Histology for Pathologists

Editors: Mills, Stacey E.

Title: Histology for Pathologists, 3rd Edition

Copyright 2007 Lippincott Williams & Wilkins

> Table of Contents > IV - Nervous System > 11 - Central Nervous System

11

Central Nervous System

Gregory N. Fuller

Peter C. Burger

Introduction

The central nervous system (CNS) is unparalleled among natural systems in terms of structural and functional complexity. As a consequence of its intricate regional architecture, heterogeneous cellular constituents, and an associated extensive and somewhat arcane lexicon, the nervous system is often viewed as a formidably Byzantine realm by many nonneuropathologists; and yet, a working familiarity with the normal morphology of this complex organ must precede optimal evaluation of the many disease states that afflict it. To this end, this chapter will present the salient features of regional neuroanatomy followed by a description of the essentials of microscopic anatomy of the CNS, with special emphasis on those aspects that constitute potential diagnostic pitfalls, including normal anatomic variations, alterations associated with advancing age, reactive changes, and common artifacts.

Regional Neuroanatomy

We have limited this discussion of regional neuroanatomy to those principles of structural organization that are of practical value to the diagnostician, emphasizing the rudiments of neuroembryology by which the basic organization

P.274

Organization of the Spinal Cord and Brainstem

Embryologically, the nascent CNS is a hollow tube formed by the invagination of the neural plate ectoderm. This primitive cylinder is subdivided functionally into a dorsal sensory (alar) plate and a ventral motor (basal) plate. The two are separated by a lateral groove, termed the sulcus limitans, along which develops the efferent autonomic system (Figure 11.1). This primitive organizational pattern is retained, essentially unaltered, in the mature spinal cord. The central gray matter consists of: (a) dorsal horns that receive sensory input from the dorsal roots; (b) ventral horns that contain motor neurons whose axons are conducted to the somatic periphery by the ventral roots; and (c) the lateral autonomic gray matter. Spinal autonomic neurons are confined to thoracic (sympathetic) and sacral (parasympathetic) levels, forming the intermediolateral cell columns. The axons of these preganglionic neurons exit the spinal cord through the ventral roots, ultimately to synapse on postganglionic neurons in the peripheral autonomic ganglia. The sympathetic intermediolateral cell column produces a third horn of gray matter in the thoracic cord, termed the lateral horn (Figures 11.1,11.2). The parasympathetic intermediolateral cell column occupies a similar lateral position in the sacral cord (at the S2, S3, and S4 levels) but does not form a distinct horn.

Spinal Cord

The anatomy of the spinal cord varies according to the level (Figure 11.2). Two enlargements of the ventral horns, one in the cervical region (Figure 11.2A) and another in the lumbosacral region (Figure 11.2C), provide motor innervation for the upper extremities and lower extremities, respectively. In contrast, the ventral horns of the thoracic cord provide innervation for the more limited axial musculature of the trunk and are, accordingly, much smaller (Figure 11.2B). As mentioned earlier, the lateral horns of the gray matter (sympathetic neurons) are a unique feature of the thoracic cord. The thickness of the surrounding white matter fiber bundles (termed funiculi) also varies with cord level, being greatest in the cervical cord, where the thickness reflects the summated accrual of ascending fiber tracts that have successively entered at lower levels, as well as the maximum content of descending tracts that are en route to lower levels, and thinnest in the lumbosacral cord. The terminus of the spinal cord, the filum terminale, is composed primarily of meningeal connective tissue in the human and is discussed separately with the pia-arachnoid (Figure 11.56).

P.275

Brainstem

The brainstem is innately more complex than the spinal cord, but its basic organization is readily understood when viewed as a slightly modified version of the basic plan. Thus, the stem is also a neural tube but one that has been stretched dorsally and splayed out laterally so that the ventrally located embryonic motor plate is now medial and the dorsal sensory plate is lateral (Figure 11.1). Therefore, within the brainstem, the cranial nerve motor nuclei are located medially, the sensory nuclei laterally, and the autonomic nuclei are intermediate in position.

The brainstem can be further subcategorized in cross section into tectum, tegmentum, and base. The tectum is the roof of the ventricular system, as exemplified by the superior and inferior colliculi (corpora quadrigemina) of the midbrain and the superior medullary vela of the pons and medulla. The tegmentum forms the floor of the cerebral aqueduct and fourth ventricle and is divisible into the medial motor and lateral sensory areas discussed previously (Figure 11.1). The base is located subjacent to the tegmentum and is the most ventral portion of the stem. It is composed principally of the so-called long tracts that is, the descending motor pathways and ascending sensory pathways that link the spinal cord with higher neural centers. The combination of long tract signs with dysfunction of specific cranial nerves allows the precise anatomic localization of brainstem lesions by clinical examination.

Cerebellum

Embryologically, the cerebellum arises as a dorsal outgrowth of the fetal brainstem and remains connected to it in the adult by the three pairs of cerebellar peduncles: the superior (brachium conjunctivum), middle (brachium pontis), and inferior (restiform body). They join with the midbrain, pons, and medulla, respectively. The cerebellum is composed of three structural and functional compartments: cortex, medulla, and deep nuclei. The cortex

P.276

The Purkinje cell dendritic arbor extends into the molecular layer like a hand with outstretched fingers. Its broad, flat palm and radiating fingers are oriented perpendicular to the long axis of the cerebellar convolutions (folia). Thus, routine folia cross sections show the typical, elaborate dendritic branching pattern, whereas longitudinal sections present a dramatically different on edge view of the arbor (Figure 11.3). This should not be mistaken for pathologic dendritic tree pruning seen in some disease states.

Diencephalon

The diencephalon is interposed between the brainstem (midbrain, pons, and medulla) and the cerebrum. Four major divisions are recognized: epithalamus (pineal gland and habenula), thalamus, subthalamus, and hypothalamus. The medial and lateral geniculate nuclei of the thalamus are sometimes considered together as the metathalamus.

The strategic location of the thalamus is related to its major role in processing and relaying information passing between the cerebral cortex and brainstem and spinal cord. All sensory data (with the exception of olfaction) are processed by specific thalamic nuclei before distribution to the primary sensory cortices.

Of clinical significance to the pathologist, certain portions of the diencephalon immediately subjacent to the third ventricle (in particular, the large dorsomedial nuclei of the thalamus and the mammillary bodies of the hypothalamus) are often prominently involved in Wernicke's encephalopathy. The lesions at these sites are postulated to account for the memory disturbance that accompanies this disorder.

