Choroid plexus papillomas: advances in molecular biology and understanding of tumorigenesis

Abstract

Choroid plexus papillomas are rare, benign tumors originating from the choroid plexus. Although generally found within the ventricular system, they can arise ectopically in the brain parenchyma or disseminate throughout the neuraxis. We sought to review recent advances in our understanding of the molecular biology and oncogenic pathways associated with this disease. A comprehensive PubMed literature review was conducted to identify manuscripts discussing the clinical, molecular, and genetic features of choroid plexus papillomas. Articles concerning diagnosis, treatment, and long-term patient outcomes were also reviewed. The introduction of atypical choroid plexus papilloma as a distinct entity has increased the need for accurate histopathologic diagnosis. Advances in immunohistochemical staining have improved our ability to differentiate choroid plexus papillomas from other intracranial tumors or metastatic lesions using combinations of key markers and mitotic indices. Recent findings have implicated Notch3 signaling, the transcription factor TWIST1, platelet-derived growth factor receptor, and the tumor necrosis factor-related apoptosis-inducing ligand pathway in choroid plexus papilloma tumorigenesis. A combination of commonly occurring chromosomal duplications and deletions has also been identified. Surgical resection remains the standard of care, although chemotherapy and radiotherapy may be considered for recurrent or metastatic lesions. While generally considered benign, these tumors possess a complex biology that sheds insight into other choroid plexus tumors, particularly malignant choroid plexus carcinomas. Improving our understanding of the molecular biology, genetics, and oncogenic pathways associated with this tumor will allow for the development of targeted therapies and improved outcomes for patients with this disease.

Fig. 1.

Representative hematoxylin/eosin and immunohistochemical staining of a CPP. These tumors feature a single layer of cuboidal or columnar epithelium in a papillary configuration (A and B) covering a fibrovascular core (C). The presence of transthyretin on immunohistochemical staining (D) can aid in confirming the diagnosis.

Fig. 2.

Molecular pathways associated with CPPs. Several genes in the TRAIL pathway, along with E-cadherin, are known to be methylated in CPPs, resulting in decreased tumor necrosis factor–induced apoptosis and increased cell migration, respectively. Aberrant signaling through PDGFR and Notch3 are associated with tumor formation and growth. Mutations of TP53 and hSNF5/INI1 (SMARCB1), which plays an integral role in chromatin remodeling, have been shown to promote CPP formation, while methylation of TWIST1, an inhibitor of p53, and stratifin, a regulator of the G2 checkpoint, are also associated with CPPs.

Fig. 3.

Radiographic features of an adult CPP. Adult CPPs are generally located in the posterior fossa, most often in the fourth ventricle, and appear iso- or hypointense on T1-weighted MRI (A) and bright on fluid attenuated inversion recovery sequences (B and C). CPPs generally demonstrate strong enhancement on T1-weighted images with contrast (D–F).

Fig. 4.

Radiographic features of a pediatric CPP. These tumors are more common in the lateral ventricles in the pediatric population. They can cause significant hydrocephalus (A–G) with transependymal flow (D) due to either increased production of CSF or obstruction by tumor debris and blood products. Intraventricular and/or intratumoral hemorrhage are not uncommon. CPPs enhance on T1-weighted MRI with contrast (A and B) due to their rich vascular supply. They are generally iso- or hypointense on T1- and T2-weighted MRI (C–E) but may demonstrate heterogeneous hyperintensity in some cases. Magnetic resonance angiography may aid in visualizing the tumor's vascular supply (F and G). These tumors are typically supplied by multiple vessels arising from the anterior and/or posterior choroidal arteries (double arrow; G), and preoperative embolization may be helpful in some cases. A large vein (bolded single arrow) arising from the tumor and draining into the right internal cerebral vein is also visible (G).