Department of Pathology, Sinai Hospital of Baltimore Pathology, Baltimore, MD, USA
The pathology of the central nervous system (CNS) is an intimidating area for pathologists. In part this is because we have virtually no role in the gross examination, just processing shreds of gray pulp on gauze, and in part because of the feeling that “it could be anything at all,” including a long list of exotic zebras that look just like the common things except behave completely differently. The fact that we are often asked to make our diagnoses on frozen section does not help matters. However, even in the brain, the list of likely diagnoses is still reasonably short if you have three pieces of key information: the age of the patient, the location, and the radiographic appearance of the tumor. Table 27.1 lists differential diagnoses that should at least put you in the right ballpark.
Differential diagnoses of CNS neoplasms , the most common entities.
Infants and young children
Adolescents and young adults
Adults to elderly
Cerebellopontine angle (cranial nerves)
Neuroblastoma (although rare in this location, more often an abdominal tumor)
Astrocytoma and glioblastoma
Germ cell tumors
Germ cell tumors
Ventricles (in or adjacent to)
Choroid plexus papilloma/carcinoma
Choroid plexus papilloma
Subependymal giant cell astrocytoma
Solitary fibrous tumor/hemangiopericytoma
The most important first step is to start by asking if your “lesion” could be normal tissue (i.e., the surgeon has missed). To answer this question you have to know a little normal histology (Figures 27.1 and 27.2). Pay attention to autopsy brain specimens to get a sense for the normal cellularity and cellular components of brain tissue. Second, you should ask if your lesion is neoplastic or non-neoplastic . The non-neoplastic lesion that pathologists worry most about is the demyelinating lesion, which can look like a tumor by radiology. Abundant foamy macrophages, and an absence of obvious malignant cells, should make you think of a possible demyelinating lesion or infarct (Figure 27.3). Gliosis, a reactive proliferation of astrocytes, can also simulate a glioma (glial tumor) histologically (Figure 27.4). However, once you have decided you have a neoplasm, the real work begins.
Normal cerebral cortex . (a) In the gray matter, there is a fine fibrillary background of neuropil (arrowhead), with glial nuclei in the background. Neurons are unmistakable, with their plump cell bodies and prominent nucleoli (arrow). (b) The white matter has a coarser texture, as it is made up of myelinated axons, and the glial nuclei are visible as small dense dots (white arrow).
Normal cerebellum . The tiny nuclei of the granule cell layer are seen at the bottom left (black asterisk), underlying a layer of large neurons called Purkinje neurons (arrowheads). The Purkinje cells send their dendrites up into the molecular layer (white asterisk). The arachnoid layer is seen between folds of the cerebellum (arrow).
Infarct . The presence of sheets of histiocytes or macrophages, with their round contours and bubbly cytoplasm, should be a flag to consider an infarct or demyelinating lesion.
Reactive astrocytes in gliosis. Normal resting astrocytes generally do not have visible cytoplasm. When responding to inflammation or injury, they become compact in shape, with dense pink cytoplasm and stubby processes (arrow).
General Principle I
First, as in any organ, there are a finite number of cell types in the brain, and each cell type can give rise to a spectrum of neoplasms. In the brain, the cells and their common neoplasms are summarized in Table 27.2. Neurons, which are thought to be nondividing terminally differentiated cells, are a pretty rare source of tumors, so most CNS tumors arise from the supporting cell types of the brain.
Probable cells of origin of CNS tumors.
Astrocytoma and variants
} Gliomas, collectively
Ependymoma and variants
Neurons and precursors
Neurocytoma and gangliocytoma
Meninges (arachnoid cells)
Meningioma and variants, hemangiopericytoma
Choroid plexus cells
Choroid plexus papilloma/carcinoma
Schwann cells (in nerves)
Stromal or vascular cells
Embryonal (immature) cells
Medulloblastoma, neuroblastoma, others
Craniopharyngioma, Rathke’s cleft cyst
Germ cell remnantsa
Germinoma, teratoma, etc.
General Principle II
There is a broad grading system used for CNS neoplasms, the World Health Organization (WHO) tumor grade, which ranges from 1 (most indolent) to 4 (most aggressive). In this system, grade 1 is equivalent to “benign” and curable by resection, but in the CNS something otherwise benign may be clinically devastating depending on where it is growing. Conversely, while grade 4 tumors are often lethal and are considered “malignant,” they do not metastasize throughout the body. For this reason, CNS tumors are not described as benign versus malignant but are graded according to the WHO scale, which predicts prognosis. The grade 1 and 2 tumors are referred to as “low grade,” whereas grade 3 and 4 lesions are considered “high grade.” There is no TNM staging for primary brain tumors; margin status and tumor size are also not usually determined by the pathologist.
Most neoplasms are assigned to a grade by definition, but some tumor families have a spectrum of grades based on certain histologic features. For these tumors , the following features are used to assign a higher grade to the lesion:
Cytologic atypia (a subjective observation requiring some experience)
Increasing cellularity relative to lowest-grade tumor (again, subjective)
Increasing numbers of mitoses (usually quantitative)
Microvascular proliferation (objective: either present or absent)
Necrosis (objective: either present or absent)
These features need to be assessed in every tumor (Table 27.3). Note that tumors with an “anaplastic” qualifier are grade 3, while tumors with a “blastoma” in the name are grade 4 (hemangioblastoma not included).
Morphologic features of glial tumors in increasing order of concern (from left to right).
EGBs or RFs
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