FINAL DIAGNOSIS: CHOROID PLEXUS CARCINOMA
Neoplasms of the choroid plexus are rare and largely considered a pediatric disease. They make up about 0.4% of all primary CNS tumors giving an incidence of about 0.3/1,000,000/yr. However, they constitute about 10-20% of all the intracranial tumors in the first year of life. Approximately 80% of choroid plexus carcinomas (CPC) arise in childhood. Interestingly, there is a regional difference between adult and childhood tumors with most pediatric CP tumors arising in the lateral ventricles and those in adult more common in the fourth ventricle with a tendency to grow through the foramen of Luschka into the cerebellopontine angle(1). Very rarely, the tumor has been described as ectopic nests intraparenchymally or suprasellarly(2).
Currently, the WHO classifies choroid plexus tumors into either papillomas (Grade I) or carcinomas (Grade III) (3). However, several authors use the term atypical choroid plexus papillomas for those tumors that show some worrisome features but do not have the fully developed carcinoma phenotype.
Grossly CP tumors are generally described as a well-circumscribed brownish red, cauliflower-like mass however the carcinoma variant may be invasive and appear hemorrhagic or necrotic. Histologically, there is delicate connective tissue fronds covered by a single layer of cuboidal epithelium. The papilloma resembles normal CP but the cells are more crowded and elongated. On the other hand, the CPC is far more cellular and displays signs of anaplasia such as nuclear pleomorphism, frequent mitoses, increased nuclear to cytoplasmic ratio, hyperchromatism, effacement of the papillary pattern, necrosis and invades brain and often spread through the cerebrospinal pathways. Rarely, these tumors can exhibit mucinous degeneration, melanization, tubular glandular architecture or osseous and cartilage metaplasia(4); exceptional is the presence of hyaline droplets of alpha 1-antitrypsin.
Immunohistochemically, these tumors are consistently EMA, CK and S-100 protein positive with approximately 20% focally expressing GFAP. The reliance of TTR immunostain as a specific marker for choroid plexus tumors is vitiated by the fact that this stain is inconstant in CPC and it may be positive in a small number of metastatic tumors(5).
The differential diagnosis for an intraventricular papillary tumor would include villous hypertrophy of the choroid plexus, papillary ependymoma, papillary meningioma, and a metastatic carcinoma to the choroid plexus. Cytologically villous hypertrophy resembles normal choroid plexus but is more voluminous. A papillary meningioma is EMA positive and does not express CK or S-100(6) protein. The papillary ependymoma immunoreacts for GFAP strongly and does not have a collagenous stroma. The differentiation between GFAP negative CPC and metastatic carcinoma may be difficult. The latter may be found to immunolabel for CEA and/or CA125,these being negative in tumors of the plexus. As well in this case, there is clear histologic evidence of transformation from a papillary pattern to sheeting. The treatment of choice for anaplastic plexus tumors is gross resection followed by radiotherapy; for recurrent lesions debulking followed by chemotherapy with carboplatin is indicated.
Molecular biology studies have shown that 14/17 CP tumors expressed the large T antigen from the SV-40 virus(7). This is one of the early expression genes of the papovavirus that can immortalize tissue culture cells. Transgenic mice with SV-40 genome develop choroid plexus tumours(8). The large T antigen is thought to interact with p53 and disrupt its function(9). As well, CP tumors have been described in children with Li-Fraumeni(10) and Aicardi Syndromes. The strong p53 reactivity of our case may represent a p53 mutation or possibly a wild-type p53 with increased half-life because of some interaction with the large T antigen of an SV-40 virus.