Original Article

Acta Radiologica
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! The Foundation Acta Radiologica
Atypical choroid plexus 2017
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DOI: 10.1177/0284185116676651
and neuroradiological features acr.sagepub.com

Yu-Zhen Shi1, Mao-Zhen Chen1, Wei Huang1, Li-Li Guo1,

Xiao Chen2, Dan Kong1, Ying-Ying Zhuang1, Yi-Ming Xu1,
Rui-Rui Zhang3, Gen-Ji Bo1 and Zhong-Qiu Wang2

Abstract
Background: Atypical choroid plexus papilloma (APP) is a rare, newly introduced entity with intermediate character-
istics. To date, few reports have revealed the magnetic resonance (MR) findings.
Purpose: To analyze the clinicopathological and MR features of APP.
Material and Methods: The clinicopathological data and preoperative MR images of six patients with pathologically
proven APP were retrospectively reviewed. The MR features including tumor location, contour, signal intensity, degree of
enhancement, intratumoral cysts, and necrosis; and flow voids, borders, peritumoral edema, and associated hydroceph-
alus were analyzed.
Results: The APP were located in the ventricle (n ¼ 4) and cerebellopontine angle (CPA, n ¼ 2). Tumor dissemination
along the spinal subarachnoid space was found in one patient. The tumors appeared as milt-lobulated (n ¼ 5) or round
mass (n ¼ 1), with slightly heterogeneous signals (n ¼ 5) or mixed signals (n ¼ 1) on T1-weighted and T2-weighted
images. Heterogeneous and strong enhancement were found in five cases on contrast-enhanced images. Three of
four intraventricular tumors had a partly blurred border with ventricle wall. Four tumors had mild to moderate
extent of surrounding edema signals. A slight hydrocephalus was seen in four patients. Incomplete capsule was seen
in four tumors at surgery. Histopathologically, mild nuclear atypia was seen in all tumors with a mitotic rate of 2–5 per 10
high-power fields.
Conclusion: APP should be included in the differential diagnosis when an intraventricular or CPA tumor appearing as a
multi-lobulated solid mass with slight heterogeneity, heterogeneous strong enhancement, partly blurred borders, mild to
moderate peritumoral edema, or slight hydrocephalus are present.

Keywords
Choroid plexus tumors, atypical choroid plexus papillomas, magnetic resonance imaging (MRI), contrast medium,
spectroscopy
Date received: 22 March 2016; accepted: 26 September 2016

Introduction
1
Choroid plexus tumors (CPTs) are rare central nervous Department of Medical Imaging, Huai’an First People’s Hospital, Nanjing
Medical University, Jiangsu, PR China
system neoplasms originating from the choroid plexus 2
Department of Radiology, Affiliated Hospital of Nanjing University of
epithelium. They account for 0.4–0.8% and 1–4% of Traditional Chinese Medicine (TCM), Jiangsu, PR China
intracranial neoplasms in adults and children, respect- 3
Department of Pathology, Huai’an First Peopler’s Hospital, Nanjing
ively (1–4). They commonly arise in the lateral ven- Medical University, Jiangsu, PR China
tricles in children and in the posterior cranial fossa
including the fourth ventricle in adults (5). CPTs are Corresponding author:
Zhong-Qiu Wang, Department of Radiology, Affiliated Hospital of
traditionally classified as either benign choroid plexus Nanjing University of Traditional Chinese Medicine, 155 Hanzhong Road,
papilloma (CPP, World Health Organization [WHO] Nanjing 210029, Jiangsu, PR China.
grade I) or choroid plexus carcinoma (CPC, WHO Email: zhq2001us@163.com
2 Acta Radiologica 0(0)

