According to the WHO classification of tumors of the nervous system, primary tumors of the choroid plexus are classified as CPP (WHO grade I), atypical CPP (grade II), and CPC (grade III) [76]. There are no remarkable histopathological differences between choroid plexus tumors in the fourth ventricle and those in other ventricular systems.

CPP resembles the native choroid plexus, showing an orderly layer of columnar epithelium on a basement membrane that overlies delicate fibrovascular stalks (Fig. 48.6a). The cells have sometimes higher cellular density and are more columnar and more varied in nuclear size (Fig. 48.6b) than those of the normal choroid plexus epithelium. Transition of the neoplasm to normal choroid plexus is common. Almost all well-differentiated CPPs are overtly papillary; however, there are exceptional cases showing acinar or tubular features, in part [3, 5]. CPP commonly exhibits focal glial differentiation in the form of elongated glial fibrillary acidic protein (GFAP)-positive cells with tapering processes [11]. Other interesting features are pigmentation [97], oncocytic change [11], calcification, xanthomatous change, and bone [23] and cartilage sclerosis (Fig. 48.6c) [11]. Large CPP may inexplicably have foci of necrosis, presumably infarction, without any other anaplastic features. Tumors of the fourth ventricle may be heavily calcified.

Atypical CPP constitutes a group that is intermediate between well-differentiated papilloma and obvious carcinoma. They exhibit significant cytologic atypia, increased nuclear to cytoplasmic ratios, and variable number of mitotic figures (Fig. 48.6d). A follow-up study of 124 choroid plexus tumors suggested that atypical CPP can be distinguished from CPP on the bases of mitotic activity − two or more mitotic figures in ten high-power fields [44]. Foci of necrosis are not uncommon. One study suggests that atypical CPPs behave like CPPs rather than CPCs [65].

The CPC demonstrates apparently anaplastic features. The cells are no longer constrained to a simple columnar epithelium, but form solid masses in variable proportions to the papillary component (Fig. 48.6e). Nuclear atypia is obvious, mitoses are abundant, and necrosis is common (Fig. 48.6f). Hyaline protein droplets may be seen. Sometimes, there are anaplastic lesions composed of sheets of cells with perinuclear halos that lend a somewhat oligodendroglial appearance. Other anaplastic features with complex architectural arrangements of rhabdoid cells, creating confusion with AT/RT. CPCs may invade the brain through the ependymal lining.

CPTs express cytokeratins (Fig. 48.7a), vimentin (Fig. 48.7b), synaptophysin, and podoplanin and often GFAP, S-100 protein (Fig. 48.7c), and epithelial membrane antigen [40], presumably indicating hybrid, epithelial-neuroepithelial nature of the choroid plexus epithelium.

Several studies have indicated the diagnostic utility of immunoreactivity of the choroid plexus for prealbumin (synonymous: transthyretin) [42]. Both neoplastic and normal choroid plexus epithelia are reactive for prealbumin (Fig. 48.7d). Since occasional metastatic carcinomas are positive, staining for transthyretin cannot be considered entirely as choroid plexus specific [6].

A clinicopathological study has demonstrated that CPCs in children are characterized by a higher MIB-1 labeling index and greater cell cycle dysregulation than CPPs [14]. In another study, the MIB-1 index was less than 10 % in 73 % of CPPs, but never above 25 %. No CPC had an index less than 10 %, and 69 % of malignant tumors had indices greater than 25 % [13].

The ultrastructural appearances of CPP are closely similar to those of the normal choroid plexus, suggesting that the neoplastic cells may have retained the ability to produce CSF. The cells rest upon basal laminae, interdigitate lateral cell membranes, grasp adjacent cells by desmosomes and regular apical junctional complexes, produce occasional bundled intermediate filaments, and project both apical microvilli and scattered cilia [31, 57].

Many CPCs arise in young children. In this clinical setting, a malignant papillary tumor in a ventricle is highly likely to be a CPC, since metastatic carcinomas from visceral organs are solely rare in children. On the other hand, intraventricular metastatic papillary carcinoma in adults becomes an important consideration. Metastasis to the choroid plexus in situ is rare but well documented [80]. Immunoreactivity for cytokeratin does not distinguish metastatic carcinoma and CPC, but when combined with positivity for S-100 protein and synaptophysin, strongly favors a primary CPT, as does the rate occurrence of GFAP staining in better-differentiated examples. The majority of CPTs have a cytokeratin (CK) 7-positive/CK20-negative immunophenotypes; therefore, these profiles may be useful in differentiating these lesions from metastatic carcinomas [40]. Complicating this issue is that positivity for prealbumin has been noted in some metastatic carcinomas [4, 6]. Antibodies Ber-EP4 and HEA-25 may be useful because only a rare CPC is positive for either antibody [34]. Synaptophysin is diffusely positive in many choroid plexus tumors, but may be also present in metastases. In some instances, only the diagnosis of high-grade papillary carcinoma can be rendered, with resolution of the problem left to a search for a systemic primary.

Solid, nonpapillary variants of CPC can resemble AT/RT. The CPC affects mainly young children but is not as likely as AT/RT to present in infancy. At present, immunostain for INI-1 is thought to be useful for identifying AT/RT, as this antigen should be lost from the nuclei of tumor cells in that tumor but retained in most of all CPCs [46].

