Journal of Medical Imaging and Radiation Oncology 55 (2011) 52–57

C O MMEN TA RY jmiro_2229 52..57

MRI findings of cerebral cryptococcosis in

immunocompetent patients
Shaoqiong Chen1, Xiaohong Chen2, Zhigang Zhang3, Li Quan1, Sichi Kuang1 and Xiao Luo1
Departments of 1Radiology and 2Neurology and 3Pathology, the Third Affiliated Hospital, Sun Yat-Sen University. Guangzhou, China

S Chen MD, PhD; X Chen MD, PhD; Z Zhang Summary

MBBS; L Quan MD; S Kuang MD; X Luo MD.
Correspondence
Dr Shaoqiong Chen, Department of Radiology,
The Third Affiliated Hospital, Sun Yat-Sen
University, 600 Tianhe Road, Guangzhou,
510630, China.
Email address: csq_q@yahoo.com
Conflict of interest: None.
Worldwide, cerebral cryptococcal infections caused by cryptococcus neofor-
mans are mostly found in immunocompromised patients, but less found in
immunocompetent patients with fewer related imaging reports in literatures.
This pictorial essay describes some important MR imaging features in arriving
at diagnosis for cerebral cryptococcosis in immunocompetent patients by way
of five illustrative cases with intact MRI data.
Key words: cerebral cryptococcosis; immunocompetent; magnetic resonance
imaging.

Submitted 10 October 2010; accepted 18

October 2010.

doi:10.1111/j.1754-9485.2010.02229.x

the basal cistern5 (Fig. 1). The dilatation of subarachnoid

Introduction
Cryptococcus neoformans is a ubiquitous organism that
primarily infects the lungs and subsequently spreads to
the central nervous system (CNS) through the hae-
matogenous route. The CNS cryptococcal infections are
mostly found in immunocompromised hosts, and less
found in immunocompetent patients.1 However, we have
collected 152 cases of cerebral cryptococcosis in immu-
nocompetent patients in our hospital during a period of
6 years (2002–2008). As is commonly known, this
disease usually appears as features of meningitis, men-
ingoencephalitis and cerebral vasculitis radiologically.2
However, the development of features can have some
differences, depending on the host immune response.1,3,4
This pictorial essay discusses the usual and unusual MRI
appearances of cerebral cryptococcosis in immunocom-
petent patients by way of five illustrative cases with
intact MRI data, including one proven pathologically and
four confirmed by cerebral spinal fluid (CSF) laboratory
investigations.
Meningitis with cerebral vasculitis (Fig. 1)
Enhancement of the leptomeninges or sometimes dura
and/or leptomeningeal nodules is a common MRI feature
of cryptococcal meningitis, which is most pronounced in
spaces and cerebral cisterns due to mucoid gelatinous
exudates or the narrow of the CSF spaces caused by
adherence can also be seen. This feature of meningeal
enhancement on MRI is absent or minimal in cases of
AIDS-related crytococcal meningitis possibly due to
impaired cell-mediated immunity.6 Hydrocephalus is a
common complication of cryptococcal meningitis, which
appears as dilatation of the ventricles (Fig. 1). Cerebral
infarction is also a common complication resulting from
the development of cerebral vasculitis with inflammation,
spasms, constriction and, eventually, thrombosis in cryp-
tococcal meningitis patients.5 In the acute stage, diffusion
weighted image (DWI) shows patchy lesions with hyper-
intense signal in the cortical areas is consistent with acute
infarction. MR angiography (MRA) may confirm the exist-
ence of cerebral arteritis by demonstrating multiple
stenoses of cerebral arteries (Fig. 1c–f).
Contrast-enhanced T1WIs (Fig. 1a,b) show diffuse
gyriform leptomeningeal enhancement with some lep-
tomeningeal nodules (bold arrows) along the cerebral
surface, cerebral sulci and subarachnoid spaces and
basal cisterns. DWIs (Fig. 1c–e) show multiple hyperin-
tense lesions (fine arrows) in the cortical areas in both
hemispheres. Hydrocephalus is also seen (Fig. 1a–e).
MRA (Fig. 1f) shows multiple segmental stenoses in the
left middle cerebral artery, bilateral posterior cerebral

