The Journal of Laryngology & Otology (2011), 125, 103–107.

CLINICAL RECORD
© JLO (1984) Limited, 2010
doi:10.1017/S0022215110001623

Aspergillus pachymeningitis mimicking

nasopharyngeal carcinoma

H S CHAN1, H Y YUEN2, W K NG3, A C VLANTIS1, A T AHUJA2, C F M TONG1,

C A VAN HASSELT1
1
Department of Otorhinolaryngology Head and Neck Surgery, 2Department of Radiology and Diagnostic Imaging,
and 3Division of Neurosurgery, Department of Surgery, The Chinese University of Hong Kong, China

Abstract
Objectives: We report a case of otogenic fungal pachymeningitis in a diabetic patient who presented with multiple
cranial nerve palsies and nasopharyngeal swelling.
Methods: We present a case report, we describe the investigations, management and clinical course of fungal
pachymeningitis, and we present a review of the world literature on fungal and non-fungal pachymeningitis.
Results: To our knowledge, this is the first report of fungal pachymeningitis with magnetic resonance imaging
features suggestive of nasopharyngeal carcinoma. It is also the first reported case with aspergillus cultured from
both a dural biopsy and the ear canal.
Conclusion: Fungal pachymeningitis is a rare condition which may present to otorhinolaryngologists. Its clinical
and radiological findings can be confused with those of nasopharyngeal carcinoma; fungal pachymeningitis should
thus be included in the differential diagnosis of nasopharyngeal carcinoma.

Key words: Aspergillosis; Central Nervous System Infections; Nasopharyngeal Neoplasm

Introduction automastoid cavity in the right ear and an atelectatic

Fungal pachymeningitis is an extremely rare opportu-
nistic infection of the central nervous system (CNS).
Only two cases have previously been reported. The
fungal infection usually spreads to the dura from the
ear, nasal cavity, paranasal sinuses or lung. Multiple
cranial nerve palsies and headache are the commonest
presenting symptoms. Inflammation of the dura may
extend beyond the skull case and cause nasopharyngeal
swelling. The combination of multiple cranial nerve
palsies and nasopharyngeal swelling is also a
common feature of nasopharyngeal carcinoma, which
must be excluded first in prevalent areas such as
Hong Kong and other parts of southern China.
Case report
A 59-year-old Chinese man presented to the otorhino-
laryngology and head and neck surgery department of a
tertiary referral teaching hospital with a two-month
history of hoarseness, diplopia and a left frontal head-
ache. He was a poorly controlled, insulin-dependent
diabetic who had impaired renal function and a
history of ischaemic heart disease.
On physical examination, the patient was found to
have a left abducens nerve palsy, a left hypoglossal
nerve palsy and a left vocal fold palsy. He had an
tympanic membrane in the left ear, but no signs of
active infection in either ear.
Nasopharyngoscopy showed smooth, bilateral full-
ness of the nasopharynx, with normal mucosa.
A gadolinium-enhanced magnetic resonance
imaging (MRI) scan of the skull base revealed a con-
trast-enhancing soft tissue lesion which was closely
related to the left pharyngeal recess and which
encased the left internal carotid artery and extended
intracranially (Figure 1).
The clinical presentation and radiological findings
raised suspicion of nasopharyngeal carcinoma
(NPC).
Immunofluorescence serological tests for immuno-
globulin (Ig) A antibody against Epstein–Barr virus
were abnormal: the IgA viral capsid antigen titre was
20 and the early antigen titre was 5.
Multiple deep nasopharyngeal biopsies were taken
to exclude NPC; all were negative for malignancy.
A positron emission tomography (PET) scan of the
head and neck showed that increased fluoro-deoxy-
glucose (FDG) uptake (maximum standardised uptake
value of 4.3) seen in the left nasopharyngeal paraphar-
yngeal space was in continuity with increased uptake in
the left posterior fossa dura (Figure 2). Increased FDG