The distinction between the CPC and small-cell embryonal tumor is not always easy, particularly if the carcinoma is largely undifferentiated, but even then, the CPC may show pleomorphic cellular features. Embryonal carcinomas are characteristically positive for placental alkaline phosphatase and CD30. In medulloepithelioma, the primitive epithelioid-appearing cells are typically negative for cytokeratin.

Papillary ependymoma infrequently enters the differential diagnosis of CPTs because ependymoma showing epithelial-papillary pattern only throughout the resected specimen seems quite rare.

The CPT in the fourth ventricle usually presents in the lower half of the fourth ventricle along the midline. Extension of the CPT toward the upper half of the fourth ventricle to the aqueduct seems unusual since the choroid plexus doesn’t exist rostral to the fastigium. The CPT tends to extend caudally as the tumor grows larger through the foramen of Magendie. It is important to be reminded that the upper half of the floor of the fourth ventricle can be secured if the tumor is detached from the cerebellar vermis in the early stage of the surgery.

Despite the fact that the CPT grows from the choroid plexus tissue attached on the roof of the fourth ventricle, the tumor can infiltrate to the brain stem as it grows larger. Preoperative finding of high signal intensity in the brain stem by MRI T2WI is a warning sign which strongly suggests tumor invasion to the fourth ventricle floor.

Vascular supply to the CPT in the fourth ventricle comes from the bilateral PICAs which feed the tumor from the ventrolateral direction. Those feeders should be cut in the cerebellomedullary fissure after the arteries to the brain stem are branched.

In general, the CPT originates from the lower half of the fourth ventricle roof and hangs in the ventricular space in the early stage. As the CPT grows, it compresses or attaches the floor of the fourth ventricle and can invade into the brain stem if the tumor is likely to be malignant. The CPT tends to extend caudally through the foramen of Magendie. The upper half of the fourth ventricle to the aqueduct often remains tumor free. Instead, the space would be enlarged due to associated hydrocephalus.

Surgical approach to the CPT in the fourth ventricle is the same with that of more common pediatric brain tumors which locate in the fourth ventricle. The choice of intradural approach to the tumor is the transcerebellomedullary fissure approach instead of the traditional vermis splitting one [26, 33, 58, 59, 70]. Postoperative mutism that could happen after the vermis splitting approach would be avoided by the transcerebellomedullary fissure approach [78].

Detail of the surgical procedure regarding the transcerebellomedullary fissure (Telovelar) approach has been described elsewhere [58, 59, 70]. We describe the procedure when it is applied for the surgery of the CPT in the fourth ventricle.

A midline skin incision is made from the inion to C2. Cervical muscle layers are divided on the midline and dissected from the occipital bone. The C1 lamina is exposed. The C1 laminectomy is required whenever the CPT is large and a secured extensive surgical field is preferred. Two burr holes are opened on the occipital bone, one on each sides, and suboccipital craniotomy is performed. Lateral edge of the foramen magnum is resected. The dura is opened between the foramen magnum and C1 lamina. The subarachnoid space has sufficient space and the venous sinus doesn’t exit this part of the dura. The dura can be safely opened without damaging the neural tissue even if the tumor is large and the cerebellum is compressed dorsally. After copious cerebrospinal fluid (CSF) is drained and the dura over the cerebellar hemisphere became slack, both rostrolateral ends of the dura are opened easily. The dura is incised toward the center of the foramen magnum and three incisions are connected to form a Y-shaped incision after shutting down the venous sinuses. Care should be paid to preserve abnormally enlarged draining veins whenever they were observed.

An operative microscope is introduced for the intradural procedure hereafter (Fig. 48.9). The tonsil is elevated and retracted laterally so that the cerebellomedullary fissure is opened widely. A slightly pinky or brownish dark-colored tumor with granular surface is exposed. The tela choroidea is incised along the taenia choroidea. Any vascular supply to the tumor from the PICA needs to be coagulated and cut while the branches to the brain stem be preserved. The tumor is detached from the inferior velum where it attaches. By this step, most of the vascular supply to the tumor is reduced markedly and debulking of the tumor becomes much easier [48]. Tumor debulking at this stage directs not to the ventral but to the rostral side so that the CSF space in the upper half of the fourth ventricle is opened. Once the rostral border of the tumor is confirmed, the rostral side of the floor of the fourth ventricle is secured. It is critical to avoid injury to the floor of the fourth ventricle (Figs. 48.9 and 48.10). The dissection plane connecting the rostral normal floor of the fourth ventricle and the obex is assumed, and the tumor resection using an ultrasonic surgical aspirator is resumed paying special attention not to cross the dissection plane. It should be reminded that the CPT tends to infiltrate on the surface of the fourth ventricle irrespective of the tumor size. Meticulous dissection technique enables gross total resection of the tumor when the tumor infiltration is limited on the surface of the fourth ventricular floor (Fig. 48.10).

Application of the intraoperative neurophysiological procedure such as brain stem mapping or the monitoring of the corticobulbar tract motor evoked potential (MEP) would help accomplish sufficient tumor resection while preserving function of cranial motor nuclei [17, 22, 67–69]. Tumors attaching the floor of the fourth ventricle can be left untouched for functional preservation.