Intraoperative Neuropathology for non-Neuropathologist
Timothy Smith and Cynthia Welsh
The after hours call from the operating suite where a neurosurgeon is operating tends to be one that
sends blood pressure soaring. It doesn't have to be that way. There are basic steps that can help make
the experience much less stressful. Generally you know the age, which narrows the differential
considerably. The location, history of the patient (neurofibromatosis, or known breast cancer for
example), and type and duration of symptoms can all be very illuminating, if you can pry that information
out of the neurosurgeon. We glean the electronic record for information prior to regularly scheduled
cases, although that doesn't generally work as well for the evening/weekend emergent surgery. The
radiologic characteristics of the lesion can be the MOST important collection of facts in compiling a
differential (well-circumscribed versus infiltrative, enhancing versus non-enhancing, diffusion and
perfusion characteristics and location for example). It never fails to amaze us how often one piece of
clinical information clears up the most confusing issues that you've been sitting at the microscope
beating your head on the wall about. Remember, even though it is brain, asking for more tissue is often
an option (many tumors are huge!). Telling the neurosurgeon you think he is close to something, but not
directly in a diagnostic area, is also permissible.
Intra-operative pathology consultations from the neurosurgeon don't require the same answers that
would need to be in the final diagnosis. Just knowing the limits of what the neurosurgeon really has to
know can be calming. Some questions have intra-operative repercussions, such as with the primary spinal
cord tumor; the operation for an ependymoma is quite different from that for an astrocytoma of any
type or grade. On the other hand, knowing that an adult cerebral tumor is a high grade glioma is all the
neurosurgeon often wants to know (not how high a grade or whether there is an oligodendroglial
component). The object of inspecting the biopsy, particularly CT guided biopsy, may be to acquire
diagnostic material (not necessarily make the diagnosis intra-operatively), so it may be that all you
have to tell them is 'yes this is a good area to acquire more tissue for diagnosis'.
Frozen sections in neuropathology have some distinct problems. There is more of a tendency toward ice
crystal artifact than in almost any other intra-operative frozen section. This can be overcome by
freezing the tissue more quickly. The other difficulties involved include those common to all tissues
(nuclear and cytoplasmic changes which unfortunately are at least semi-permanent) and the parsimonious
amount of tissue usually provided by neurosurgeons (even if the lesion is 6 cm!). Some of the problems
inherent to frozen sections can be compensated for by cytologic preparations. A smear preparation takes
very little tissue, just a pinpoint fragment, so it isn't really taking away from the frozen diagnosis.
Never forget that it may not be representative if you don't sample all the different areas. Some
structures are just so much easier to see in a smear preparation, and nuclear detail and nucleoli are
actually useful as compared to many frozens. Some cell types which tend to blend into the background,
but can actually save you from making the wrong diagnosis (such as macrophages), can be seen much better
in cytologic preps. We don't usually make only smears like some institutions. We are very pattern
(architecture) oriented and like to see a frozen section as well as the cytology prep, which we feel are
complimentary. We almost never rely only on smears, but some institutions do. We feel cellularity is
information that is only reliably obtained from frozen sections, not cytology.
The way the tissue smears, allows you to begin making some decisions about it. Normal brain/cord
smears very easily and evenly. Some tumors (i.e. schwannoma, most meningiomas) and normal structures
(i.e. dura) do not really smear at all. There are a lot of things both neoplastic and non-neoplastic
which smear partly and therefore do not add much information that way.
Start by deciding which stain you are comfortable with using. If you like Diff-Quik stains for your
other cytology, they are an alternative for this purpose also (whether air dried or fixed Diff-Quik). If
you prefer H&E stains, then air drying can be a big problem and can render them fairly useless, so
the slides need to go into fixative immediately. We have our residents fix the smeared slides while they
cut the frozen sections, and then run them all through the H&E stain together (saves time and
effort). We intentionally use Diff-Quik stains for possible lymphomas of course, they work well for
metastases, and often the Diff-Quik is what the resident chooses.
| ||Smear ||Frozen|
|Advantages ||Nuclear detail ||Architecture|
Effacement of vessels
Effacement of macrophages
Degranulation of pituicytes
Evaluating neuropathology slides intra-operatively starts where you always start:
- is this nervous system tissue?
- if yes, where?
- if no, what kind of tissue is it?
- is it abnormal ? ; too cellular ?
- what kind of cells are present, are they normal constituents, inflammatory cells, etc?
- if the hypercellularity is inflammation and astrocytes, is this reactive?
- if not reactive, is it neoplastic, and what cells are neoplastic ?
Location-based Major Tumor Differential Diagnosis in an Adult
Other primary bone lesions/tumors
Metastases and locally invasive tumors (sinonasal, orbital, other head/neck)
Meningeal involvement by glioma
Subcortical white matter
High grade fibrillary astrocytoma, esp. glioblastoma
Low grade fibrillary astrocytoma
Primary CNS Lymphoma
Germ cell tumor
Pineal parenchymal tumor
Germ cell tumor
Choroid plexus tumor
Other primary bone lesions/tumors