© 2011 The Authors

52 Journal of Medical Imaging and Radiation Oncology © 2011 The Royal Australian and New Zealand College of Radiologists
 MRI findings of cerebral cryptococcosis in immunocompetent patients
arteries (arrowheads) and anterior cerebral arteries
consistent with arteritis.
Encephalitis with clustered fine cysts (Fig. 2)
The leptomeningeal infection may produce voluminous
mucoid gelatinous exudates within the subarachnoid
space, which then spread through the perivascular spaces
© 2011 The Authors
Journal of Medical Imaging and Radiation Oncology © 2011 The Royal Australian and New Zealand College of Radiologists
Fig. 1. Cerebral cryptococcal infection
mainly with meningitis and vasculitis in a
27-year-old man. Cryptococcus is identified
with CSF India ink stain.
(Virchow-Robin (V-R) spaces) into the brain parenchyma
along with the organisms resulting in dilatation of V-R
spaces and forming of gelatinous pseudocysts.3,7 The
dilated V-R spaces and pseudocysts are mostly found in
the basal ganglia, typically appearing as clustered linear
or punctate cystic lesions with enhancing cystic wall
(Fig. 2a–d); and may be widely scattered over the thala-
mus, midbrain (Fig. 2e), periventricular white matter and
Fig. 2. Cerebral cryptococcal infection
mainly with clustered small cysts in a 36-year-
old man. Cryptococcos is identified with CSF
India ink stain.
53
S Chen et al.
cerebellum (Fig. 2f).3 These gelatinous pseudocysts
show higher signal intensity than the CSF on T2-fluid-
attenuated inversion recovery (T2-FLAIR) owing to their
mucoid content. Enhancement of the pseudocyst wall is
thought to be a chronic inflammatory reaction in immu-
nologically intact hosts.3,4
Non-contrast MRIs show numerous clustered small
lesions (fine arrows) with hypointensity on T1WI
(Fig. 2a) and hyperintensity on T2WI (Fig. 2b) in bilat-
eral basal ganglia. T2-FLAIR (Fig. 2c) shows that the
signal intensity of these small cystic lesions is higher
than that of CSF with extensive surrounding hyper-
intense edema. Postcontrast images (Fig. 2d–f) show
typical clustered small cystic lesions (5~10 mm) with
intense rim-enhancing wall in bilateral basal ganglia,
midbrain (bold arrow) and cerebellum (arrowhead)
around the fourth ventricle.
Meningoencephalitis with clustered fine
nodules (Fig. 3)
Previous studies have indicated that gelatinous
pseudocysts would develop into cryptococcomas with
disease progression. The cerebral cryptococcomas is a
collection of cryptococcus, gelatinous mucoid material
and chronic granulomatous reaction. They are usually
several millimetres (>3 mm) to several centimetres in
size.4,6 On MR images, small cryptococcomas are focal
Fig. 3. Cryptococcal infection mainly with clustered nodules in a 28-year-old
man. Cryptococcus is identified with CSF India ink staining.
54 Journal of Medical Imaging and Radiation Oncology © 2011 The Royal Australian and New Zealand College of Radiologists
solid nodules that often show no or minimal contrast
enhancement and surrounding edema in immuno-
compromised patients.6 Whereas in immunocompetent
patients, these small parenchymal cryptococcomas often
show fine solid enhancing nodules clustered in basal
ganglia and sparsely scattered over bilateral cerebral
hemispheres, cerebellums and brainstem. It is believed
that the feature of clustered enhancing cysts or nodules
found in bilateral ganglia is diagnostic for cerebral
cryptococcosis in immunocompetent patients.
Contrast-enhanced T1WIs (Fig. 3a–d) show diffuse
gyriform leptomeningeal enhancement with some lep-
tomeningeal nodules distributed along the gyrus sulci,
various basal cisterns and Sylvian fissures (bold arrows).
Numerous linear enhancing nodules (4~12-mm long)
