Case 6 -

Infarcts Timothy Smith and Cynthia Welsh

Cerebral infarcts may imitate neoplasia because of patient symptoms, and imaging. Cerebral edema and vascular reaction achieves maximum about 3 or 4 days after initiation. Imaging suspicious of neoplasia may lead to biopsy. Infarcts can occur anywhere but are most common in the distribution of the middle cerebral artery. Patients are over 50 and have focal symptoms similar to those expected for neoplasms. Squash smears have elements of normal brain, thin capillaries, and histiocytes. The histiocytes are necessary to carry away the lipid debris and begin to appear at about 2-4 days. Sometimes, eosinophilic, anoxic neurons are present and can be seen in fragments of cortex. Reactive astrocytes and fibrillarity will be seen on smears. In cryostat sections, the edge of the anoxic zone will be identified by a difference in the stain density of the neuropil and sometimes by reactive capillaries. The anoxic infarcted area will be paler and possess more spaces that the viable brain tissue. Ice crystal artifact may be severe and thus mark the ischemic edematous area. The neurons with bright eosinophilic cytoplasm, nuclear pyknosis and karyorrhexis can be seen in the infarct zone. White matter will appear pale and edematous. Remember that the first piece of tissue often sent is a piece of cortex containing neurons. Gliomas arise in the white matter. The neurosurgeon may be expecting a diagnosis of glioma, but the cell density will be no greater than in normal brain. Gliomas possess cellularity greater than in normal brain. Edges of infarcts, where there is viable tissue, show prominence of glial fibers (gliosis). The reactive astrocytes are evenly spaced from one another and do not touch one another. By strict definition, there is not increased cellularity in gliosis. The diagnosis of 'probable infarct, deferred to permanents,' will be appropriate. Increased nuclear number may be simulated by the influx of histiocytes and can simulate glioma to the unwary. Cerebral abscesses can be caused by a wide variety of organisms. The architectural layers of the abscess are important. The center of the abscess like everywhere in the body consists of organisms, neutrophils and debris. Next there is a zone of true fibrosis often with collagen. Collagen is a significant clue that glioma is not the problem. There is no collagen in the brain. Collagen occurs in the brain only around abscesses, around parasites/ foreign bodies, and after radiation. The next layer of neuropil around the abscess is gliotic and has decreasing mononuclear inflammation. The gliotic zone contains some very atypical malignant-looking single astrocytes that can suggest high grade glioma. Don't take the bait! Don't make a diagnosis of glioma based on a single atypical cell. Similar atypical gliotic zones can be seen adjacent to craniopharyngiomas, and rarely around pineal cysts or meningiomas. Other considerations: Macrophages and eosinophilic neurons are important clues that the process is not a glioma but is instead hypoxia. Macrophages are typically not present in untreated gliomas. Macrophages are also a prominent feature of multiple sclerosis which occurs in young individuals. The plaques are multiple, living up to the name, and are unrelated to vascular supply. The imaging appearance showing multiple periventricular and gray-white-junction plaques can be very helpful. Macrophages are also a component of the lesions of progressive multifocal leukoencephalopathy. PML is a papova virus infection that occurs in the immunocompromised producing multiple white matter lesions. There are very atypical astrocytes and enlarged oligodendroglial nuclei containing dark viral inclusions. Again the clinical situation should be helpful in distinguishing PML from glioma but on frozen section the diagnosis should be deferred. Historically this lesion was first considered to be a form of glioma, but the atypia is zonal and lacks the diffuse atypia of glioblastoma. Encephalitis of viral origin shows widely scattered foci of lymphocytes and microscopic necrotic foci with macrophages. Clinical information, specifically high fever and neurological signs, will help make the distinction from infarct and glioma. This is another diagnosis that can wait until permanent sections.