J Neurosurg 108:751–756, 2008

The vestibular aqueduct: site of origin of endolymphatic

sac tumors

RUSSELL R. LONSER, M.D.,1 MARTIN BAGGENSTOS, M.D.,1 H. JEFFREY KIM, M.D.,2,4

JOHN A. BUTMAN, M.D., PH.D.,3 AND ALEXANDER O. VORTMEYER, M.D.1
1
Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke; 2Otolaryngology
Branch, National Institute on Deafness and Other Communication Disorders; 3Diagnostic Radiology
Department, The Clinical Center of the National Institutes of Health; National Institutes of Health,
Bethesda, Maryland; and 4Department of Otolaryngology–Head and Neck Surgery, Georgetown
University Medical Center, Washington, D.C.

Object. Although endolymphatic sac tumors (ELSTs) frequently destroy the posterior petrous bone and cause hear-
ing loss, the anatomical origin of these neoplasms is unknown. To determine the precise topographic origin of ELSTs,
the authors analyzed the imaging, operative, and pathological findings in patients with von Hippel–Lindau disease
(VHL) and ELSTs.
Methods. Consecutive VHL patients with small (# 1.5 cm) ELSTs who underwent resection at the National Insti-
tutes of Health were included. Clinical, imaging, operative, and pathological findings were analyzed.
Results. Ten consecutive VHL patients (6 male and 4 female) with 10 small ELSTs (# 1.5 cm; 9 left, 1 right) were
included. Serial imaging captured the development of 6 ELSTs and revealed that they originated within the intraosseous
(vestibular aqueduct) portion of the endolymphatic duct/sac system. Imaging just before surgery demonstrated that the
epicenters of 9 ELSTs (1 ELST was not visible on preoperative imaging) were in the vestibular aqueduct. Inspection
during surgery established that all 10 ELSTs were limited to the intraosseous endolymphatic duct/sac and the immedi-
ately surrounding region. Histological analysis confirmed tumor within the intraosseous portion (vestibular aqueduct)
of the endolymphatic duct/sac in all 10 patients.
Conclusions. ELSTs originate from endolymphatic epithelium within the vestibular aqueduct. High-resolution imag-
ing through the region of the vestibular aqueduct is essential for diagnosis. Surgical exploration of the endolymphatic
duct and sac is required for complete resection. (DOI: 10.3171/JNS/2008/108/4/0751)

KEY WORDS • anatomy • endolymphatic sac tumor • origin • pathology •

vestibular aqueduct

sac tumors were first established as a Although ELSTs can occur sporadically, they are fre-

E
NDOLYMPHATIC
pathological entity by Heffner in 19893 after he de- quently associated with VHL disease.7 Because of the asso-
scribed the unique anatomical and histological fea- ciation of ELSTs with VHL disease, investigators have per-
tures in 20 benign papillary-cystic neoplasms in the region formed serial imaging studies—MR imaging and CT of the
of the posterior temporal bone. Based on anatomical es- temporal bones—using high-resolution protocols that can
timations derived from the approximate epicenter of large capture the development of the tumors in these patients.4,6
tumors, Heffner concluded that the “probable” region of These findings from these imaging studies, when correlated
neoplastic origin was the posterior-medial face of the pe- with operative and pathological findings, provide direct in-
trous temporal bone. Because the extraosseous portion of sight into the precise origin of these tumors. Because accu-
the endolymphatic sac is located in this anatomical region rate determination of the site of origin of ELSTs has impor-
and because the tumors analyzed had histological similari- tant clinical and pathological implications, we analyzed the
ties to endolymphatic epithelium, he attributed the origin of clinical, imaging, operative, and pathological findings in
these neoplasms to the endolymphatic sac. Despite these cases in which ELSTs developed in patients with VHL dis-
critical insights and findings, Heffner felt that the precise ease, the development was captured on serial imaging, and
“region of origin is limited to a small size” but was not able the ELSTs were resected.
to define this site because of the large and extensive in-
volvement of the ELSTs available for his evaluation. Clinical Materials and Methods
Patient Population and Clinical Evaluation
Abbreviations used in this paper: CT = computed tomography; Consecutive patients with VHL disease who were eval-
ELST = endolymphatic sac tumor; MR = magnetic resonance; uated at the National Institutes of Health, had small ELSTs
RLPP = retrolabyrinthine posterior petrosectomy; VHL = von Hip- (# 1.5 cm in diameter), and underwent resection between
pel–Lindau. July 2001 and the end of December 2006 were included.

