Annals of Diagnostic Pathology 49 (2020) 151594

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Annals of Diagnostic Pathology

journal homepage: www.elsevier.com/locate/anndiagpath

Original Contribution

Nasal meningoencephalocele: A retrospective study of clinicopathological T

features and diagnosis of 16 patients
Li Xuea, Dong Gehonga, Wu Yinga, Tao Jianhuab, Zhang Hongc,d, Liu Honggangc,d,
⁎

a
Department of Pathology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China
b
Department of Imaging Center, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China
c
Department of Pathology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China
d
Beijing Key Laboratory of Head and Neck Molecular Diagnostic Pathology, Capital Medical University, Beijing 100730, China

ARTICLE INFO ABSTRACT

Keywords: Objective: Nasal meningoencephalocele (encephalocele or cephalocele) is a rare condition with congenital,
Encephalocele traumatic, or spontaneous origins. We investigated the clinicopathological characteristics of nasal en-
Nose cephaloceles to improve pathologists' and clinicians' understanding of this disease.
Pathology Methods: Sixteen patients with nasal encephaloceles were enrolled in this retrospective study investigating the
Diagnosis
condition's clinical and morphological features.
Results: Patients' average age was 37.8 ( ± 20.8) years. The ratio of men to women was 2.2:1, patients' mean age
was 47.4 ( ± 11.8) years, and 10/16 patients had spontaneous encephaloceles. All patients with traumatic and
spontaneous encephaloceles presented with cerebrospinal fluid leak. In 9/16 patients, the skull defect site oc-
curred on the lateral wall of the sphenoid sinus. Both congenital patients experienced nasal obstruction.
Histopathology, herniated tissues were brain and/or meningeal tissue, and the brain tissue was almost mature
glial tissue.
Conclusion: Nasal meningoencephalocele is a rare condition that can be challenging to diagnose. In patients with
recurrent clear nasal discharge or in children with a unilateral nasal mass, a high index of suspicion for en-
cephalocele is essential. In this study, spontaneous cases were most common in adults, and the lateral wall of the
sphenoid sinus was the most common location.

1. Introduction 35,000–40,000 newborns [3,4,8,9]. Generally, congenital defects are

Nasal meningoencephalocele (encephalocele or cephalocele) is a
herniation of cranial contents into the nose through a skull-based de-
fect. Encephaloceles can consist of meninges alone, which are called
meningoceles, or can also include brain tissue, which are known as
meningoencephaloceles [1]. This condition is uncommon, and con-
genital, traumatic, or spontaneous origins are possible.
The first medical report of encephalocele was published in the 16th
century and depicted a stillbirth with encephalocele accompanied by
severe deformity with what is now referred to as Robert's syndrome [2].
Most cases of nasal encephaloceles arise in Southeast Asian countries
such as Burma, Cambodia, Thailand, Malaysia, Indonesia, and India,
with rare cases reported in Europe, North America, and the Middle East
[3-6]. The underlying reasons for these differences are unclear. [3,6,7].
In Thailand, the morbidity of encephalocele is approximately 1 in
5000–6000 live fetuses, while the incidence in the West is 1 in
most common in childhood, while in adulthood, the etiology may be
traumatic or iatrogenic [1,10-12].
Patients with nasal encephalocele often see a doctor for clear nasal
fluid and nasal obstruction, and improper handling can easily cause
serious complications, such as meningitis and seizures [3,10-13]. In the
literature, clinicopathological case series are extremely uncommon, and
this lack of information makes early diagnosis more challenging. The
aim of this study was to analyze the clinicopathological characteristics
of patients with nasal encephalocele, to improve our understanding of
the disease.
2. Patients and methods
2.1. Patient selection
The clinical and pathological data for 16 patients diagnosed with

⁎
Corresponding author at: Department of Pathology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China.
E-mail address: liuhonggang2020@163.com (L. Honggang).