Cerebrum

Supratentorially, the CNS becomes so much more complicated that it is difficult to describe in terms of any general pattern of orientation. It remains a hollow structure, but

P.277

Basal Ganglia

The term basal ganglia refers to the deep gray matter masses of the telencephalon and encompasses the caudate nucleus, putamen, globus pallidus, and amygdala (Figure 11.4). The term ganglion was formerly used interchangeably with nucleus, and ganglion cell was synonymous with neuron to earlier neuroanatomists. With the exception of the basal ganglia, the current definition of a ganglion is now generally restricted to mean a collection of neuronal cell bodies located outside the CNS, namely, the sensory and autonomic ganglia of the peripheral nervous system. Reference to CNS neurons as ganglion cells is still occasionally encountered, and this historical sense of the term is reflected in the names of such neoplastic entities as ganglioglioma, ganglioneuroma, and ganglion cell tumor.

The amygdala (archistriatum) is located in the mesial temporal lobe immediately rostral to the hippocampus and is functionally related to the limbic system. The remaining nuclei of the basal ganglia play an integral role in the modulation of motor function and probably participate in other higher neural systems as well. The caudate nucleus, as the name implies, has a long tapering tail that intimately follows the curvature of the lateral ventricle. The caudate is morphologically and functionally closely related to the putamen. These two nuclei are appropriately referred to collectively as the neostriatum, or simply the striatum. For descriptive purposes, the putamen and the medially situated globus pallidus (paleostriatum, or pallidum) are collectively referred to as the lenticular (lentiform) nucleus. The putamen and globus pallidus are separated from one another by the external medullary lamina of the globus pallidus, whereas the globus pallidus is itself divided into medial and lateral segments by the internal medullary lamina. The globus pallidus (pale globe) is so named because of its pallor in the fresh state compared to the putamen. This contrast is attributable histologically to the dense meshwork of myelinated fibers in the globus pallidus. In contrast, myelinated axons in the putamen are grouped into slender fascicles (pencil bundles of Wilson) that project medially to the globus pallidus and to the substantia nigra. The histologic appearance of the lentiform nucleus is distinctive and permits unambiguous identification of even very limited amounts of tissue from this site.

The basal ganglia are prominently involved in a variety of pathological processes, including kernicterus (literally, nuclear jaundice) in the neonate and lacunar infarction in adults. Carbon monoxide poisoning classically produces selective necrosis of the inner segment of the globus pallidus. A frequent incidental finding of no diagnostic significance on routine sections of the lentiform nucleus is micronodular mineralization of small blood vessels, which is typically most prominent in the globus pallidus. Histologically, similar micronodular mineralization is also commonly seen in the hippocampus (Figure 11.5C).

Hippocampal Formation

The hippocampal formation comprises the subiculum, Ammon's horn (hippocampus proper), and dentate gyrus (Figure 11.5). In coronal sections of the medial temporal lobe, the subiculum forms the inferior base of the hippocampal formation, joining the parahippocampal

P.278

P.279

There are several notable features that are frequently encountered incidentally in the examination of routine hippocampal sections and can be mistakenly interpreted as evidence of disease. One is an asymptomatic micronodular mineralization comparable to that seen in the globus pallidus. In the hippocampal formation, it is most commonly seen just outside the apex of the dentate gyrus (Figure 11.5B, C). A second common finding is a residual hippocampal fissure, which produces a rarefied lamina or cystic cleft that can be mistaken for a healed infarct (Figure 11.5B, D). In addition, pyramidal neurons of the CA are often dark and shrunken in autopsy material, and care must be taken not to overinterpret such changes as evidence of ischemia (Figures 11.16, 11.17).

Cerebral Cortex

From antiquity, neuroscientists have sought to divide the cortical mantle into discrete, functionally significant units. Early efforts yielded fanciful maps akin to those of phrenology and physiognomy. More recently, the application of light microscopy and special staining techniques for cell bodies (Nissl stains), dendritic arbors and unmyelinated axons (Golgi's stains), and the myelin sheaths of myelinated axons (myelin stains such as the Weil's, Weigert's, and Luxol fast blue methods) have permitted a more scientific approach, although the details are beyond the scope of this chapter. In brief, the parcellation of the cortex is based on regional variation in the relative number, composition, and distribution of cortical neurons and their processes (cytoarchitectonics and myeloarchitechtonics). Various neuroanatomists have divided the cortex into a number of regions, varying from 20 to more than 200 and depending on the particular morphologic criteria and degree of subtlety employed. Currently, the most popular cortical map is that devised by Korbinian Brodmann in 1909. Brodmann's map and the classical nomenclature for the gross anatomy of the cerebral sulci and gyri are the two systems most commonly used at present for reference purposes in the neuroanatomic and clinical literature.

Within the context of even the simplest cortical map, it is generally not possible to assign a given histologic section of cortex to a precise anatomic locus without prior knowledge of the section's provenance. However, two cortical areas do exhibit distinctive features: primary motor cortex and primary visual cortex. The motor cortex, located on the precentral gyrus of the frontal lobe, is distinguished by the presence of the giant pyramidal cells of Betz. Pyramidal cells generally range from 10 to 50 mm in soma height from base to origin of the apical dendrite. By comparison, Betz cells may exceed 100 mm in soma height. The primary visual cortex, located on the banks of the calcarine fissure of the medial occipital lobe, is remarkable for the presence of a prominent external band of Baillarger, termed the line (or stria) of Gennari. This myelinated stratum located in lamina IV is usually visible to the naked eye and permits exact delineation of the primary visual cortex (Brodmann area 17) from the adjacent visual association cortex (Brodmann area 18).

Cellular Constituents of the Central Nervous System

Gray Matter and White Matter

By volume, most of the central nervous system is composed of gray matter and white matter. Specialized types of CNS tissues include the choroid plexus, pineal gland, circumventricular organs, and the infundibulum and neurohypophysis (discussed later). The hallmark of gray matter (Figure 11.6A) is the presence of neuronal cell bodies embedded within a finely textured eosinophilic background termed neuropil (Figure 11.6B, C). Neuropil (literally, nerve felt) is an interwoven meshwork of neuronal and glial cell processes. The individual neurites that compose the neuropil are not generally distinguishable in routine hematoxylin-eosin (H&E) stained sections (Figure 11.6B) but are resolvable at the ultrastructural level (Figure 11.6C). White matter, in contrast, is composed primarily of myelinated axons and the supporting cells, oligodendroglia, that produce and maintain the myelin sheaths (Figure 11.6D).

P.280

Neurons

Normal Microscopic Anatomy

The prototypical neuron is exemplified by the large multipolar Betz cells of the motor cortex, the motor neurons of the ventral horn of the spinal cord, and the Purkinje cells of the cerebellum. These neurons are characterized by large perikarya (cell bodies or somas) with abundant Nissl substance (rough endoplasmic reticulum), robust dendritic arborizations, and large nuclei with prominent single nucleoli (Figure 11.7A). Such large multipolar forms, however, represent only one type of neuron; the diapason of neuronal morphologies is remarkable. This is readily apparent by comparison of a motor neurons with granular cell neurons (Figure 11.7A, D). These two neuronal populations typify the classical dichotomous subdivision of CNS neurons into large extroverted projection neurons with long axons (Golgi type I neurons) and small introverts that function regionally with restricted connections (Golgi type II

P.281

With respect to morphologic variants, one unique population of CNS neurons merits brief mention. The mesencephalic nucleus of the trigeminal nerve, which is concerned chiefly with the mediation of jaw proprioception, is composed of true primary (first order) sensory neurons that possess only a single process emanating from the cell body (Figure 11.8A). This nucleus constitutes the only intraparenchymal example of this class of neurons; all other primary sensory neuronal perikarya are gathered outside the CNS in the spinal and cranial nerve ganglia (Figure 11.8B D).

