A major challenge in the routine practice of surgical neuropathology is the distinction between reactive
astrocytosis, which may be because of non-neoplastic and neoplastic conditions, and a low-grade infiltrating diffuse
astrocytoma [World Health Organization (WHO) grade II]. This can be particularly challenging with small biopsies that often yield limited amounts of tissue for pathologic study, especially considering the marked differences in prognosis and
therapy after a pathologic diagnosis. This paper will review some basic principles of
gliosis as an astrocytic reaction to a wide range of central nervous system insults and focus on some common diagnostic pitfalls such as (1)
gliosis associated with
brain tumor mimics, including
demyelinating disease and
infections, (2)
gliosis associated with nonglial
tumors such as
craniopharyngioma,
hemangioblastoma,
metastases, and central nervous system
lymphoma. New diagnostic methods have facilitated the differentiation between reactive
astrocytosis and the diffuse
gliomas. Of these, the use of mutated
isocitrate dehydrogenase-1 (IDH-1) as a marker of diffuse infiltrating astroctomas,
oligodendrogliomas, and a subset of
glioblastomas (secondary
glioblastomas) is particularly exciting for tissue diagnosis and patient prognosis. In addition IDH-1 may be useful to distinguish a diffuse infiltrating
glioma from low-grade "focal"
neoplasms such as the pilocytic astocytoma in histologically ambiguous cases. The discovery of BRAF mutations as molecular signatures of some
pilocytic astrocytomas,
gangliogliomas, and
pleomorphic xanthoastrocytomas has provided another diagnostic tool for the pathologist. Only after a definitive diagnosis of a diffuse infiltrating
glioma or a focal
glioma is made should a
tumor grade be applied and some practical issues in current
glioma grading are provided.