Transcript Patient Case Presentation - Keck School of Medicine of USC

Patient Case Presentation
Neurosurgery Red Service
Gabriel Zada, MD
Sean McNatt, MD
LAC-USC Medical Center
May 24, 2006
Patient J.P.
• History of Present Illness:
– 22 year old caucasian female
– Long history of headaches
– Presented with 2 days of:
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Sinus headache progressing to
Bifrontal headache
Somnolence
Altered mental status
Nausea/vomiting
– No fevers, chills
– No history of trauma
Patient J.P.
• Past Medical History:
– Headaches x 2 years
– Otherwise unremarkable past medical history
• Medications:
– None
• Allergies:
– None Known
• Social History:
– Mother of a 2 year old child
– No tobacco, drug, or alcohol use
Patient J.P.
• Physical Exam
– Mental Status
• Patient somnolent, partially arousable
• Oriented inconsistently to name only
• Responds inappropriately with one word responses
– Cranial Nerve Exam
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Right partial ptosis
Papilledema
Right pupil 54 mm, sluggish
Left pupil 53 mm, brisk
Extraocular movements intact
Cranial Nerves otherwise intact
Patient J.P.
• Motor exam
– Normal tone
– Follows simple commands intermittently
– Squeezes hands, wiggles toes
– Diffusely weak in all extremities
• Sensory Exam
– Sensation intact to light touch in all extremities
• Reflexes
– Reflexes 2+, symmetrical
– No Hoffman’s sign
– Toes downgoing
• Cerebellar/Gait exam
– Mild dysmetria bilaterally on finger-nose test
– Gait Deferred
CT Scan
Initial Management
• Patient transferred to LAC Medical Center
• Right ventriculostomy placed
– CSF sent for cytology  “atypical cells”
• Patient’s exam significantly improved:
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Awake, alert
Oriented to name only (San Dimas , 1993)
Significant short-term memory deficits
Partial right IIIrd nerve palsy improved
No pronator drift, power 5/5 throughout
CT Scan
MRI Brain
Surgery
• Right interhemispheric transcallosal
approach to third ventricle
• Patient’s right side down
• Frozen pathology  malignant glial tumor
with high cellularity
• Gross total resection
Transcallosal Approach to the Third Ventricle
• Position with head in lateral position to allow
gravity to facilitate in retraction
• Bone flap 2/3 anterior to coronal suture and 1/3
posterior to coronal suture
– May modify accordingly for anterior versus posterior
third ventricular lesions
• Callosal incision between 2 ACAs
• Must account for shift involved with lateral
positioning
• Callosotomy approximately 2-3 cm in length
– Some authors advocate transverse callosotomy
Video
Postoperative MRI Brain
Postoperative Course
• Patient with unchanged neurological status
following procedure
• Ventriculostomy left in place yet unable to wean
off
• Left VP shunt placed on postoperative day 7
• Short term memory slightly improved over
course of week
• Patient transferred to step-down
Pathology
Diagnosis:
Intraventricular
Anaplastic Oligodendroglioma
(WHO Grade III)
Oligodendroglioma: Background
• Two recognized grades:
– WHO grade II: oligodendroglioma
– WHO grade III: anaplastic oligodendroglioma
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4% of all primary brain tumors
Mean age: approximately 43 years
6% during infancy and childhood
No known patterns of inheritance
Most commonly occur in white matter of frontal and
temporal lobes
• Intraventricular oligodendroglioma:
– Approximately 20 case reports in the literature
Anaplastic Oligodendroglioma: Epidemiology
• Account for ~3% of all adult supratentorial primary
malignant gliomas
• Account for 20-54% of all oligodendrogliomas
• Most common in adults (mean age 49 years)
– Older than patients with grade II oligodendrogliomas
• Male to female ratio 1.5 : 1
• Preference for frontal lobe (60%) followed by temporal
lobe (33%)
Anaplastic Oligodendroglioma: Histopathology
• Share with oligodendroglioma:
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Honeycomb appearance with clear cytoplasm
“Fried egg yolk” appearance
Frequent calcification
