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(8th Edition - Robbins and Cotran, p. 1290-1295 | 7th Edition - Robbins and Cotran, p. 1361-1365)

NP001 [WebScope] [ImageScope]

Acute infarction (H&E)

A 70-year-old woman had a sudden stroke and died about a day later. She had had an aneurysm of the middle cerebral artery operated on three weeks earlier and it was necessary to clamp her carotid artery temporarily at that time. The stroke was thought to be due to a subsequent thrombotic occlusion of the internal carotid artery.

The affected hemisphere was pinker than normal and swollen at autopsy. The microscopic section of cortex and white matter illustrates the appearance of the brain during the first 24 hours after its blood supply has been completely or almost completely interrupted. The nervous tissue is undergoing necrosis: neurons show poor staining and often appear to be disintegrating. Similar to recently dead liver or myocardial cells, the cytoplasm of the neurons becomes eosinophilic and the nuclei disintegrate (karyorrhexis). Neutrophils are emigrating from the capillaries into the margins of the necrotic tissue and minute hemorrhages are sometimes present. If the carotid was occluded, where have these leukocytes come from? They would have had to come from collateral patent vessels. Macrophage phagocytes would not begin to appear for at least another day, and astrocytic responses begin considerably later, sometime during the third week. The neutrophils have exuded into the subarachnoid region, but there is little or no fibrin and no mononuclear cells accompanying the neutrophils as would occur in an infectious meningitis.

NP002 [WebScope] [ImageScope]

Subacute infarction (about 17 days' duration)
(Luxol stain)

A 71-year-old man had a cerebral vascular accident (CVA) involving a part of the left hemisphere in the domain of the anterior cerebral artery, manifested clinically by weakness of his right arm and leg, about three months before he died. Approximately 17 days before his death, he suffered another CVA of a portion of the right hemisphere in the domain of the middle cerebral artery.

His brain showed two corresponding infarcts, one older and quite shrunken, the other represented by a region of soft friable tissue. This section shows the shorter duration infarct in the domain of the middle cerebral artery.

The vessel showed marked atherosclerosis that had narrowed the lumen but did not completely occlude it. The section of cortex and white matter contains myelinated fibers that have disintegrated to varying degrees. Phagocytes are engulfing fragments of these dead but still stained fibers. Capillaries and small vessels show adventitial connective tissue and endothelial cells that have proliferated. The dead cortex contains phagocytes and reactive vessels. Some parts of the white matter show phagocytes (some engulfing blue myelinated fiber fragments), and enlarged astrocytes with pink cytoplasm, side by side. By the third week, astrocytes begin the process of responding to ischemic and other injuries by hypertrophying, growing large fibers, and sometimes multiplying. This process, when it is fully developed, is termed gliosis.

The observation that viable astrocytes are present indicates that the ischemia did not produce total necrosis. If this patient had lived only a couple of days, the histologic picture would have been much like that in section NP001. If the patient had lived ten days, there would be active macrophage phagocytic and vascular responses, but as yet no hint of astrocyte changes (gliosis).

NP003 [WebScope] [ImageScope]
NP004 [WebScope] [ImageScope]

Remote infarction (three months’ duration)
(Luxol and PTAH stains)

Please refer to the previous medical history for Section NP002.
Sections NP003 and NP004 show the infarct of longer duration (three months).

This older infarct shows cortex and white matter illustrating what the brain looked like several months after the blood supply had been shut off, or nearly shut off. There are regions of nearly complete destruction with amorphous residual dead brain tissue in which a loose mesh of vessels remains. Many of these vessels are no more than connective tissue strands, but some are patent functioning vessels. Contrast them with those of the infarction of 17 days (Section NP002). Phagocytes are mostly inactive. Within the cortical surface and the regions around the nearly completely destroyed zone, where some blood supply was retained, there are hypertrophied astrocytes. They have prominent fibers and the cells themselves have increased in numbers. These cells are shown best as dark purple in the PTAH (Section NP004) stained section, but can also be seen well as pink with the Luxol stain (Section NP003).

Almost any process that destroys brain tissue sets in motion the same basic progression of morphologic changes that the infarct demonstrates: first, morphologic evidence of necrosis of the killed tissue elements, sometimes with neutrophils and hemorrhages in the initial stage; second, macrophage phagocytes and vascular proliferative activity; lastly, a cavity with surrounding gliosis in a zone of tissue that wasn’t completely destroyed.

Almost any process that destroys brain tissue sets in motion the same basic progression of morphologic changes that the infarct demonstrates: first, morphologic evidence of necrosis of the killed tissue elements, sometimes with neutrophils and hemorrhages in the initial stage; second, macrophage phagocytes and vascular proliferative activity; lastly, a cavity with surrounding gliosis in a zone of tissue that wasn’t completely destroyed.

There are swollen neurons in the partly damaged zone at the margin of the infarct. These are known as “chromatolytic neurons.” These neurons show an “axonal reaction” because their axons were essentially cut off some distance away in the actual infarct. Such cells may die, or remain chromatolytic for a long time, or they may slowly (many weeks or months) be restored to normal appearance as they regenerate their axons. In such circumstances, the axons commonly go to the wrong places and make the wrong synapses. Abnormal electrical activity and clinical seizures may be the clinical manifestations of these abnormal connections.

Questions related to Slides NP001 through NP004:

  1. Cerebral arterial occlusion may lead to focal ischemia and, ultimately, if it is sustained, to infarction of a specific region of CNS tissue within the territory of distribution of the compromised vessel. What modifying factors determine the size, location, and extent of tissue damage that result from the focal cerebral ischemia?

