Choroid plexus neoplasms

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Choroid plexus neoplasms

CHOROID PLEXUS NEOPLASMS

The choroid plexus (CP) is a specialized epithelium that secretes cerebrospinal fluid (CSF) and is sited in the ventricles of the brain. Most neoplasms of CP are papillomas (CPPs), but some show an increased mitotic count, often in combination with atypical architectural and cytological features (atypical CPPs), or the histologic and behavioral characteristics of carcinomas (CPCs). Atypical CPPs represent approximately 15% of CPPs. CPCs are rare, and mostly occur in children. In the latest edition of the WHO classification (2007), the CPP corresponds to WHO grade I, the atypical CPP to WHO grade II, and the CPC to WHO grade III.

MACROSCOPIC APPEARANCES

CPPs are well-circumscribed neoplasms with a stippled surface that reflects their papillary structure (Fig. 40.1). In contrast, CPCs tend to invade local structures. Both types of neoplasm can be highly vascular, and CPCs frequently contain foci of hemorrhage (Fig. 40.2).

40.1 CPP.
The cerebellopontine angle is an unusual site for a CPP; nearly all are intraventricular. A stippled surface resembling that of a cauliflower is evident.

40.2 CPC.
A large, hemorrhagic mass fills the ventricles.

CHOROID PLEXUS NEOPLASMS

Constitute approximately 0.5% of CNS neoplasms, approximately 3% of childhood CNS neoplasms, and may be congenital.

Occur over a wide age range, but over 50% are present before 2 years of age.

Are generally in the lateral ventricles in children.

Are predominantly in the fourth ventricle in adults.

Are frequently associated with hydrocephalus due to blocked CSF drainage pathways ± increased CSF production.

GENETIC FACTORS AND CP NEOPLASMS

CPP occasionally occurs in patients with Aicardi syndrome (agenesis of the corpus callosum/infantile spasms/chorioretinal lacunae).

CPC have been reported in members of families with Li-Fraumeni syndrome (germline mutation of TP53). However, TP53 mutations are rare in CP neoplasms.

CP neoplasms are induced in transgenic mice by the large T antigen of simian virus 40. However, the presence of this virus in a proportion of human CP neoplasms (and other CNS neoplasms) is probably related to contamination of a polio vaccine with this virus; the phenomenon is only found in patients from countries that used contaminated vaccine.

CPP and CPC show multiple cytogenetic losses and gains of chromosome arms. In CPC, longer survival is associated with loss of 10q and gain of 9p.

MICROSCOPIC APPEARANCES

CPPs resemble normal CP, being characterized by a columnar epithelium that rests on a delicate fibrovascular network and forms multiple papillary projections (Figs 40.3, 40.4). However, CPPs can be distinguished from CP because they demonstrate minor atypical cytologic features, such as:

40.3 CPP.
(a) In many areas, an obvious papillary architecture is found. A more complex pattern may be present in atypical CPPs (b) but this and superficial invasion of the stroma (arrow) do not warrant a diagnosis of CPC.

40.4 CPP.
(a) A layer of cuboidal or columnar cells rests on a fibrovascular stroma. (b,c) In addition to architectural abnormalities, mild cytological atypia and occasional mitoses distinguish the CPP from CP. (d) Immunoreactivity for cytokeratins is a feature of CP tumors. (e) Kir7.1 antibodies label the membrane of epithelial cells in CP neoplasms. (f) Rare CPPs contain oncocytic cells, or (g) melanin.

a more columnar epithelium

an increased nuclear:cytoplasmic ratio

nuclear pleomorphism and hyperchromasia

(sparse) mitotic figures.

