Preparation for an IC begins with a careful review of the patient’s clinical history. Based on the age, clinical history, lesion location, and other neuroimaging findings, one can establish a preoperative list of potential diagnoses (see Chapter 20). This list of diagnoses allows for assessment of whether the observed histology is representative of the targeted lesion and can frame the degree of certainty one should place in the interpretation of that histology. For instance, a stereotactic biopsy in a 65-year-old of a ring-enhancing hemispheric lesion that reveals mildly hypercellular brain tissue with scattered atypical glial cells and no mitosis or other findings was probably taken in the vicinity of a glioblastoma and not sufficient for that diagnosis. In such cases, more tissue should be requested.

Neuroimaging is a crucial component of surgical neuropathology, serving as a sort of gross examination of the entire lesion in the context of the adjacent structures. Although it’s not practical to know neuroradiology in detail, the pathologist should know what helpful features to look for in the imaging report, if not the images themselves. Some important questions include: What is the location? Is it intrinsic or extra-axial? Is it circumscribed and discrete, or ill-defined? Is it cystic? Is it multifocal? Does it have associated edema (T2/FLAIR signal)? Does it expand involved structures or have other mass effect? Is it contrast-enhancing? Does it demonstrate restricted diffusion? At a minimum, one should be familiar
with the findings of the neuroimaging report and the radiologist’s opinion as to what the findings represent.

Although not always feasible, direct communication with the surgeon prior to the procedure can be helpful to fill in potential gaps in the patient’s history that may not be fully communicated in the medical record. In emergent cases, direct communication may be the only source of patient history. The pathologist should also inquire as to whether there are any special considerations for allotment of tissue, such as for research, culturing, clinical trials, or molecular testing. In cases where lymphoma is suspected, it is crucial to know whether the patient received corticosteroids because it can drastically alter and obscure the usual histopathology.

One should be vigilant when reviewing clinical histories of prospective IC patients for potential cases of Creutzfeldt-Jakob disease (CJD). Such patients are typically at least 60 years of age and have rapidly progressive dementia, visual impairment, and myoclonus. When a brain biopsy is undertaken in a potential case of CJD, the tissue should not be examined intraoperatively, rather it should be processed separately from all other tissue using a special protocol for potential prion disease specimens. Contamination of the frozen section laboratory with prion protein from such specimens could potentially halt IC operations while decontamination is performed. A protocol for handling potential prion disease specimens is publicly available on the Internet from the United States National Prion Disease Pathology Surveillance Center at Case Western Reserve University.

There are three types of specimens that account for most neurosurgical ICs; from largest to smallest they are: open biopsy/resection, stereotactic needle biopsy, and endoscopic biopsy. Open biopsies or resections are
typically large, and there is no question as to whether the lesion has been sampled, rather the purpose of ordering an IC is to identify the general tumor type, which may impact how aggressively the lesion is excised, or, in the case of metastasis or infectious lesion, what other testing or imaging may be needed. Needle core biopsies, on the other hand, are performed by stereotactic coordinates without direct visual guidance, introducing a number of factors that may result in unsatisfactory or nonrepresentative tissue cores. For these specimens, the IC is primarily for ensuring tissue adequacy for diagnosis and ancillary testing. Endoscopic biopsies are under direct visual guidance, but are only able to collect minute fragments of tissue that may not be representative.

Regardless of the type of IC specimen, a few principles should guide the triage and apportionment of tissue. The most important is to always reserve some of the tissue sent for IC for routine paraffin embedding. Most of the time, a separate specimen will be sent for routine processing, but conditions may prevent the surgeon from collecting additional tissue, or the additional tissue may be unsatisfactory. Not only does frozen tissue have degraded histomorphology, freezing can alter the immunoreactivity of the tissue for some antibodies, making it less suitable for establishing the final diagnosis. In the event that all of the tissue must be used for IC, that should be communicated to the surgeon so that more can be collected if possible. In IC cases with limited tissue, cytologic preparation alone without frozen section is better to preserve tissue for processing.

Beyond retaining some of the tissue for paraffin embedding and depending on the IC diagnosis, additional tissue may need to be submitted for other testing, such as flow cytometry for lymphoma, culturing for infectious process, or frozen tissue for clinical trial eligibility or molecular testing. Communication with the surgeon about who is responsible for submitting what testing is crucial to avoiding duplicate efforts or lost opportunities.

Although most neuropathology IC specimens are small, many of the common diagnostic entities have typical gross appearances that can further inform histopathologic observations (Table 19-2). With experience, one can anticipate the histologic diagnosis in many cases by gross examination, as can some experienced neurosurgeons.

An important and time-honored component of neuropathology IC is the smear or squash preparation, in which a small amount (1 to 2 mm3) of fresh tissue is placed on a glass slide and smeared across the surface by another slide (Figure 19-1), spreading out the cellular elements and allowing for examination of the cytologic details without the distortion caused

by the freezing process. Smear preparations are alone sufficient in many cases to identify lesional tissue and are used for IC without concurrent frozen section in some institutions, allowing for more tissue to remain unfrozen for routine processing. Indeed, if tissue is limited, frozen section should be omitted and only cytologic examination should be performed, preserving the maximal amount of specimen for paraffin embedding.