Transcript Endolymphatic Sac Tumors

Endolymphatic Sac Tumors: A Pictorial
Review and Review of the Literature
Christopher J Stevens, MD – [email protected]
Christopher Wood, MD
Felix Diehn, MD
Christopher Hunt, MD
Steven Weindling, MD
Joseph Hoxworth, MD
Jonathan Morris, MD
Mark Jentoft, MD
John Lane, MD
Mayo Clinic
Department of Radiology
Exhibit Number: eEdE-147
Rochester, Minnesota
Disclosure
• The contributing authors have nothing to
disclose.
Purpose
• To provide a comprehensive review of endolymphatic
sac tumors, including clinical presentation, imaging
and pathologic characteristics, surgical staging and
treatment outcomes.
• To demonstrate, with case examples, the imaging
characteristics of endolymphatic sac tumors.
Methods
• The available radiology studies of 11 patients with
pathologically proven endolymphatic sac tumors (ELSTs)
were reviewed, including CT, MRI and angiography.
• A comprehensive literature review was performed and the
clinical presentation, radiologic and pathologic features,
surgical staging and management and treatment outcomes
of ELSTs discussed.
• Characteristic imaging findings of ELSTs observed in our
patients are demonstrated using case examples and
mirrored those discussed in the literature.
Discussion
Diagnostic History
• Endolymphatic sac tumors (ELSTs) are a relatively new
diagnosis.
• Endolymphatic sac first recognized as a source of tumor
in 1984 when Hassard et al. incidentally found a small
reddish tumor in the endolymphatic sac at the time of a
decompression operation.
• Heffner et al. (1989), with Armed Forces Institute of
Pathology materials, published first pathologic series of
20 low-grade adenocarcinomas of probable
endolymphatic sac origin.
• Previous reports of “cerebellopontine angle ceruminoma”,
“extradural choroid plexus papilloma” and “metastatic
papillary adenocarcinoma of unknown origin” are likely
accounted for by ELST’s.
Anatomy
• The endolymphatic sac and duct
are components of the
membranous labyrinth of the inner
ear.
• The endolymphatic duct
communicates with the utricle and
saccule via the utricular and
saccular ducts, respectively (not
shown).
• The endolymphatic duct fans out
within the bony vestibular aqueduct
to form the endolymphatic sac,
which has an intraosseous and
extraosseous component.
• The extraosseous portion of the
endolymphatic sac is paddleshaped and is located within leaves
of the dura mater along the
posterior ridge of the petrous
temporal bone.
Clinical History
• Unilateral hearing loss is typical presentation with
some degree of hearing loss seen in vast majority
of reported patients. Often hearing loss is sudden
and irreversible and is thought to be caused by
intra-labyrinthine hemorrhage,
• Other symptoms include facial nerve palsy,
tinnitus and vertigo or symptoms mimicking
Meniere’s disease.
• Locally aggressive, but low-grade tumors.
Metastases extremely rare, with only a couple of
reported cases.
Clinical History
• Usually unilateral and sporadic. The tumors have
an unexplained proclivity for the left ear
(approximately 70%).
• Associated with von Hippel-Lindau disease.
• In 30% of patients with VHL and ELST’s,
•
tumors are bilateral.
In patients with VHL, there is some evidence
that these tumors are smaller at presentation
and may have a less aggressive course.
Bone
Pathology
• At histopathology, ELST’s consist
of interdigitating papillary and
cystic processes which invade
surrounding bone and connective
tissues.
• Usually lined with single layer of
cuboidal epithelium typical of the
endolymphatic sac.
• Nuclear pleomorphism is absent
Figure 1: Low-power H and E stain of an endolymphatic sac tumor
demonstrates the papillary (red arrow) and cystic processes (blue arrow) typical
of this tumor.
and mitotic figures are not a
typical feature. Thus,
histologically has a low-grade
appearance.
Figure 2: High-power H and E stain demonstrates papillary processes
with a single layer of cuboidal epithelium (green arrow).
Pathology
• Papillary tumor often surrounded
by hemorrhagic cysts, hemosiderin
and inflammatory cells.
