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

• 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:– 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

Patient J.A.

CT Imaging

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

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• 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

• 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

Choroid Plexus Tumors: Clinical presentation

• 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 Tumors: Pathophysiology

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

• 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

Choroid Plexus Tumors: Significance of Stromal Invasion

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

•From M Levy et al, Neurosurgery, 2001

• 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

Choroid Plexus Tumors: Radiographic Features

• 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

Choroid Plexus Tumors: MR Spectroscopy

CP Papilloma:Prominent mI Peak

CP Carcinoma:Prominent Cho Peak

From Krieger et al, Neurosurgical Focus, 2005

• 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: 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: Adjuvant Treatment

• 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

Choroid Plexus Tumors: Outcomes

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; 353:2126• 6. Wolff JE et al. Choroid Plexus Tumors. Br J Cancer.

2002;87:1086-1091

Thank You