  2. What causes the majority of thrombotic occlusions?

  3. What are the differences between hemorrhagic and nonhemorrhagic infarcts?

  4. What are some of the origins of emboli that travel to the brain?

(8th Edition - Robbins and Cotran, p. 1330-1332 | 7th Edition - Robbins and Cotran, p. 1401)

NP005 [WebScope] [ImageScope]


A 35-year-old man who had a head injury in 1948 began to have blackout spells in 1953, during which he laughed uncontrollably. These psychomotor seizures (transient clouding or lapse of consciousness with some pattern of motor activity) were not controlled with drugs, and by 1958 a right craniotomy had been done to see whether a brain tumor was present. None was recognized, but the patient became worse, then psychotic. By 1962, hemiparesis had developed. Appropriate x-rays and the localized uptake radioactive mercury compound in a brain scan indicated a growth in the right parietal region. It could only be partially removed and the patient died later of this tumor.

The section, in a coronal plane, includes cortex and basal ganglia near the rostral part of the superior horn of the ventricle. The tumor near the ventricle is composed of little astrocytes and many small cysts are formed. Little residual normal brain tissue is present here. More laterally the pattern is residual brain tissue infiltrated by tumor. Tumor cells become scarcer and scarcer as this part of the cortex is approached, illustrating how ill defined astrocytomas may be.

  1. Based on their pathologic features, why are astrocytomas difficult to completely resect?

  2. What are a few of the genetic alterations that have been observed in low grade astrocytomas?

  3. Which histologic features are used to classify and grade the malignant potential of this neoplasm?

NP006 [WebScope] [ImageScope]
NP006A [WebScope] [ImageScope]

(H&E and GFAP)

A 38-year-old man came to the hospital because his family said he was behaving peculiarly, which included eating a great many carrots to improve his vision. He had seizures. Examination showed hemiparesis, a visual field defect, mild papilledema, and carotinemia. An arteriogram showed a large temporal lobe tumor, and it was partly removed surgically. He survived for several months, the course of his disease from the clinical onset being about 5 months.

The tumor showed homogenous tissue resembling gray matter in some places, regions of necrosis and hemorrhage in others, and still other regions that were firm, fibrous, and vascular. The tumor is truly multiform microscopically, with certain characteristics to look for. That it is a glioma is shown by parts of the tumor being composed of astrocytes (as shown in the H&E and immunohistochemically by GFAP – glial fibrillary acidic protein) of many sizes and shapes. Mitotic figures, often bizarre and polypoid, are common. Elongate and polygonal cells, sometimes differentiating as fibrillary astrocytes, form palisades at the margins of zones of necrosis. Vascular endothelial and adventitial connective tissue proliferation is extensive, making up a large proportion of the tumor.

  1. What are a few of the histopathologic features that distinguish glioblastoma from an anaplastic astrocytoma?

(8th Edition - Robbins and Cotran, p. 1333-1334 | 7th Edition - Robbins and Cortan p. 1404)

NP007 [WebScope] [ImageScope]


A man, then 22 years old, had had grand mal seizures for 4 years before coming to the hospital, and headaches, nausea, and vomiting just before admission. Examination showed bilateral papilledema. A brain scan and carotid arteriogram indicated a growth in the right parietal region. A 0.5 cm, bloody, dark yellow tumor was removed in 1964. The patient did well and had no signs of recurrence in seven years, though he complained of malaise at that time. He had returned to work. In 1975 he was thought possibly to have a recurrence of his tumor because of headaches, vomiting, and seizures, but at this hospital it was elected not to operate. At the Mayo Clinic an operation was performed, presumably to determine whether there was a recurrence, but no record was obtained. His seizures were medically controlled. In 1979 he was seizure free and there was no roentgenographic or CAT scan evidence that he had a recurrence of his tumor. Microscopically, the tumor shows rounded cells with clear cytoplasm packed close to each other and arranged in a trabeculated matrix of vascular connective tissue (“fried egg” appearance). In some places the clear cytoplasm is not evident and there is a slight resemblance to ependymoma as the cells radiate from the trabeculae. The cells of this kind of tumor somewhat resemble swollen normal oligodendroglia.

  1. In which parts of the brain are oligodendrogliomas most often found?

  2. What is the prognosis for patients with oligodendroglioma?

  3. Genetic alterations have been observed in oligodendrogliomas; loss of heterozygosity for chromosomes 1p and 19q are the most common. How does the loss of 1p and 19q, in the absence of other alterations, affect the prognosis?

(8th Edition - Robbins and Cotran, p. 138-1339 | 7th Edition - Robbins and Cotran p. 1409)

NP008 [WebScope] [ImageScope]


A 50-year-old man had frontal headaches, weakness of the left hand, and difficulty remembering for about 9 months before he came to the hospital. Examination revealed right papilledema in addition to the other abnormalities. Carotid angiography showed a vascular tumor on the right sphenoid ridge. Although the tumor adhered to the right middle cerebral artery, it was surgically removed and the patient recovered, later to win a Best Speaker Award in a Dale Carnegie course. He took up golf and excelled at it. Six years after operation he reported himself in good health, active, and working. No further follow-up is available.

Microscopically, the tumor is composed of polygonal cells arranged in sheets and whorls. The cells look like normal arachnoid cells in Pacchionian granulations and elsewhere they normally occur in aggregates. In the center of a few whorls the cells have degenerated, or died, and have formed or begun to form concentric rings of solid material – psammoma bodies (psammos = sand). Normal arachnoid makes these bodies, too. Miotic figures in meningiomas are usually rare, but this one shows a few.

  1. What is the presumed cell of origin of meningiomas?

  2. What are some common sites of involvement by meningioma?

  3. Which associated disorder is often present when meningiomas are found at multiple sites in a patient who also has a glial neoplasm?

  4. What is the prognosis for a patient with a meningioma?


Questions or comments? Dr. Killen:

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