Transcript Patient Case Presentation

Patient Case Presentation
Neurosurgery Red Service
Gabriel Zada, MD
Sean McNatt, MD
LAC-USC Medical Center
May 3, 2006
Patient J.A.
• History of Present Illness:
– 22 month old female I
– Irritability, nausea/vomiting, decreased p.o.
intake for 6 days prior to admission
– Low grade fever per parents
– Multiple visits to emergency room + clinics
over last week, got intravenous fluids and
parents told her illness was viral
Patient J.A.
• History of Present Illness (continued):
– Presented again to Pediatrics ER with lethargy, altered
mental status
– Bradycardic to pulse of 70s, hypertensive
– Intubated and sedated in ER for airway protection
– No recent seizures, no sick contacts
• Past Medical History:
– Past medical and surgical history unremarkable
– Term birth, uncomplicated
– Normal developmental milestones
Patient J.A.
• Physical Exam:
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Patient intubated, sedated
Somnolent but arousable
Regards examiner, not following commands
Pupils briskly reactive and equal
Extraocular movements intact
Tone normal
Moving all extremities with full power
Normocephalic, no external signs of trauma
CT Imaging
Initial Management
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Patient admitted to Neurosurgical ICU
Right ventriculostomy placed
Initial ICPs in the 20s, normalized with drainage
CSF yellow, proteinaceous
High ventriculostomy output (150 cc/12 hours)
Patient transferred to CHLA for definitive
management
MRI Brain
MR Spectroscopy
MR Spectroscopy
Operative Management
• Right parieto-occipital craniotomy
• Intraoperative ventriculostomy used to
cannulate ventricle
• Gross Total Resection
Choroid Plexus Tumors: Epidemiology
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Comprise 0.5% of all brain neoplasms
Comprise 6% of primary pediatric neoplasms
45% occur within the first year of life
70% occur within first 2 years of life
Median age at diagnosis is 3.5 years
1.2 : 1 male to female ratio
Location:
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50% in lateral ventricles
37% in 4th ventricle
9% in third ventricle
Remainder in other locations
Choroid Plexus Tumors: Clinical presentation
• Most present with hydrocephalus secondary to CSF
overproduction (78-95%)
• Tumor hemorrhage found in 2 of 21 patients, in one study
• Most common symptoms:
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Nausea,vomiting
Irritability
Headaches
Visual changes
Seizures
• Most common signs:
– Craniomegaly
– Papilledema
– Stupor or coma in 25% of presentations
Choroid Plexus Tumors: Pathophysiology
• Believed to arise spontaneously
• Many tumors demonstrated to harbor
chromosomal aberrations (usually chromosome 22)
• CPP has been linked experimentally to the SV40
DNA primate virus
• Large T antigen is the major regulator of the SV40
virus protein products, and interacts with the
product of the p53 and RB tumor suppressor genes
• When expressed in mice, T antigen induces
formation of CPPs
Choroid Plexus Papilloma: Pathology
• “Cauliflower-like” appearance
• Evidence of prior hemorrhage often observed
• Tumor surface is frond-like, similar to normal
choroid plexus
• Stroma has a fibrous consistency
• Can differentiate CPP from papillary ependymoma
based on histology:
– Ependymoma has stroma composed of neuroglia and
epithelial cells with cilia
• Immunohistochemistry not extremely helpful for
these lesions
Choroid Plexus Carcinoma: Pathology
• 29-39% of choroid plexus neoplasms are
carcinoma
• Differentiating features: (per WHO criteria)
– Nuclear atypia, N/C ratio, mitotic figures
– Loss of normal papillary architecture
– Invasion of brain parenchyma through ependyma
• Immunohistochemistry with higher Ki67 index
labeling
• Variant of CPP with stromal invasion ???
