Case 578 -- A 28-year-old man with headache, visual and aphasic speech disturbances

Contributed by Stephan Frank 1, Dominik Cordier 2, Markus Tolnay 1 and Marc K. Rosenblum 3
     1 Institute of Pathology, Department of Neuropathology, University Hospital Basel, Basel/Switzerland
     2 Department of Neurosurgery, University Hospital Basel, Basel/Switzerland
     3 Memorial Sloan-Kettering Cancer Center 1275 York Avenue, New York, NY 10065, U.S.A


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.


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. 3). In these areas, tumor cells were radially anchored to the central, often hyalinized vessel structures (Fig. 4, Masson-trichrome) by variable, sometimes short and stout processes (Fig. 5). Whereas tumor cell nuclei appeared round to oval and frequently featured intranuclear inclusions, cell bodies often showed coarse cytoplasmic vacuolization (Fig. 6). 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.

The majority of tumor cells were strongly immunopositive for GFAP (Fig. 7), S100 and vimentin. Focally, tumor cells expressing MAP2 as well as CD34 (Fig. 8) 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. 9).

In contrast, the recurrent tumor appeared fibrosarcoma-like with a pronounced and mitotically active spindle cell component (Fig. 10) replete with a dense reticulin fibre network surrounding most of the individual tumor cells. Numerous intermingled osteoclast-type giant cells were found (Fig. 11). In addition to this sarcomatous component pseudopapillary gliovascular structures reminiscent of those featuring prominently in the primary lesion were identified (Fig. 12). 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. 13). Moreover, EGBs were encountered at the periphery of the focally well-demarcated tumor (Fig. 14). Mitotic activity was dramatically increased (see Fig. 10). 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. 15). 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.


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