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Patients underwent serial neurotologic examinations at (Fig. 2). Findings from these cases revealed that an enhanc-
intervals of approximately 6–12 months. Data from inpa- ing ELST originated in the portion of the endolymphatic
tient charts, clinic notes, audiograms, operative reports, and system contained within the osseous vestibular aqueduct.
pathological findings were analyzed. One patient had no MR imaging or CT evidence of a tumor
mass but had evidence of intralabyrinthine hemorrhage on
Imaging Evaluation T1-weighted and FLAIR MR imaging. Surgical explo-
ration revealed a 0.2-cm tumor confined to the endolym-
Patients underwent serial (pre- and postcontrast), high- phatic duct.
resolution, T1-weighted, T2-weighted, and FLAIR MR-
imaging. They also underwent serial, high-resolution CT Operative Findings. The RLPP provided excellent expo-
of the temporal bones. Tumor size was determined by sure to the ELST, the osseous endolymphatic system (dis-
the largest tumor diameter in any single plane measured on tal duct and proximal sac) within the vestibular aqueduct,
MR images. and the extraosseous endolymphatic system (distal sac)
contained within the dura mater of the anterior region of the
posterior fossa. The direct exposure permitted selective
Operative Evaluation resection of each of these structures for separate anatomi-
To resect small ELSTs (# 1.5 cm), we use an RLPP ap- cal histopathological analysis. Gross tumor was identified
proach.4 This approach permits direct access and visualiza- within the vestibular aqueduct and the immediately sur-
tion of the intra- and extraosseous endolymphatic duct/sac rounding temporal bone in all cases. While the extraos-
system. Specimens including gross tumor, the intraosseous seous portion of the endolymphatic sac (anterior posterior
(within the vestibular aqueduct) endolymphatic duct/sac, fossa dura) appeared vascularized relative to other distant
and the extraosseous endolymphatic sac (within posterior dural regions in all cases, there was no gross evidence of tu-
fossa dura) were removed separately and separately sub- mor seen at surgery.
mitted for site-specific histopathological analysis. Pathological Findings. In all 10 cases, the material that
was resected from the intraosseous portion of the endolym-
Pathological Evaluation phatic sac and separately submitted contained ELST upon
histological examination. In 8 cases, separately submitted
Surgically resected tissues labeled “tumor,” “extraosse- samples of the extraosseous portion of the endolymphatic
ous portion of endolymphatic sac,” or “intraosseous portion sac were tumor-free upon histological examination, and
of endolymphatic sac” were separately received in the pa- lack of tumor was confirmed after serial sectioning of the
thology department, separately processed, and individual- specimens at 50-mm intervals. In 2 other cases, microscop-
ly analyzed. Histopathological detection of pathological ic amounts of papillary-cystic tumor were observed to ex-
changes was followed by immunohistochemical analysis of tend into the extraosseous part of the endolymphatic sac.
well-established epitopes of interest including MAK6 and Overall, all 10 tumors were located within the intraosseous
CD31.2 portion of the endolymphatic sac, 8 of them exclusively.

