Choroid plexus carcinoma

Choroid plexus carcinomas are malignant neoplasms arising from the choroid plexus. They are classified as a WHO grade 3 tumor and while there is considerable overlap in imaging characteristics they carry a significantly poorer prognosis than both WHO grade 2 atypical choroid plexus papilloma, and WHO grade 1 choroid plexus papilloma. 

Epidemiology

Choroid plexus carcinomas occur predominantly in children, typically in the first 5 years of life. They are rare, far less common than choroid plexus papillomas (which account for 80% of primary choroid plexus tumors), representing only 1-4% of pediatric brain tumors ^5,7.

Associations

• Li-Fraumeni syndrome ^5,8

• Aicardi syndrome ⁸

• simian virus 40 (SV40), on the basis of this virus' DNA having been identified in up to 50% of cases ⁵

Clinical presentation

As is the case with choroid plexus papillomas, presentation is usually as a result of hydrocephalus. Symptoms include increasing head circumference and headaches. Papilledema may be visible on fundoscopy. In addition, choroid plexus carcinomas have a tendency to invade the adjacent brain and thus may present with focal neurological dysfunction ^7,10.

Pathology

Choroid plexus carcinomas are designated as WHO grade 3 tumors in the 2021 WHO classification of CNS tumors ⁹. They originate from choroid plexus epithelium and typically arise de novo; rarely they may represent malignant transformation of a pre-existing choroid plexus papilloma ⁴. 

Macroscopic appearance

Macroscopically, choroid plexus carcinomas are lobulated masses with cystic and necrotic areas.

Microscopic appearance

It has been suggested that to make the diagnosis of choroid plexus carcinoma, at least 4 of the following 5 features should be present ⁸:

• increased mitotic rate: >5 per 10 high-power fields

• increased cellularity 

• nuclear pleomorphism

• necrosis

• blurred papillary structure

Microcalcifications and hemorrhage may be present. Brain parenchymal invasion is a feature, and if present helps to distinguishes choroid plexus carcinomas from choroid plexus papillomas. 

Immunophenotype

The immunophenotype of choroid plexus carcinomas is similar to that of choroid plexus papillomas, with both S11 and transthyretin more likely to be negative ⁸.

• cytokeratins: positive

• S100: often negative

• transthyretin: often negative

• EMA: negative

• p53 protein: positive in individuals with TP53 mutation

• KIR7.1: only positive in ~50% of cases

Genetic markers

The most common underlying genetic mechanism identified in their formation is dysfunction of the p53 tumor suppressor gene (TP53).

Radiographic features

Choroid plexus carcinomas are markedly enhancing intraventricular tumors, usually arising in the trigone of a lateral ventricle and invading adjacent brain parenchyma.

Hydrocephalus may be present but is less likely than with choroid plexus papillomas. In choroid plexus carcinomas, hydrocephalus is generally a consequence of mechanical CSF pathway obstruction by the mass or CSF seeding, whereas, in choroid plexus papillomas, there is at least a component of CSF overproduction. 

CT

On non-contrast CT choroid plexus carcinomas are heterogeneous and typically iso to hyperdense to grey matter. Calcification may be seen in 20-25% of cases.

Contrast enhancement is usually prominent but heterogeneous with areas of necrosis and cyst formation evident. 

MRI

Reported signal characteristics include

• T1: iso- to hypointense

• T2: iso- to hypointense with hyperintense necrotic areas

• T2* GRE: blooming from calcifications/hemorrhage

• T1 C+ (Gd): can show marked, heterogeneous enhancement.  

The tumors may have CSF seeding, therefore imaging of the entire neural axis is recommended prior to surgery.

Treatment and prognosis

Choroid plexus carcinomas are rapidly growing tumors with a 40% 5-year survival. TP53 mutation, brain invasion and CSF seeding are considered poor prognostic factors ^3-5.

Surgical en-bloc resection is the mainstay of treatment and can result in a cure, achieved in as many as 50% of cases, but this result has only been reported in some selected series ⁵. In general, survival seems to be much worse than this, and hinges upon the ability to achieve gross complete macroscopic resection. In such cases, a 5-year survival of up to 86% can be achieved. In cases where resection is incomplete, 5-year survival is much lower 26% ⁶. Both radiotherapy and chemotherapy are used ⁵. 

Differential diagnosis

General imaging differential considerations include:

• choroid plexus papilloma and atypical choroid plexus papilloma

  • generally difficult to categorically distinguish these on imaging alone, however some features are helpful: 

    • homogeneous

    • lack of necrosis

    • lack of cerebral parenchymal invasion

    • older age favors choroid plexus papilloma

• central neurocytoma

  • older demographic

  • usually in the body of the lateral ventricle, typically abutting the septum pellucidum

• intraventricular meningioma

  • older demographic 

  • more homogeneous outline and contrast enhancement

• choroid plexus metastasis

  • rare in children

Further differentials to be considered in a large tumor, where the intraventricular origin may be difficult to ascertain, include PNET and glioblastoma.

See also

• intraventricular masses (differential)

• intraventricular masses - an approach