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Current Concepts in the Diagnosis of Gliomas
Richard A. Prayson and Gene H. Barnett
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INTRODUCTION
A variety of neoplastic lesions are encountered in the routine practice of surgical
neuropathology. These often present a considerable diagnostic challenge and can be the source of much
confusion and anxiety. Obtaining an accurate final pathologic diagnosis is the goal of the biopsy
procedure and is often dependent on how tissue is initially evaluated and processed. For this reason,
the importance of intraoperative consultation cannot be underestimated.
The vast majority of lesions for which a diagnostic brain biopsy is being performed will
require intraoperative consultation. The process is important for a number of reasons. It ensures that
the tissue sampled is adequate for purposes of diagnosis and is a true representation of what is
visualized radiographically. Intraoperative consultation can guide further operative management, e.g.
whether or not additional tissue is required for purposes of diagnosis or in the case of certain lesions,
what type of surgical procedure should be performed. It affords the pathologist a sense of what kind of
lesion he or she is dealing with and subsequently will guide how tissue is processed or triaged.
Finally, it may afford the neurosurgeon or neuro-oncologist an opportunity to begin preparing the patient
and family for a diagnosis.
Tissue sent for intraoperative consultation may be obtained either by an open procedure
and resection or via a needle biopsy stereotactic procedure. Often, the stereotactic needle biopsy
procedure is preferred because of
- a decreased risk of morbidity and mortality versus an open craniotomy procedure,
- better accessibility of deep-seated lesions or lesions in vital areas,
- in situations where a pathologic diagnosis is required prior to a more definitive open surgery procedure, and
- situations where cytoreductive surgery is not deemed necessary.
The morbidity associated with the
stereotactic biopsy procedure has been reported to range from 2% to 6%, with mortality rates reported
between 0% and 2.3%. Diagnostic yields have exceeded 90% in number of series, although several core
biopsies may need to be taken before a diagnosis can be made. In one study reviewing stereotactic
biopsies performed in a 185 patients, Brainard et al reported a diagnosis rate of 67% when only one
biopsy was evaluated at the stereotactic target site. In 16% of cases, additional biopsies were required
(in some instances up to 6) before a correct diagnosis could be made. This underscores the importance of
communication at the time of surgery between the neurosurgeon and the pathologist in terms of assessing
the adequacy of each biopsy.
Evaluation of the tissue received in the pathology suite at the time of intraoperative
consultation begins with an assessment of the clinical scenario. Information including age of the
patient, location of the lesion or lesions, radiographic impression, and prior surgical history may all
be helpful in the early formulation of a differential diagnosis. Frequently, the neuro-oncologist and
neurosurgeon have a good idea of what the biopsy material may represent beforehand, based on the clinical
and radiographic presentation.
There is considerable debate in the literature with regard to the relative benefit of
processing intraoperative consultative material via frozen section or cytologic preparation. Certainly
in situations when there is ample tissue, utilization of both procedures may be helpful. However, in the
context of stereotactic biopsies where the amount of material is limited, judicious use of the tissue is
required. There is certainly many advantages and disadvantages to each approach. Deciding factors as to
which methodology one decides to employ often focuses on three main issues:
- the amount of tissue actually received,
- the quality of histologic material obtainable from frozen section at a given institution, and
- the comfort level of a given pathologist in interpreting a frozen section versus cytologic preparation (which is often dependent on how one was trained to look at neuropathologic material).
Regardless of which method one decides to employ, the entire specimen should generally not be
exhausted in the intraoperative consultative process; some tissue should be retained for standard
fixation and tissue processing. Even with small stereotactic biopsies, where material is particularly
limited, one can usually divide the specimen in half and obtain satisfactory frozen section results.
Obviously, cellular morphologic detail is better visualized in the cytologic preparation, but it often
comes at the expense of lost architectural detail, which is somewhat preserved on frozen section. In
certain situations, cytologic preparations may be particularly advantageous i.e. evaluation of
macrophages or viral inclusions.
