**Acknowledgements**

The distinction of reactive from tumor astrocytes has always been a crucial point in the diagnosis of OA. Their recognition as reactive is a point of reference in denying the existence of such tumor category. Reactive astrocytes retain nuclear ATRX protein expression, as tumor

By comparing our results with those of the literature, it is noteworthy that the change of diagnosis from the initial to the current analyses of cases, largely depends on the criteria used in the initial recognition of OAs. Upon the reclassification of the 35 cases as astrocytoma, oligodendroglioma, or reactive gliosis, only one could deserve the dignity of OA among the

It must be incidentally remark that total 1p/19q co-deletion occurred in 43/113 (38.1%) of our oligodendroglioma series (selected by the typical morphology of honeycomb appearance and chicken wire vessel distribution); partial 1p and/or 19q deletions occurred in 36/82 (43.9%) of oligodendrogliomas and in 12/24 (50%) astrocytomas. Referring to the 40 cases with initial diagnosis of OA, two had total 1p/19q co-deletion, 14 partial 1p/19q deletion, 12 intact 1p/19q, and one a gain of function on the chromosome 19q. For the remaining 11 cases, the 1p/19q status was not available. It is widely accepted that partial 1p/19q deletions may occur in other gliomas, but one wonders how tumors with an oligodendroglial phenotype with partial

By applying the "integrated" approach to the revision of our OA series, we conclude that, OA could no longer be regarded as a separate tumor entity. However, rare cases might retain the OA denomination [74, 75, our case], indicating that tumors can differentiate in oligodendro‐ glial and astrocytic sense, even maintaining the same molecular genetics [71], or that they can

Two points must be emphasized: one is the importance of the double immunostaining to recognize the astrocytic nature of tumor cells, especially the association between IDH and ATRX expression, considering that IDH1/2 mutations prevail in oligodendrogliomas in comparison to astrocytomas [52, 79]. In supposed mixed tumors with the two separate components, it has been observed that these share the same molecular asset and that astro‐ cytes in the tumor are reactive cells [71]. However, in tumors with the two cell types inter‐ mingled, tumor cells can be distinguished from reactive astrocytes by the double ATRX/GFAP immunostaining. It must be remarked that in rare instances 1p/19q co-deletion can be associated with ATRX mutations/ATRX protein loss [64] and that, since a quota of astrocyto‐ mas do not harbor IDH1/2 mutations, tumor astrocytes with wild type IDH may be found. Minigemistocytes show definitely the oligodendroglial nature due to their ATRX-positive

The other point is the great influence that microglia/macrophage occurrence may exert in the recognition of tumor oligodendrocytes due to their nuclear ATRX positivity. In cases where

oligodendrocytes, while tumor astrocytes lack ATRX expression.

arise from progenitors before differentiation in the two lineages.

remaining five cases.

352 Neurooncology - Newer Developments

**9. Conclusions**

nuclei (**Figure 7B**).

deletions or intact 1p/19q can be classified.

We thank Dr. M.C. Valentini (Neuroradiology Department / Città della Salute e della Scienza Hospital, Turin, Italy) for providing the MRI figures.

We thank Fondazione Cassa di Risparmio di Vercelli (Vercelli, Italy) for the support to the elaboration of this chapter.

#### **Disclosure of Potential Conflicts of Interest:**

Authors declare no potential conflicts of interest.
