 HPF) and/or with areas of necrosis may be designated as “pleomorphic xanthoastrocytoma with anaplastic features” [10].

Pleomorphic xanthoastrocytomas account for less than 1 % of all astrocytic neolasms. They are mainly encountered in the second decade of life and account for 1.9 % of pediatric brain tumors [1], with two-thirds of patients being under 18 years of age without gender predilection [10]. A superficial location involving the meninges and cerebrum is typical for pleomorphic xanthoastrocytomas; however, they can also occur in the cerebellum [11].

Pleomorphic xanthoastrocytomas are mainly superficial tumors attached to the meninges; they are frequently accompanied by a cyst, sometimes forming a mural nodule within the cyst wall [10].

The key histopathological features are contained in its designation: “pleomorphic” refers to the variable histological appearance of the tumor in which spindly elements are intermingled with mono- or multinucleated giant astrocytes with hyperchromatic and pleomorphic nuclei with frequent intranuclear inclusions (Fig. 28.2). “Xanthoastrocytoma” refers to the presence of large xanthomatous cells showing intracellular accumulation of lipid droplets. Granular bodies are an almost constant feature as well as focal collections of small lymphocytes and reticulin fibers visualized using silver impregnation surrounding the individual tumor cells.

Immunohistochemically, tumor cells express GFAP and S-100 protein but also show significant neuronal differentiation (synaptophysin, neurofilament protein, MAP2) as well as CD34 expression. The MIB-1/Ki-67 labelling index is usually <1 % [10].

A diffusely infiltrating astrocytoma characterized by a high degree of cellular differentiation and slow growth. The tumor has an intrinsic tendency for malignant progression to anaplastic astrocytoma and, ultimately, glioblastoma [12].

Diffuse astrocytomas represent 10–15 % of all astrocytic CNS tumors with an incidence rate of 1.4 per million per year. Fibrillary astrocytomas are fairly rare in childhood and make up 5.0 % of CNS tumors encountered in this period [1]. Epidemiological data suggest that the incidence in children has increased slightly over the past three decades. There is a slight predilection for males (1.18:1), and approximately 10 % occur below the age of 20 years. Localization in the cerebellum is distinctly uncommon [12].

Because of their infiltrative nature, diffuse astrocytomas usually show blurring of the gross anatomical boundaries. There is enlargement and distortion but no destruction of the invaded structures. Smaller or larger cysts, granular areas, and zones of firmness or softness may be seen. Extensive microcyst formation may cause a gelatinous appearance. Focal calcification may be present [12].

Diffuse astrocytoma is composed of well-differentiated fibrillary or gemistocytic neoplastic astrocytes in a background of a loosely structured, often microcystic, tumor matrix (Fig. 28.3). The cellularity is moderately increased and occasional nuclear atypia is a typical feature. Mitotic activity is generally absent; however, a single mitosis does not yet allow the diagnosis of anaplastic astrocytoma. The presence of necrosis or microvascular proliferation is incompatible with the diagnosis of diffuse astrocytoma. Histological recognition of neoplastic astrocytes depends mainly on nuclear characteristics of atypia: whereas normal astrocyte nuclei are oval to elongate and vesicular, often with a distinct nucleolus, neoplastic astrocytes show enlarged, cigar-shaped, or irregular hyperchromatic nuclei. Reactive astrocytes, on the other hand, present with stainable cytoplasm while normal and tumor astrocytes show no discernible or scant cytoplasm (“naked nuclei”) [12].

A diffusely infiltrating malignant astrocytoma histologically characterized by nuclear atypia increased cellularity and significant proliferative activity. The tumor may arise from diffuse astrocytoma or de novo, i.e., without evidence of a less malignant precursor lesion, and has an inherent tendency to undergo progression to glioblastoma [13].

Anaplastic astrocytomas are rare in children and within the cerebellum. They account for 7.2 % of childhood brain tumors [1] and show a male gender predilection with a ratio of between 1.1 and 1.6:1 [13].

Anaplastic astrocytomas have a tendency to infiltrate the surrounding brain without frank tissue destruction which often leads to a marked enlargement of invaded structures such as gyri and basal ganglia. Cysts are uncommon but areas of granularity, opacity, and soft consistency are frequent. On cut surface the higher cellularity of anaplastic astrocytomas produces a discernable tumor mass with a clearer distinction from surrounding structures than in diffuse astrocytomas WHO grade II [13].

