Contributed by Jamie Nicole LaBuzetta1, Daniel Mordes2, Isabel Arrillaga1, Andrew Chi1, Jorg Dietrich1
Departments of 1Neurology and 2Pathology, Massachusetts General Hospital
A 34 year-old otherwise healthy man presented with new onset headaches, mild confusion, and subtle left-sided weakness. An MRI scan showed a large heterogeneous 8.9cm x 6.0cm right fronto-temporo-parietal mass with nodular enhancement, significant surrounding edema, and 15mm of midline shift. He underwent an urgent right craniotomy, and began appropriate therapy. Unfortunately, within one week of completion of this therapeutic regimen, his symptoms worsened. He was found to have multiple new bilateral dural-based nodular enhancing lesions on repeat brain MRI. No spinal abnormalities were found. He underwent resection of one of the new lesions. The patient was initiated on a new treatment plan, but unfortunately, neuroimaging revealed further progression of disease (Figure 1). He passed away 5 months and 1 day after diagnosis.
Initial histopathology revealed a biphasic appearance. Some areas contained densely packed, markedly pleomorphic round cells with scant cytoplasm and frequent mitotic figures (Figure 2). Other areas contained abnormal cells with fibrillary processes or cells with a gemistocytic appearance (Figure 3). Abundant necrosis was present. Immunohistochemistry demonstrated that the small round cell component was positive for synaptophysin, but negative for GFAP, while the astrocytic component was strongly positive for GFAP and negative for synaptophysin. Additionally, round cells were strongly positive for p53 and the R132H variant of IDH1, and had retained expression for INI-1 (BAF-47). Molecular testing revealed that the tissue was positive for MGMT promoter methylation and negative for MET amplification.
At the time of recurrence and the second resection, histology revealed only regions of densely packed round cells on low power (Figure 4) that on high power showed marked pleomorphism, scant cytoplasm and frequent mitotic figures (Figure 5). These cells remained positive for synaptophysin (Figure 6) and IDH1 R132H (Figure 7).
Autopsy examination revealed eight tan-grey, dural-based lesions (Figures 8 and 9). Histologic examination of the dural lesions revealed small round blue cells with very frequent mitotic figures; there was evidence of prior microhemorrhage and necrosis. Overall, there was extensive subarachnoid spread of the round cells, including invasion of the cerebellum and brainstem (Figure 10). Further testing with FISH analysis revealed high-level N-MYC amplification. What is your diagnosis?