approaches that will be most beneficial for their future practice of neurosurgery. It is our opinion that the answers to the following three questions should be emphasized:
How is a histopathological diagnosis made?
How can one understand the changing diagnostic terminology?
What are the limitations of the histopatho-
logical diagnosis of surgical specimens?
1. How is a Histopathological Diagnosis Made?
Neuropathology can frequently be used simply to confirm or disprove a clinical diagnosis that is made by clinicians based on the clinical presentation and on radiological and laboratory findings. Owing to remarkable advances in diagnostic techniques with high-tech equipment and sophisticated laboratory assays, the clinical diagnosis is probably correct in the great majority of cases. MRI can easily demonstrate neoplasms in the brain and spinal cord and can differentiate extra- or intra-axial site, low or high grade, with or without cyst, calcification and hemorrhage. One can reach a fairly accurate histopathological diagnosis of tumors without a biopsy by combining these factors. Of special note is the fact that MRI is especially sensitive to water, which is notoriously difficult for pathologists primarily because we extract all of the water before embedding the tissue to be stained!
However, there are still groups of pathological processes in which the clinical data cannot be so precise, especially in non-neoplastic lesions, when histopathological study becomes crucial. Students who are trained in particular clinical skills tend to rely on their own clinical experiences and can be prejudiced by their own knowledge. They may be searching for only those signs to support their clinical diagnosis and may overlook other important evidence leading to other diagnoses. On the other hand, those who are trained in basic pathological skills tend to rely on their primary trade and may be caught not only on relatively insignificant artifacts but also on their lack of familiarity with clinical signs and specific neuroanatomical points.
In order to decrease such inevitable bias we encourage students to study the surgical specimens first without any prior demographic and clinical information and to leave the clinico-pathological correlation to later, when the final diagnosis can be revised as appropriate. If the histopathological findings were unique and specific in each disease, one should be able to make a diagnosis of a disease solely by histopathological study with total objectivity. Unfortunately, this has proven frequently not to be the case. The definition of a disease is often too arbitrary and there have been too many diseases for the number of conceivable pathogenetic reactions of human tissue. Therefore, pathologists may not be able to form a specific diagnosis when they examine the specimen without other supportive information, although they should be able to form a group of diagnoses to be differentiated from each other by more advanced techniques or by other clinical information.
In order to be an unbiased observer, one should not assume: (1) that all specimens are pathological, or (2) that all surgical specimens represent some kind of tumor. For those who are not very familiar with histopathological diagnoses, we recommend that they consider the following questions when they confront an unknown slide:
What is the origin of the tissue?
Is it normal or abnormal?
If abnormal, is the abnormality specific or non-specific?
If specific, to which of the following categories does it belong:
Neoplasms? If it belongs to one of the above processes, can you narrow your diagnosis more specifically as to the type of process? Does your tentatively final diagnosis make sense clinically and anatomically?
Let us consider each of these in turn.
What is the Origin of the Tissue?
The more abnormal the tissue, the more difficult it may be to identify the origin of the tissue. Frequently, however, some clues can be found at the edge of the specimen. One may see gray matter, recognizable with neurons, but bits of cerebral cortex cannot easily be differentiated from basal ganglia or spinal cord gray unless one sees leptomeninges on the surface. One may see white matter or myelinated fibers, which should differ in CNS or peripheral nervous system (PNS), but bits of CNS white matter in the cerebrum cannot be distinguished from those in the spinal cord or cerebellum unless one sees other landmarks - again, leptomeninges being helpful in non-cortical locations. White matter bundles separated by thin connective tissue septa are a relatively specific architecture of the optic nerve. Other structures, such as the pituitary gland, pineal gland, peripheral nerve, choroid plexus and leptomeninges can usually be identified with little difficulty.
Is the Tissue Normal or Abnormal?
If one can recognize the site, the degree of abnormality becomes relatively easy to determine. Otherwise, the hypercellularity of most neoplasms and inflammation is usually easy to see. But in other diseases, especially in so-called "borderline cases", hypercellularity may be absent or very difficult to see. A mild increase in glial cells and a mild decrease in neurons can also relate to the thickness and plane of the section. In addition, one may have to struggle with artifacts, especially those that can appear during the removal of the tissue or during the preparation of the slides. It should be noted that the presence of nodular clusters of neurons without lamination is abnormal in neocortex but normal in the pyriform cortex - found in the parahippocampal gyrus. The presence of an external granular cell layer in the cerebellar cortex is normal in the infant up to about 18 months of age. Large clusters of immature granular cells in the striato-thalamic junction or over the caudate nucleus, known as the "germinal matrix", are normal components of fetal brains.
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