**3.2. Microscopic appearance**

On histopathologic analysis, OA was characterized by highly cellularlesions composed of both tumor astrocytes and oligodendrocytes that could be separated or intermingled [5], *i.e*. the tumor could be defined as "biphasic" (**Figure 2A**–**C**) or "diffuse" (**Figure 2D**). Astrocytic tumor cells scattered within oligodendroglial cells hadto be recognizedas neoplastic andnotreactive/ hypertrophic astrocytes.

**Figure 2.** Histopathologic features of OA. A – OAII with separated astrocytic and oligodendroglial components, x100; B – Id, astrocytic component, x400; C – Id, oligodendroglial component, x400; D – OAII with intermingled astrocytic and oligodendroglial cells, x200; E – OAIII, x200. All hematoxylin and eosin (H&E).

*OAII*. The tumor showed a moderate cellularity with no or low mitotic activity. Microcalcifi‐ cations and microcystic degeneration could occur.

Reactive astrocytes are present in all gliomas, OA included; in the latter, their distinction from tumor astrocytes was the most important problem since the protean appearance of reactive astrocytes, with large cytoplasms, and thick and long processes or with small cytoplasms with short processes and in variable number, did not allow a clear-cut distinction from tumor astrocytes.

An important bias was the occurrence of minigemistocytes, GFOC, and true gemistocytes. Both minigemistocytes and GFOC were regarded as either transitional forms between oligoden‐ drocytes and astrocytes, corresponding to a bipotential glial progenitor cell [16], or as glial fibrillary acidic protein (GFAP) expressing oligodendrocytes [12], remnants of myelin forming glia of the developmental period [13].

A high frequency of minigemistocytes could confer an astrocytic aspect to the tumor.

*OAIII*. The tumor was mainly characterized by a significant or brisk mitotic activity (≥ 6 mitoses *per* 10 high power field [HPF]) and a high Ki-67/MIB-1 proliferation index, nuclear atypia, necrosis, and apoptotic cells (**Figure 2E**). The malignant transformation was considered as proceeding either from the one or the other cell component. In the differential diagnosis towards glioblastoma (GBM), the occurrence of circumscribed necroses was decisive; the presence of microvascular proliferations (MVPs) would indicate the grade III when occurring in the oligodendroglial part and the grade IV when in the astrocytic one.