https://doi.org/10.1016/j.anndiagpath.2020.151594

Available online 13 August 2020

1092-9134/ © 2020 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/by-nc-nd/4.0/).
L. Xue, et al. Annals of Diagnostic Pathology 49 (2020) 151594

encephalocele in the Department of Pathology in one hospital (case 1)
from May 2008 to January 2018 and the Department of Pathology in a
second hospital (case 2–16) from June 2010 to October 2018 were
collected and analyzed. We excluded patients with 1) insufficient data,
and 2) encephaloceles outside of the nose. All patients had a confirmed
clinical and pathological diagnosis. The diagnosis for each patient was
confirmed using morphological analysis, and for patients in whom the
diagnosis was difficult, we confirmed the diagnosis using im-
munohistochemical analysis in accordance with the criteria of Rosai
and Ackerman's Surgical Pathology [14]. Clinical data, such as age, sex,
primary symptoms, and imaging data were obtained from telephone
interviews or electronic medical records. The follow-up period ended in
January 2018.
2.2. Method
The diagnostic methods were primarily morphological pathology
and immunohistochemistry. All tissue specimens were fixed with 10%
neutral formaldehyde, embedded in paraffin, and stained with hema-
toxylin and eosin. We analyzed the following antibodies: cytoplasmic
glial fibrillary acidic protein, epithelial membrane antigen, neuron-
specific nuclear protein, vimentin, and nuclear/cytoplasmic S100. The
staining was processed in accordance with the manufacturer's proto-
cols, and both positive and negative controls were used. Antibodies
were purchased from Beijing Zhong Shan Jin Qiao Biological Company
(Beijing, China). This article does not contain any studies with human
participants or animals performed by any of the authors. Written in-
formed consent was provided by all patients.
flowed from the right nasal cavity for 12 years, when the patient low-
ered her head, and the patients developed vision loss. Case 8 had empty
sella and diabetes, and case 11 had vision loss and diplopia in the left
eye, as well as hypertension and forehead headache. Case 12 experi-
enced watery discharge from the right nasal cavity for 20 years, which
was more obvious in the morning or when bending down. Six years
prior to presentation, case 16 experienced headache, vomiting, and a
fever of up to 40 °C, with loss of consciousness, and a local hospital
diagnosed purulent meningitis. The patient experienced symptoms 20
times in the 2 years before presentation, and the symptoms resolved
after anti-infective treatment. Case 14 had bilateral aeration of the
middle turbinate. There were no obvious initiating or precipitating
events in 7 patients (7/10), and the underlying causes in the remaining
three patients were: case 8, empty sella and diabetes; case 11, hy-
pertension; case 14, bilateral aeration of the middle turbinate.
Two patients (2/16) had congenital encephaloceles, and their
average age was 2.5 years. Both patients experienced nasal obstruction
and snoring without CSF leak.
Four patients (4/16) had traumatic encephaloceles and presented
with CSF leak; encephaloceles in two patients were caused by surgery,
and encephaloceles in two patients were caused by trauma. Case 3
experienced temporal headache and hyposmia after nasal polyp sur-
gery; case 5 lost the sense of smell after sinusitis surgery; case 4 suffered
a head injury 4 years before presentation, without symptoms; and case
6 had intermittent fever after head injury.
3.2. Imaging features