• Often associated with
endolymphatic sac hydrops or
intralabyrinthine hemorrhage (not
shown).
• Hemosiderin staining is common in
the periphery of the tumor.
Figure 1: Intra-operative photograph
during resection of an endolymphatic
sac tumor. Peripheral hemorrhagic
cysts and hemosiderin deposition
give the tumor a brown color (green
arrow).
Figure 3: Low-power hematoxylin and eosin stain of an endolymphatic sac
tumor demonstrates the papillary tumor (yellow boundary) with surrounding
hemorrhagic cysts and organizing hemorrhage (blue boundary).
Figure 2: Intra-operative photograph
in a different patient then Figure 1
again demonstrates the brown color
of the tumor due to peripheral
hemosiderin (green arrow).
Figure 4: High-power hematoxylin and eosin stain of an endolymphatic sac
tumor demonstrates hemosiderin deposition at the periphery of the tumor (brown
arrows).
Radiology
• Imaging workup remains key for diagnosis of
endolymphatic sac tumors and pre-operative
planning.
• Both CT and MRI have a role in imaging workup.
CT is useful to evaluate for degree of osseous
destruction and presence of calcification,
whereas MRI better defines the typical
characteristics of the tumor.
Computed Tomography
• Centered on the posterior aspect of the
petrous temporal bone in the location of
the endolymphatic sac.
• Invariably appear as aggressive soft
tissue lesions with permeative osseous
destruction of the posterior temporal
bone.
• Usually contain central spiculated
calcifications or rim-like calcification along
the posterior margin of the tumor.
• Posterior extension into the
cerebellopontine angle, anterior extension
into the middle ear cavity or cavernous
sinus and inferior extension into the skull
base correlated with size of tumor.
Figure 1: CT scan in a 55-yo male with pathologically
proven endolymphatic sac tumor demonstrates the
tumor’s typical CT characteristics. The tumor is usually
centered on the posterior temporal bone with permeative
osseous destruction (yellow arrows). Central spicules of
calcification are commonly seen (red arrow).
Magnetic Resonance Imaging
•
T1:
•
Majority have intrinsic T1
hyperintensity. Smaller lesions tend to
have peripheral T1 hyperintensity
whereas larger lesions are often
heterogeneously T1 hyperintense.
Peripheral T1 hyperintense nonenhancing cysts are frequently seen,
similar in appearance to a cholesterol
granuloma. A “cap” of T1 hypointense
hemosiderin can sometimes be
appreciated along the margins of the
tumor.
•
Post-contrast T1:
• Invariably enhance. Enhancement
pattern variable.
•
T2:
•
•
•
Invariably heterogeneous with at least
some areas of T2 hyperintensity
relative to the cerebellum. Low
intensity rim compatible with
hemosiderin.
Larger lesions often contain flow
voids.
DWI
•
Restricted diffusion not a prominent
feature.
A
B
C
D
Figure 2: Typical MRI imaging characteristics are demonstrated.
A) T1WI: Peripheral T1 hyperintensity is common, often in the
shape of small T1 hyperintense cysts (red arrow). B) Postcontrast, the central non-cystic component of the mass enhances
avidly (green arrow). C) T2WI demonstrate heterogeneous T2
hyperintensity (blue arrow). Peripheral hemosiderin is seen as a
peripheral T1 and T2 hypointense rim (yellow arrow). D) The
peripheral cysts and hemosiderin rim (yellow arrow) are well
appreciated on the FIESTA sequence.
Angiography
• Invariably hypervascular tumors.
• Smaller lesions (< 3 cm) have
demonstrated supply predominately
from the external carotid artery,
whereas larger lesions often have
supply from both the internal and
external cerebral arteries.
• External carotid artery supply usually
arises from the ascending pharyngeal
artery and stylomastoid artery (which
can arise from the posterior auricular
or occipital arteries).
Figure 3: Selective occipital artery digital subtracted
angiogram anteroposterior view demonstrates a
vascular tumor blush with supply predominately from
a stylomastoid branch of the occipital artery.
