Choroid plexus carcinoma

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Status

Done

Parent item

Choroid plexus tumours

Definition

• Essential:
• Demonstration of choroid plexus differentiation by histopathological and immunophenotypic features AND
• Presence of at least four of the following five histological features: AND
• Increased cellular density
• Nuclear pleomorphism
• Blurring of the papillary pattern with poorly structured sheets of tumour cells
• Necrotic areas
• Frequent mitoses, usually > 2.5 mitoses/mm2 in a minimum of 2.3 mm2 (equating to > 5 mitoses/10 HPF of 0.23 mm2)
• Intraventricular location

• Desirable:
• TP53 mutation analysis
• Methylation profile of choroid plexus carcinoma
• In select cases: demonstration of hypoploidy by genome-wide chromosomal copy number analysis

Numbers

• 34.4% of choroid plexus tumours

• 80% of all choroid plexus carcinomas occur in children

CNS WHO grading

• Grade 3

Localization

• Lateral ventricles

Histopathology

• High propensity to bleed

• > 5 mitoses per 10 high-power fields
• Ki-67 proliferation index of
• 1.9% (range: 0.2-6%) for choroid plexus papilloma,
• 13.8% (range: 7.3-60%) for choroid plexus carcinoma,
• < 0.1% for normal choroid plexus

• Frequent mitoses,

• Increased cellular density,

• Nuclear pleomorphism,

• Blurring of the papillary pattern with poorly structured sheets of tumour cells,

• Necrotic areas.

• Less frequently positive for S100 protein and transthyretin vs papiloma

• Usually no membranous positivity for EMA.

• +: KIR7.1 (50%), SMARCB1 and SMARCA4 (100%), p53

Genetic

• Aicardi syndrome

• Li Fraumeni syndrome
• 50% have TP50 mutations

Clinical presentation

• Hydrocephalus
• Blockage of flow
• Inc. production

Radiological

• Large intraventricular lesions with irregular enhancing margins, a heterogeneous signal on T2-weighted and T1-weighted images, oedema in adjacent brain, hydrocephalus, and disseminated tumour

 

Treatment

Surgery:

• After emergency correction of hydrocephalus, the treatment of choice is maximal safe surgical resection.

• Pre op
• Embolisation

• Can perform
• Biopsy for diagnosis

• Two-stage definitive procedure.
• 1st stage
• For suspected choroid plexus carcinoma, a conservative approach should be considered to limit surgical morbidity and mortality
• 2nd stage
• Resection post chemotherapy has been reported to be technically easier.

Chemotherapy: (SIOP studies protocol 2000)

• After surgery, 6 cycles of CarbEV (carboplatin, etoposide, and vincristine) chemotherapy should be given, with assessment of response after every 2 cycles of chemotherapy. Given over a 7 month period.

• If complete remission is achieved by the end of treatment, a watch and wait strategy may be adopted in patients too young for radiotherapy, however radiation should be carefully considered in all patients.

Radiotherapy: (SIOP studies protocol 2000)

• High-risk features (CPC, metastatic, incompletely resected APP or metastatic CPP)

• RT would be planned after 2 cycles of chemotherapy
• Because
• reasonable to fully assess response to chemotherapy prior to a decision to irradiate, particularly in younger children.
• Wait for TP53 testing prior to radiation and delaying until the end of chemotherapy may be preferable.
• Li-Fraumeni syndrome
• Exclusion of germline TP53 mutations.
• If radiation is planned, it should be given as soon as appropriate, with completion of chemotherapy following radiation.

• When radiotherapy is to be given with curative intent, consider of proton therapy.

• Indication for RT
• Radiotherapy indications in localised disease:
• Complete remission – (either before or after chemotherapy):
• No RT due to RT toxicity
• Watch and wait especially in younger children.
• focal RT upfront would generally preclude the use of future CSRT.
• Residual, inoperable disease post-chemotherapy:
• Radiotherapy recommended for those >3 years.
• Focal radiotherapy rather than CSRT in view of the toxicity associated with CSRT.
• CSRT can be considered in the older child as CPC appears to carry a considerable risk of metastatic disease and focal RT upfront would generally preclude the use of future CSRT. Focal RT + CSRT has the risk of over exceeding cumulative radiation dose limits to the central nervous system and other at-risk organs.
• For those 1.5-3 years focal radiotherapy would be recommended when the decision to deliver radiotherapy has been taken.
• Progressive, inoperable disease on chemotherapy:
• Radiotherapy is advised.
• Focal irradiation.
• CSRT can be considered in the older child as CPC appears to carry a considerable risk of metastatic disease and focal RT upfront would generally preclude the use of future CSRT.
• Radiotherapy indications in metastatic disease
• Complete resection of primary site with complete metastatic response to chemotherapy treat as per localised disease, i.e. watch and wait or upfront RT may be appropriate.
• CSRT should be considered rather than focal fields.
• Residual or progressive disease post-chemotherapy and surgery
• CSRT would be favoured in patients > 3 years of age.
• Those aged 18-36 months should be considered individually weighing up toxicity of CSRT against disease control.

Prognosis (poor)

• Frequently invades neighbouring brain structures and metastasizes via cerebrospinal fluid.

• Metastases at diagnosis in 21% of cases

• Local recurrence or metastasis 20x more than typical choroid plexus papiloma

• Progression free survival
• 3-year: 58%
• 5-year 38%

• Overall survival rates
• 3-year: 83%
• 5-year: 62%

• Extent of surgery had a significant impact