A 28‐YEAR‐OLD MAN WITH HEADACHE, VISUAL AND APHASIC SPEECH DISTURBANCES

CLINICAL HISTORY AND NEURORADIOLOGY

In April 2006, a 28‐year‐old previously healthy man experienced headache, visual and aphasic speech disturbances. MR‐imaging revealed a large, partly cystic mass of the left temporal lobe with significant contrast enhancement (Fig. 1). At surgical resection, due to infiltration of Wernicke's speech area, only subtotal tumor removal was achieved. Subsequent adjuvant therapy consisted of external beam radiotherapy (60 Gy) combined with temozolomide chemotherapy (75 mg/m²). After an uneventful clinical course of 14 months, a follow‐up MRI in June 2007 showed a nodular and contrast‐enhancing lesion at the anterior aspects of the former resection cavity. At subsequent craniotomy, the recurrent lesion could be dissected from cortical tissue circumferentially and gross total resection was achieved. Second‐line chemotherapy with bevacizumab and irinotecan was initiated.

Figure 1.

MICROSCOPIC PATHOLOGY

Neuropathological examination of the 2006 specimen revealed a polymorphous astroglial tumor with microvascular proliferates and areas of geographic necrosis (Fig. 2). Remarkably, the tumor featured large portions with conspicuous gliovascular, rosette‐like histoarchitectures imparting a pseudopapillary appearance (Fig. 4). In these areas, tumor cells were radially anchored to the central, often hyalinized vessel structures (Fig. 3, Masson‐trichrome) by variable, sometimes short and stout processes (Fig. 4). Whereas tumor cell nuclei appeared round to oval and frequently featured intranuclear inclusions, cell bodies often showed coarse cytoplasmic vacuolization (Fig. 5). Only rarely, globoid hyaline structures reminiscent of eosinophilic granular bodies (EGB) were observed, whereas Rosenthal fibres were absent. In other, more compact and cellular regions of the tumor, a spindle cell‐like cytomorphology was predominant. Induction of reticulin fibres was observed only focally. No ganglion cell component was identified.

Figure 2.

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Figure 5.

The majority of tumor cells were strongly immunopositive for GFAP (Fig. 6), S100 and vimentin. Focally, tumor cells expressing MAP2 as well as CD34 (Fig. 7) at moderate levels were identified. A subfraction of tumor cell nuclei was immunopositive for p53. No expression of synaptophysin, neurofilament, neuron‐specific enolase, Melan A, cytokeratin and epithelial membrane antigen was noted. Whereas the Ki67 proliferation index exceeded 10% focally, only few mitotic figures were identified (Fig. 8).

Figure 6.

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Figure 8.

In contrast, the recurrent tumor appeared fibrosarcoma‐like with a pronounced and mitotically active spindle cell component (Fig. 9) replete with a dense reticulin fibre network surrounding most of the individual tumor cells. Numerous intermingled osteoclast‐type giant cells were found (Fig. 10). In addition to this sarcomatous component pseudopapillary gliovascular structures reminiscent of those featuring prominently in the primary lesion were identified (Fig. 11). Again, coarse cytoplasmic vacuolization of the glial component was found, and intracytoplasmic lipid accumulations could be demonstrated on oil‐red‐O‐stained frozen sections (Fig. 12). Moreover, EGBs were encountered at the periphery of the focally well‐demarcated tumor (Fig. 13). Mitotic activity was dramatically increased. Diagnostic immunohistochemical work‐up of the recurrent tumor revealed strong GFAP as well as focal MAP2 and CD34 expression by the glial component. In addition, many ramified CD34‐positive satellite cells were found within non‐infiltrated cortex bordering the tumor (Fig. 14). In subfractions of the glial and spindle cell populations nuclear immunoreactivity with antibodies against the p53 protein was observed. The Ki67 labeling index now exceeded 20% within wide portions of the tumor, and numerous mitotic figures were encountered.

Figure 9.

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Figure 14.

DIAGNOSIS

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

DISCUSSION

This report illustrates the previously unprecedented case of a PXA 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 featured short and rather stout processes that together with the hyalinized vessel structures also prompted inclusion of an astroblastoma into our differential. Because of 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 additionally featured large fibrosarcoma‐like portions, and was diagnosed as pleomorphic xanthoastrosarcoma (WHO grade IV), conceptually to be considered as gliosarcoma.

PXAs are uncommon, often seizure‐associated tumors typically occurring in the temporal lobe of children and young adults. They are unique neoplasms which despite an often striking cellular pleomorphism feature a relatively benign clinical behavior (see (1) and refs. therein). 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. Mitotic index and extension of resection appear to be important prognostic indicators of recurrence‐free and overall survival (1), as may be necrosis. However, even the absence of increased mitotic activity and necrosis does not preclude a dramatically malignant clinical course, suggesting that additional histomorphological and (yet to be identified) molecular‐genetic parameters may be of importance.

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 (2), so that their presence may warrant close postoperative follow‐up. 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 (3).

ABSTRACT

A 28‐year‐old man presented with a short history of headache, visual and aphasic speech disturbances. MR scans revealed a large, partly cystic, contrast‐enhancing lesion of the left temporal lobe that upon microscopic examination was diagnosed as pleomorphic xanthoastrocytoma (PXA) with anaplastic features (WHO grade III). Remarkably, this tumor featured an unusual gliovascular, rosette‐like histoarchitecture, which had previously been hypothesized to possibly indicate a greater likelihood of PXA recurrence. Indeed, only 14 months later, the patient presented with a recurrent lesion, which contained the previous histology, but now also featured a distinct fibrosarcoma‐like component replete with numerous osteoclast‐type giant cells. In addition, whereas eosinophilic granular bodies were plentiful at the lesion's periphery, numerous CD34 ‐ positive satellite cells were found in the adjacent non‐infiltrated cortex. Regarding the origin of this recurrent tumor and in reflection of its composition of distinct PXA as well as sarcomatous components, the diagnosis of a pleomorphic xanthoastrosarcoma, to be conceptually considered as a gliosarcoma subtype, was made. To our knowledge, this is an unprecedented case of sarcomatous transformation of a PXA. Particular attention should be given to gliovascular pseudopapillary structures in PXAs, the presence of which may potentially herald a more aggressive clinical behavior.