Occasional gemistocytes
Often GFAP and S-100 positive
Perinuclear halos
• Diffuse features of malignancy:
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Increased cellularity
Cellular atypia
High mitotic index
Necrosis and microvascular proliferation may be present
• Occasional multinucleated giant cells of Zulch
Anaplastic Oligodendroglioma: Differential Diagnosis
• All with neoplastic cells with round nucleus and clear
cytoplasm (oligodendroglioma-like cells or OLCs)
• Clear cell ependymoma:
– ependymal features (ie rosettes) help differentiate
• Central neurocytoma:
– Synaptophysin positive, more commonly originates in ventricles
• Clear cell meningioma:
– PAS positive, EMA immunoreactivity
• Metastatic renal cell tumor
Oligodendroglioma: Molecular Genetics
• Chromosome 19:
– Loss of heterozygosity (LOH) on long arm of chromosome 19
(19q)
– 50-80% of cases
• Chromosome 1:
– LOH on short arm (1p) in 67% of cases
– Almost always coexists with LOH at 19q
• Polysomia, deletions on other chromosomes (ie 9,10)
• Progression to malignancy correlates with EGFR, PDGF
overexpression
• Fluorescence In Situ Hybridization (FISH) used to detect
• Lack of correlation between histology and molecular
markers
Oligodendroglioma: Molecular genetics
• Several molecular subtypes:
• 1) Combined/isolated loss of 1p/19q:
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More likely frontal, parietal
Diffuse enhancement
Close to 100% response rate
Survival greater than 10 years
• 2) 1p loss without 19q loss
– Close to 100% response rate
– Survival approximately 6 years
• 3) No deletion of 1p/19q with TP53 mutation
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More likely temporal, insular
Ringe enhancement more likely
33% response rate
Survival approximately 6 years
• 4) No deletion of 1p/19q, no TP53 mutation, yet other
mutations
– 18% response rate
– Survival generally less than 18 months
Anaplastic Oligodendroglioma: Multimodal treatment
• Surgery is still primary treatment:
– Gross total resection whenever possible
• Mixed data regarding adjuvant radiotherapy
– Postoperative radiation therapy has been shown to extend
survival, yet carries associated morbidity
– Delayed XRT as effective as immediate postop XRT in one study
– Another study showed no benefit to radiotherapy
• XRT/chemo current standard in recurrent, high-grade
oligodendroglioma
• Salvage therapy frequently chemotherapy with stem cell
rescue
Anaplastic Oligodendroglioma: Response to chemotherapy
• Tumors with combined 1p and 19q deletions are
often responsive to chemotherapy
– Procarbazine, CCNU, Vincristine (PCV)
• Many side effects including myelosuppression in 46%
– More recently, temozolamide (in trials)
– Half of such tumors show complete radiological
responses to chemotherapy
– Mean survival time 10 years with these deletions
compared to patients without these deletions (mean 2
years)
Anaplastic Oligodendroglioma: Prognosis
• Median survival time of 4 years
– Five year survival: 41%
– Ten year survival: 20%
• Local tumor recurrence occurs frequently
• Leptomeningeal spreading (‘oligodendrogliomatosis’)
has also been described
• Metastatic disease uncommon, yet incidence may be
increasing
– Most common sites bone, lymph nodes, scalp
• Good prognostic factors:
– Younger patient age
– Female sex
– Seizure as presenting symptom
References
• 1. Merrell R et al. 1p/19q chromosome deletions in metastatic
oligodendroglioma. J Neurooncology. 2006
• 2. Waldron JS, Tihan T. Epidemiology and pathology of
intraventricular tumors. Neurosurgery Clinical of N America. 14
(2003) 469-482
• 3. Dumont AS et al. Intraventricular gliomas. Neurosurgery Clinical
of N America. 14 (2003) 571-591
• 4. Reifenberger G. Anaplastic oligodendroglioma. In Tumours of the
Nervous System. (Kleihues P, Cavanee WK, eds.) IARC Press,
2000.
• 5. Kasowski HJ et al. Transcallosal Transchoroidal Approach to
Tumors of the Third Ventricle. Neurosurgery 57, Suppl 3. 361-366,
2005
• 6. Engelhard HH. Current diagnosis and treatment of
Oligodendroglioma. Neurosurgical Focus. 12(2), 2002.
Thank You