Results
Discussion
Patient Characteristics
Endolymphatic Sac and Duct Anatomy
Included in this study were 10 consecutive patients with
VHL disease (6 male and 4 female patients) who under- The endolymphatic sac and duct are part of the membra-
went resection of 10 (9 left, 1 right) small ELSTs (# 1.5 cm nous labyrinth of the inner ear (Fig. 3).5 The endolymphat-
in diameter). Their mean age (6 standard deviation) at the ic duct is connected to the membranous labyrinth of the in-
time of tumor resection was 39.0 6 7.4 years (range, 28– ner ear by the saccular and utricular ducts. These ducts are
50 years). Mean duration of follow-up after surgery was directly connected to the saccule and utricule, respectively,
32.8 6 13.4 months (range 3–48 months). Overall, the du- by bidirectional valves. The saccular and utricular ducts
ration of follow-up was 81.9 6 64.6 months (range 4.9– form the sinus of the endolymphatic duct, which is located
143.3 months). The mean tumor diameter at the time of in the bony vestibule. The sinus of the endolymphatic duct
resection was 0.8 6 0.5 cm (range 0.2–1.5 cm). All patients tapers and becomes the isthmus of the endolymphatic duct
had audiovestibular symptoms at the time of surgery, in- as it enters the bony vestibular aqueduct. The isthmus of the
cluding hearing loss (10 [100%] of 10 patients), vertigo endolymphatic duct connects to the intraosseous portion
(8 [80%] of 10 patients), tinnitus (8 [80%] of 10 patients), (within the vestibular aqueduct) of the endolymphatic sac.
and/or aural fullness (5 [50%] of 10 patients). Distally, the extraosseous portion of the endolymphatic sac
begins as the sac exits the aperture of the vestibular aque-
duct. The extraosseous portion of the sac resides between
Tumor Origin the leaves of the posterior fossa dura mater on the posteri-
Imaging Findings. Nine of 10 patients had imaging evi- or wall of the petrous ridge.
dence of an ELST at the time of surgery. Magnetic res-
Endolymphatic Sac Tumors
onance imaging in these patients revealed an enhancing
tumor mass centered in the vestibular aqueduct and CT Endolymphatic sac tumors are associated with erosion of
demonstrated osseous erosion in the region immediately the posterior petrous bone. These tumors occur sporadical-
surrounding the ELST (Figs. 1 and 2). The development of ly or in the context of the autosomal dominant neoplasia
an ELST was captured in neuroimaging studies in 6 cases syndrome, VHL disease (ELST incidence of 15%).1,7 In pa-

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Endolymphatic sac tumor origin

FIG. 1. Characteristic imaging and histological findings from a 40-year-old patient with VHL disease who had a right-
sided ELST and preoperative symptomatology that included right-sided hearing loss, tinnitus, and vertigo. A: Axial, T1-
weighted, enhanced MR image demonstrating a small (3-mm) enhancing lesion (arrowhead) within the right vestibular
aqueduct (external aperture of vestibular aqueduct, arrow). B: Corresponding axial unenhanced CT image demonstrating
osseous erosion by tumor (arrowhead) within the proximal vestibular aqueduct (external aperture of vestibular aqueduct,
arrowhead). Consistent with imaging findings, a small ELST was identified within the vestibular aqueduct. C: Hema-
toxylin and eosin staining demonstrates a papillary-cystic ELST. Original magnification 3 20. D: Immunohistochemical
staining for CD34 antigen (dark staining) demonstrates the intense vascularization characteristic of ELSTs. Original mag-
nification 3 20.

tients with VHL disease, bilateral ELSTs can be frequent- tion (vestibular aqueduct) of the endolymphatic duct/sac
ly found (occurring in 30% of patients with VHL who have system. Imaging demonstrating development of these tu-
an ELST).9 Endolymphatic sac tumors are locally invasive mors in the vestibular aqueduct and the fact that the epi-
(invading the temporal bone), and as a result, are frequent- center of larger tumors is at this site provide support for
ly associated with significant audiovestibular morbidity, in- this anatomical origin. Operative findings, consistent with
cluding deafness, tinnitus, and vertigo.1,7–9 Because surgical the imaging evidence, lend further support to this topo-
resection is curative and the onset of audiovestibular mor- graphic origin of ELSTs. Moreover, similar to the findings
bidity is unpredictable and not related to tumor size, early in our series of small ELSTs showing preferential tempo-
surgery has been recommended to reduce the morbidity re- ral bone erosion, all the large ELSTs in Heffner’s origi-
lated to these neoplasms.4,6,8 nal series demonstrated bone destruction,3 which would not
Heffner’s classification of ELSTs as “low-grade adeno- be expected to occur so frequently if the tumors originated
carcinoma of probable endolymphatic sac origin” left the outside of bone. Finally, separate site-specific histopatho-
exact anatomical and cellular origin unclear.3 The imaging, logical analysis of the osseous (vestibular aqueduct) endo-
operative and histopathological data from the patients in lymphatic duct/sac system and extraosseous endolymphat-
this study indicates that ELSTs arise from the osseous por- ic duct/ sac system (posterior fossa dura mater including the

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 R. R. Lonser et al.

