Keywords
Ependymoma - meningioma - multiple inherited schwannomas - and neurofibromatosis
Introduction
Neurofibromatosis type 2 (NF2) incidence is 1 in 33,000 and prevalence is 1 in 60,000.[1]
[2] It has no predilection for sex, race, and ethnicity, and it is most commonly seen
in the second and third decades of life that too most commonly between 16 and 24 years
of age.[3] Approximately 50% of cases are familial and remaining 50% are sporadic in nature.[4] NF2 is caused by the mutation in merlin gene, which is located on the long arm of
chromosome 22 (22q12.2).[5] The hallmark for the diagnosis of NF2 is bilateral vestibular schwannomas on magnetic
resonance imaging (MRI) of the brain. Here, we are reporting a rare case of multiple
inherited schwannomas, meningiomas, and ependymomas (MISME) syndrome or triple tumor
in a 30-year-old patient presenting with unilateral vestibular schwannomas, frontal
meningioma, and histopathologically confirmed intramedullary ependymoma at L3-L5 region
and intramedullary schwannomas at D12-L2.
Case Report
A thirty-year-old male patient presented to our hospital outpatient department in
December 2014 with the chief complaints of lower back pain for the past 1 year weakness
in bilateral lower limb for the past 1 year, urinary incontinence for the past 15
days and decreased vision in the left eye for the past 1 week. Neurological examination
of motor system shows tone to be normal in the upper limb and power grade 5/5 in the
bilateral upper limb. Tone reduced in bilateral lower limbs. Deep tendon reflex was
absent in bilateral lower limbs. Pure-tone audiometry showed bilateral sensory neural
deafness, which was more on the right side. Ophthalmic evaluation was done and was
suggestive of macular corneal opacity of the left eye and central serous retinopathy
with nystagmus in the right eye. MRI brain with contrast showed a well-defined enhancing
extra-axial space-occupying lesion (SOL) at left cerebellopontine (CP) angle largest
measuring 1.4 cm × 1.2 cm. The lesion is showing typical ice-cream cone appearance
of CP angle mass with a smaller extracanalicular component. There was a distinct cerebrospinal
fluid cleft between SOL and adjacent cerebellum, which was suggestive of acoustic
schwannoma [Figure 1]. Multiple well-defined round-to-oval extra-axial-based homogeneously enhancing soft-tissue
lesions largest measuring 3.2 cm × 2.2 cm × 2.0 cm were seen in the bilateral frontal,
right temporal, right parietal region, right cerebellar hemisphere, and right CP angle
and along the falx in midline which is suggestive of meningioma [Figure 2]a, [Figure 2]b, [Figure 2]c. Perifocal edema and dural thickening were also noted around few of the lesions.
Contrast-enhanced MRI of the lumbosacral spine with screening of dorsal and cervical
spine study showed a focal well-defined intradural SOL of size approximately 8.1 cm
× 1.5 cm × 1.6 cm seen at D12 to L2 vertebral levels related to the conus medullaris,
nearly completely occupying the thecal sac with ill-defined outline of the conus medullaris
[Figure 3]. Another small intradural enhancing lesion (10 mm in size) was seen at L3 vertebral
level inferior to the above lesion and another large intradural lesion (5 cm × 1.6
cm × 1.2 cm) at L4 vertebral level. The above findings are suggestive of multiple
intraspinal schwannomas large lesion at D12-L2 and L4-L5 vertebral levels [Figure 3]. The patient has undergone D11 partial D12-L5 laminectomy with excision of D12-L2
intramedullary SOL and L3-L5 multiple intradural SOL. Histopathological examination
of two lesions at vertebral site L3-L5 SOL showed ependymoma [Figure 4], and D12-L2 SOL showed schwannoma [Figure 5].
Figure 1: A well-defined enhancing extra-axial space-occupying lesion at left cerebellopontine
angle largest measuring 1.4 cm × 1.2 cm. The lesion is showing typical ice-cream cone
appearance of cerebellopontine angle mass with a smaller extracanalicular component.
There was a distinct cerebrospinal fluid cleft between space-occupying lesion and
adjacent cerebellum, which was suggestive of acoustic schwannoma
Figure 2: (a–c) Multiple well-defined round-to-oval extra-axial-based homogenously
enhancing soft-tissue lesions largest 3.2 cm × 2.2 cm × 2.0 cm were seen in the bilateral
frontal, right temporal, right parietal region, right cerebellar hemisphere, and right
cerebellopontine angle and along the falx in midline which is suggestive of meningioma
Figure 3: A focal well-defined intradural space-occupying lesion of size approximately
8.1 cm × 1.5 cm × 1.6 cm seen at D12 to L2 vertebral levels related to the conus medullaris,
nearly completely occupying the thecal sac with an ill-defined outline of the conus
medullaris
Figure 4: Tumor arranged around blood vessels forming pseudorosettes as well as lying
singly (H and E)
Figure 5: Show predominantly hyperdense (Antoni A) with the hypodense area along with
few congested blood vessels. Hyperdense areas (Antoni A) show palisade appearance
(Verocay) of cells (H and E)
Discussion
NF2 is basically characterized by neoplasms in the central nervous system and peripheral
nervous system. Neurofibromatosis was classified into two types based on their clinical
and pathological features.[6] About 90%–95% of cases of NF2 have eighth cranial nerve schwannomas, and two-thirds
of patients develop spinal neoplasms.[7]
[8] Nearly 90% of patients suffer from ocular abnormalities with most of them presenting
with early cataract, but retinal hamartomas and corneal lesions have also been documented.
Definitive diagnosis of NF2 is bilateral eighth cranial nerve schwannomas on imaging
or first-degree relative with NF2 and unilateral eighth cranial schwannoma at <30
years or any two of following: glioma, schwannoma, neurofibroma, meningioma, and juvenile
posterior subcapsular lenticular opacity. The criteria for probable or presumptive
diagnosis of NF2 are unilateral eighth cranial schwannoma before the age of 30 years
and glioma, schwannoma, neurofibroma, meningioma or cortical cataract or posterior
subcapsular cataract or unilateral vestibular schwannoma <30 years, and multiple meningiomas
(two or more) or at least one schwannoma, glioma, and juvenile lens opacity.[9]
[10]
[11]
[12] The investigation of choice in NF2 patients is the MRI of the brain and spine with
contrast. NF2 patients should be managed by multidisciplinary team which includes
neuroradiologist, neurologists, neurosurgeons, ophthalmologist, otologist, audiologist,
and geneticist. Few cases have been reported with the occurrence of all three tumors,
i.e., schwannomas, meningioma, and ependymoma in a single patient. In this case report,
an adult patient with triple tumor unilateral acoustic schwannoma, right frontal meningioma,
lumbar intramedullary ependymoma, and dorsal intramedullary schwannoma has been presented.
Conclusion
NF2 or MISME syndrome is rare in occurrence, in which the development of bilateral
eighth cranial nerve schwannomas is must for diagnosis. Treatment is mainly focused
on the maintenance of quality of life and preservation of cranial nerve and their
function, as there is always a tendency of formation of new tumors. Simultaneous occurrence
of triple tumors in an NF2 patient is rare. To rule out the possibility of tumors
at a different location, we should get the imaging of the brain and whole spine while
treating these cases.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms.
In the form the patient(s) has/have given his/her/their consent for his/her/their
images and other clinical information to be reported in the journal. The patients
understand that their names and initials will not be published and due efforts will
be made to conceal their identity, but anonymity cannot be guaranteed.