3. Results Data regarding the skull defect site related to the encephalocele are
summarized in Table 2. The lateral wall of the sphenoid sinus (LWSS)
3.1. Clinical features was the most common location in 9/16 patients, and the LWSS was the
location in 7/10 patients with spontaneous encephaloceles. In trau-
The principal clinicopathologic attributes of the 16 patients with matic encephaloceles, the LWSS was the affected location in two pa-
encephalocele are summarized in Table 1. Patients' mean age was tients. Sieve plate malformations constituted 4/16 of the lesions in our
37.8 years ( ± standard deviation: 20.8 years) (range, 1.2–64 years), series, and two patients with congenital encephaloceles had defects in
with a male predominance and a male to female ratio of 2.2:1 (11/5). the sieve plate (Fig. 1A–D).
Ten (10/16) patients had spontaneous encephaloceles, and their
average age was 47.4 years ( ± standard deviation: 11.8 years) (range,
28–64 years), with a male to female ratio of 2.3:1 (7/3). All patients 3.3. Pathological characteristics
presented with watery nasal discharge (cerebrospinal fluid (CSF) rhi-
norrhea confirmed by laboratory analysis), and nasal discharge flow Macroscopically, using nasal endoscopy, 6/16 patients had round,
increased in three patients when they bent down or when then lowered semi-circular, soft, and smooth masses in the nasal cavity.
their heads. Four patients had symptoms of nasal obstruction, and two Histopathology showed a mass surface with or without columnar or
patients presented with headache. In case 9, clear watery discharge cuboidal epithelium and with or without a dense fibrous dura-like band.
Brain tissue was covered by a layer of leptomeninges, and the brain
Table 1 tissue was mature neuroglial tissue (Fig. 2A–C). Neurons and large
Clinical features of the encephaloceles in the 16 patients in this study. ovoid or spindle astrocytes are seen in the inset in Fig. 2D. In some
lesions, chronic inflammation and fibrous tissue were seen (Fig. 2A).
Number Gender Age (years) Skull defect site (imaging) Origins
Immunohistochemistry showed that the brain glial tissue was po-
1 M 1.2 Sieve plate Congenital sitive for neuron-specific nuclear protein (Fig. 2E), glial fibrillary acidic
2 M 3.7 Sieve plate Congenital protein (Fig. 2F), S100, and vimentin, and that the meningeal tissue was
3 M 56 LWSS Traumatic positive for epithelial membrane antigen.
4 F 41 LWSS Traumatic
5 F 28 Ethmoid roof Traumatic
6 M 1 Sieve plate Traumatic
7 M 56 PWFS Spontaneous Table 2
8 M 54 PWFS Spontaneous Skull defect site causing encephaloceles in the16 patients in our study
9 F 64 LWSS Spontaneous
(number).
10 M 44 LWSS Spontaneous
11 M 51 LWSS Spontaneous Classification LWSS SP PWFS ER Total
12 M 54 LWSS Spontaneous
13 F 53 LWSS Spontaneous Congenital 0 2 0 0 2
14 M 28 LWSS Spontaneous Traumatic 2 1 0 1 4
15 M 41 LWSS Spontaneous Spontaneous 7 1 2 0 10
16 F 29 Sieve plate Spontaneous Total 9 4 2 1 16

F, female; M, male; LWSS, lateral wall of the sphenoid sinus; PWFS, posterior LWSS, lateral wall of the sphenoid sinus; SP, sieve plate; PWFS, posterior wall of
wall of the frontal sinus. the frontal sinus; ER, ethmoid roof.

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L. Xue, et al. Annals of Diagnostic Pathology 49 (2020) 151594

Fig. 1. (A, B) Cerebrospinal fluid rhinorrhea at the base of the left anterior cranial fossa. The coronal view shows discontinuity of the left sieve plate. The sagittal view
shows a soft tissue density protruding into the nasal cavity (arrow). (C) Cerebrospinal fluid leak from the right frontal sinus. The bone in the posterior wall of the right
frontal sinus is discontinuous, and a soft tissue density can be seen in the sinus (arrow). (D) The bone in the lateral wall of the right sphenoid sinus and the base of the
middle cranial fossa are discontinuous, and soft tissue densities can be seen in the sinus (arrow).

