Patient Case Presentation

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Patient Case Presentation

• Neurosurgery Red Service
• Gabriel Zada, MD
• Sean McNatt, MD
• LAC-USC Medical Center
• May 3, 2006

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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

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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

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Patient J.A.

• Physical Exam
• 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

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CT Imaging
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Initial Management

• 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

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MRI Brain
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MR Spectroscopy
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MR Spectroscopy
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Operative Management

• Right parieto-occipital craniotomy
• Intraoperative ventriculostomy used to cannulate
  ventricle
• Gross Total Resection

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Choroid Plexus Tumors Epidemiology

• 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
• 50 in lateral ventricles
• 37 in 4th ventricle
• 9 in third ventricle
• Remainder in other locations

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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
• Nausea,vomiting
• Irritability
• Headaches
• Visual changes
• Seizures
• Most common signs
• Craniomegaly
• Papilledema
• Stupor or coma in 25 of presentations

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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

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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

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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

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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
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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

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Variant (Invasive) CPP -Replacement of
epithelium, -Invasion into surrounding
brain
Typical CPP

• From M Levy et al, Neurosurgery, 2001

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Choroid Plexus Tumors Radiographic Features

• CT often demonstrates punctate calcification
• MRI
• 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

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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, plt0.01)
• Elevated mI/Cho and Glx/Cho ratios
• CP carcinoma
• Lack of mI elevation
• Elevated Choline
• Low NAA/Cho, Cr/Cho, mI/Cho ratios (significant)

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Choroid Plexus Tumors MR Spectroscopy
CP Papilloma Prominent mI Peak
CP Carcinoma Prominent Cho Peak
From Krieger et al, Neurosurgical Focus, 2005
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Choroid Plexus Tumors Treatment

• Hydrocephalus
• Requirement for VP shunting ranges from 37 to
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• 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

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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)

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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

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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

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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 48 303-309, 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
  3532126
• 6. Wolff JE et al. Choroid Plexus Tumors. Br J
  Cancer. 2002871086-1091

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Thank You