Pleomorphic xanthoastrocytomas: immunohistochemistry, grading and clinico-pathologic correlations. An analysis of 34 cases from a single Institute.

Pleomorphic xanthoastrocytomas (PXAs) are characterized as a well-delineated tumor entity with clear peculiarities in clinico-radiological picture, pathological appearance and biological behavior. Usually the PXAs are associated with relatively good prognosis. Nevertheless, up to 35% of patients die following one and more recurrence with or without tumor malignant transformation. Till now, there is no agreement on what histopathological features constitute to objective and reliable signs of PXAs malignancy and clinical outcome. Thirty-four PXAs were subdivided on three subsets: typical (Grade I) - tumors without mitoses per 20 high power fields, proliferating (Grade II) tumors with mitoses but without necroses, and malignant (Grade III) - tumors with elevated mitotic index and necrotic foci. Also, immunohistochemical investigation with various tumor-associated antigens was performed. All PXAs subtypes showed differences in clinical outcomes. There were no recurrences and death among the tumors Grade I. Five out of 14 (36%) Grade II PXAs have recurred and one of them died. All 5 patients with PXAs Grade III have rapidly recurred and four of them died. Immunohistochemical variables, such as Ki-S1, p27/Kip1, vascular endothelial growth factor expression, p53 immunoreactivity and apoptotic index also exhibited significant differences among the three PXAs grades. The progression-free survival was significantly reduced for PXAs grade and presence of mitoses, whereas overall survival was reduced for mitotic index >or= 3 and presence of necroses. No one from immunohistochemical variables reached significant value. In summary, the three-tiered PXAs subdivision proposed by us is carrying some element of rationality but, undoubtedly, requires further prospective studies.