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Neuropathology
Monday, March 9, 2009, 7:30 PM
Convention Center 302
Clinical histories are printed below.
Click on the case numbers for text and references of each case.
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Practical Surgical Neuropathology: A Potpourri of Lesions
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Moderator:
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DAVID N. LOUIS
Massachusetts General Hospital, Boston, MA
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Disclosure:
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In accordance with ACCME guidelines regarding disclosure, the USCAP policy requires that faculty members who have a significant financial or other relationship with a commercial company, entity, or service (which will be discussed in this Symposium) must disclose this to attendees. The Academy also requires that speakers disclose any products that are not labeled for the use under discussion. The speakers listed below have indicated they have nothing to disclose.
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Panelists:
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REBECCA FOLKERTH, Brigham and Women's Hospital, Boston, MA
MATTHEW FROSCH, Massachusetts General Hospital, Boston, MA
ELISABETH RUSHING, Armed Forces Institute of Pathology, Washington, DC
ARIE PERRY, Washington University School of Medicine, St. Louis, MO
DAVID ELLISON, St. Jude Children's Research Hospital, Memphis, TN
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Clinical histories are displayed below.
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for Text and References
Submitted by: Matthew Frosch - Massachusetts General Hospital, Boston, MA
A 58 y/o right-handed woman initially complained of being in a "brain fog," with fuzzy thinking and difficulty concentrating. She next reported feeling dizzy/off balance and short-term memory loss became apparent to her family and co-workers. She also noted bilateral hand-eye apraxia (e.g., unable to correctly utilize the remote control or microwave). She also began having staring spells where she would have a glassy look in her eye lasting for less than one minute. She additionally had jerking/twitching irregularly, temporally unrelated to the staring spells and without loss of consciousness or changes in her baseline degree of mental status. Her husband reported that she had begun to startle quite easily and that she had occasional visual hallucinations (e.g. telling her husband that he had a cut on his chin when he didn't). He also reported that she had mild word-finding difficulty. She was admitted to the hospital approximately 3 months after the first symptoms.
Her neurologic examination revealed her to be unable to state her name, age, location or history. She mis-stated the date and perseverated with the incorrect answer. She was unable to name the months of the year forward, let alone backward. She had minimal speech production, either spontaneously or in response to questions. She was unable to name objects, read or write but repetition was preserved. She was able to hold a pen but was unable to put it to paper. Cranial nerve exam was unremarkable, although inadequate cooperation prevented testing of I, XI or XII. Motor, sensory and coordination testing were compromised because of poor cooperation, but she showed moderate rigidity in the upper extremities along with myoclonus in all extremities.
Because of a history of lupus, she was treated with 1 gm solumedrol IV x 3 days, without improvement. A lumbar puncture revealed an opening pressure of 12, glucose 67, protein 40, no oligoclonal bands, WBC 3, RBC 30. Cultures of CSF did not grow any organisms and PCR studies for herpes virus were negative. MRI revealed restricted diffusion and subtle T2 hyperintensity along the L >R frontal cortical ribbon, as well as the L striatum. An EEF showed generalized slowing and delta of varying asymmetry over each anterior rolandic regions, but no spikes or slow wave discharges. She was discharged to hospice care and died several days later. An autopsy was performed.
Case 1 - Slide 1
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Case 1 - Figure 1
Diffusion weighted MR images at two levels showing ribbon-like multifocal cortical restricted diffusion as well as restricted diffusion in the striatum.
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Case 1 - Figure 2
Cerebral cortex shows mild spongiform change in some areas (LHE stain)
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Case 1 - Figure 3
Vacuolization of cerebral cortex shows some degree of clustering (LHE stain)
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Case 1 - Figure 4
A mixture of larger and smaller vacuoles can be seen, including some which are evident within neuronal cytoplasm (LHE stain)
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Case 1 - Figure 5
Even some of the larger vacuoles are present within neuronal cell bodies (LHE stain)
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Case 1 - Figure 6
Involvement of the grey matter of the striatum is in clear contrast to the absence of vacuoles in the pencil fibers of Wilson (LHE stain)
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Case 1 - Figure 7
The involvement of cerebellar cortex is mostly observed in the molecular layer, with good preservation of the folial white matter (LHE stain)
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Case 1 - Figure 8
The vacuoles progress from small individual lesions to larger more confluent areas.