Immunohistochemistry

Antibodies have been raised against a wide variety of the many unique neuronal proteins that are being isolated and characterized at an ever-increasing rate. A majority of these markers are confined to use for research purposes but several have found utility in the diagnostic laboratory. One of the earliest such markers, neuron specific enolase (NSE), has proven notoriously unreliable as a marker of neuronal differentiation. Its use for this purpose in evaluating neoplasms of the central nervous system is not recommended.

P.282

Antibodies directed against epitopes on the constituent proteins of neurofilaments, which are major cytoskeletal elements of the neuronal perikaryon and cytoplasmic processes, have been used extensively in both experimental and clinical studies (Figure 11.9).

One of the most useful and widely employed neuronal markers is synaptophysin. Synaptophysin is an integral membrane protein of synaptic vesicles. In the normal nervous system, antisynaptophysin antibodies yield a diffuse, finely granular pattern throughout the gray matter neuropil (Figure 11.10A). In addition, punctate granular decoration is seen along the cell bodies and proximal dendrites of several types of large, projection class neurons, including the Purkinje cells of the cerebellum, motor neurons of the spinal cord, extraocular motor neurons of the brainstem, and Betz cells of the precentral gyrus (Figure 11.10B).

Age-Related Neuronal Inclusions

A variety of inclusions, largely intracytoplasmic, appear with increasing frequency as we age. By far, the most common is lipofuscin (lipochrome, or aging pigment), whose yellow-to-pale-brown color is unaltered by most histologic procedures, including the H&E method (Figure 11.11). Its autofluorescence and partial avidity for the acid-fast stain can be used to visualize differentially this wear-and-tear pigment, although little functional significance is generally assigned to lipochrome accumulation in normal aging. In larger neurons, lipofuscin may accumulate to such an extent that it displaces organelles and creates an appearance similar to the cell swelling of central chromatolysis, described below (Figure 11.18). The lateral geniculate body provides an example of a densely populated nucleus whose constituent neuron's prominent accumulation of lipofuscin

P.283

Functionally more significant neuronal inclusions that may be seen in asymptomatic individuals are those associated with Alzheimer's disease. They are neurofibrillary tangles, neuritic plaques, granulovacuolar degeneration, and Hirano bodies. These illustrate the often ill-defined distinction between health and disease, because these changes can be seen in the elderly, albeit in limited numbers, in the absence of antemortem disturbances of mentation.

In some cases, neurofibrillary tangles may be found in asymptomatic individuals in occasional neurons of the subiculum or CA. Although silver stains greatly aid visualization and quantitation, these structures may be identified on routinely stained H&E sections if the observer is familiar with their appearance. In pyramidal cells, they appear as a slightly basophilic wisp of faintly fibrillar material that extends out into cell processes, most notably the apical dendrite, and they are often more prominent on one side of the nucleus (flame-shaped tangle; Figure 11.12A). This morphology reflects the fact that tangles generally conform to the shape of the cell body. For example, in the pigmented neurons of the locus ceruleus, which are multipolar and lack the dominant apical dendrite of pyramidal neurons,

P.284

P.285

The senile plaque is also a manifestation of cell injury, but one that, like slight atherosclerosis, is not an unexpected finding in the brains of asymptomatic adults. In such individuals, the plaque is usually seen in its primitive form as a somewhat ill-defined, roughly circular region of abnormal argyrophilic neurites that is not visualized in the H&E-stained section. As the plaques mature they become visible in the latter preparation, particularly when a central core of eosinophilic amyloid appears (Figure 11.12B). The latter can be more readily seen by Congo red or periodic acid-Schiff (PAS) staining. As noted earlier, both neurofibrillary tangles and neuritic plaques are more easily identified and quantitated with special techniques such as immunofluorescence or silver stains (Figure 11.12C).

Two additional intraneuronal inclusions that are seen in Alzheimer's disease, but only rarely in nondemented individuals, are granulovacuolar degeneration (GVD) and Hirano bodies (Figure 11.13). As the name implies, the inclusion of GVD consists of a dark, basophilic granule inside a small, clear vacuole. Clusters of these cytoplasmic inclusions may be present within a single neuron (Figure 11.13A). Depending on the plane of section, Hirano bodies appear in H&E-stained sections as brightly eosinophilic oval, elliptical, or elongated rodlike refractile inclusions that are located either in very close apposition to a neuronal perikaryon (Figure 11.13B) or within the neuropil. Ultrastructural examination supports a localization in neuronal cell bodies and processes, and immunohistochemical studies reveal the presence of actin and actin-associated proteins. Unlike neurofibrillary tangles and neuritic plaques, both GVD and Hirano bodies exhibit a very limited neuroanatomic distribution and are, in fact, virtually confined to the hippocampal formation. Encountering more than one or two cells with these alterations should raise the issue of Alzheimer's disease and prompt a search for other attendant histologic features.

A particularly striking cytoplasmic inclusion occasionally encountered in routine sections of the hypoglossal nuclei of the medulla (less often in the ventral horn motor nuclei of the spinal cord) is the hyalin (colloid) inclusion (Figure 11.14). These inclusions, which consist of ectatic cisternae of endoplasmic reticulum, are rarely seen in the first few decades of life but appear with increasing

P.286

Catecholaminergic neurons throughout the brainstem gradually accumulate neuromelanin as a byproduct of neurotransmitter synthesis. The largest and most densely populated of these nuclei is the substantia nigra (black substance), which contains dopaminergic neurons. The locus ceruleus (blue spot), which is also seen by the unaided eye, is a collection of noradrenergic neurons in the rostral pontine tegmentum. It is of practical importance that the Lewy bodies of Parkinson's disease can be found in both of these neuroanatomic locales. Of the smaller and more diffusely distributed pigmented neurons, those in the vicinity of the dorsal motor nucleus of the vagus nerve in the medulla oblongata are most commonly encountered during routine histologic examination. Microscopically, neuromelanin appears as coarse, dark brown granules (Figure 11.15A) and should not be confused with melanocytic melanin. The latter is also present in the central nervous system but is confined to leptomeningeal melanocytes as discussed below (see Figure 11.57).