– Branching papillae with thin-walled, ectactic blood
vessels
– More complex architecture than standard CPPs
Choroid Plexus Tumors: Pathology
Choroid Plexus Papilloma
-Normal papillary architecture
-Columnar + Cuboidal cells
-Single layer stalks
Choroid Plexus Carcinoma
-Piled up epithelium
-Loss of papillary architecture
Choroid Plexus Tumors:
Significance of Stromal Invasion
• Study by M Levy et al, Neurosurgery, 2001
• Many other series of CPCs have a wide variability in
survival times and outcomes
• Variant of (benign) CPP with invasive characteristics
• Retrospective review of 12 patients
• 8 patients with traditional CPPs, 4 patients with variant
CPPs yet invasive (patchy, local invasion) yet benign
histology
• Only one subtotal resection in patient with variant
• Five year survival rate: 100%
• Summary: Stromal invasion may not be as useful a
criterion of carcinoma as nuclear features and loss of
architecture
• Gross total resection is the key in all cases
Typical CPP
Variant (Invasive) CPP:
-Replacement of epithelium,
-Invasion into surrounding brain
•From M Levy et al, Neurosurgery, 2001
Choroid Plexus Tumors: Radiographic Features
• CT often demonstrates punctate calcification
• MRI:
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Isodense to brain on T1 imaging
Brightly enhancing lesions
Enlarged choroidal artery can be noted
CP carcinomas with necrosis, calcification,
hemorrhage, homogeneous enhancement
– CP papillomas with “mottled” appearance
Choroid Plexus Tumors: MR Spectroscopy
• Study by Krieger et al, Neurosurgical Focus, 2005
• MR Spectroscopy analysis of 6 children with
newly diagnosed intraventricular brain tumors
• Retrospectively, 3 with CP papilloma, 3 with CP
carcinoma
• CP papilloma:
– Significant peak of myoinositol (mI) (20.4 vs. 4.1,
p<0.01)
– Elevated mI/Cho and Glx/Cho ratios
• CP carcinoma:
– Lack of mI elevation
– Elevated Choline
– Low NAA/Cho, Cr/Cho, mI/Cho ratios (significant)
Choroid Plexus Tumors: MR Spectroscopy
CP Papilloma:
Prominent
mI Peak
CP Carcinoma:
Prominent
Cho Peak
From Krieger et al, Neurosurgical Focus, 2005
Choroid Plexus Tumors: Treatment
• Hydrocephalus
– Requirement for VP shunting ranges from 37%
to 78%
– Raimondi and Gutierrez recommend initial of
shunting all patients with 3rd or 4th ventricular
tumors
– Hydrocephalus can resolve completely with
gross total resection
– High likelihood of VP shunt obstruction:
• Secondary to high protein, debris, blood
Choroid Plexus Tumors: Treatment
• Operative Treatment
– Focus on exposure of feeding artery
– Avoiding eloquent cortical regions
– Third ventricular lesions:
• Approach is midline transcallosal
– Fourth ventricular lesions:
• Approach is midline posterior fossa craniectomy
– Emphasis on minimizing blood loss (papilloma
versus carcinoma)
Choroid Plexus Tumors: Adjuvant Treatment
• CP Carcinomas:
– GTR achieved in less than 50% of cases given
hemorrhagic tumor, invasiveness
– No definitive guideleines following surgery
– Postoperative chemotherapy:
• Cyclophosphamide, etoposide, vincristine, platinum agent
• Low response rate (8 of 22 in one study)
– Postoperative radiation therapy:
• One study: 5 year survival following GTR was 68% with
subsequent XRT versus 16% without XRT
• Recommended even following GTR given high relapse rates
Choroid Plexus Tumors: Outcomes
• CP Papillomas:
– 5 and 10 year survival: 81% and 77%
– Mortality usually in younger patients (less than one
year)
– Up to 33% with significant morbidity
– Postoperative subdural fluid collections may require
subdural-peritoneal shunting
• CP Carcinomas:
– 5 and 10 year survival: 41% and 35%
• Most important prognostic factor is extent of
surgical resection
References
• 1. Gupta N. Choroid Plexus tumors in children. Neurosurg
Clin N AM. 14 (2003) 21-631
• 2. Levy M et al. Choroid Plexus Tumors in Children:
Significance of Stromal Invasion. Neurosurgery 48: 303309, 2001
• 3. Krieger MD et al. Neurosurgical Focus. 18(6a):E4, 1-4,
2005
• 4. Ellenbogen RG et al. Tumors of the choroid plexus in
children. Neurosurgery 25: 327-335, 1989
• 5. Wolff JE et al. Radiation therapy and survival in choroid
plexus carcinoma. Lancet 1999; 353:2126
• 6. Wolff JE et al. Choroid Plexus Tumors. Br J Cancer.
2002;87:1086-1091
Thank You