The principal histological features are those of a diffusely infiltrating astrocytoma with increased cellularity compared with a WHO grade II tumor, distinct nuclear atypia (variations in nuclear size, shape, coarsening and dispersion of chromatin, prominent and multiple nucleoli) and mitotic activity (Fig. 28.3), the latter depending on the size of the sample (one mitosis in stereotactic biopsy sample equals a significant proliferation but not in a large surgical tumor sample; immunohistochemistry for MIB-1/Ki-67 may be helpful which usually ranges between 5 and 10 %). Additional signs of anaplasia are multinucleated cells and abnormal mitoses. By definition, microvascular proliferation (multilayered vessels) and necrosis are absent [13].

The most malignant neoplasm with predominant astrocytic differentiation; histopathological features include nuclear atypia, cellular pleomorphism, mitotic activity, vascular thrombosis, microvascular proliferation, and necrosis. Most glioblastomas manifest rapidly de novo, without recognizable precursor lesions (primary glioblastoma). Secondary glioblastomas develop slowly from diffuse astrocytoma or anaplastic astrocytoma. Due to their invasive nature, glioblastomas cannot be completely resected. The term “glioblastoma” is used synonymously with “glioblastoma multiforme” [14].

Glioblastoma may manifest at any age but is the most frequent CNS tumor in adults, accounting for 12–15 % of all intracranial neoplasms and 60–75 % of astrocytic tumors with an incidence of 30–40 new cases per million per year. The majority (>90 %) develops very rapidly with a short clinical history (usually <3 months): primary or de novo glioblastomas, whereas secondary glioblastomas develop through progression from diffuse (WHO grade II) or anaplastic (WHO grade III) astrocytomas. Glioblastomas are relatively rare in children with 1 % of glioblastomas encountered in patients under the age of 20 years. They account for 7.2 % of childhood brain tumors and are rarely encountered in the cerebellum [1]. The male to female ratio is about 1.26–1.28 [14].

Despite the short duration of symptoms in many cases of glioblastoma, the tumors are often surprisingly large. The lesion is usually unilateral but bilateral symmetrical extension is seen supratentorially due to growth along myelinated structures like the corpus callosum (“butterfly glioma”). Glioblastomas are diffuse and poorly delineated with the cut surface showing a variable color with peripheral grayish tumor masses and central areas of yellowish and red from necrosis, myelin breakdown, and hemorrhage. The central necrosis may occupy as much as 80 % of the total tumor mass and is typically stippled with red and brown foci of recent and remote bleeding; extensive hemorrhages may occur and evoke stroke-like symptoms. Macroscopic cysts contain a turbid fluid and represent liquefied necrotic tissue. Most glioblastomas have their epicenter in the white matter. Multifocal glioblastomas occur in approximately 2.4 % of cases; penetration of the subarachnoid space, dura, venous sinus, or bone is exceptional [14].

Glioblastoma is a malignant cellular glioma composed of poorly differentiated, often pleomorphic astrocytic tumor cells with marked nuclear atypia and brisk mitotic activity (Fig. 28.4). Prominent microvascular proliferation (multilayered vessels) and necrosis are essential diagnostic features. Necroses often take the shape of multiple band-like or serpiginous foci surrounded by radially oriented and densely packed tumor cells in a pseudopalisading pattern. As the term “glioblastoma multiforme” implies, the histopathology of this tumor is extremely variable. While some tumors show a high degree of cellular and nuclear pleomorphism with multinucleated giant cells, others are highly cellular but rather monotonous. The regional heterogeneity of glioblastoma is remarkable and poses challenges to the diagnosis of specimens obtained by stereotactic needle biopsies.

The diagnosis of glioblastoma is typically based on the tissue pattern rather than the identification of certain cell types. The distribution of the diagnostic key elements (highly anaplastic glial cells, mitotic activity, vascular proliferation and/or necrosis) is variable, but large necrotic areas usually occupy the tumor center, while viable tumor cells tend to accumulate in the periphery. The circumferential region of high cellularity and abnormal vessels corresponds to the contrast-enhancing ring seen radiologically. Occasionally, glioblastomas contain foci of glandular epithelial structures which usually can unequivocally be established as being astrocytic in nature. Cellular pleomorphism also includes formation of small undifferentiated as well as lipidized, granular, and large multinucleated giant cells. The latter are often considered a hallmark of glioblastoma; however, they are not an obligatory feature, are not associated with a more malignant clinical course, and are generally regarded as a type of regressive change. If they dominate, a designation of “giant cell glioblastoma” is justified. In addition to necrosis, the presence of microvascular proliferations is a histopathological hallmark of glioblastoma. They typically appear as “glomeruloid tufts” which are most commonly located in the vicinity of necrosis and appear directionally oriented to it. Microvascular proliferations consist of multilayered, mitotically active endothelial cells together with smooth muscle cells and pericytes. Proliferative activity is usually prominent with detectable and frequently atypical mitoses in nearly every high-power field. The growth fraction shows great regional variation with mean MIB-1/Ki-67 values of 15–20 % [14].