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Neuropathology Laboratories
Laboratory 1
Infarcts and tumors

Case 1-1
NP001 (H&E) [WebScope] [ImageScope]

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.

Diagnosis: Acute Infarction


  1. What is the normal brain weight?
  2. In the gross picture of the full brain (see PowerPoint Lab 1), what are the most significant abnormalities?
  3. What are the microscopic features of acute, subacute and chronic ischemia?
  4. What are the areas of the brain most susceptible to acute ischemic changes in the adult?

Case 1-2
NP002 (Luxol) [WebScope] [ImageScope]

NP003 (Luxol) [WebScope] [ImageScope]

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.

Diagnosis: Subacute and chronic Infarction


  1. Identify the major vascular territories in the CNS.
  2. Identify subacute and chronic ischemic changes.
  3. Explain the causes of cerebrovascular accidents and the anatomical distribution of the lesions.
  4. What are the differences between hemorrhagic and non-hemorrhagic infarcts?
  5. What are some of the origins of emboli that travel to the brain?

His brain showed two corresponding infarcts, one older and quite shrunken (ACA), the other represented by a region of soft friable tissue (MCA). 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 macrophages and reactive vessels. Some parts of the white matter show macrophages (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. The 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. Macrophages 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. 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.

From Robbins and Cotran, 9th edition

"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.

Infarcts are subdivided into two broad groups based on the presence of hemorrhage. As infarcts begin with loss of blood supply, they are often initially nonhemorrhagic. Secondary hemorrhage can occur from ischemia-reperfusion injury, either through collaterals or following dissolution or fragmentation of the intravascular occlusive material. The clinical management of patients with these two types of infarcts differs greatly as thrombolytic therapy is contraindicated in hemorrhagic infarcts.

Hypoxia, ischemia, and infarction resulting from impairment of blood supply and oxygenation of CNS tissue; in the brain, embolism is a more common etiology than thrombosis. This can either be a global process or focal, with the clinical manifestations determined by the region of brain affected.

Hemorrhage resulting from rupture of CNS vessels. Common etiologies include hypertension and vascular anomalies (aneurysms and malformations)."

Case 1-3
NP008 (H&E) [WebScope] [ImageScope]

A 65 year-old woman with several years’ history of blurred vision and reduced peripheral vision. Bilateral cataract removal was performed, however her vision did not improved. MRI showed a 4 x 4.3 cm right sphenoid wing extra-axial mass with mild compression to the optic nerve. The patient underwent gross total resection. Her post-operative course was uneventful. At six months follow up the patient has dramatically improved her overall and peripheral vision. Not further therapy was required.

The tumor has grown to great dimension causing chronic progressive symptoms; this suggests a low grade neoplasm. The tumor is extra-axial, meaning it is localized outside of the central nervous system proper. It is attached to the dura matter. On radiology one often sees a “dural tail”, think about it as the attachment of the tumor to the dura matter. Grossly the tumor is often firm, rubbery, lobular and well defined. Sometimes small gritty calcifications can be appreciated if one scrapes with a knife.

Histological sections often show a tumor growing in lobules. The cells have a syncytial (tissue culture like) pattern of growth with no evident cytoplasmic borders. The nuclei are oval. Some nuclei may have intranuclear inclusions. The cells roll over each other forming whorls. With time those whorls calcify and form distinctive psammomatous calcifications (calcification with multiple concentric lines, such as a tree trunk).

Diagnosis: Meningioma


  1. What is the presumed cell of origin of meningiomas?
  2. What are some common sites of involvement by meningioma? (refer to video lecture on brain tumors)
  3. Which associated disorder is often present when there are multiple meningiomas and schwannomas?
  4. What is the clinical prognosis for the majority of patient with a meningioma?

