Choroid plexus carcinoma
Neurosurgery Department, University General Hospital of Alicante, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Alicante, Spain
Choroid plexus carcinoma (CPC) is a choroid plexus tumor originating from the ventricular choroid plexus.
Often associated with Li Fraumeni Syndrome (LFS), the germline mutation was detected in a homozygous state due to copy-neutral LOH/uniparental disomy 3).
On histologic examination, these tumors are characterized by increased cell density, increased mitotic figures (>5 per 10 high power field), nuclear pleomorphism and necrosis.
Headache, diplopia, and ataxia are the most common symptoms usually caused by mechanical obstruction of cerebrospinal fluid flow followed by hydrocephalus, regardless of tumor location.
Choroid plexus carcinomas can metastasize to the spine, therefore imaging of the entire neuraxis and CSF cytology are highly recommended. Approximately two thirds of the tumors disseminate throughout the entire CSF space. Extraneural metastases may also occur 9).
On MRI, choroid plexus carcinomas show heterogeneous intensities on both T1 and T2, with irregular enhancement and edema. Flow voids are often seen reflecting the vascular nature of the tumor. Tumor hemorrhage and necrosis are commonly seen as well 11) 12).
Choroid plexus carcinoma and papilloma was characterized by high levels of choline-containing compounds and a complete absence of creatine and the neuronal/axonal marker N-acetyl aspartate. However, the Choroid plexus carcinoma showed higher levels of choline compared with the choroid plexus papilloma, and it also had elevated lactate 13).
However, it is only achievable in 40-50% of cases. A number of factors contribute to the difficulty in obtaining a complete resection, including young patient age, large tumor size and vascularity. Operating on choroid plexus carcinomas carries a high risk of intraoperative hemorrhage. Pre-operative angiography, often combined with embolization, is done to help facilitate a complete resection 21). Blood losses of several total blood volumes in small children are not uncommon, sometimes forcing the neurosurgeon to abort the procedure, often leaving residual tumor. Great extent of tumor resection is an accepted beneficial factor for overall survival. Therefore, a second resection usually follows the administration of adjuvant chemotherapy. Second-look surgery appears to be associated with markedly decreased blood loss.
Histological examination of specimens obtained at a second intervention shows decreased vascularity and fibrotic changes in tumor tissue
Multivariate Cox proportional hazard model adjusting for confounding factors showed that combined therapy was associated with better OScompared to chemotherapy alone (HR: 0.291, p = 0.027). Both chemotherapy alone and combined chemo-radiation improved OS independent of age, gender, tumor location and extent of resection, while radiation alone did not 22).
Adjuvant radiotherapy is recommended in children and adults after a subtotal resection. Radiation is generally avoided in infants and children younger than 2-3 years.
In patients with a complete tumor resection, the role of adjuvant radiotherapy is controversial. Wolff et al. reported a cohort of 48 patients with gross total resection, half of whom received radiation. The 5 year OS was significantly higher in irradiated patients, compared with those without radiation (68% vs 14%).16 On the other hand, Fitzpatrick reported that in a cohort of 37 patients with a gross total resection, four patients did not receive adjuvant therapy, whereas the remaining 34 patients received either chemotherapy, radiation or both. The addition of chemotherapy and/or radiation after surgery did not seem to improve survival. However, the size and characteristics of the two groups (GTR with and without adjuvant therapy) were too imbalanced to draw any statistically meaningful conclusions.13 A recent SEER analysis (in abstract form) showed that radiation did not impact survival in patients with complete resection, suggesting a gross total resection may be sufficient in a subset of patients 31).
The optimal field of radiation is also controversial. Given the high propensity for CSF seeding, some investigators have advocated for prophylactic cranial spinal irradiation without positive CSF cytology or MRI findings in the spine, whereas others use involved field radiation. A retrospective analysis of radiation fields by Mazloom et al. showed patients who received cranial spinal irradiation had improved survival compared to those who did not, 44% vs 15% at 5 years 32).
Additional studies are needed to examine the patterns of failure and need for prophylactic cranial spinal irradiation.
Five-year overall survival is about 40-50%. Gross total resection is the most consistent predictor of survival 33).
Ten patients did not receive neoadjuvant chemotherapy, and 12 were treated with 2-5 cycles of ICE (ifosfamide, carboplatin, etoposide) chemotherapy in a neoadjuvant fashion. The 22 patients included in the study underwent a total of 37 tumor resection surgeries. In all of the cases in which neoadjuvant chemotherapy was used, at least a near-total resection (> 95% of tumor volume) was achieved. Patients who underwent gross-total resection had prolonged overall survival. Of the 37 resections, 18 were performed after chemotherapy. Mean blood loss in the neoadjuvant chemotherapy group was 22% of total estimated blood volume as opposed to 96% in patients without preoperative chemotherapy.
The administration of neoadjuvant chemotherapy decreases intraoperative blood loss and increases extent of resection with a significant positive effect on overall survival 34).
Twenty-eight patients were documented with CPC and LFS. Eleven out of 17 patients received radiation therapy. The survival of patients receiving radiation was inferior to that of those without radiation [median (±95% confidence interval) 2-year OS=0.18 ± 0.12% versus 0.58 ± 0.12%]. The log-rank tests suggested the difference to be marginally significant (p=0.056).
This finding provides evidence for pursuing treatment approaches that do not include radiation therapy for patients with LFS 35).
Twelve children with CPC (median age of 19.5 months) have been treated with HS regimens. Ten patients had >95% resection. Three patients had disseminated disease at diagnosis. Ten patients completed consolidation of whom five are alive, irradiation and disease free at 29, 43, 61, 66 and 89 months from diagnosis. Seven patients experienced tumor recurrence/progression at a median time of 13 months (range 2-43 months). Five patients received irradiation, one for residual disease and four upon progression or recurrence, of whom one is alive at 61 months. The 3- and 5-year progression-free survivals are 58% and 38% and overall survivals 83% and 62% respectively. Late deaths from disease beyond 5 years were also noted.
Head Start strategies may produce long-term remission in young children with newly diagnosed CPC with avoidance of cranial irradiation 36).
Surgery associated with chemotherapy led to long-term survival in 2/3 patients. Clinical results achieved confirm that a therapeutic regimen with surgery and chemotherapy (carboplatin, cyclophosphamide, etoposide, doxorubicin, and methotrexate) is feasible and efficient as a possible adjuvant treatment 37).
A 1-year-old male child presented with ataxia and intracranial hypertension since 2 months. The noncontrast computerized tomography (CT) scan showed a heterogenously hyperdense lesion in right posterior fossa region with gross hydrocephalus. The magnetic resonance imaging (MRI) revealed a posterior fossa lesion with the epicenter being located in the 4th ventricle, the presence of a solid and cystic component with extension into the right cerebellar hemisphere. The cystic component was uniformly hyperintense on MRIT1 and T2 sequences, and the fluid attenuation inversion recovery (FLAIR) sequence. The solid component appeared isointense on T1, T2 sequences and had a heterogeneous contrast enhancement . Although diffusion weighted imaging (DWI) would provide us with added information, this was not available as the patient was referred to us with imaging. At surgery, the cyst had machine oil like fluid, usually characteristic of craniopharyngioma cysts. The solid component of the tumor was soft, friable, and vascular with a clear margin separating the tumor from the brain stem with an absent interface and vermian infiltration at places. 41).