Several eosinophilic inclusions may be seen in pigmented brainstem neurons. The most striking of these are the commonly encountered Marinesco bodies (Figure 11.15B). These bright red, hyalin-appearing structures are located within the nucleus, often adjacent to and about the same size as a nucleolus (an alternative designation is paranucleolar body). Multiple Marinesco bodies may occur within a single nucleus, and, in some cases, a large percentage of pigmented neurons exhibit these eye-catching inclusions. In such cases, they may raise concern about a viral infection to the unaccustomed observer but are not

P.287

Autolysis and Basic Neuronal Reactions to Injury

As captured in their normal state by perfusion fixation or rapid immersion fixation, neurons are generally rotund with lightly eosinophilic cytoplasm that is stippled with basophilic Nissl substance in the case of the larger neurons. The surrounding glia are inconspicuous, and few clear vacuoles are seen. This perfection in fixation is rarely achieved in human material, however; and, in virtually all autopsy and surgical specimens, autolysis alters this ideal appearance to a greater or lesser extent. Neurons are, thereby, rendered somewhat contracted and basophilic. Nuclei are also somewhat condensed. Simultaneously, the processes of glia that surround neurons and blood vessels imbibe water to produce clear vacuoles (Figure 11.29). The neuronal response to injury overlaps in some cases with these autolytic changes, and it may not be possible to distinguish agonal hypotensive injury from autolysis in autopsy specimens. In the former setting, the neuronal contraction is pronounced, and the perineuronal and perivascular spaces are exceptionally prominent.

There are, however, three neuronal changes that provide unequivocal evidence of antemortem injury. One is the red neuron, which is the sine qua non of ischemic damage. The second is central chromatolysis, and the third is ferruginization. The red neuron is characterized by a shrunken cell body and intense cytoplasmic eosinophilia with complete loss of Nissl basophilia (Figure 11.16). The nucleus is dark and usually lacks a distinguishable nucleolus but may be pale and demonstrate early karyolysis. At times, it has a somewhat fragmented look suggesting karyorrhexis, although clearly defined karyorrhexis is rare. In surgical specimens, tissue-handling artifact ( crush artifact) also results in dark, shrunken neuronal perikarya; however, as with autolytic autopsy specimens, these cells lack the distinctive cytoplasmic eosinophilia of ischemia (Figure 11.17).

Central chromatolysis, the second unequivocally abnormal finding, consists of a loss of central basophilic staining of the cell body with peripheral margination of the Nissl substance (Figure 11.18). It is seen in a number of pathologic

P.288

A striking finding sometimes encountered near old infarcts is the presence of ferruginized or fossilized neurons, in which both perikarya and axons are encrusted by blue-staining minerals (Figure 11.19). This arresting phenomenon is not limited to the vicinal tissue of old infarcts, although this is the most common context, nor is it confined to the adult nervous system, because prenatal insults may result in similar findings. Clusters of axons thus affected can be mistaken for fungal hyphae (Figure 11.20).

A common reaction of axons to injury seen in a wide variety of pathologic states is the formation of localized dilatations known as axonal spheroids or axon retraction balls (Figure 11.21A). Ultrastructural examination shows greatly distended axis cylinders filled with bundles of neurofilaments and cellular organelles. A regional variant of this process may be observed in the granular cell layer of the cerebellum where focal dilatations of Purkinje cell axons are termed torpedoes. These structures are seen in a number of cerebellar degenerative diseases, as well as in normal aging. The most common site in the central nervous system where scattered axonal spheroids are routinely encountered as an incidental finding in aged individuals is in the rostral fasciculus gracilis of the medulla (Figure 11.21B). Spheroids in this location are often mineralized.

Astrocytes

Normal Microscopic Anatomy

Like neurons, astrocytes are also heterogeneous. The cells of one class conform to the classic star shape and occur as either the fibrillary or protoplasmic form. Fibrillary astrocytes populate the white matter, whereas the latter inhabit the gray matter. Other important subtypes of astrocytes include the Bergmann astrocytes, which are distributed in a narrow lamina between the cell bodies of Purkinje neurons in the cerebellar cortex, and the pilocytic astrocytes of the periventricular region, cerebellum, and spinal cord (Figure 11.22).

P.289

P.290

In gray matter, nuclei of protoplasmic astrocytes cannot generally be distinguished from those of small neurons because the cytoplasm of both blends imperceptibly into the surrounding neuropil and is not normally discernible as a discrete entity. In white matter, it is usually difficult in H&E-stained sections to distinguish fibrillary astrocytes from the much more numerous oligodendroglia. The nuclei of oligodendrocytes are smaller and more hyperchromatic, but usually these two cell types do not fall into two clearly defined groups. In sections stained for myelin, a very small amount of eosinophilic cytoplasm may occasionally, but not invariably, be seen surrounding normal astrocytic nuclei. This helps distinguish this cell from the oligodendrocyte whose cytoplasm, other than the myelin sheath, is not usually apparent by conventional light microscopy (Figure 11.32). Astrocytic cytoplasm becomes much more prominent when astrocytes respond to CNS injury, culminating in the abundant glassy cytoplasm of the gemistocyte (Figure 11.24).

To appreciate the distinctive morphology of the star cell, one must visualize its radiating processes. These threadlike extensions reach out to define a sphere of influence that is many times greater in extent than one would have suspected by looking at an H&E-stained section alone. Historically, this tinctorial feat was achieved through the technically capricious metallic impregnations but now is accomplished with ease and predictability by the immunohistochemical localization of glial fibrillary acidic protein (GFAP) (Figure 11.24). In the case of the fibrillary astrocyte, processes branch infrequently, whereas those of the protoplasmic astrocyte are more numerous and divide more frequently. They are often less well stained with GFAP than the fibrillary types. Neither type of resting astrocyte is as apparent immunohistochemically as are reactive astrocytes.

The polar forms of astrocytes include the pilocytic and Bergmann types. The pilocytic astrocyte is not conspicuous in its native state but becomes so when responding as gliosis and forming Rosenthal fibers. The latter are hyaline, often corkscrew-shaped, eosinophilic structures that are wedged within one of the cell's bipolar processes (Figure 11.25). These structures are occasionally seen in normal brains in the hypothalamus or pineal gland but become much more prominent in gliosis about such lesions as craniopharyngiomas, pineal cysts, cerebellar hemangioblastomas, and chronic lesions of the spinal cord.

The Bergmann astrocytes are confined to a one-to-two-cell thick lamina. Their polar processes extend to the pial surface of the cerebellum and are only faintly seen with difficulty in standard sections. Yet, they are well visualized with immunohistochemistry for GFAP and at the margins of old cerebellar infarcts (Figure 11.22). The Bergmann glia provide an excellent illustration of astrocytic specialization. Their processes are a form of scaffold and serve as a reminder of the cooperative interplay between astrocytes and neurons during embryological development. At that time, the small neurons of the external granular cell layer spiral down the Bergmann processes to reach their final destination in the internal granular cell layer.

