The pathology of the central nervous system (CNS) is an intimidating area for pathologists. In part this is because we have virtually no role in the gross examination, just processing shreds of gray pulp on gauze, and in part because of the feeling that “it could be anything at all,” including a long list of exotic zebras that look just like the common things except behave completely differently. The fact that we are often asked to make our diagnoses on frozen section does not help matters. However, even in the brain, the list of likely diagnoses is still reasonably short if you have three pieces of key information: the age of the patient, the location, and the radiographic appearance of the tumor. Table 27.1 lists differential diagnoses that should at least put you in the right ballpark.

The most important first step is to start by asking if your “lesion” could be normal tissue (i.e., the surgeon has missed). To answer this question you have to know a little normal histology (Figures 27.1 and 27.2). Pay attention to autopsy brain specimens to get a sense for the normal cellularity and cellular components of brain tissue. Second, you should ask if your lesion is neoplastic or non-neoplastic . The non-neoplastic lesion that pathologists worry most about is the demyelinating lesion, which can look like a tumor by radiology. Abundant foamy macrophages, and an absence of obvious malignant cells, should make you think of a possible demyelinating lesion or infarct (Figure 27.3). Gliosis, a reactive proliferation of astrocytes, can also simulate a glioma (glial tumor) histologically (Figure 27.4). However, once you have decided you have a neoplasm, the real work begins.