1. HARBOR UCLA NEURO CASE # 9
Marcia Cornford, MD, PhD, Department of Pathology
Anton Mlikotic, MD, Department of Radiology
Los Angeles County
Department of Health Sciences

2. Clinical presentation
The patient is a 37 year old woman referred from an
outside hospital for workup of an intracranial mass.

3. T1 and contrast-enhanced T1 weighted images centered on the posterior fossa reveal a complex
mass in the region of the cerebellopontine angle cistern. There is an enhancing solid component and
suggestion of a discrete cystic component. There is mass effect on the brain stem which is partially
effaced and displaced to the left, although there was no hydrocephalus.

4. This FLAIR image shows associated edema and / or gliosis in the neighboring brachium pontis
and superior cerebellum.

5. The FIESTA sequence demonstrates the relationship of the mass to the subarachnoid space and
provides better anatomic detail of its structure. This image shows the solid component (S), which
is isointense to the brain signal, and both a macrocystic (A) and microcystic component (B).

6. A cluster of microcysts rests against lateral wall of the fourth ventricle (4), causing inward bowing
of the wall and stretching of the ventricle. Note visualization of the facial and vestibular nerves in
the porus acousticus of the internal auditory canal (arrow).

7. Note the normal caliber of the foramen of Lushka on the left (arrow). On the right, it is occupied
by the mass which extends into the cerebellopontine angle cistern.

8. Digital subtraction diagnostic cerebral angiography
Digital subtraction angiography reveals subtle enhancement of the solid component of the mass,
supplied by tiny choroidal branches arising from the posterior inferior cerebellar artery.

9. Differential Diagnosis
Based on location, which of the following entities should be considered ?
 Arachnoid cyst  Endolymphatic sac tumor
 Dermoid cyst  Pituitary adenoma
 Epidermoid cyst  Trigeminal nerve schwannoma
 Neurenteric cyst  Vestibular nerve schwannoma
 Neuroepithelial cyst  Hypoglossal nerve schwannoma
 Aneurysm  Brain stem glioma
 Metastasis  Lymphoma
 Cholesterol granuloma  Ependymoma
 Paraganglioma  Choroid plexus papilloma
 Petrous apicitis  Hemangioblastoma
 Chordoma  Medulloblastoma
 Chondroma  Dysembryoplastic neuroepithelial
 Lipoma tumor

10. Differential Diagnosis
A mass in the cerebellopontine angle cistern may include all of these entities, although
many only rarely present in this location:
 Arachnoid cyst  Endolymphatic sac tumor
 Dermoid cyst  Pituitary adenoma
 Epidermoid cyst  Trigeminal nerve schwannoma
 Neurenteric cyst  Vestibular nerve schwannoma
 Neuroepithelial cyst  Hypoglossal nerve schwannoma
 Aneurysm  Brain stem glioma
 Metastasis  Lymphoma
 Cholesterol granuloma  Ependymoma
 Paraganglioma  Choroid plexus papilloma
 Petrous apicitis  Hemangioblastoma
 Chordoma  Medulloblastoma
 Chondroma  Dysembryoplastic neuroepithelial
 Lipoma tumor

11. At low power, the surgical specimen stained with hematoxalin and eosin shows a partially encapsulated
tumor with an internal papillary architecture and highly vascularized fibrous stroma.

12. At higher power, some cells appear to be ciliated and secretory, and there are collections of
proteinaceous material forming cystic spaces.

13. The papillary pattern differs from that of normal choroid plexus.

14. Immunohistochemical staining with synaptophysin shows uptake within the cytosol, with
concentration along the surface. No synaptic connections are identified.

17. On histochemical staining, the papillary pattern of the tumor is different from that
expected for normal choroid plexus. This pattern may be appreciated with certain
papillary neoplasms, including thyroid cancer and endolymphatic sac tumors. However,
immunohistochemical positivity for synaptophysin favors a tumor of choroid plexus
lineage. The mass is strongly positive for cytokeratin and vimentin. The frond-like
architecture with highly vascularized fibrous stroma is typical for choroid plexus
papilloma.
In contradistinction, choroid plexus carcinomas show a brisk proliferation index on
MIB-1 (Ki-67) immunohistochemical staining and the majority show nuclear positivity
for p53. In addition, INI-1 reactivity is also maintained, which would distinguish this
malignant subtype from atypical rhabdoid-teratoid tumor.