grade III). However, differential diagnosis between degree of enhancement, intratumoral cysts and necro-
these two entities is difficult in some cases. In 2007, sis, intratumoral flow voids, borders of tumor, peritu-
the WHO introduced a new entity with intermediate moral edema, and associated hydrocephalus were
characteristics, atypical choroid plexus papilloma analyzed. All images were reviewed by two neuroradiol-
(APP), in the central nervous system (CNS) tumor clas- ogists (GB, YX) with more than 20 years of experience,
sification. The refined classification affects clinical treat- and agreement was reached by consensus.
ment management and prognosis (1).
Although the clinical, pathological, and magnetic
resonance (MR) features of CPP and CPC have been
Pathology diagnosis
well described (6–8), few reports have described the MR Histopathologic specimens were obtained in all patients
findings of APP. Several case reports on imaging find- by excisional biopsy. Histological diagnosis was made
ings (9,10) and serial studies focusing on the clinical on the basis of the distinct histological morphology of
characterization and pathology of APP (1,8) have CPTs, which consists of characteristic papillary struc-
been published. Here we present six cases of APP ture with a fibrovascular core lined by a single layer of
proved by pathological examination and characterize columnar cells. Immunohistochemical study of all spe-
the clinicopathological and MR features, in particular cimens was performed to confirm the histogenesis and
the correlation between MR features and clinicopatho- tumor grading. APP was distinguished from CPP by
logical behavior. increased mitotic activity, two or more mitoses per 10
high-power fields (HPF), but did not reach the criterion
for CPC, which is greater than 5 per 10 HPF (11,12).
Material and Methods
All cases were reviewed by a pathologist with more
This retrospective study was approved by our institu- than 10 years of experience.
tional review board. Informed consent was waived. The
medical records of six patients with histologically
proven APP were reviewed, including the medical his-
Results
tory, imaging examinations, and surgical and patho- The mean age of the six patients with APP was 30 years
logical data. (age range, 21–56 years) with a male:female ratio of 2:1.
For the three supratentorial APPs, the mean age was 19
years, whereas for the three infratentorial APPs, the
Imaging protocol
mean age was 41 years. The presenting clinical symp-
Six patients were examined with MR on a 3.0 T system toms included dizziness (n ¼ 2), headache (n ¼ 3), tin-
(three cases: Magnetom Verio, Siemens, Erlangen, nitus (n ¼ 2), limb weakness (n ¼ 2), nausea and
Germany) or 1.5 T system (three cases: Signal 1.5 T, vomiting (n ¼ 1), and blurred vision (n ¼ 1). The dur-
GE Healthcare, Milwaukee, WI, USA). Axial spin- ation from onset to admission ranged from 1 month to
echo T1-weighted (T1W) images (TR/TE, 500–600/14– 1 year with a median duration of 8 months.
20), axial fast spin-echo T2-weighted (T2W) images (TR/ The MR features of the six cases are summarized in
TE, 2500–4500/90–110) and axial or coronal T2W fluid Table 1. The tumors were located in the ventricle (n ¼ 4,
attenuated inversion recovery sequence (T2FLAIR) Figs. 1–3) or cerebellopontine angle (CPA, n ¼ 2,
images (TR/TE/TI, 8000/130/2200) were acquired. Fig. 4). Tumor dissemination along the spinal sub-
Diffusion-weighted images (DWI, single-shot spin-echo arachnoid space was found in one patient (Case 6),
echoplanar sequence with b factors of 0 and 1000 s/mm2) where the primary tumor was located in the left CPA
of the axial plane were also acquired in five patients. with metastasis in the foramen magnum region and the
Multiple-voxel proton MR spectroscopy (MRS) with a lumbosacral area (Fig. 4). The contour of the tumors
short echo time (7.4 ms) was performed in one patient, was multi-lobulated in five cases and round in one case
and absolute metabolite concentrations (mmol/kg) were (Case 6). In five of the six cases, the tumors appeared
determined using fully automated quantitation. as solid masses with slightly heterogeneous signals
Contrast-enhanced T1W images in the axial, coronal, (Figs 2–4). They were isointense to the cerebral gray
and sagittal planes were acquired after intravenous injec- matter on T1W imaging (n ¼ 5), isointense (n ¼ 3) or
tion of gadolinium-diethylenetriamine pentaacetic acids slightly hyperintense (n ¼ 2) on T2W imaging. The
(Gd-DTPA, 0.1 mmol/kg) in all patients. remaining case (Case 1, Fig. 1) was mixed iso-/hypoin-
tense on T1W imaging and mixed iso-/hyperintense on
T2W imaging. Of the five patients who underwent
Image analysis
DWI, tumors were isointense (n ¼ 3) or hyperintense
The MR findings, including tumor location, contour, (n ¼ 1) or mixed iso-/hyper-/hypointense (n ¼ 1) on
signal intensity relative to the cerebral gray matter, DWI. The MRS at short TE in Case 3 showed high
Shi et al. 3

Table 1. The MR features in six patients with APP.