Once the specimen is processed for intraoperative consultation, the pathologist has the
task of determining whether or not the specimen is diagnostic or representative of the lesion seen
radiographically. This involves assessment as to whether or not the tissue is normal or abnormal, and
whether the tissue represents a neoplasm or not. If one decides that the lesion is neoplastic, an
attempt to evaluate tumor type and tumor grade should follow. Care needs to be taken not to "over-call"
or over-diagnose. Similarly, one should not succumb to pressures to make a diagnosis simply to
accommodate the radiographic or intraoperative impression. This may lead to a premature termination of
the biopsy procedure with a false expectation that adequate tissue has been obtained. Obviously, one's
ability to interpret these cases is somewhat dependent on previous experience and understanding of the
lesions and their differential diagnoses. Consequently, if one is not familiar with a particular entity,
one is not likely to make the diagnosis.
Once a preliminary diagnosis is rendered or decision made that representative tissue has
been obtained, the pathologist is responsible for triaging the remaining tissue appropriately for
potentially useful ancillary studies. In addition to routine processing of tissue for histology,
triaging tissue (or obtaining blood for control purposes in DNA testing) for potential molecular biologic
studies or immunofluorescent studies may be indicated. Placing tissue into the appropriate fixative for
ultrastructural analysis when of potential utility (e.g. differential diagnosis of ependymoma versus
astrocytoma) is also important. In cases of suspected infectious processes, tissue should be obtained
for microbiologic cultures.
Selected References
- Alesch F, Kitz K, Koos WT, et al. Diagnostic potential of stereotactic biopsy of midline lesions. Acta Neurochir (Suppl). 53:33-36, 1991.
- Apuzzo MLJ, Chandrasoma PT, Cohen D, et al. Computed imaging stereotaxy: experience and perspective related to 500 procedures applied to brain masses. Neurosurgery 20:930-937, 1987.
- Bernstein M, Parren AG. Complications of CT-guided stereotactic biopsy of intra-axial brain lesions. J Neurosurg 81:165-168, 1994.
- Brainard JA, Prayson RA, Barnett GH. Frozen section evaluation of stereotactic brain biopsies. Arch Pathol Lab Med 121:481-484, 1997.
- Burger PC, Nelson JS. Stereotactic brain biopsies. Specimen preparation and evaluation. Arch Pathol Lab Med 121:477-480, 1997.
- Chandrasoma PR, Smith MM, Apuzzo ML. Stereotactic biopsy in the diagnosis of brain masses: comparison of results of biposy and resected surgical specimen. Neurosurgery 24:160-165, 1989.
- DiDivitiis E, Spaziant R, Cappabianca P, et al. Reliability of stereotactic biopsy: a model to test the value of diagnosis obtained from small fragments of nervous system tumors. Appl Neurophysiol 46:295-303, 1983.
- Grunert P, Ungersbock K, Bohl J, et al. Results of 200 intracranial stereotactic biopsies. Neurosurg Rev 17:59-66, 1994.
- Kepes J. Pitfalls and problems in the histopathologic evaluation of stereotactic needle biopsy specimens. Neurosurg Clin N Am 5:19-33, 1994.
- Taratuto AL, Selever G, Piccardo P. Clues and pitfalls in stereotactic biopsy of the central nervous system. Arch Pathol Lab Med 115:596-602, 1991.
- Wen DY, Hall WA, Miller DA, et al. Targeted brain biopsy: a comparison of freehand and computed tomography-guided and stereotactic techniques. Neurosurgery 32:407-413, 1993.
TEXT AND REFERENCES
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CASES
31-year-old male with a non-enhancing mass in the right frontal lobe.
Case 1 - Figure 1 - Hypercellular white matter parenchyma with a slight unevenness in cell distribution.