18. Immunohistochemical profile for choroid plexus papilloma
MARKER
CYTOKERATIN ++
VIMENTIN ++
SYNAPTOPHYSIN +
S 100 +
GFAP +
TRANSTHYRETIN +
Information derived from the Manual of Basic Neuropathology, 4th Edition

19. Choroid plexus papilloma
The choroid plexus consists of neuroepithelial tissue that is responsible for
cerebrospinal fluid production within the ventricular system. Most of this
tissue is concentrated in the region of the atrium, although it does extend
anteriorly towards the foramen of Monro and is present in the third and
fourth ventricle, where it exits the foramen of Lushka.
The lateral ventricle is the most common site for neoplasms arising from
choroid plexus tissue (50% of cases), followed by the fourth ventricle (40%).
Approximately 5% of choroid plexus tumors are multicentric. Extra-
ventricular locations have also been reported, including the cerebellopontine
angle cistern, suprasellar region, pineal space, posterior commissure, and
within the supratentorial and intratentorial brain matter. It is purported
that an embryonic rest of choroid plexus tissue may account for these extra
ventricular lesions.

20. Choroid plexus papilloma
Choroid plexus neoplasms account for 0.4to 0.6% of all intracranial tumors, half of
which occur in the first decade of life. Nearly 80% occur as a benign, slowly growing
papilloma although as many as 20% are more aggressive most of which present in
childhood.
The age of presentation varies with location. Those seated in the lateral ventricle are
much more common in patients under the age of ten whereas those arising in the fourth
ventricle are much more common in the older population.

21. Choroid plexus papilloma
Choroid plexus tumors are associated with hydrocephalus and symptoms relate to
increased intracranial pressure, secondary to an increased production of cerebrospinal
fluid by the tumor, far exceeding the average of 450 ml per day normally produced. In
addition, persistent hydrocephalus requiring post-operative shunting directs to a
problem in CSF absorption at the level of the arachnoid granulations.
In addition to headache, clinical findings may include focal neurologic deficits, cranial
nerve palsies, seizures, and coma. There have also been associations with Li-Fraumeni
and Aicardi syndrome.

22. Choroid plexus papilloma
Macroscopically choroid plexus papillomas are described as soft, cauliflower like masses
with prominent peripheral lobulations. Hemorrhage and cyst formation may be seen,
and necrosis and parenchymal invasion findings associated with more aggressive
(malignant) varieties . Many are attached via a vascular pedicle to the choroid plexus in
the lateral ventricle in the region of the trigone.
Prominent fronds of fibrovascular connective tissue surrounded by columnar or
cuboidal cells without significant mitotic activity are characteristic features.
Choroid plexus carcinoma demonstrates clear signs of malignancy with hypercellularity,
nuclear pleomorphism, a high nucleus-cytoplasmic ratio, brain invasion, and high
mitotic activity.

23. Choroid plexus papilloma
Surgical resection of these highly vascular tumors has been facilitated by improved
techniques to secure the vascular supply and pre-operative embolization. The prognosis
for patients with choroid plexus papilloma today continues to be excellent, with 100%
survival at 5 years.
Unfortunately, the patient prognosis for patients with choroid plexus carcinoma
remains guarded, with a 5 year survival of only 26-50%. Adjuvant radiation therapy is
often prohibited in younger populations and chemotherapy has yet known proven
efficacy.

24. Imaging Characteristics
On unenhanced CT imaging, the mass shows hyperattenuation, with possible cystic
components and calcifications and, in some cases, erosion of the petrous bone.
On MRI, the mass is isointense to hypointense with respect to the brain parenchyma,
and shows homogeneous enhancement of the solid component following gadolinium
administration. Internal flow voids are commonly appreciated, with minimal, if any
edema in the adjacent brain stem.
As the lesion may cause subarachnoid seeding, complete imaging of the neuroaxis
is recommended.
Angiography reveals blood supply arising from the anterior and posterior choroidal
artery, when located in the lateral ventricle, and by choroidal branches of the
posterior inferior cerebellar artery when located in the fourth ventricle or foramen of
Lushka.

25. World Health Organization (WHO) Classification
 Choroid Plexus Papilloma WHO Grade I
 Atypical Choroid Plexus Papilloma WHO Grade II
 Choroid Plexus Carcinoma WHO Grade III

26. Operative course and follow-up
A suboccipital craniotomy was performed to remove the mass,
with successful debulking of 95% of the tumor burden. Follow-up
imaging at four months showed expected post-operative findings
although there was no evidence for a residual or recurrent mass.

27. Which neurocutaneous syndrome is suggested by the presence of
bilateral cerebellopontine angle masses?

28. According to recent World Health Organization (WHO) criteria, the
presence of bilateral CPA masses suggests Neurofibromatosis Type 2,
a tumor suppressor gene disorder localized on the long arm of
Chromosome 22.

29. References
1) Bonneville F, Sarrazin JL, Marsot-Dupuch K, et al. Unusual
lesions of the cerebellopontine angle: A segmental approach.
Radiographics. 2001; 21(2) 419-438.
2) Smirniotopoulos JG, Yue NC, Rushing EJ. Cerebellopontine angle
masses: radiologic-pathologic correlation. Radiographics 1993;
13 (5): 1131-1147.
3) Koeller K, Sandberg G. Cerebral Intraventricular Neoplasms:
Radiologic-Pathologic Correlation. Radiographics 2002;
22:1473-1505.