Common histologic features found in both CPPs and CP include dystrophic calcification and xanthomatous change. Glial differentiation can very occasionally be found in CPPs, and focal immunoreactivity for GFAP is common. Sometimes, cilia are observed on the surface of epithelial cells in CP neoplasms. Uncommon histologic features in CPPs are glandular metaplasia, oncocytic change (Fig. 40.4f), melanin pigment (Fig. 40.4g), chondroid metaplasia, and osseous metaplasia. Histological atypia may be more advanced in some CPPs (Fig. 40.5), and can progressively worsen in recurrent neoplasms. The atypical CPP is defined as a CPP with: increased frequency of mitotic figures (≥ 2/10 high-powered fields). The following features are not required for diagnosis, but may be present:

40.5 Atypical CPP.
An atypical CPP may have a more complex architectural pattern than a classic CPP, demonstrating focal loss of papillary structure (a), but the diagnosis is made by detecting increased mitotic activity (b). Glial differentiation is a feature of some CPPs (c), this atypical CPP containing a focus of astrocytic cells that demonstrated immunoreactivities for both GFAP (d) and cytokeratins (e). Ki-67 immunolabeling is increased in atypical CPPs (f), in parallel with the mitotic count.

complex architectural features, such as a cribriform pattern of anastamosizing papillae, or areas where cells form patternless sheets

foci of increased cellular pleomorphism and nuclear hyperchromasia

an increased Ki-67 immunolabeling index.

CHOROID PLEXUS NEOPLASMS

CPP is distinguished from:

Normal CP on architectural and cytologic grounds.

Papillary ependymomas by a prominent PAS-positive basement membrane beneath the epithelium, widespread immunolabeling with cytokeratin antibodies, only scanty GFAP immunoreactivity, and the absence of perivascular pseudorosettes.

CPC may be difficult to distinguish from some primitive (embryonal) neuroepithelial neoplasms, anaplastic ependymoma, and undifferentiated germ cell neoplasms in children. CPC differs from:

Medulloepithelioma because the medulloepithelioma contains multilayered ribbons of primitive cells with very scanty cytoplasm and numerous apoptotic bodies, and is not immunoreactive for cytokeratins.

Atypical teratoid/rhabdoid tumor because the atypical teratoid/rhabdoid tumor often shows immunoreactivities for neurofilament proteins, smooth muscle actin and epithelial membrane antigen, and in nearly all cases has a characteristic genetic profile (monosomy 22 with mutation of the SMARCB1 gene) and demonstrates loss of the SMARCB1 (INI1) gene product.

Anaplastic ependymoma because perivascular pseudorosettes and true rosettes are not found in CPC, and CPC shows widespread immunolabeling with anti-cytokeratin antibodies, but not anti-GFAP antibodies.

Embryonal carcinoma because embryonal carcinoma has a predominantly sheet-like or trabecular architecture and frequently labels with antibodies to CD30 and OCT4.

Metastatic papillary carcinoma in adults because CPC may express Kir7.1 and/or S-100 in addition to cytokeratins, and may show focal immunoreactivity for GFAP. Also, clinical features (i.e. patient’s age, site of the neoplasm, a history of a non-CNS primary neoplasm) can obviously aid diagnosis.

CPCs are characterized by marked architectural and cytologic atypia. They may invade adjacent brain, have a high mitotic index, and contain areas of necrosis (Fig. 40.6). Poorly differentiated CPCs may retain only small foci with a papillary architecture.

40.6 CPC.
This CPC shows marked architectural and cytological abnormalities, including invasion of adjacent brain, loss of papillary architecture, foci of necrosis, nuclear pleomorphism and a high mitotic count (a), (b), and (c). Note the focal formation of cilia (arrowhead) in (a). Immunoreactivity for cytokeratins is often restricted in CPC (d).

Immunohistochemistry reveals that most cells in CPPs label with antibodies to cytokeratins (Fig. 40.4d), S-100 and vimentin. CPPs also show focal GFAP immunoreactivity. Antibodies to transthyretin (prealbumin) label CP neoplasms, but this reactivity is not specific. However, antibodies to Kir7.1 (Fig. 40.4e), an inwardly rectifying potassium channel, appear almost entirely specific for CP neoplasms.

Ultrastructural examination may reveal features of CP in the neoplasms (i.e. cilia, apical junctions, apical microvilli, and a basement membrane covering a cell’s basal surface).

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