DIAGNOSIS Cerebellar pleomorphic xanthoastrocytoma
A differential diagnosis based on imaging alone would include juvenile pilocytic astrocytoma (JPA), a common cerebellar tumor in the pediatric population, and ependymoma, given the lesion's association with the fourth ventricle. Expanding the radiologic differential to include other lesions of the cyst/mural nodule variety would include ganglioglioma, hemangioblastoma and pleomorphic xanthoastrocytoma (PXA). Medulloblastoma might be considered in this midline cerebellar mass in a young man, but cysts are unusual in medulloblastomas. On histologic grounds, a diagnosis of JPA is not fitting for a tumor with such abundant cellularity, extreme pleomorphism and lack of microcystic architecture. The lesion is clearly not a "small round blue cell tumor" like medulloblastoma. Ependymomas should show perivascular pseudorosettes, even in the rare giant cell ependymoma. The tumor has neither the fine diffuse vascular network of a hemangioblastoma, nor cells with clear-lipidized cytoplasm. Gangliogliomas have synaptophysin or neurofilament immunoreactivity, features absent in this tumor. Other neoplasms with similar cytology include glioblastoma and metastatic melanoma, but features such as increased mitotic activity, endothelial proliferation and necrosis are not present in this low-grade neoplasm. Malignant histiocytic neoplasms may enter the differential but are exceedingly rare in the central nervous system and lack GFAP. Therefore, the diagnosis for this cerebellar neoplasm is PXA.
PXA was first recognized as a distinct type of astrocytoma by Kepes, et al, in 1979. Most patients are adolescents or young adults who present with seizures. Though typically regarded as superficial meningocerebral neoplasms, PXAs have occurred in the cerebellum, as in this case, and other unusual locations such as spinal cord (3,7) and retina (8). Sixteen cases of cerebellar PXA, including the present case, have been described in the literature, six of which showed combined features of PXA and ganglioglioma and two others with oligodendroglioma (2). Of the previously reported cases of cerebellar PXA, most have occurred in adults, and the range of age at diagnosis was 3 months to 68 years (2). Of the cases of cerebellar PXA with clinical follow-up, only two had poor outcomes with patient death 17.5 months and 3 years after presentation, and both tumors had oligodendroglial components (2). While conventional PXA is a WHO grade II lesion, findings such as necrosis and/ or greater that 5 mitotic figures per 10 high power fields are generally regarded as anaplastic features (5). A study of 71 predominately supratentorial PXAs confirmed the overall favorable prognosis of PXA and showed that extent of resection and mitotic index were the main predictors of recurrence free survival and overall survival (1). Genetic changes associated with infiltrating gliomas (i.e., TP53 mutation, loss of CDKN2A, amplification of CDK4, MDM or EGFR, and loss of heterozygosity at chromosomes 9p, 10, and 17) are rare to absent in cerebral PXAs according to one study (4). To our knowledge, there are no studies addressing prognostic markers or molecular features specific for cerebellar PXA. This case stresses the importance of including PXA in the differential diagnosis of a cerebellar lesion.
Contributed by Gabrielle A. Yeaney, MD, Siobhan M. O'Connor, MD, Brian T. Jankowitz, MD, Ronald L. Hamilton, MD