Age-Related Inclusions in Astrocytes: Corpora Amylacea

The ubiquitous corpora amylacea are, by far, the most salient astrocytic inclusions encountered in routine sections. These faintly laminated, slightly basophilic polyglucosan bodies accumulate with age and are observed in greatest numbers where astrocytic foot processes are most numerous, particularly around blood vessels and beneath the pia (Figure 11.23). The olfactory tracts of adults are also typically rich in corpora amylacea (Figure 11.45).

The similarity between corpora amylacea and fungal yeast forms such as cryptococcus is a source of potential diagnostic error since both are strongly positive for methenamine silver, Alcian blue, and PAS (Figure 11.23).

In some individuals, corpora amylacea are strikingly numerous although no pathologic significance has yet been attributed to this abundance.

Astrocytic Reactions to Injury

Although normally among the most morphologically demure of nervous system constituents (only naked nuclei are typically visible on routine H&E histology), astrocytes respond rapidly and dramatically to CNS injury. This response typically consists of two components: hypertrophy and hyperplasia. The initial hypertrophic response, an increase in cell size and cytoplasmic prominence, occurs rapidly following CNS insult. Conspicuous cytoplasm is generally indicative of reactive gliosis and constitutes prima facie evidence of CNS injury. Reactive astrocytes display a broad range of cytoplasmic quantity, from just barely perceptible to robustly embonpoint (Figure 11.24). The latter cells are known as gemistocytes (literally stuffed cells). Gliosis may, of course, also present as an increase in the number and density of astrocytic nuclei (hyperplasia) without attendant cytoplasmic prominence. This chronic type of gliosis is frequently subtle and often requires special stains for confirmation and quantitation.

The end result of acute reactive astrogliosis, such as that accompanying cerebral infarction, is frequently a dense fibrillary gliosis (Figure 11.24D). The often-invoked analogy of the astrocyte as the fibroblast of the CNS (i.e., a ubiquitously distributed cell with mitotic capability that responds with alacrity to a wide range of deleterious stimuli) is quite apt.

A distinctive cytoplasmic inclusion seen in fibrillary astrogliosis is the Rosenthal fiber (Figure 11.25). These strikingly eosinophilic, elongated, anfractuous structures are observed in a wide variety of reactive states that share in common significant chronicity. Rosenthal fibers are also characteristic of several specific nosologic entities, including

P.291

P.292

P.293

There are several specialized forms of reactive astrogliosis that deserve brief description. Reactive astrocytes with multiple small, variably sized, nuclei (micronuclei), termed Creutzfeldt astrocytes, may be seen in a number of reactive states but are especially typical of demyelinative processes (Figure 11.26). A specific type of astrocytic reaction to injury is seen in a variety of hepatic diseases that produce hyperammonemia. The reaction consists of nuclear changes exclusively: swelling with contortion of the nuclear membrane, chromatin clearing, and development of one or two prominent nucleoli (Figure 11.27). In sharp contrast to all of the other types of reactive astrocytes, these Alzheimer type II astrocytes fail to exhibit prominent (or even subtle!) cytoplasm by routine H&E microscopy. Alzheimer type II astrocytes may be seen throughout the neuraxis but are particularly prominent in certain locations, most notably the globus pallidus. Alzheimer type I astrocytes differ from type II astrocytes in displaying abundant eosinophilic cytoplasm (Figure 11.27) and are only seen with frequency in

P.294

Among astrocytic reactions to injury, none is more striking than that observed in some cases of progressive multifocal leukoencephalopathy (PML). Not infrequently, the most eye-catching aspect of a PML biopsy is an alarming nuclear hyperchromatism and pleomorphism exhibited by scattered astrocytes a vignette that has on more than one occasion elicited a mental frisson from even the most experienced observer (Figure 11.28).

Perivascular clearing is a routinely observed artifact of autolysis (Figure 11.29). By electron microscopy, these clear spaces are revealed to be greatly dilated astrocytic perivascular foot processes. This phenomenon of water imbibition by astrocytes is seen both as an autolytic change in virtually all autopsy specimens and, when extreme, as a marker of antemortem hypoxic/ischemic injury.

Oligodendroglia

The oligodendroglia ( few branch glia) are small cells that are active in the formation and maintenance of myelin and in the, as yet, poorly understood capacity of attending to neuronal cell bodies (satellitosis). In white matter, the oligodendrocytes' obligatory orientation to fiber pathways is occasionally made apparent by a fortuitous plane of section wherein the fascicular distribution of these cells is seen (Figure 11.30). In gray matter, oligodendrocytes are encountered as two to three small, dark nuclei that are pressed against the cell membrane of larger neurons (Figure 11.31). In surgical specimens obtained from infiltrating gliomas, these normal satellite oligodendroglia must be distinguished from infiltrating neoplastic cells that, like their nontransformed counterparts, are attracted to the immediate perineuronal region. Both astrocytomas and oligodendrogliomas

P.295

Identification of normal oligodendroglia in both gray and white matter is greatly facilitated by these cells' perinuclear halo (the so-called fried egg appearance), which results from swelling and vacuolation of the cytoplasm (Figure 11.32A). This is analogous to the perivascular swelling and vacuolation of astrocytic foot processes. In oligodendroglial neoplasms (oligodendrogliomas), the perinuclear halo is a well-known, distinctive, and diagnostically useful feature (Figure 11.32B). Oligodendroglia and their neoplastic counterparts exhibit strong immunopositivity for S-100 protein (Figure 11.32C).

Ependyma

This cuboidal-to-columnar epithelium provides a lining for the CNS ventricular system (Figure 11.33) and specializes focally as a covering for the choroid plexus (Figure 11.47). The ciliated nature of the ependyma is readily appreciable in the child but is generally less so thereafter. Tanycytes (literally, stretched cells) are specialized constituents of the ependyma, the elongated abluminal processes of which reach the subependymal vasculature. Thus, these cells provide a physical link between the ventricular, vascular, and intraparenchymal compartments of the CNS. Tanycytes are

P.296

P.297

The closely apposed ependymal surfaces of the tips of the lateral ventriculur horns frequently fuse during development, resulting in cords of ependymal cell nests and rosettes. This is especially typical of the distal portions of the posterior horns in the occipital lobes (Figure 11.34). The white matter in such areas appears pale and can simulate the rarefaction seen after ischemic insult. Detached ependymal rosettes may be encountered subjacent to the ventricular lining at any location throughout the neuraxis.

The ependyma-lined central canal of the spinal cord is patent in the child (Figure 11.35) but generally becomes obliterated about the time of puberty unless obstructive hydrocephalus is present. In the latter case, the canal may remain patent and even become dilated (hydromyelia). In the normal adult, however, the spinal ependymal cells have completed their role as a generative epithelium and remain as scattered clumps and rosettes (Figure 11.35). Occasional sections of adult spinal cord may exhibit a focally patent central canal.