MR

Case T1W T2W Contrast- Cysts/ Peritumoral

no. Age/sex Location image image DWI enhanced necrosis edema Hydrocephalus

1 20/M R of LV Mixed Mixed Mixed Hetero strong Multiple þ þ

2 21/F R of LV Iso Iso High Hetero strong Small foci þ þ
3 17/M L of LV Iso Sl high Iso Hetero strong Small foci þ þ
4 26/F FV Iso Iso Iso Homo strong – – þ
5 56/M R of CPA Iso Sl high Iso Hetero moderate – – –
6 40/M L of CPA Iso Iso – Hetero strong Small foci þ –
CPA, cerebellopontine angle; DWI, diffusion-weighted imaging; FV, fourth ventricle; Hetero, heterogeneous; Homo, homogeneous; L, left; LV, lateral
ventricle; R, right; Sl, slightly; T1W, T1-weighted; T2W, T2-weighted.

Fig. 1. Case 1. MR images of a 20-year-old man with APP in the trigone and temporal horn of the right lateral ventricle. (a) Axial T1W
image shows the tumor is iso/hypointense to the cerebral gray matter with scattered slightly high signals. (b) Axial T2W image shows
the tumor is iso/hyperintense. Flow void (arrow) in the tumor is noted. (c) Axial T2FLAIR image shows the tumor is slightly
hyperintense with scattered high signals. Partly blurred border (arrow) between the tumor and the ventricle wall and surrounding
edema in the brain are noted. (d) Axial Gd-enhanced T1W images show heterogeneous, strong enhancement of the tumor. Multiple
small non-enhanced areas suggestive of necroses and cysts (arrows) are seen. (e) Photomicrograph (hematoxylin and eosin [H&E],
100) shows disturbed papillary structures with cuboidal to columnar epithelial cells. The nucleus size is inconsistent and some cell
nuclei appear pleomorphism. Multiple cystic changes (arrows) and foci of necrosis (stars) are noted.

levels of choline (Cho) and myoinositol (mI) and low (Cases 1–3). Mild to moderate extent of peritumoral
levels of N-acetylaspartate (NAA) and creatine (Cr), edema signals were seen in four patients. After contrast
with slightly decreased lipids. Multiple cysts and injection, tumors showed heterogeneous enhancement
necroses were seen in one case. Small focal necroses in five patients and homogeneous enhancement in one
were seen in three cases. Intratumoral flow voids were patient. Enhancement was strong in five patients and
seen in three patients. Partly blurred borders between moderate in one patient. Slight hydrocephalus was seen
tumor and ventricle wall were seen in three patients in four patients with intraventricular APP.
4 Acta Radiologica 0(0)

Fig. 2. Case 2. MR images of a 21-year-old woman with APP in the trigone of right lateral ventricle. Axial T1W (a) and T2W image (b)
show a lobulated tumor isointense to the cerebral gray matter. (c) Coronal T2FLAIR image shows that part of the border between the
tumor and ventricle wall is blurred. Digitiform signal of peritumoral edema is noted. (d) Axial DWI shows the tumor is hyperintense.
(e) Axial Gd-enhanced T1W image shows heterogeneous, strong enhancement of the tumor. Small foci of necrosis is seen (star).
Engulfment of the choroid plexus is noted (arrow). (f) Photomicrograph (H&E, 100) shows papillary growing tumor consists of the
cuboidal to columnar epithelial cells with microscopic foci of necrosis (arrowheads). Neoplastic cells with high cell density and nuclear
pleomorphism (arrows) are noted.