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for Text and References
Submitted by: Rebecca Folkerth - Brigham and Women’s Hospital, Boston, MA
This 14-year-old right-handed girl was seen by her primary physician for a 2-month history of progressively severe headaches, which occurred mostly in the morning. There was no history of nausea or vomiting, or of seizures. She also complained of a recent sore throat.
On physical examination, her temperature was 38.4C, and she had erythematous and enlarged tonsils. Laboratory analysis disclosed an elevated peripheral white count and leukocytosis. Neurologic examination was normal.
Magnetic resonance imaging revealed a T2-hyperintense, rounded, partially enhancing lesion in the right superior frontal gyrus near the vertex. The lesion was based in the cortex, extending to involve the subcortical white matter, with T2 prolongation and FLAIR hyperintensity. There was also evidence of hemosiderin and/or calcification.
At surgery, the cerebral cortical surface was normal, so ultrasound was used to localize the lesion. Upon incision, a small cyst was found to be surrounded by abnormal rubbery tissue. A complete surgical resection was accomplished.
Case 2 - Slide 1
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Case 2 - Figure 1
Low-power view of lesional cells: lack of organized cytoarchitecture, and presence of bizarre cells with cytologic features of neurons (vesicular cytoplasm, prominent nucleoli, Nissl substance) (arrows) as well as ballooned cells with glassy cytoplasm (arrowheads).
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Case 2 - Figure 2
Lesion with mineralizations: "droplet"-like calcifications, astrocyte with abundant cytoplasm (arrow), and clustered round glial nuclei ("oligodendroglial hyperplasia") (arrowheads).
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Case 2 - Figure 3
Lesional cell, mineralization, and Rosenthal fiber (arrow).
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Case 2 - Figure 4
High-power view of lesional cells: bizarre cells with cytologic features of neurons (vesicular cytoplasm, prominent nucleoli, Nissl substance) as well as ballooned cells with glassy cytoplasm.
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Case 2 - Figure 5
Luxol-fast blue and cresyl violet stain: Nissl substance in cytoplasm of ballooned cell, and disorganized myelinated fibers (blue threads) in background white matter.
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Case 2 - Figure 6
Immunostain for glial fibrillary acidic protein: variably sized astrocytes, some with large, bizarre nuclei; largely negative cytoplasm of balloon cell.
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Case 2 - Figure 7
Immunostain for phosphorylated neurofilaments: negative in balloon cell cytoplasm.
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Case 2 - Figure 8
Immunostain for NeuN neuronal antigen: malorientation of cortical neurons, with apical dendrites pointing in all directions.
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for Text and References
Submitted by: Elisabeth Rushing - Armed Forces Institute of Pathology,
Washington, DC
The patient is a 9 year-old boy who has had seizures since age 2, at which time he was discovered to have a right frontal mass. The seizures were controlled with anticonvulsant medication until age 8, when the frequency increased to several per week. The patient's mother also reported behavioral disturbances that paralleled the increased number of seizures.
Coronal T2 weighted image demonstrates low signal along the cortex of the right frontal lobe and the morphology of the cortex is abnormal. The subjacent white matter reveals T2 hyperintensity. On the axial post-contrast T1 weighted image, contrast enhancement is noted in the region of the abnormal cortical signal on T2.
Intraoperative findings are that of a firm, discrete lesion that follows the contours of the cortical ribbon. The cut sections of the lesion are gritty.
- Low-power examination is the key to recognizing the characteristic histopathologic features
- Immunohistochemical studies contribute little to the practical diagnosis
- Sporadic and inherited forms of this entity differ clinically and histologically
Case 3 - Slide 1
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Case 3 - Figure 1
Clinical history
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Case 3 - Figure 2
(a) Coronal T2 weighted image demonstrates low signal along the cortex of the right frontal lobe and the morphology of the cortex is abnormal. The subjacent white matter reveals T2 hyperintensity. (b) On the axial post-contrast T1 weighted image, contrast enhancement is noted in the region of the abnormal cortical signal on T2.
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Case 3 - Figure 3
Intraoperative findings are that of a firm, discrete mass that follows the contours of the cortical ribbon.
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Case 3 - Figure 4
Spindle cell and angiomatous microvascular proliferation permeate the cortex.