Radiology-Pathology Correlation
FIESTA
T1
T1 w/ GAD
•
Tumor
•
Hemorrhagic
cysts
•
Organizing
hematoma/
hemosiderin
Case 1- Small tumor
Figure 1: Axial CT scan of the temporal
bones demonstrating a lesion centered
on the posterior temporal bone in the
location of the endolymphatic sac with
intratumoral spiculated calcification (red
arrows).
History: 54 yo male with 5 month history of left-sided nonpulsatile tinnitus, spells of vertigo and gradual hearing loss.
Audiometry demonstrates moderate to severe sensorineural
hearing loss.
Figure 2: Axial MRI scan demonstrating typical MRI characteristics of
small ELSTs. A) T1-weighted image demonstrates peripheral T1
hyperintensity (red arrow). B) Post-gadolinium T1WI demonstrates avid
tumor enhancement (green arrow). C) T2-weighted FLAIR image
demonstrates heterogeneous T2 hyperintensity (blue arrow). D) FIESTA
sequence better demonstrates the intrinsic heterogeneity of the tumor
(yellow arrow).
Case 2 – Large Tumor
History: 38 yo male with 2 year history of
pulsatile tinnitus and subjective left-sided
hearing loss.
Figure 1: Otoscopic
examination demonstrates
a red retrotympanic mass.
Figure 2: Axial CT of the temporal bones demonstrates a
mass centered on the posterior temporal bone with
permeative osseous destruction and internal spicules of
calcification. The mass just extends into the middle ear
cavity accounting for the red mass seen on otoscopic
examination (red arrow).
A
B
C
D
Figure 3: Axial MRI examination demonstrates typical imaging characteristics
of larger endolymphatic sac tumors. A) T1-weighted image demonstrates
typical peripheral T1 hyperintense cysts (red arrow). B) Following contrast, the
cystic components do not enhance (red arrow) whereas the central solid
component enhances avidly (green arrow). A peripheral T1 hypointense rim
presumably represents hemosiderin (blue arrow). C) T2-weighted images
show the typical T2 hyperintensity of the tumors. D) The peripheral T2
hypointense rim is better appreciated on the FIESTA sequence (blue arrow).
Case 2 – Large Tumor
A
B
Figure 4: Selective occipital artery digital subtracted angiogram lateral view in
early (A) and late (B) arterial phase demonstrates a vascular tumor
predominately supplied by the stylomastoid artery arising from the occipital artery
(red arrows).
Case 3 - VHL
Figure 1: Axial CT of the temporal
bones demonstrates a mass
centered on the posterior temporal
bone with permeative osseous
destruction and central spicules of
calcification (red arrows).
History: 68 yo female with known von Hippel-Lindau syndrome. Her presenting
symptom of VHL was rapid progression of left-sided hearing loss and vertigo in he
20’s. She has since had permanent hearing loss in the left ear and no treatment
for her presumed longstanding stable left-sided endolymphatic sac tumor.
A
B
C
D
Figure 3: Axial MRI examination demonstrates typical imaging characteristics of a small
endolymphatic sac tumor. Post-surgical gliosis is incidentally noted in the left middle cerebellar
peduncle and left dentate nucleus from remote resection of a hemangioblastoma. A) T1-weighted
image demonstrates typical peripheral T1 hyperintensity (red arrow). B) Following contrast, there
is heterogeneous enhancement (green arrow). Note the tiny hemangioblastoma in the right
cerebellar hemisphere (red arrow). C) T2-weighted and D) FLAIR images demonstrate the
tumor’s T2 hyperintensity (yellow arrow).
Oct. 2005
Dec. 2009
Jan. 2013
Aug. 2014
Figure 3: Serial MRI examinations demonstrates the stability in size and appearance of this endolymphatic sac
tumor over a 5 year period (red arrows). Despite the variable aggressivity of these tumors, most authors advocate
early surgical excision while the tumors are easily resectable. This is also advocated to avoid complications of
intralabyrinthine hemorrhage leading to hearing loss or complications related to extensive temporal bone
involvement. Note the left cerebellar hemangioblastoma, which was subsequently removed following the first MRI
exam (green arrow) and the developing hemangioblastoma of the right cerebellar hemisphere (blue arrow).