FIG. 2. Serial imaging and histological findings in a 38-year-old patient with VHL disease that demonstrate the devel-
opment of a left-sided ELST within the vestibular aqueduct. The patient presented in 2000 with acute onset of left-sided
tinnitus. A: Axial, T1-weighted, enhanced MR imaging did not demonstrate evidence of an ELST. In 2002, the patient
presented with worsening tinnitus and acute left-sided hearing loss. B: Axial, T1-weighted, enhanced MR imaging at that
time demonstrated an enhancing tumor (arrow) within the proximal vestibular aqueduct. C: Corresponding axial, unen-
hanced CT imaging demonstrated tumor-associated erosion in the vestibular aqueduct (arrowhead). Consistent with imag-
ing findings, a small ELST was identified within the vestibular aqueduct. D: Hematoxylin and eosin staining demon-
strates a papillary-cystic ELST. Original magnification 3 20.

sac) provided confirmation that these tumors arise in the re- tion of the endolymphatic sac) may reduce the possibility
gion of the vestibular aqueduct. of missing a small ELST in patients with audiovestibu-
lar symptomatology. This is particularly important in pa-
Clinical Implications tients with VHL disease and audiovestibular dysfunction in
Because early surgical intervention can reduce the mor- whom an ELST may be missed because MR imaging and
bidity associated with ELSTs and because these tumors CT studies incompletely evaluated the region of the vestib-
cause significant audiovestibular morbidity when they are ular aqueduct. Furthermore, because ELSTs arise in the os-
small (, 2 mm), understanding the precise topographical seous (vestibular aqueduct) portion of the endolymphatic
location of these lesions provides critical insights that aid in duct/sac system, complete surgical resection of these tu-
their diagnosis and successful surgical treatment. High-res- mors requires exploration and removal of tumor from the
olution MR imaging and CT directed to the region of the osseous vestibular aqueduct and possibly the extraosseous
vestibular aqueduct (in addition to the extraosseous por- portion of the endolymphatic sac.

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Endolymphatic sac tumor origin

FIG. 3. Schematic illustration detailing the anatomy of the endolymphatic system and its relationship to surrounding
petrous bone structure. The endolymphatic sac and duct are part of the membranous labyrinth of the inner ear. The endo-
lymphatic duct is connected to the membranous labyrinth of the inner ear by the saccular and utricular ducts. The saccu-
lar and utricular ducts form the sinus of the endolymphatic duct. The sinus of the endolymphatic duct tapers and becomes
the isthmus of the endolymphatic duct as it enters the bony vestibular aqueduct. The isthmus of the endolymphatic duct
connects to the intraosseous portion (within the vestibular aqueduct) of the endolymphatic sac. Endolymphatic sac tumors
arise from the endolymphatic epithelium of the endolymphatic duct and sac with the vestibular aqueduct (osseous portion,
striped area). Distally, the extraosseous portion of the endolymphatic sac begins as the sac exits the aperture of the vestibu-
lar aqueduct. The extraosseous portion of the sac resides between the leaves of the posterior fossa dura mater on the poste-
rior wall of the petrous ridge.

Developmental Implications the site of origin of ELSTs, we therefore focused on a group

Previous studies of tissues from patients with VHL dis- of patients with tumors that were small enough to be com-
ease revealed multifocal, VHL-deficient epithelial cell pro- pletely confined to their site of origin, but large enough to
liferations throughout the endolymphatic duct and sac that be grossly visible and qualify as an independent tumor. By
are likely to represent potential precursor structures for the studying this group of patients in detail we consistently ob-
development of frank tumor.2 At the same time, the abun- served tumorigenesis to occur in the intraosseous portion of
dance of precursor structures detected in the endolymphat- the endolymphatic sac and duct. It remains to be clarified
ic sac and duct in a patient without an ELST at autopsy sug- whether the progression from microscopic precursor into
gested that most precursor structures do not develop into frank tumor is the result of specific molecular signaling and
frank tumor during the lifetime of an individual patient.10 whether specific environmental conditions within the intra-
While evidence is emerging in other VHL target sites that osseous portion of endolymphatic sac/duct may facilitate
tumor progression is associated with activation of separate such events.
proteins, which are undetectable in potential precursor le- Conclusions
sions, no “activating” mechanism is currently known that
would differentiate early tumor from precursor state in the Serial focused screening and evaluation of at-risk pa-
endolymphatic sac or duct. To obtain definitive insight into tients with VHL disease captured the development of small

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aqueduct will enhance imaging discovery and the effective- cock ME 3rd: Hearing preservation surgery for small endolym-
ness of surgical treatment. phatic sac tumors in patients with von Hippel-Lindau syndrome.
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