Accepted for publication 16 April 2010 First published online 27 September 2010
104
FIG. 1
Axial, T1-weighted, gadolinium-enhanced magnetic resonance
image of the nasopharynx, with fat saturation, showing abnormally
enhancing soft tissues deep to the left posterolateral nasopharyngeal
wall (arrow), with extension into the left parapharyngeal space and
carotid space to encase the left internal carotid artery (arrowhead).
uptake in the left mastoid tip (maximum standardised
uptake value 4.6) was also seen.
The patient’s condition deteriorated, with increasing
headache severity and diplopia and decreasing visual
acuity bilaterally.
Although he was afebrile, he had a mild leukocytosis
of 11.6 × 109/l and an elevated erythrocyte sedimen-
tation rate (ESR) of more than 130 mm/hour.
Cerebrospinal fluid (CSF) collected by lumbar punc-
ture was clear, with no organisms seen on microscopy.
The CSF glucose level was 5.7 mmol/l and the CSF
protein level was elevated, at 1.27 g/l.
The abnormal dural enhancement seen on MRI and
PET, together with the elevated inflammatory markers,
raised suspicion of pachymeningitis.
This prompted us to undertake an open dural biopsy,
taken from the left posterior cranial fossa dura via a retro-
sigmoid approach. The dura was found to be thickened and
to form a plaque-like lesion between the brain and the
bone.
Histological examination of the dural biopsy showed
fibrous tissue with a dense small lymphocyte infiltrate
involving most of its layers. Immunohistochemical
studies showed that most of the lymphocytes were T
cells. Degenerated fungal filaments with septate
branching were also found.
These finding were compatible with a diagnosis of
fungal pachymeningitis.
Fungal infection was later confirmed by a finding of
elevated serum titres of 1,3-β-D-glucan and galacto-
mannan. The presence of galactomannan suggested
an aspergillus infection.
H S CHAN, H Y YUEN, W K NG et al.
A fungal culture from the dural biopsy grew
Aspergillus flavus after two weeks.
The patient’s ears were re-examined. An ear swab from
deep in the external meatus showed a focus of fungal fila-
ments on microscopy. The infected ear canal was cleaned
and miconazole anti-fungal cream instilled. The same ear
swab later grew Aspergillus flavus.
Once the diagnosis had been made, systemic antifun-
gal treatment with oral voriconazole 200 mg twice
daily was commenced. However, the patient developed
a pancytopenic crisis after two weeks of voriconazole
therapy, and the antifungal agent was thus changed to
intravenous caspofungin 50 mg daily.
After four weeks of antifungal treatment, the
patient’s ESR had dropped to 35 mm/hour, his head-
aches had improved and his left hypoglossal nerve
function had recovered; however, his vocal fold palsy
and ophthalmoplegia persisted.
In addition, during the course of antifungal treatment
the patient’s visual acuity had deteriorated further bilat-
erally. A follow-up MRI scan showed possible involve-
ment of both optic nerves by the disease (Figure 3). In
view of the continued deterioration of his visual acuity,
the patient was rechallenged with voriconazole (after a
four-week break from the drug). However, despite this
aggressive antifungal treatment, and tight control of
blood glucose levels, the patient suffered permanent,
bilateral loss of vision.
The patient was subsequently discharged to a conva-
lescent hospital for rehabilitation.
Seven months after initial presentation, a follow-
up MRI scan showed persistent dural thickening. As
a result, the patient was prescribed lifelong oral
voriconazole.
Discussion
Hypertrophic cranial pachymeningitis is a rare clinical
condition which is characterised by localised or diffuse
thickening of the dura mater.1 Most cases are idio-
pathic, but rare causes need to be excluded. These
include infectious diseases (such as tuberculosis, syphi-
lis, and fungal infections such as aspergillus, candida,
cryptococcus and histoplasmosis), inflammatory dis-
eases (including sarcoidosis, rheumatoid arthritis and
Wegener’s granulomatosis), dural carcinomatosis and
intracranial plasmacytosis.2,3
Only two previous cases of fungal pachymeningitis
have been reported. Murai et al.4 reported a possible
case of fungal pachymeningitis, which was not con-
firmed by dural biopsy. Ismail et al.5 reported a case in
which a positive fungal culture was obtained from the
frontal sinus, but they did not state clearly whether or
not the fungal infection involved the meninges.
To the best of our knowledge, our patient represents
the first reported case of fungal pachymeningitis in
which the same fungal species was identified in both
an ear culture and a dural culture.
Most CNS fungal infections occur in immunocom-
promised patients. Aspergillus infections usually
CLINICAL RECORD 105