Case 4 –
Recurrence
History: 65 yo female who developed rapid onset of left-sided hearing loss and deafness 8
year ago. She was diagnosed with an endolymphatic sac tumor and underwent surgery with
a combined left translabyrinthine and suboccipital approach with gross total tumor removal.
Upon follow-up with serial MRI examinations, she developed recurrent tumor 8 years later.
A
B
C
D
E
F
G
H
Figure 1: A-B) T1-weighted images demonstrate a tumor centered on the left posterior temporal bone with heterogeneous
T1 intensity. At least some components are hyperintense to cerebellum (yellow arrow). Peripheral T1 hypointense rim (red
arrow). C-D) Contrast-enhanced T1WI demonstrate nearly homogeneous tumor enhancement (blue arrow). A peripheral
cystic component inferiorly does not enhance (green arrow). E-F) T2-weighted images demonstrate typical heterogeneous
T2 hyperintensity (purple arrow). A posterior rim of hemosiderin can again be appreciated (red arrow). G) Coronal GRE
demonstrates susceptibility artifact from the hemosiderin rim (red arrow). H) DWI demonstrates isointensity to cerebellum.
Restricted diffusion is not a prominent feature of endolymphatic sac tumors.
Case 4 - Recurrence
A
B
Figure 2: Left external carotid artery digital subtraction angiogram, AP (A)
and lateral views (B), demonstrate a vascular tumor blush at the left petrous
ridge. Supraselective angiography better delineated the vascular supply of
the tumor (not shown). The tumor was predominately supplied by the
stylomastoid artery arising from the occipital artery. These arteries were
subsequently embolized with 250-350 micron PVA particles prior to surgical
resection.
Figure 3: Postoperative CT of the
temporal bones demonstrates the
surgical approach without evidence of
recurrent tumor. The previous left
retrolabyrinthine approach was extended
to a translabyrinthine approach with
resection of the vestibule and
semicircular canals and the posterior and
superior walls of the internal auditory
canal (red arrows).
Treatment
• As ELST’s are locally aggressive tumors, gross total resection is
currently advocated.
• The risk of tumor recurrence is significantly higher in patients with
subtotal resection. This increased risk of recurrence persists
following the addition of adjuvant external beam radiation therapy.
• Sole therapy with external beam radiation has been performed with
dismal results in the literature. The added benefit of external beam
radiation therapy following complete resection remains
controversial.
• Although not advocated as first line therapy, stereotactic
radiosurgery has shown to be effective in treatment of small
tumors or tumor recurrence in patients who are poor surgical
candidates.
Case 5
Treatment Radiation Therapy
History: 72 year old female with a 2-year course of hearing loss and spontaneous
vertigo 25 years ago diagnosed and treated as Meniere’s disease. She reports poor
hearing in the left ear since. An MRI exam was performed at an outside institution
following a presentation of left ear pain and headache and the diagnosis of
endolymphatic sac tumor made. She was subsequently treated with a 6-week course
of external beam radiation therapy and presented to the Mayo Clinic for follow-up.
Figure 1: CT of the temporal bones prior to radiation treatment
demonstrates the typical appearance of an ELST. The mass is
centered on the posterior temporal bone with permeative osseous
destruction and Intrinsic spiculated calcification (red arrows). There
is medial extension to the petrous apex (green arrow) inferior
extension to the jugular fossa (blue arrow) and anterior extension
into the middle ear cavity (yellow arrow).
Figure 2: MRI examination prior to radiation treatment further characterizes
the ELST. A) T1-weighted images demonstrate peripheral T1 hyperintensity
(red arrow). B) Following gadolinium, there is homogeneous enhancement
of the tumor (blue arrow). C) T2-weighted images demonstrate
heterogeneous T2 hyperintensity (yellow arrow). Note the mastoid air cell
fluid. D) T2-weighted FLAIR images demonstrate intralabyrinthine
hemorrhage (green arrow).
