Grossly, astrocytoma of the brain stem expands normal tissues in a fusiform fashion. Brain stem astrocytomas are frequently centered in the pons and an exophytic component may encircle the basilar artery [17, 21]. Because of their infiltrative nature, these tumors usually show blurring of the gross anatomical boundaries [18].

If there is only a limited material for histopathologic examination, e.g., from a stereotactically obtained biopsy, diagnosis of astrocytoma may be difficult to make, especially if the biopsy is sampled from infiltrating edge of tumor [17]. A firm intraoperative diagnosis of infiltrative astrocytoma requires an unequivocal increase in cellularity, irregular distribution of glial cells, nuclear atypia, and, in some instances, presence of microcysts [21] (Fig. 35.2). Intraoperative smears readily demonstrate the fibrillary matrix, which is usually more ill defined than the background accompanying reactive astrocytosis. The nuclei of the tumor cells are slightly larger and more irregular and hyperchromatic with coarser chromatin than those of reactive astrocytes. Cytoplasmic morphology ranges from a scant perinuclear rim with ill-defined borders to more stellate shape [20].

Histologically fibrillary astrocytoma is predominantly composed of fibrillary neoplastic astrocytes. Cellularity is moderately increased, and nuclear atypia is a typical future but mitotic activity, necrosis, and microvascular proliferation absent [18]. The cells of fibrillary astrocytomas may appear as bare nuclei, their tenuous fibrillary processes blending with the brain’s parenchyma. Alternatively they show varying degrees of astrocytic differentiation, exhibiting prominent fibrillary strands of eosinophilic cytoplasm, or a plump cell body in which the nucleus is displaced by homogeneously eosinophilic cytoplasm, the gemistocytic phenotype [17, 18] (Fig. 35.3).

The presence of microcystic spaces is a distinctive and diagnostically helpful feature of gliomas. Microcysts containing mucinous fluid are a characteristic feature. Cartilage formation is very rare [18, 21].

Immunohistochemical Findings. The cytoplasm often is immunopositive for glial fibrillary acidic protein (GFAP), although to a variable degree and not by all cells of tumor (Fig. 35.4). The fibrillary matrix forms diffuse GFAP positive background. Vimentin is usually expressed in astrocytic tumors, with similar distribution to GFAP but with less prominence. Tumor cells are also immunoreactive for S-100 protein, in both nuclei and cytoplasmic processes, but this feature has no diagnostic relevance [18, 20, 21] (Fig. 35.5).

The growth fraction, as determined by the Ki67/MIB-1 labeling indices of astrocytoma grade II, has generally been less than 4 %, with a mean of 2.5 % (Fig. 35.6). Staining for p53 protein is variable in diffuse astrocytomas (Fig. 35.7). A higher percentage is present in gemistocyte-rich lesions [18, 21].

Genetic abnormalities have been described in less than 100 pediatric patients with diffuse brain stem gliomas in the literature. Half of the patients exhibited TP53 mutations, and in one study, half of the patients with this mutation also exhibited loss of the other p53 allele [5, 15].

Similarly, both p53 gene mutations and increased expression of platelet-derived growth (PDGF) and insulin-like growth factor I (IGF-1) appear to occur early in the tumorigenesis of the diffuse type astrocytomas. Altered growth factor activity occurs in the astrocytic tumors either by changes in ligand or receptor expression, including PDGF, bFGF, TGFα, TGFβ, and IGF-1 [17, 20].

Comparative genomic hybridization (CGH) analyses showed a gain of chromosome 7q and amplification of 8q as the most frequent genomic imbalance. Loss of heterozygosity (LOH) on 22q was found at one or more loci in 27–33 % grade II diffuse astrocytomas. Approximately 50 % of all pediatric patients with diffuse brain stem gliomas in one series demonstrated allelic loss in the long arm of chromosome 10 [18].

In a study EGFR gene amplification was observed in only a minority of low grade II diffuse astrocytomas neoplasms [16] (Fig. 35.8). Approximately one third of low-grade astrocytomas show p14ARF promoter methylation. MGMT promoter methylation was detected in approximately 50 % of low-grade diffuse astrocytomas, and this was significantly associated with TP53 mutations [18–20] (Fig. 35.9).