Brain Pathology Case of the Month - September 2008


Pleomorphic xanthoastrocytoma with anaplastic features (WHO grade III) rapidly progressing towards pleomorphic xanthoastrosarcoma (WHO grade IV)


To our knowledge, this report illustrates the previously unprecedented case of a pleomorphic xanthoastrocytoma rapidly undergoing transformation into pleomorphic xanthoastrosarcoma (WHO grade IV). Most remarkably, both primary and recurrent tumor featured large areas of gliovascular, pseudopapillary, rosette-like structures. Therefore, among others, the differential diagnosis of an ependymal tumor was considered for the primary lesion. However, temporal lobe location and absence of the dot-like EMA reactivity frequently seen in ependymal tumors argued against this entity. In addition, the tumor cells radially anchoring to the central vessel did not possess the long, tapering processes of ependymomas but instead featured short and rather stout processes that together with the hyalinized vessel structures also prompted inclusion of an astroblastoma into our differential. Because the tumor also comprised larger solid, spindle cell-predominant areas, this possibility was dismissed. Furthermore, the absence of traversing neurofilaments largely excluded a diffusely infiltrating glioma, in particular, glioblastoma multiforme. Finally, the possibility of an anaplastic (pilocytic) astrocytoma was also given consideration but this appeared unlikely due to focal cytoplasmic tumor cell vacuolization as well as due to the absence of pronounced piloid cytomorphological features including missing Rosenthal fibres. The immunophenotype of this non-infiltrative GFAP expressing lesion with detection of CD34 expression by at least a focal tumor cell subpopulation in combination with a conspicuous coarse cytoplasmic vacuolization (on frozen sections demonstrated to represent lipidization), the finding of sparse EGBs complemented by the presence of necrotic changes and a significant proliferative activity collectively prompted the diagnosis of a PXA with anaplastic features (WHO grade III). The recurrent tumor that, in addition to recapitulating the primary lesion`s gliovascular architectures and EGBs also featured large fibrosarcoma-like portions, was diagnosed as pleomorphic xanthoastrosarcoma (WHO grade IV), conceptually to be considered as gliosarcoma. At the lesion`s periphery, remarkably, numerous CD34 expressing satellite cells, previously associated with PXAs as well as gangliogliomas (11), were found within non-infiltrated cortical tissue.

PXAs are uncommon, often seizure-associated tumors typically occurring in the temporal lobe of children and young adults (3). They are unique neoplasms which despite an often striking cellular pleomorphism feature a relatively benign clinical behavior (2). Apart from its pleomorphism, characteristic microscopic features of PXA include lipidization of tumor cells and the presence of EGBs. Whereas the majority of patients experience long-term survival, some 10-15% of cases may progress to high-grade lesions. Prediction of rapid malignant progression remains difficult (1, 8). Mitotic index and extension of resection appear to be important prognostic indicators of recurrence-free and overall survival (2, 5, 6), as may be necrosis (9). However, even the absence of increased mitotic activity and necrosis does not preclude a dramatically malignant clinical course (8), suggesting that additional histomorphological and (yet to be identified) molecular-genetic parameters may be of importance. Of note, in contrast to diffuse astrocytomas, neither TP53, nor CDKN2A (p16INK4a), CDK4, MDM2 or EGF receptor status seem to be involved in PXA pathogenesis nor, in the case of TP53, prove to be a discriminating factor in the identification of progression-prone PXAs (4, 7).

Strikingly, the perivascular rosette-like pseudopapillary structures dominating the histomorphology within large areas of both primary and recurrent lesion, have previously been hypothesized to be potentially associated with a greater likelihood of PXA recurrence (10). From our case, it appears that these rosette-like gliovascular structures may potentially not only indicate a greater chance of recurrence but may possibly also herald rapid malignant progression warranting close postoperative follow-up which is not normally applied in the clinical management of PXA cases. Perhaps, larger PXA series should be analyzed with particular attention to unusual histomorphological features including gliovascular pseudopapillary structures to firmly validate - or revise - the previous notion that histological appearance of PXA is of little benefit in prognosis (12). Finally, whether or not the numerous osteoclast-type giant cells found within the fibrosarcoma-like portion of the recurrent tumor could possibly be attributed to the pleomorphic cellular component of the primary PXA lesion remains a thought-provoking but speculative consideration.


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Contributed by Stephan Frank, Dominik Cordier, Markus Tolnay and Marc K. Rosenblum

International Society of Neuropathology