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Case 1 - Figure 2 - Scattered atypical appearing astrocytes marked by nuclear enlargement and irregular nuclear contours.
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Case 1 - Figure 3 - Infiltrating atypical astrocytes satelliting around cortical neurons (secondary structures of Scherer).
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44-year-old female with a non-enhancing left frontal lobe mass.
Case 2 - Figure 1 - Hypercellular parenchyma with a perivascular lymphocytic infiltrate commonly seen in this variant.
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Case 2 - Figure 2 - Gemistocytic astrocytoma consisting of two cellular components: a prominent large cell component characterized by gemistocytic astrocytes with abundant eosinophilic cytoplasm and eccentric nucleus and a small cell component marked by atypical astrocytes with high nuclear to cytoplasmic ratio and irregular nuclear contours.
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Case 2 - Figure 3 - Strong glial fibrillary acidic protein (GFAP) immunoreactivity in the gemistocytes.
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Case 2 - Figure 4 - MIB-1 immunoreactivity is generally confined to background astrocytic tumor cells and is absent in the gemistocytes.
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36-year-old male with a left temporal lobe enhancing mass.
Case 3 - Figure 1 - Prominent vascular (endothelial) proliferative marked by a piling up of cells around vascular lumina.
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Case 3 - Figure 2 - Focal area of tumor necrosis without perinecrotic pseudopalisading in a GBM.
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Case 3 - Figure 3 - Moderate hypercellularity and nuclear pleomorphism with readily evident mitotic activity.
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Case 3 - Figure 4 - Prominent MIB-1 immunoreactivity corresponding to a rapid rate of cell proliferation in GBM.
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51-year-old male with changes and possible expansion of a right parieto-occipital lobe lesion, s/p radiotherapy.
Case 4 - Figure 1 - Prominent perivascular sclerosis in an irradiated astrocytoma.
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Case 4 - Figure 2 - Perivascular chronic inflammation likely related to radiation and adjacent reactive astrocytosis.
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Case 4 - Figure 3 - Focus of geographic necrosis lacking a pseudopalisade of cells with astrocytosis and adjacent sclerotic vessel.
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Case 4 - Figure 4 - Marked macrophage infiltrate most likely related to radiation.
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26-year-old female with a well-demarcated non-enhancing mass.
Case 5 - Figure 1 - Moderately hypercellular white matter with a prominent delicate capillary pattern.
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Case 5 - Figure 2 - Increased oligodendroglial cells marked by round, monomorphic nuclei, scant cytoplasm and perinuclear halos ("fried egg").
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Case 5 - Figure 3 - Satellitosis of infiltrating tumor cells around pre-existing structures (neurons and vessels in the cortex).
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Case 5 - Figure 4 - Subpial accumulation of tumor cells in the cortex.
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48-year-old male with a focally enhancing right frontal lobe tumor.
Case 6 - Figure 1 - Markedly hypercellular parenchyma without obvious vascular proliferation.
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Case 6 - Figure 2 - Somewhat monotonous proliferation of atypical oligodendroglial cells.
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Case 6 - Figure 3 - The infiltrative edge of the tumor demonstrates cytologic features (including the fried egg artifact) more easily recognizable as oligodendroglioma.
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33-year-old female with a C7 intramedullary mass and associated syrinx.
Case 7 - Figure 1 - Hypercellular lesion with prominent blood vessels.
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Case 7 - Figure 2 - Perivascular pseudorosettes in an ependymoma.
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Case 7 - Figure 3 - Focally an epithelial component was evident with ciliated columnar cells reminiscent of normal ependyma.
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17 year old male with a left lateral ventricular-based mass.
Case 8 - Figure 4 - Focal perinecrotic pseudopalisading in a high grade ependymoma. Some might designate such lesions as glioblastoma.
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Case 8 - Figure 5 - The ultrastructural appearance confirms the ependymal nature of the neoplasm – microvilli and blepharoplast are evident.
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