The primary ependymal response to injury is loss. The resultant focal denudation of the ventricular wall is often accompanied by a proliferation of local cells, the subependymal glia. This nonspecific reaction, termed granular ependymitis (Figure 11.36A), is the potential product of a broad range of disparate etiologies, from viral infection to hydrocephalus. It is seen frequently at autopsy as a very focal, limited response and has, in this setting, little diagnostic significance. The normal ependyma is commonly thrown into folds, termed plicae, in many parts of the ventricular system (Figure 11.36B). These normal undulations should not be confused with granular ependymitis.

Microglia and the Monocyte Macrophage System

Normal Microscopic Anatomy

The small, dark, elongated nuclei of microglia are ubiquitous in the normal brain. They are so small and inconspicuous

P.298

Response to Injury

In contrast to the relative passivity and anonymity of microglia in healthy nervous tissue, their activity is by no means subtle when called to action by parenchymal injury. Two variants are seen: microglial nodules and diffuse microgliosis. Microglial nodules (also called microglial stars) are frequent concomitants of viral or rickettsial infection, and they are generally acknowledged to consist of both astrocytes and microglia (Figure 11.38A). The microglia have an elongated shape and are known as rod cells. A form of glial nodule is also seen about degenerating neurons, as in amyotrophic

P.299

Destruction of nervous tissue, by whatever mechanism, generally elicits a macrophage response that serves to clear nonviable debris (Figure 11.39A). Both the activation of autochthonous tissue microglia and the diapedesis of blood monocytes are sources for these scavengers. The weight of evidence suggests that the recruitment of blood monocytes plays a predominant role in large lesions such as infarcts but that the supply of indigenous cells is sufficient for lesser insults.

Macrophages are proliferative cells (Figure 11.39A, B). Mitotic figures will, therefore, usually be present in disease processes that elicit a macrophage response, such as infarction and demyelination. They should not be interpreted as suggestive of a neoplastic process. Macrophages often contribute substantially to the cellularity of tissue samples and, depending on preservation and fixation conditions, their identity may not always be obvious. For example, in some specimens, clearing of the macrophage cytoplasm lends an appearance similar to that of oligodendroglial cells, to the extent that, together with the attendant hypercellularity, an infiltrating glioma might be suspected. In such instances a number of antibodies, such as CD68 or HAM-56, can be used to identify the macrophage component (Figure 11.39C, D).

P.300

Specialized Organs of the Central Nervous System

Pineal Gland

The pineal body (epiphysis, or conarium) presents a singular histologic appearance among CNS tissues with a prominently lobulated architecture (Figures 11.40,11.41). This glandular appearance might be mistaken for carcinoma by the unwary, and it can be difficult to distinguish the normal pineal gland from a well-differentiated pineocytoma in small surgical specimens.

Generally present in the pineal gland after puberty are corpora arenacea (acervuli cerebri, or brain sand). These mineralized concretions accrue with age and confer the radiologic hyperdensity that, before the era of computerized tomography and magnetic resonance imaging, made the normal midline position of the pineal gland a useful radiologic landmark (Figure 11.40).

The increase in corpora arenacea with senescence is accompanied by gradual gliosis and cystic change, with attendant effacement of the lush glandular appearance of the pineal gland seen in the earlier decades of life. The ubiquitous incidental pineal cysts typically have densely gliotic walls with scattered Rosenthal fiber formation (Figure 11.41C). The investing leptomeninges of the pineal contain arachnoid cell nests that occasionally give rise to meningiomas of the pineal region (Figure 11.41D).

Pineocytes express strong immunopositivity for the neuronal marker synaptophysin (Figure 11.42A). This useful phenotypic marker is retained by most pineal parenchymal neoplasms. In addition to pineocytes, the pineal gland also

P.301

Median Eminence and Infundibulum

The median eminence, infundibulum, and neurohypophysis display a unique constellation of morphologic features that reflect their specialized neuroendocrine functions. The background stroma is highly spindled (Figure 11.43A) and contains nodular microvascular tangles termed gomitoli (Figure 11.43B), spherical granular bodies called Herring bodies (Figure 11.43C; Table 11.1), which are storage sites for oxytocin and vasopressin, and scattered cells bearing lipofuscin-like brown pigment (Figure 11.43D). The constellation of features comprising a highly spindled background, vascular tangles, and granular bodies gives this region of the CNS more than a passing resemblance to pilocytic astrocytoma. An additional incidental finding, particularly in tissue sections of the infundibulum, is the presence of small clusters of granular cells, termed granular cell tumorlets (Figure 11.43E).

Olfactory Bulbs and Tracts

The intracranial components of the olfactory apparatus (the olfactory bulbs and tracts) have a very distinctive histologic appearance. Familiarity with these structures is useful, not only for the neuropathologist, but also for the general surgical pathologist who may encounter them in resections performed as part of the surgical treatment for regionally invasive entities of the nasal and paranasal sinuses. In such situations, the surgical pathologist may be called upon to render an intraoperative frozen-section assessment of tissue resected superior to the cribriform plate. The ability to recognize the normal histologic features of olfactory bulb tissue is, thus, of more than pedantic importance.

P.302

P.303

P.304

The olfactory bulb has a laminar organization (Figure 11.44). The outer layer is composed of spindled bundles of entering olfactory nerve fascicles intermixed with distinctive spherical, anuclear areas (termed glomeruli) that constitute specialized zones of synaptic contact between olfactory nerve collaterals and the dendrites of intrinsic olfactory bulb neurons. Mitral cells are large neurons, so-named for a resemblance of the perikaryon shape to a bishop's mitre. Their cell bodies are located in a lamina deep to that of the glomeruli (Figure 11.44). The deepest layer consists of a thick lamina of granular cell neurons that are comparable in size to those of the cerebellum and dentate gyrus.

The olfactory tracts (sometimes incorrectly referred to as olfactory nerves) extend posteriorly from the olfactory bulbs. They are triangular in cross section and, in adults, are notable for their profuse numbers of corpora amylacea (Figure 11.45).

Choroid Plexus

The choroid plexus is a specialized organ of the CNS that is responsible for the production of cerebrospinal fluid. It is found in the body, atrium, and temporal horns of the lateral ventricles, in the interventricular foramina of Monro, in the roof of the third ventricle, and in the roof and lateral recesses of the fourth ventricle. The frontal and occipital horns of the lateral ventricles and the aqueduct of Sylvius

P.305

Microscopically, choroid plexus consists of invaginated fronds of vascular leptomeninges covered by an ependyma that is modified to become a highly secretory epithelium (Figure 11.47). The cells are larger and more cobblestoned than those of the adjacent ependyma (Figure 11.33). In addition to collagen and blood vessels, small nests of meningothelial (arachnoid) cells are common normal habitu s of the choroid plexus; whorls of these cells frequently give rise to psammoma bodies (Figure 11.47G). Nonspecific deposition of mineral salts also occurs commonly throughout the connective tissue core with increasing age and accounts for most of the plexuses' radiodensity. An additional aging change of no specific pathological significance is cytoplasmic vacuolization of the ependyma-derived lining cells (Figure 11.47E).