clustered in bilateral basal ganglia (fine arrows) and
sparsely scattered over bilateral cerebral hemispheres
(temporal lobes and frontal lobes), cerebellums and
brainstem are also seen. The ventricles are normal in
size but basal cisterns and Sylvian fissures are mostly
narrowed.
Solitary larger arachnoid cyst (Fig. 4)
Intracranial cryptococcal infection can sometimes
develop a larger arachnoid cyst with only minimal
meningeal enhancement6 (Fig. 4). This is a very unusual
feature in this infection and can be mimicked as
the common non-infectious arachnoid cyst in the
Fig. 4. Intracranial cryptococcal infection with arachnoid cyst in a 22-year-old
woman. Cryptococcus is identified with CSF culture.
© 2011 The Authors
 MRI findings of cerebral cryptococcosis in immunocompetent patients
Fig. 5. Intracranial cryptococcal infection with choroids inflammation in a
22-year-old woman. Cryptococcus is identified with CSF culture. (The same
patient as that of Figure 4).
© 2011 The Authors
Journal of Medical Imaging and Radiation Oncology © 2011 The Royal Australian and New Zealand College of Radiologists
subarachnoid spaces, especially in the cerebello-pontine
angle cistern. However, the feature of rim-enhancing
cyst with circumferential edema and accompanying
meningeal enhancement is different from the non-
infectious arachnoid cyst in imaging appearances. Pos-
sibly, the rim- enhancement is due to the patient’s ability
to induce an inflammatory response as other changes
such as pseudocysts and cryptococcomas in immuno-
competent patients.
Magnetic resonance images (Fig. 4a–c) show a
dumbbell-like arachnoid cyst (arrows) in the left cerebel-
lopontine angle which is hypointense on T1WI (Fig. 4a)
and hyperintense on T2WI (Fig. 4b) and isointense to
CSF with surrounding hyperintense edema on T2-FLAIR
(Fig. 4c). Contrast-enhanced T1WI (Fig. 4d) shows ring
enhancement of the cyst wall. Meningeal enhancement is
also seen (arrowhead).
Choroid inflammation (Fig. 5)
Choroid plexitis appearing as an enhancing enlarged
choroid with dilatation of the ventricular horn has been
described in literature.8 Our case is consistent with these
findings. However, a solitary enlargement of the occipital
horn is a very uncommon MRI feature in cerebral cryp-
tococcosis and other infections, which may be due to the
obstruction of cerebral spinal flow caused by crypto-
coccal choroid plexitis with ependymal inflammatory
reaction and synechiae.
Fig. 6. Cryptococcal infection in a 47-year-
old man with insidious onset. The patient had
normal CSF preoperatively and underwent a
craniotomy with an initial diagnosis of brain-
stem tumour confirmed as cryptococcal
infection pathologically.
55
S Chen et al.
Magnetic resonance images show the dilated and
trapped occipital horn of the left lateral ventricle (fine
arrows) with periventricular extravasation of cerebrospi-
nal fluid (Fig. 5a–c). Postcontrast image (Fig. 5c) shows
the intense enhancement of ependyma and the thick-
ened choroid plexus (bold arrow). The dilated occipital
horn shrinks resulting in a smaller enhancing solid lesion
(arrowhead) on the follow-up enhanced scan (Fig. 5d)
11 days after anti-fungal treatment.
Solitary parenchymal mass without associated
meningitis (Figs 6,7)
When the patient’s immunocompetency is strong enough
to limit the spread of the disease, the infection may only
present as a solitary parenchymal mass without the
common features of meningitis or clustered pseudocysts
Fig. 7. The specimens with haematoxylin and eosin stain (magnification ¥200)
(a) reveals numerous small cysts containing yeasts (arrows), as well as diffuse
fibroplasia and inflammatory cell infiltrates within the granulomatous tissues.