T1-weighted
image
T1-weighted
image
post-contrast
Aug. 2013
Oct. 2014
Figure 3: MRI examinations before and after external beam radiation therapy. The patient received 6 weeks of
radiation therapy shortly after the first MRI examination. Serial MRI examinations over 1 year show no evidence
of tumor progression. The patient will receive ongoing MRI surveillance every 6 months, with the plan for tumor
resection if there is evidence of tumor progression. Despite this patient’s initial treatment with external beam
radiation therapy and 1 year of stability on MRI, previous attempts in the literature to treat endolymphatic sac
tumors with external beam radiation therapy have reported dismal results.
Case 6
Treatment Radiosurgery
History: 43 yo female with known von Hippel Lindau syndrome and multiple prior surgeries for
resection of recurrent cerebellar hemangioblastomas. She presents with new onset left-sided
hearing loss and an enlarging left temporal bone endolymphatic sac tumor on routine follow-up
MRI examinations. Given her multiple prior surgeries and external beam treatment for recurrent
cerebellar hemangioblastomas, it was elected to treat the tumor via gamma knife stereotactic
radiosurgery.
Figure 1: CT of the temporal bones demonstrates a lytic
lesion of the posterior temporal bone, compatible with an
endolymphatic sac (red arrows). Intrinsic spiculated
calcification is seen, characteristic of ELST’s (green
arrows).
Figure 2: MRI examination better characterizes the ELST(red
arrows). Note the encephalomalacia from prior resection of a
right cerebellar hemangioblastoma (green arrows). A) T2weighted FLAIR and T2 FSE (B) show intrinsic heterogeneous
T2 hyperintensity. T1WI (C) demonstrates a predominately
hypointense tumor with minimal peripheral T1 hyperintensity.
Post-gadolinium images (D) show avid central enhancement.
Sept. 2004
May 2005
Nov. 2006
July 2013
Figure 3: Serial MRI examinations with T1-weighted post-gadolinium images demonstrate
regression of the left ELSTafter gamma knife stereotactic radiosurgery. The gamma knife surgery
was performed in October 2004. The tumor regressed in size and enhancement over time (red
arrows), consistent with successful treatment. Some ill-defined enhancing tissue was seen within
the left mastoid bone and was stable from 2006 to 2013, thought to represent radiation-related
change (green arrows).
Surgical Approach
• The choice of surgical approach depends on
preoperative hearing status and extent of
disease.
• Smaller tumors confined to the posterior
temporal bone may be resected with
preservation of hearing and facial nerve
function.
• Since ELST are usually highly locally
aggressive, using a subtotal tumor resection in
order to spare hearing in advanced tumors is
not advisable.
Surgical Approach
• Schipper et al. devised a grading system for endolymphatic sac tumors based on
tumor extent and surgical approach.
Stage
Tumor Description
Surgical
Approach
CN7
Spared
CN8
Spared
Diagram
Description
A
Tumor limited to the dura
of the posterior fossa
without infiltration of the
petrous bone.
Transmastoid
Yes
Yes
This approach has the
narrowest corridor to
cerebellopontine
angle. Spares the
labyrinth anteriorly.
The facial nerve is
skeletonized, but left in
place.
B
Tumor infiltrates lateral
semicircular canal and/or
cochlea.
Translabyrinthine
Yes
No
This approach
removes all of the
mastoid bone,
including the labyrinth,
with uncovering of the
posterior, superior and
inferior wall of the IAC.
This allows for
superior access to the
CPA. The cochlea and
facial nerve is left in
place.
C
Tumor infiltrates sigmoid
sinus and/or jugular bulb
Infratemporal
approach (Fisch
A)
Yes
No
This approach gives
better exposure to the
inferior temporal bone,
particularly the jugular
foramen, lower clivus
and upper neck. The
facial nerve is
anteriorly transposed.