3.4. Treatment and follow-up
All patients underwent nasal endoscopic surgery. Except for one
patient who relapsed after a strong cough after 5 years of treatment, no
patients had experienced recurrence at the end of the follow-up.
4. Discussion
Nasal encephalocele is a rare entity. In our study population,
spontaneous encephaloceles were most common, with a male pre-
dominance. All patients with spontaneous encephaloceles presented
with CSF rhinorrhea. The LWSS was the most common location in pa-
tients with spontaneous encephaloceles, compared with the sieve plate
in the two patients with congenital encephaloceles.
Some previous studies reported a female predominance for en-
cephalocele [1,13,15-17], while other studies reported an equal dis-
tribution between male and female patients [2,7,18,19]. Piao et al. [20]
and Lu et al. [21] reported a male predominance, similar to our series.
Congenital encephalocele is the most common nasal encephalocele,
with the majority seen in early childhood [2,3,20-24]. When a uni-
lateral nasal mass is seen in a child, a high index of suspicion for en-
cephalocele is essential [2]. In our series, the mean age of the two
patients with congenital encephalocele was 2.5 years, and both patients
presented with nasal obstruction but without CSF rhinorrhea. The low
number of patients in our study may be related to patient distribution
(most congenital patients were in children's hospitals), folic acid sup-
plementation, or antenatal ultrasonographic examination.
The pathogenesis of encephalocele is still poorly understood.
However, various theories have been proposed to explain the reasons
for the disease [3,17,22,23]. The most widely held view is that the
anterior neuropore is not closed properly, and intracranial tissue
herniates out of the skull base through these lesions [17].
Encephaloceles occurring during adulthood have been ascribed to
many etiologies, such as infection, trauma, surgery, tumors, and ra-
diation therapy. Encephaloceles are considered spontaneous when
there is no definite cause [25,26]. In our study, spontaneous en-
cephalocele predominated, and a possible explanation is our patients'
distribution; one of our institutions is an Otolaryngology Head and
Neck Surgery Center, and the second is a Neurology Center, and
spontaneous encephaloceles are relatively common in adults. Lu et al.
[21] summarized data for a group of adult patients aged 20–64 years
(average, 41.5 years). Six patients had spontaneous encephaloceles, and
five patients had traumatic encephaloceles, with all patients presenting
with CSF leakage with or without meningitis.
The LWSS is the most common site of encephalocele and sponta-
neous CSF leak [27], which was confirmed in our series. CSF leak is

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L. Xue, et al. Annals of Diagnostic Pathology 49 (2020) 151594

Fig. 2. (A) The masses have surfaces covered with columnar epithelium, and a dense fibrous dura-like band is seen (black arrow). Brain tissue is covered by a layer of
leptomeninges (red arrow), and chronic inflammatory cells are seen. HE, Hematoxylin and eosin staining, ×100 (B) The masses' surfaces are covered with cuboidal
epithelium (black arrow). Brain tissue is covered by a layer of leptomeninges (red arrow). HE, Hematoxylin and eosin staining, ×100 (C) Brain tissue is covered by a
layer of leptomeninges (black arrow) without columnar or cuboidal epithelium. HE, Hematoxylin and eosin staining, ×100 (D) Neurons (black arrow) and large
ovoid astrocytes (red arrow) are visible in the inset. HE, Hematoxylin and eosin staining, ×400 (E) Immunohistochemistry showing neurons staining positive for
neuron-specific nuclear protein. ×400 (F) Immunohistochemistry showing glial tissue staining positive for glial fibrillary acidic protein. ×100.