The cellular infiltrates are composed of monocytes, lymphocytes and plas-
mocytes. Perl stain (magnification ¥200) (b) shows blue colour staining of the
iron material (arrow).
56 Journal of Medical Imaging and Radiation Oncology © 2011 The Royal Australian and New Zealand College of Radiologists
or nodules on MRIs, and is very easy to be misdiagnosed
as a tumour if the laboratory study reveals normal CSF.
Thus, it is important to make a correct diagnosis to avoid
improper operation in patients with insidious onset.
Solitary cryptococcoma is a very rare lesion in lite-
rature reports.9 It is characterised by a localised,
tumour-like mass in which the fungus has invaded the
parenchyma, producing a chronic granulomatous reac-
tion composed of macrophages, lymphocytes and foreign
body-type giant cells.1,4 On MRI, the cryptococcoma can
present as a rim-enhancing mass. The contrast enhance-
ment probably represents the patient’s ability to mount
an immune response.2,4 In our case (Fig. 6), contrast-
enhanced MRIs show the occupying mass in the brain-
stem to be a mixed signal mass with an enhancing rim
and non-enhancing core after administration of gado-
linium. The non-enhanced MRIs show the mass to be
isointense in wall with some hypointense areas in core on
T1WI, and hypointense in wall with some hyperintense
areas in core on T2WI, which essentially reflects the
mass is mainly composed of solid materials like granu-
lomatous and fibrous tissues with some filled fluid mate-
rials histo-pathologically. However, the shorter T1 signal
and shorter T2 signal in the mass may also reflect the
mass containing some degree of iron materials, a para-
magnetic substance that can shorten T1 & T2 relaxation
times. Besides, DWI shows hyperintense areas in the
mass seems to be an indication that the mass may
contain some collections of viscous materials. Surgical
histo-pathological specimen confirms a lot of cryptococ-
cus and mucoid gelatinous materials in the granuloma-
tous mass with prominent iron deposits on Perl stain for
iron (Fig. 7). This finding is somewhat similar to cerebral
aspergillus granuloma in previous report that the dense
population of hyphal elements and haemorrhage in
aspergillus granulomas may show T2 hypointensity due
to the paramegnatic elements such as iron, magnesium,
zinc, calcium, chromium and nickel within the hypha.10
Thus T2 hypointensity in the mass is probably a MRI
characteristic feature of some cerebral fungal infections.
The tumour-like cryptococcomas should be considered in
the differential diagnosis of rim-enhancing mass lesion in
brainstem or other unusual site.
T1WI (Fig. 6a) shows a mass of 2.6 cm ¥ 2.3 cm ¥
2.2 cm in size with surrounding hypointense edema and
posterior displacement of fourth ventricle in the pons
(more on its left side); The mass is isointense in peri-
pheral part with some hypointense areas in core and
isointense septum (fine arrow). T2WIs (Fig. 6b,c) show
the mass having a significant hypointense rim and
septum (fine arrow) and hyperintense areas in core. DWI
(Fig. 6d) shows two significant hyperintense areas
(bold arrow) in corresponding part of T2 hyperintense
area in the core. Post-contrast images (Fig. 6e,f) show
intense rim enhancement of the mass without central
enhancement (arrowheads). No feature of meningitis
is seen.
© 2011 The Authors
 MRI findings of cerebral cryptococcosis in immunocompetent patients

infection in an immunocompetent patient. Am J

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6. Miszkiel KA, Hall-Craggs MA, Miller RF et al. The
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Journal of Medical Imaging and Radiation Oncology © 2011 The Royal Australian and New Zealand College of Radiologists 57