Surgical Approaches
Transmastoid approach: Example of a patient
who had a gross total resection of an endolymphatic
sac tumor via a transmastoid approach. Note the
sparing of the semicircular canals (red arrows).
Permeative osseous destruction seen along the
posterior petrous bone is secondary to recurrence of
the endolymphatic sac tumor (green arrows). T1WI
again demonstrates recurrent tumor (blue arrow).
Translabyrinth approach: Example of a
patient who had a gross total resection of an
endolymphatic sac tumor via a translabyrinth
approach. The labyrinth has been resected to the
cochlea (red arrow) and the inferior, posterior and
superior walls of the internal auditory canal have
been removed. The surgical defect has been
replaced with fat (green arrow). T1WI post-contrast
demonstrates the typical T1 hyperintensity of the
fat graft (blue arrow).
Infratemporal approach (combined
with left suboccipital approach):
Example of a patient who underwent gross total
resection of an endolymphatic sac tumor. Since
the tumor involved the skull base near the jugular
foramen, an infratemporal approach was chosen.
Note the fat within the surgical defect (green
arrows). T1WI demonstrates the T1 hyperintense
fat graft (blue arrow).
Surgical Outcomes
• Numerous studies have looked at post-surgical outcomes with similar
results (Megerian 2002, Hansen 2004, Schipper 2006, Carlson 2013)
• Outcomes are generally good following gross total resection with the
majority of patients demonstrating long-term recurrence-free survival
(12/14 patients in Hansen et al., 7/7 in Schipper et al, 11/12 in Carlson et
al)
• Partial tumor resection has poor results with tumor recurrence (5/7
patients with recurrence in Heffner et al, 2/2 patients in Hansen et al)
• Early diagnosis improves surgical outcome. In patients with early
surgical intervention prior to sensorineural hearing loss, hearing can be
spared. (Hansen et al)
• Endolymphatic sac tumors are usually resistant to external beam
radiation therapy (Hansen et al, Heffner et al, Megerian et al.)
• When recurrence does occur, it has a similar imaging appearance to the
primary tumor
Case 7
Outcomes - Recurrence
with progression
59 yo female with history of Meniere’s disease 8 years prior treated with left
mastoidectomy and endolymphatic sac decompression. She presents with new onset
left-sided hearing loss, vertigo and hemifacial spasm. CT and MRI imaging
demonstrates likely endolymphatic sac tumor (not shown) and she undergoes
mastoidectomy and gross total tumor resection in October 2008. She is subsequently
followed with serial MRI examinations over 5 years with progression of tumor
recurrence.
T1
T1 postcontrast
Oct 2008
July 2009
March 2011
Oct 2013
Figure 1: Serial MRI examinations with T1-weighted images pre- and post-gadolinium demonstrate slow growth of the
recurrent ELST along the medial margin of the mastoidectomy cavity over 5 years (red arrows). The tumor
demonstrates the typical MRI characteristics of endolymphatic sac tumors, with heterogeneous T1 hyperintensity and
enhancement. Note the typical retraction of the fat graft over time (green arrows). New peripheral T1 hyperintense
cysts developed over time (blue arrows). Between March 2011 and October 2013, the normal fatty marrow T1
hyperintensity of the left petrous apex was replaced by tumor (yellow arrows).
Summary
• Endolymphatic sac tumors are rare, benign, but locally aggressive
tumors that can be sporadic or associated with von Hippel Lindau
syndrome.
• Radiology with CT and MRI play an important role in the diagnosis of the
tumors and defining their extent.
• Pathologically, the tumors are characterized by papillary and cystic
processes with surrounding hemorrhagic cysts and hemosiderin
deposition.
• Characteristic radiology features include location along the posterior
temporal bone, permeative osseous destruction and calcification on CT
and T1 hyperintensity with variable enhancement on MRI. Often, the
peripheral hemorrhagic cysts on pathology can be seen as peripheral T1
hyperintense cysts lined by hemosiderin staining.
• The tumors are best treated by gross total resection.
• Follow-up with serial MRI examination can be used to evaluate for tumor
recurrence. Recurrent tumors mimic the findings of the primary tumor.
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