Multicentric malignant glioma with striking morphologic heterogeneity and early and extensive metastatic spread to...

We document the case of a young adult female patient who presented with multiple intracerebral and extracerebral bone lesions, the latter most prominently along the vertebral column. The spatially distinct intracerebral lesions included a superficial frontal tumor nodule as well as diffuse enlargement of the pons. Differential diagnoses ranged from neoplastic to inflammatory conditions. Repeated bone biopsies yielded uncharacteristic reactive changes whereas cerebrospinal fluid cytology pointed towards a neoplastic disease. Resection of the superficial frontal tumor nodule prompted the diagnosis of an unusual "gliofibroma" with anaplastic features, WHO grade III. TMZ chemotherapy was initiated and led to intracranial disease stabilization, whereas the bone lesions were progressive. At 16 months after diagnosis, new brain lesions occurred, and further progression of the brain stem lesion led to clinical deterioration and patient death. Postmortem examination confirmed extensively disseminated intracranial disease with unusually striking morphologic heterogeneity across the various lesions ranging from diffuse spindle-celled areas to perivascular rosettes and embryonal-like areas. The morphologic heterogeneity was in contrast to shared epigenomic and copy number profiles supporting a common origin. Of note, molecular markers and DNA methylation-based classifier scores did not allow for unequivocal glioma classification. Ultimately, the bone lesions revealed scattered nests of GFAP-positive cells, thus confirming them as glioma-derived metastases. No other systemic organ involvement was found. In summary, this case 1) illustrates the strikingly heterogeneous morphological landscape of malignant gliomas, 2) serves as an example for rare cases that do not fit in any diagnostic category despite extensive molecular profiling, and 3) highlights the potential of gliomas for early systemic metastases - in the present case with selectivity for the bones.