Surgical records showed that three tumors (Cases has malignant characteristics including nuclear pleo-
1–3) had incomplete capsule and tight adhesion to the morphism, brisk mitotic activity, blurring of the papil-
ventricle wall, one (Case 6) had incomplete capsule and lary growth pattern, necrosis, and invasion of
tight adhesion to the brainstem and left cerebellar hemi- surrounding brain parenchyma (13). The APP is a
sphere. The reviewed pathological diagnoses were con- newly introduced entity as an intermediate grade in
sistent with the initial diagnoses. Characteristic the 2007 WHO CNS tumor classification to describe
papillary structures were noted in all tumors with those tumors with an intermediate histology between
areas of solid growth or effacement of the papillary. CPP and CPC. CPP can usually be resected completely
Focal necrosis and hemorrhage were seen in four with good prognosis. Chemotherapy for CPC has been
and two cases, respectively. Mild nuclear atypia was well established (6). For APP, maximal surgical resec-
seen in all tumors. The number of mitoses per 10 tion is recommended (1). Some APP patients are still
HPF was 2 (n ¼ 1), 3 (n ¼ 3), and 5 (n ¼ 2). There was curable with complete tumor resection, but the tumor
no evidence of invasion into brain parenchyma. recurrence rate is higher than CPP (1,8,14).
Immunohistochemical staining showed the tumor cells Chemotherapy and radiotherapy have great value for
being positive for S-100 (n ¼ 5), glial fibrillary acidic the treatment of APP patients with incompletely
protein (GFAP) (n ¼ 4), pancytokeratin (CK) (n ¼ 2), resected, metastatic, or recurrent tumors. Before 2007,
and vimentin (Vim) (n ¼ 2). Ki-67 proliferation index APP may have been over-diagnosed as CPC or under-
was 2%þ and 5%þ in two and four cases, respectively. diagnosed as CPP. The clearer definition enhances clin-
ical treatment and prognosis (1).
CPTs affect both children and adults. Lateral ven-
Discussion
tricular tumors have a propensity to occur in patients
CPTs are rare primary intracranial tumors, usually aged 10 years or younger, whereas infratentorial
occurring intraventricularly. The majority of CPTs tumors are much more common in adults (7,15,16).
are well-differentiated CPPs. CPC, on the other hand, For the lateral ventricle APPs in our series, the mean
Shi et al. 5

Fig. 3. Case 3. MR images of a 17-year-old man with APP in the trigone of left lateral ventricle. (a) Axial T2W image shows the tumor
is slightly hyperintense. Scattered low and high signals, and flow void (arrow) in the tumor are noted. (b) Coronal T2FLAIR image
shows that the tumor is slightly hyperintense and the boundary between the tumor and the choroid plexus (arrow) is indistinguishable.
Slight edema signal in brain parenchyma is seen. (c) Axial DWI shows the tumor is isointense. (d) Sagittal Gd-enhanced T1W image
shows heterogeneous, strong enhancement of the multi-lobulated tumor. A portion of the tumor has a blurred margin (arrow) with
the ventricle wall and an edema signal in the adjacent brain observed. (e) MR spectroscopy at short TE shows increase of Cho and mI,
and decrease of NAA and Cr.