Circumventricular Organs

The circumventricular organs (CVOs) comprise a diverse group of specialized CNS centers that share two morphologic features: a periventricular location and vasculature that lacks the characteristic blood-brain barrier properties found throughout the rest of the brain and spinal cord. There are six CVOs: the pineal gland, subfornical organ, organum vasculosum of the lamina terminalis, area postrema, subcommissural organ, and the median eminence-infundibulum-neurohypophysis (Figures 11.48,11.49). Of these, all except the subcommissural organ are fully developed in the adult human (Figure 11.49). The subcommissural organ, which is located on the ventral surface of the posterior commissure just caudal to the pineal gland, is a very prominent CVO in most vertebrates (Figure 11.49B); although it generally regresses near the end of gestation in humans, vestigial remnants may be present (Figure 11.49C).

Intradural Elements of the Peripheral Nervous System

The major intradural representatives of the peripheral nervous system are the cranial and spinal nerves and small autonomic fibers in the adventitia of blood vessels. In all of the cranial nerves except cranial nerve VIII, the transition from central to peripheral nervous system occurs within 2

P.306

P.307

P.308

Two additional intrathecal components of the peripheral nervous system may pique interest on fortuitous encounter. The first is the so-called microneuroma, which is usually found in the parenchyma of the spinal cord or, more rarely, the medulla (Figure 11.51). These structures consist of a Gordian knot of unmyelinated axons that have been hypothesized to arise secondary to traumatic injury of peripheral nerve roots whose regenerating axons follow penetrating spinal or medullary arteries into the CNS parenchyma along the Virchow-Robin spaces. According to the hypothesis, the tapering perivascular spaces ultimately block further advance of the regenerating axons and, thereby, result in the observed neuroma.

An additional component of the peripheral nervous system that occasionally arouses interest is the unmyelinated terminal nerve (variously termed nervus terminalis, cranial nerve zero, and terminal nerve), which courses in the subarachnoid space covering the gyri recti of the orbital

P.309

Meninges

Dura Mater (Pachymeninx)

The dura mater is composed of two tightly annealed layers of fibrous connective tissue. The outer layer functions as the periosteum of the cranium, whereas the inner meningeal layer is joined to the arachnoid membrane by weak intercellular junctions and focally forms the four dural reduplications that compartmentalize the cranial cavity: the falx cerebri, falx cerebelli, tentorium cerebelli, and diaphragma sellae. The two layers of the dura separate to accommodate the dural venous sinuses; the inner meningeal layer is pierced by draining veins and by arachnoid villi. The latter conduct cerebrospinal fluid back into the venous circulation and are obvious over the superior parasagittal convexities of the cerebral hemispheres, where they project into the superior sagittal sinus (Figure 11.53). They are present in all other major venous sinuses, as well. They are often observed along the posterior margin of the cerebellar hemispheres in relation to the sinus confluens and the transverse venous sinuses. Small villi are also present intraspinally.

P.310

P.311

The epithelial properties of arachnoid granulations are reflected ultrastructurally in elongated, interdigitating cell processes bonded together with desmosomes and immunohistochemically, by positivity for epithelial membrane antigen (Figure 11.53). These features are also characteristic of meningiomas.

With age, the deposition of collagen enlarges the arachnoid villi, which are then referred to as pacchionian bodies (Figure 11.53). Such large granulations frequently press through the overlying roof of the superior sagittal sinus and its lateral lacunae to produce small pits or depressions in the inner table of the calvarium. These are known as the foveolae granulares or pacchionian foveolae. Portions of the dura, particularly the falx cerebri and parasagittal dura associated with the superior sagittal sinus, often calcify nonspecifically with age. Calcification may also be seen in association with chronic renal failure. Focal ossification is sometimes encountered as an incidental finding.

Pia-Arachnoid (Leptomeninges)

The arachnoid forms a continuous sheet immediately subjacent to the dura. Based on descriptive and experimental ultrastructural observations, it is now generally accepted that the dura and arachnoid exist in vivo as a physically continuous tissue, with sparse but unequivocal intercellular junctions linking these two historically discrete membranes. The storied subdural space has, thus, taken its rightful place in the pantheon of neuromythology, alongside brain lymphatics and the syncytial theory of the neural net. It has been proposed that the term spatium subdurale be eliminated from the standardized nomenclature of Nomina Anatomica. Nevertheless, there is no disputing the fact that the interface between dura and arachnoid constitutes the weak link or path of least resistance for pathologic processes that tend to disrupt the meninges. It seems unlikely that such venerable terms as subdural hematoma will soon be cashiered.

The pia mater and arachnoid are often considered as a single delicate covering of the brain and spinal cord (the pia-arachnoid, or leptomeninges). The arachnoid is connected to the pia by delicate strands termed arachnoid trabeculae (Figure 11.54A). In the young, the arachnoid is crystal clear, but with age it becomes gradually thickened. The extent of this change varies considerably. In some cases, it is severe enough to raise concern about a pathologic process meningitis and meningeal carcinomatosis being the two usual suspects. This normal age-related arachnoid thickening is typically most pronounced over the dorsal parasagittal cerebral convexities. Microscopically, it results from the deposition of dense bundles of collagen (Figure 11.54B), analogous to the collagenous hypertrophy of arachnoid villi that occurs prominently in the same vicinity.

Focal nests of arachnoid cells (also called meningothelial cells) may be seen throughout the arachnoid membrane but are concentrated over the arachnoid villi (arachnoid cap cells) (Figure 11.53C). These distinctive elements become more obvious and more clustered with advancing age and, in the adult, often form whorls with centrally placed psammoma bodies. At this point, the resemblance of these nests to those of the meningioma is inescapable. As mentioned previously, small nests of arachnoid cells are also present intraventricularly in the vascular connective tissue core of the choroid plexus (Figure 11.47G). Both normal and neoplastic meningothelial cells are immunoreactive for epithelial membrane antigen an understandable property considering the epithelial phenotype of the desmosome-containing meningothelial cell (Figure 11.53).

The dorsal leptomeninges of the thoracic and lumbosacral spinal cord occasionally contain white waferlike

P.312

Like the dura, the pia is traditionally divided into two layers: the epipia, which covers the surface of the CNS parenchyma and surrounds the vasculature, and the intima pia, which extends into the CNS parenchyma as the posterior median and intermediate septa of the spinal cord. Classically, three specialized structures of the epipia are recognized: the denticulate ligaments on either side of the spinal cord, the linea splendens adjacent to the anterior spinal artery, and the filum terminale. All three structures are composed primarily of dense bundles of collagen.