Case 1-4
NP005 (H&E)
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A healthy, athletic 35-year-old man with no significant past medical history suffered a motor-vehicle accident (MVA) and a concussion. The patient was transfer to the emergency department. An initial CT scan shows a non-displaced fracture of the right parietal bone. Subsequent MRI studies revealed a small epidural hemorrhage at the site of the fracture and an ill-defined, non-enhancing, intra parenchymal lesion of the left frontal lobe. The lesion expanded the gyrus and blurred the grey and white matter junction. The patient recovered from the MVA and was told to return in six months to evaluate both the fracture and the non-enhancing contralateral lesion. A new MRI revealed normal healing at the site of fracture with no other changes associated with the prior trauma. There was re demonstration of the left frontal lobe lesion with mild perilesional edema and FLAIR abnormality but no evidence of enhancement. A decision was made to sample the lesion and an excisional biopsy was performed.

The gross picture of the resected tumor shows several gyri of brain with a glistening appearance and no clear delineation between the grey and white matter border. This indicates that the tumor is infiltrating both the grey and white matter, blurring the normal neuroanatomy. The glistening appearance often indicates microcytic and fluid components commonly seen in low grade infiltrating gliomas. It is also common to see distension or enlargement of the affected gyri.

Histological section shows a hypercellular tissue. Some areas have multiple micro cyst formation, not uncommon in infiltrating gliomas. Most importantly there is evidence of infiltrating cortex (in this case deep grey nuclei and infiltration of white matter tracts. This is NOT a well-circumscribed tumor. In the contrary this tumor cells, sneak and infiltrate even in areas that appear to be normocellular. Therefore this tumor will be very hard to be cured by surgical resection only. The majority of tumor cells have an oval nuclei and abundant eosinophilic (pink) cytoplasm with many spider-like processes. Indicating this is an astrocytoma. Different than reactive gliosis, tumor cells do not respect each other boundaries, overlap and aggregate. In this case high grade features such as necrosis; vascular proliferation and necrosis are not evident.

Diagnosis: Diffuse Infiltrating Astrocytoma, WHO grade II, IDH-mutant.


  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?

Case 1-5

NP006A (H&E) [WebScope] [ImageScope]
[WebScope] [ImageScope]

A 76 year-old woman accountant, who has been complaining of hearing loss and short term memory problems form about 4 months. Her husband indicated that she was having abnormal behavioral issues, including having a very messy desk at home which was a typical for her who always obsessed with order and cleanliness. In a recent trip to their favorite city the patient was lost and confused in familiar places. The patient complains of fatigue, headaches and altered vision. MRI studies revealed a heterogeneously enhancing mass in the right basal ganglia with extension into the anterior commissure and involvement of the contralateral deep grey nuclei. A diagnostic biopsy was performed. The patient rapidly declined postoperatively and died few weeks after initial presentation.

Grossly a horizontal section of the brain shows a mass in the midline of the brain with variegated appearance some areas of hemorrhage and other areas of necrosis. There is evidence of midline shift and edema.

Histological section of the basal ganglia shows a diffuse infiltrating glial neoplasm. The cells have marked nuclear atypia and pleomorphism. Some nuclei are enlarged and atypical. Some cells are multinucleated whereas others are small with irregular hyperchromatic oval nuclei. The tumor cells have eosinophilic (pink) cytoplasm and processes. There is evidence of necrosis, microvascular proliferation and mitotic activity.

Diagnosis: Glioblastoma, WHO grade IV


  1. What is the prognosis of glioblastoma in the adult?
  2. What does WHO grade IV means?
  3. Could the tumor in this patient have been debulked to increased survival? And why

Case 1-6
NP007 (H&E)
[WebScope] [ImageScope]
A 24 year-old man presented to the emergency department grand mal seizures and altered mental status. Examination showed bilateral papilledema. MRI demonstrated a non-enhancing, partially hemorrhagic mass in the left insular cortex, with peripheral edema. The lesion was biopsied.

Microscopically, the tumor shows rounded cells with clear cytoplasmic halos (“fried egg” appearance) packed close to each other. There are delicate branching capillaries, focal micro calcifications and focal hemorrhage. Mitoses, vascular proliferation or necrosis are not identified. The tumor is mostly centered in the white matter, but there is evidence of tumor infiltration into the cortex with the presence of neuronal and vascular satellitosis.

Diagnosis: Oligodendroglioma, WHO grade II


  1. What is the prognosis for patients with oligodendroglioma?
  2. What is the characteristic molecular alteration in oligodendrogliomas?


Questions or comments? Dr. Killen:

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