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Case 3 - Figure 5
Spindle cells ensheathe blood vessels; psammoma bodies are present.
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Case 3 - Figure 6
In some areas, only small islands of uninvolved cortex remain.
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Case 3 - Figure 9
Thickened leptomeninges containing numerous blood vessels are flanked by gyri with exuberant spindle-cell proliferation and psammoma bodies.
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Case 3 - Figure 10
Discrete interface between involved cortex and white matter.
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for Text and References
Submitted by: Arie Perry - Washington University School of Medicine, St. Louis, MO
The patient is a 24-year woman who presented with a history of partial seizures since the age of 13. EEG mapped her seizure focus to the left medial temporo-occipital lobe and MR images showed a vaguely enhancing, T2/FLAIR hyperintense, gyriform lesion in the same region. The lesion was slightly enlarged compared to studies performed 8 years and 1 year previously. Therefore, a surgical resection was performed. There is no evidence of recurrence after one year of clinical followup.
Case 4 - Slide 1
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Case 4 - Figure 1
T2-weighted MRI showing a bright gyriform lesion involving the cortex of the left medial temporo-occipital lobe.
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Case 4 - Figure 2
Moderately cellular intracortical tumor with nuclear palisading in subpial and perivascular regions.
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Case 4 - Figure 3
The tumor cells have oval to elongate nuclei with delicate fibrillary processes, reminiscent of astrocytoma.
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Case 4 - Figure 4
Perivascular nuclear free zone resembling the pseudorosettes of ependymoma.
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Case 4 - Figure 5
Subpial palisades with nuclei arranged both perpendicular and parallel to the pial surface.
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Case 4 - Figure 6
Perivascular and subpial aggregates of tumor cells.
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Case 4 - Figure 7
GFAP stain highlighting thin tumoral processes, some of which radiate towards blood vessels.
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Case 4 - Figure 8
The immunostain for neurofilament protein highlighted numerous entrapped axons, consistent with an infiltrative growth pattern. The angiocentric tumor pattern is also highlighted in relief.
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Case 4 - Figure 9
A subset of tumor cells displayed dot-like cytoplasm immunoreactivity for epithelial membrane antigen (EMA).
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Case 4 - Figure 10
Electron microscopy revealed spindled tumor cells with electron dense cytoplasm rich in intermediate filaments and numerous microvilli.
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for Text and References
Submitted by: David W. Ellison - St. Jude Children’s Research Hospital, Memphis, TN
The patient is a male infant presenting at the age of 18 months with symptoms and signs of raised intracranial pressure. MRI revealed a mass in the right frontal lobe, which was removed without apparent residual. Macroscopic report of surgical specimen: soft pink-tan tissue measuring 2.5 x 2.0 x 1.0cm. Adjuvant chemotherapy failed to prevent relapse at 9 months, and overall survival was 12 months.
Case 5 - Slide 1
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Case 5 - Figure 1
A neuroepithelial tumor with contrasting regions of high / low cell density and rosette formation is evident.
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Case 5 - Figure 2
Extensive low cell density regions contain a neuropil-like matrix, in which oval and round nuclei occasionally with a single nucleolus are embedded.
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Case 5 - Figure 3
High cell density regions contain undifferentiated embryonal cells, some of which form ependymoblastic rosettes.
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Case 5 - Figure 4
Widespread neuropil-like regions are synaptophysin-immunopositive.
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Case 5 - Figure 5
Clusters and rosettes of embryonal cells are synaptophysin-negative.
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Case 5 - Figure 6
Scattered embryonal cells are immunoreactive for neurofilament proteins.
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Case 5 - Figure 7
Scattered large differentiated cells are immunoreactive for neuronal nuclear antigen (NEU-N).
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Case 5 - Figure 8
The luminal surface of rosette-forming cells shows immunoreactivity for epithelial membrane antigen (EMA).
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Case 5 - Figure 9
Cell proliferation, as assessed by Ki-67 immunolabeling, is high in regions of embryonal cells and in rosettes, but low or absent in neuropil-like regions.
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Case 5 - Figure 10
Cell proliferation, as assessed by Ki-67 immunolabeling, is high in regions of embryonal cells and in rosettes, but low or absent in neuropil-like regions.
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