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: • 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

• 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:

– 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 • 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: – 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: – 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

markers between histology and molecular

Oligodendroglioma:

Molecular genetics

• Several molecular subtypes: • 1) Combined/isolated loss of 1p/19q: – 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 – 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