FIG. 2
Positron emission tomography scan showing increased fluoro-deoxy-glucose uptake deep to the left posterolateral nasopharyngeal wall
(maximum standardised uptake value = 3.7). A = anterior; P = posterior; R = right; L = left

spread from the ear, nasal sinuses or lungs to the CNS.
The presence of aspergillus in both an ear swab and an
ipsilateral dural biopsy would suggest an otogenic
source of the CNS infection. Cases of non-fungal
pachymeningitis secondary to ear infections are well
documented in the literature; most are inflammatory
in nature.6,7 Headache is the commonest symptom,
and most such headaches are chronic and severe.1,3
The thickening of the meninges encasing the cranial
nerves results in their inflammation and ischaemia,
and ultimately in nerve paralysis.2
Detection of fungal infection in the CNS is difficult.
However, immunoassay for fungal cell wall components
now provides a sensitive tool for the detection of fungal
infections in CSF specimens. Relevant fungal wall com-
ponents include β-D-glucan, a non-specific polysaccharide
present in most fungal cell walls, and galactomannan,
which is more specific to aspergillus species.8,9
Gadolinium-enhanced MRI is an indispensable tool
which facilitates the diagnosis of pachymenigitis and
localises the affected meninges for subsequent dural
biopsy.1 More subtle foci of pachymeningitis can be
localised using PET, as in our patient. Dural biopsy is
the ‘gold standard’ for establishing the diagnosis of
fungal pachymeningitis.
The treatment of fungal pachymeningitis is not well
established due to the lack of reported cases. The stan-
dard steroid regime used for idiopathic cranial pachy-
meningitis may not be applicable when an infective
agent is present. In our patient, antifungal treatment
was given empirically to treat fungal meningitis.
Surgical decompression of involved cranial nerves
has been reported in idiopathic cases, with mixed
results.1–3 The clinical course of fungal pachymeningi-
tis is unpredictable and can be fatal despite antifungal
treatment.4,5
106 H S CHAN, H Y YUEN, W K NG et al.

patient presented with similar symptoms, to a hospital

in south-eastern China, NPC had to be excluded
before other diagnoses were considered. Although
most NPC tumours are obvious on nasopharyngo-
scopy, we do encounter cases of submucosal NPC in
which there is no apparent mucosal abnormality
(Figure 4). It is therefore difficult to quickly exclude
NPC in this group of atypical patients, unless serology
or imaging is grossly abnormal. While PET scanning is
a sensitive means of detecting early nasopharyngeal
tumours, false positives do occur due to inflammatory
conditions, as in our patient. Multiple deep nasophar-
yngeal biopsies are usually required when a submuco-
sal tumour is suspected. Surgical navigation aids are
useful in assisting biopsy in more difficult cases.

• Fungal pachymeningitis should be included in

FIG. 3
Coronal, T1-weighted, gadolinium-enhanced magnetic resonance
image showing abnormally enhancing dural thickenings over both
sphenoid wings, with suspicious compression of the optic nerves
at the anterior clinoids especially on the right (arrow).
Nasopharyngeal carcinoma (NPC) is prevalent in
south-eastern China, and is the commonest head and
neck cancer seen in this region.10 Most patients with
NPC present with the typical symptoms of epistaxis,
metastatic cervical lymphadenopathy and otitis media
with effusion.11 There are however a small group of
patients who present with atypical symptoms such as
headaches and multiple cranial nerves palsies. As our
the differential diagnosis of nasopharyngeal
carcinoma, especially in
immunocompromised patients
• When fungal pachymeningitis is suspected,
magnetic resonance imaging is useful in
localising the extent of dural involvement and
guiding subsequent dural biopsy
• The ear, nasal cavity, paranasal sinuses and
chest should be examined to seek a primary
source of infection
• In the presented case, treatment of fungal
pachymeningitis consisted of eradicating the
infective source and commencing lifelong
systemic antifungal medication (systemic
steroids are indicated in non-infective
pachymeningitis but their role in fungal
pachymeningitis is yet to be established)

There are similarities between the presenting symptoms

and the radiological findings of NPC and pachymenin-
gitis. The clinician should be aware of these similarities
when investigating patients with multiple cranial
palsies and nasopharyngeal swelling. Fungal pachyme-
ningitis characteristically affects immunocompromised
patients, and such patients have more florid CNS symp-
toms (e.g. headaches). Markedly elevated levels of
inflammatory markers and the absence of cervical lym-
phadenopathy favour a diagnosis of pachymeningitis
over NPC, especially in immunocompromised patients.
On MRI scans, extensive dural involvement would be
more suggestive of fungal pachymeningitis than intra-
cranial NPC.

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