age was higher than those reported in the literature (1). differences compared to those of the CPPs reported.
This may be due to the small sample size in our study. However, signal heterogeneity, especially on enhanced
Infratentorial APPs occurred in adults in the present images, was observed in a majority (83%) of our cases,
study, which is consistent with previous reports (2,10). which is higher than that in CPPs. The heterogeneity of
The clinical presentation of our patients was non- signal in our cases was not caused mainly by obvious
specific and their symptoms resembled those of previ- necrosis, cysts, and hemorrhage, because only small
ous reports (17,18). foci necrosis or hemorrhage can be seen on MR
Typical MR findings of CPP have been described as images or under the microscope in these tumors
a well-defined multi-lobulated or mulberry-like mass except for Case 1 which presented with multiple cysts
with homogeneous slight hypointense or isointense on and necroses. This heterogeneity of signal in APP on
T1W imaging and isointense or slight hyperintense on MR images may be closely related to their pathological
T2W imaging (7,8,19,20). They may also contain foci of features. Compared to CPP, APP has increased mitotic
hypointense signal on T1W imaging and T2W imaging activity and tumor growth, heart rate, and respiration
corresponding to calcifications, and flow voids when influence on macroscopic blood, and CSF flow speed,
high flow vessels feed the tumor (7,19). Marked homo- resulting in heterogeneous distribution of local neoplas-
geneous enhancement is another characteristic of tic cells and blood vessels (2,9). Another notable finding
hypervascular CPPs (6,8,20). CPCs, however, appear was that 75% of the intraventricular APPs in our study
heterogeneous because necrosis, calcification and hem- had a partly blurred border with the ventricle wall
orrhage are much more common (21). Extraventricular accompanied by a mild or moderate extent of peritu-
extension of a CPT into the brain parenchyma and moral edema. The finding of tumor borders and peri-
obvious surrounding edema favor the MR diagnosis tumoral edema in our series was different from that in
of CPC (20). CPP or CPC in previous reports (19–21). This imaging
The signal intensity on T1W imaging, T2W imaging, finding may also be explained by its pathobiological
and enhanced images of our cases did not show clear behavior of intermediate grade. In our cases, partial
6 Acta Radiologica 0(0)

Fig. 4. Case 6. MR images of a 40-year-old man with metastatic APP. (a) Axial Gd-enhanced T1W images show a round, strong
enhanced mass in the left cerebellopontine angle. (b) Sagittal Gd-enhanced T1W images show strong enhanced multi-nodules in
foramen magnum (black arrow) and lumbosacral spinal subarachnoid space (white arrows). (c) Photomicrograph (H&E, 200) shows
papillary structures with columnar epithelial cells. Nuclear pleomorphism and increased cellularity with mitoses (arrows) are noted.

blurred borders of the tumors on MR were confirmed NAA levels are noted in both CPPs and CPCs (22). In
by the broken capsule and or tight adhesion to ventricle one APP in our series, high Cho, mI and low NAA, Cr
wall at surgery. were observed at short TE. Whether MRS provides a
Tumor signal on DWI usually has a positive correl- differential value for APP needs further investigation.
ation with its malignancy degree and cell density. In our Hydrocephalus is one of the characteristic imaging
series, the tumors did not present noticeable character- findings of CPTs. Overproduction of cerebrospinal
istics on DWI. Systematic studies have not shown fluid (CSF) or obstruction of the CSF pathway by the
whether the signal intensity on DWI and the apparent tumor is the common pathogeneses for hydrocephalus
diffusion coefficient (ADC) values show statistical dif- (7). In our series, slight hydrocephalus was observed in
ferences among the three subtypes of CPT. Therefore, the cases with intraventricular APP, but not in the cases
more cases and further comparative studies are needed. in the CPA. This may be due to the fact that the
Compared with other intracranial tumors, CPPs have obstruction of the CSF pathway caused by the latter
been reported to show high mI þ Gly and relatively low is not as serious as the former. In addition, the
Cho on MRS (22–24). CPCs show higher Cho levels, decreased blood supply in the CPA may also contribute
but lower mI compared with CPPs (24). Low Cr and to the inability of CPTs in the CPA to overproduce
Shi et al. 7

CSF (7). Metastases of CPTs usually disseminate Authors’ Note

through CSF, even in CPP patients. Wrede et al. (1) Yu-Zhen Shi and Mao-Zhen Chen contributed equally to this
reported that APP had a higher metastatic rate (17%) work.
than CPP (5%), but had a similar rate with the CPC
group (21%). Metastases were noted in one (17%)
Declaration of conflicting interests
patient of our six cases, which was consistent with the
literature. The authors declared no potential conflicts of interest with
respect to the research, authorship, and/or publication of this
The differential diagnoses for intraventricular CPT
article.
include ependymoma, meningioma, and astrocytoma.
Highly suspected metathetic CPT in the CPA should
be differentiated from common tumors at this location, Funding
e.g. neurinoma, meningioma, and ependymomas. The authors received no financial support for the research,
Engulfment rather than compression or invasion of authorship, and/or publication of this article.
the choroid plexus has been described as a means to
differentiate CPT from other trigonal tumors (24). With References
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