frequent as a primary, and the most common clinical symptom, but may
be ignored [13,24]. One of our patients had a CSF leak for 20 years.
Tomaszewska et al. [26] observed other clinical features, such as empty
sella, female sex, mid-life, and obesity. Gaab [24] reported that 10% of
patients have epileptic seizures. In our series, spontaneous en-
cephalocele was not associated with female sex or obesity; case 8 had
empty sella and diabetes, case 11 had hypertension, and case 16 ex-
perienced loss of consciousness. In the remaining patients, inciting or
precipitating events were not noted.
The pathogenesis of encephalocele is still poorly understood, al-
though several theories have been suggested. Anomalies in Sternberg's
canal (lateral craniopharyngeal canal) have been suggested as a po-
tential factor related to spontaneous encephalocele [13,26]. These
anomalies involve ossification disorders in the fusion planes of the
sphenoid bone, which keeps Sternberg's canal open until adulthood.
Furthermore, the presence of a sufficiently pneumatized sphenoid sinus
is required. The formation of the sphenoid sinus continues until the age
of 20 [13,26]. Jabre et al. [18] suggested that encephalocele develop-
ment in adults is rare because congenital facial abnormalities are subtle
or absent, and diagnosis is delayed until the occurrence of rhinorrhea.
Kaufman et al. [28] considered that pneumatization of the sinuses along
the skull base in conjunction with pulsatile forces and intermittently
increased CSF pressure may erode the thin bone along the sinocranial
border. Ommaya et al. [29] considered that CSF pressure in the ara-
chnoid pouch could erode the thin sellar floor. O'Connell [30] proposed
a theory that the nontraumatic CSF rhinorrhea was secondary to a fis-
tula in the sieve plate, and found a pulsating pocket of CSF. McPheeters
et al. [25] believed that many seemingly spontaneous encephaloceles
may be post-traumatic, and that traumatic events are not recalled, or
are considered irrelevant by the patient. Wu et al. [19] considered that
patients were more likely to have a recessive skull defect, but the me-
sodermal lobe was well-differentiated to prevent herniation of the
cranial contents. According to the authors, trauma increases the defect,
and the resultant increased intracranial pressure induces an en-
cephalocele. It is also possible that trauma causes a fracture or defect in
the weakest part of the skull, and that the skull contents then herniate.
In the present study, case 5 suffered a head injury 4 years prior to
presentation, without symptoms. It is possible that spontaneous en-
cephalocele adult cases are secondary to trauma or to congenital en-
cephaloceles, but with delayed manifestation.
Nasal encephalocele should be distinguished from other nasal
masses, such as nasal glioma, dermoid cyst, teratoma, nasal polyps, and
nasal mucosal cyst. However, it is difficult to identify glioma or en-
cephaloceles according to histopathological findings [2,23]. Mature
glial tissue can be the observed in both types of lesion, but if meningeal
tissue is present, the diagnosis of encephalocele is more possible [17].
When identifiable meninges are absent, glioma can be distinguished
from encephaloceles only by imaging, which shows an intact skull base.
The hallmark of a dermoid cyst is a punctum with a single hair located
on the nasal dorsum [2,23]. Nasal polyps are rare in infants and more
common in adults [2,23]. In the remaining similar lesions, a complete
skull base is present.
A diagnosis of encephalocele can be made according to the patient's
history, physical examination findings, and imaging. Biopsies prior to
final repair are unnecessary and should be discouraged, and because of
the risk of meningitis, rough manipulation of the mass should be
avoided [2,23].
4.1. Study limitations
The most important limitations of this study are the small sample
size and possible selection bias. As cases of nasal encephalocele con-
tinue to be reported, future studies with larger statistical power may be
possible.
In summary, nasal meningoencephalocele is a rare condition that
can be challenging to diagnose. When a patient repeatedly experiences
clear nasal discharge, or when a child presents with a unilateral nasal
mass, a high index of suspicion for nasal meningoencephalocele is es-
sential. In the current study, spontaneous cases were most common in
adults, and the LWSS was the most common site.

4
L. Xue, et al.
Funding
This study was supported by the Beijing Municipal Administration
of Hospitals Clinical Medicine Development of Special Funding (No.
ZYLX201814).
Consent to participate
All authors wrote and are in agreement with the content of the
manuscript.
Consent for publication
Yes.
Author contributions
Xue Li and Honggang Liu conceived the project. Xue Li, Gehong
Dong and Ying Wu analyzed the data. Xue Li, Gehong Dong, Ying Wu,
Jianhua Tao, Hong Zhang and Honggang Liu contributed towards the
interpretation of the data. All authors wrote and are in agreement with
the content of the manuscript.
Declaration of competing interest
The authors have no conflicts to declare.
Acknowledgment
We thank Jane Charbonneau, DVM, from Liwen Bianji, Edanz Group
(https://en-author-services.edanzgroup.com/), for editing the English
text of a draft of this manuscript.
Ethics approval
This article does not contain any studies with human participants or
animals performed by any of the authors.
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