The interpretation of routine H&E-stained sections and immunohistochemistry from CNS lesions can be difficult and risky when performed outside of the context of clinical and neuroimaging data. Indeed, many difficulties may arise from attempts to establish a diagnosis based on morphology alone. As detailed in the preceding chapters, the differential diagnosis for surgical neuropathology specimens varies widely depending on the lesion location, imaging characteristics, and patient age. Together, these variables should guide the establishment of pretest probabilities of diagnoses and streamline the interpretation of histologic findings, winnowing numerous distinct entities to a manageable few. Outside of the context of these clues, some CNS lesions with vastly divergent outcomes may differ only very subtly from one another histologically. Simply put, surgical neuropathology cannot be practiced in a vacuum, and the most appropriate diagnosis will only be reached consistently with a disciplined approach that includes input from as much clinical and neuroimaging information as is available.

The following series of tables lists differential diagnoses based on clinical/imaging information (Tables 20-1 to 20-8) and covers most surgical neuropathology specimens but is not intended to be exhaustive.

After establishing a differential diagnosis based on age and neuroimaging, microscopic examination in surgical neuropathology progresses in an algorithmic fashion, starting with a determination of whether the tissue is normal. This can be a daunting task in some cases where the histologic findings are minimal, as in some lower-grade infiltrating gliomas. Abnormal tissue can then be categorized into one of several general pathophysiologic processes, such as reactive/inflammatory, infectious, or neoplastic, from which more specific diagnoses are developed. Another approach is to separate lesions by overall low-magnification pattern, such as circumscribed, infiltrative, perivascular, and leptomeningeal, which to some
extent recapitulates neuroimaging data. Regardless of approach, systematic histologic evaluation for all entities consistent with a particular lesion’s clinical/imaging features is encouraged and will help to prevent inadvertent omission of the correct diagnosis from consideration.