The filum terminale, which forms the terminus of the spinal cord, warrants additional brief description. As noted earlier, it is composed largely of leptomeningeal collagen but also contains small blood vessels and occasional small nerve fascicles; it may harbor focal collections of adiposites in a minority of normal individuals. Most importantly, however, is an ependymal remnant of the central canal (Figure 11.56). This structure is the source of origin for a unique neoplasm of the conus medullaris and filum terminale: the myxopapillary ependymoma.

Leptomeningeal Melanocytes

True melanocytes like those found in the skin are normal cellular constituents of the meninges. They are typically most concentrated in the leptomeninges of the ventral aspect of the upper cervical spinal cord and medulla oblongata (Figure 11.57). In individuals with an abundant melanocytic presence, the distribution territory extends upward through the pontine cistern and mesencephalic interpeduncular fossa, lateral to the inferior cerebellar hemispheres and mesial aspects of the temporal lobes, and as far rostrally as the gyri recti of the orbitofrontal cortex. It is not unusual for melanocytes to follow the investing leptomeninges of the perivascular Virchow-Robin spaces around large penetrating arteries for short distances into the CNS parenchyma.

P.313

P.314

Intrinsic melanocytes of the leptomeninges may be involved in a spectrum of proliferative conditions ranging from benign melanocytoma to primary CNS melanoma, with all of these entities being exceptionally rare. In contrast, the normal presence of melanocytes in the leptomeninges must always be borne in mind when examining surgical biopsies from CNS sites known to harbor these distinctive elements; one must avoid misinterpreting them as evidence of a melanocytic neoplasm or as hemosiderin-laden macrophages (Table 11.2). With regard to the latter, the long dendritic processes of the melanocytes are generally quite distinctive (Figure 11.57).

Optic Nerve

The optic nerves (as well as the optic tracts and optic chiasm) are direct extensions of the CNS and not peripheral nerves. The significance of this fact is that the myelin of the optic nerves is of the central type and is produced by oligodendroglia, not Schwann cells. Thus, the optic nerves are susceptible to diseases of CNS white matter, such as multiple sclerosis. Being extensions of the CNS, the optic nerves are surrounded by the three meninges, pia mater, arachnoid, and dura mater, with the enclosed subarachnoid space (Figure 11.58). The presence of an arachnoid layer surrounding the optic nerve explains the occurrence of optic sheath meningiomas.

Fetal Brain

The two most distinctive histologic features of fetal brain compared to adult brain are active neurogenesis and paucity of myelin. The former is observed as a prominent, dense aggregation of neuroblasts and immature neurons in the periventricular and subpial zones. A similarly transient layer of migrating neurons in the fetal and infant

P.315

Artifacts

A variety of gross and macroscopic artifacts may complicate evaluation of the CNS. Many of these are seen frequently in surgical neuropathology practice, while a few are limited primarily to autopsy neuropathology (Table 11.3). Artifacts can be broadly separated into those that hinder diagnostic evaluation versus those that mimic histopathologic lesions. Among the former are artifacts of the crush-burn-freeze-suck-soak group (Figure 11.59). The cavitron ultrasonic surgical aspirator (CUSA) is widely employed by neurosurgeons for the safe removal of diseased CNS tissue, particularly soft tumors, and a trap can be used to collect the aspirated tissue and saline irrigation solution for submission for histologic evaluation. Although microscopic examination of CUSA material can be very informative, the

P.316

Iatrogenically introduced foreign material is also encountered with regularity by pathologists who examine CNS specimens and warrants brief mention (Table 11.5; Figure 11.61). A variety of foreign agents are used to control bleeding during surgery and may be introduced preoperatively by the interventional radiologist for embolization of vascular lesions or intraoperatively by the surgeon to control hemorrhage during and after surgery. All of these agents periodically appear in tissue sections. Because they are designed to be resorbable and can therefore be left in place, the morphologic appearance will vary depending on the time interval from placement at the initial surgery and subsequent resection during a second surgery (as, for example, resection of recurrent tumor). Resorbable hemostatic agents elicit a chronic inflammatory reaction of variable intensity, which occasionally may be severe enough to create mass effect and clinical symptoms (textiloma, gossypiboma).

There are a few artifacts with which the pathologist who examines postmortem CNS specimens should be familiar (Figure 11.62), the most common being autolysis of the cerebellar granular cell layer (cerebellar conglutination), mechanical distortion of the spinal cord produced by forceps pressure during removal ( toothpaste artifact), and the production of cystic cavities of varying size in the brain by the postmortem proliferation of gas-forming bacteria ( Swiss cheese brain ).

P.317

P.318

P.319

Suggested Readings

Neuropathology Textbooks

Burger PC, Scheithauer BW. Tumors of the central nervous system. In: Atlas of Tumor Pathology, series 4. Washington, DC: Armed Forces Institute of Pathology; 2006.

McLendon RE, Rosenblum M, Bigner DD. Russell & Rubinstein's Pathology of Tumors of the Nervous System. 7th ed. London: Arnold; 2006.

Prayson RA, ed. Neuropathology. Philadelphia: Elsevier; 2005.

Love S, Louis D, Ellison D, eds. Greenfield's Neuropathology. 8th ed. London: Arnold; 2006.

Burger PC, Scheithauer BW, Vogel FS. Surgical Pathology of the Nervous System and Its Coverings. 4th ed. New York: Churchill Livingstone; 2002.

Ironside JW, Moss TH, Louis DN, Lowe JS, Weller RO. Diagnostic Pathology of Nervous System Tumours. New York: Churchill Livingstone; 2002.

Neuropathology Review Books

Gray F, De Girolami U, Poirer J, eds. Escourolle and Poirier's Manual of Basic Neuropathology. 4th ed. Boston: Butterworth-Heinemann; 2004.

Nelson JS, Mena H, Parisi JE, Schochet SS, eds. Principles and Practice of Neuropathology, 2nd ed. New York: Oxford University Press; 2003.

Citow JS, Wollmann RL, Macdonald RL. Neuropathology and Neuroradiology: A Review. New York: Thieme; 2001.

Fuller GN, Goodman JC. Practical Review of Neuropathology. Philadelphia: Lippincott Williams & Wilkins; 2001.

Prayson RA. Neuropathology Review. Totowa, NJ: Humana Press; 2001.

Neuropathology Atlases

Ellison D, Love S, Chimelli L, Harding B, Lowe JS, Vinters H. Neuropathology: A Reference Text of CNS Pathology. 2nd ed. London: Mosby; 2004.

Hirano A. Color Atlas of Pathology of the Nervous System. 2nd ed. New York: Igaku-Shoin; 1988.

Okazaki H, Scheithauer BW. Atlas of Neuropathology. New York: Gower Medical; 1988.

Schochet SS, Nelson J. Atlas of Clinical Neuropathology. East Norwalk, CT: Appleton & Lange; 1989.

Weller RO. Color Atlas of Neuropathology. London: Oxford University Press; 1984.

Veterinary Neuropathology

Summers BA, Cummings JF, de Lahunta A, eds. Veterinary Neuropathology. St. Louis: Mosby; 1995.