Interdisciplinary Neurosurgery 20 (2020) 100657

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Interdisciplinary Neurosurgery
journal homepage: www.elsevier.com/locate/inat

Case Reports & Case Series

Glomus jugulare tumor presenting as mastoiditis in a patient with familial T

paraganglioma syndrome: A case report and review of the literature
⁎
Georgios Alexopoulosa, , Joshua Sappingtonb, Philippe Merciera, Richard Bucholza,
Jeroen Coppensa
a
Department of Neurosurgery, Saint Louis University Hospital, 3635 Vista Ave, St. Louis 63104, MO, United States
b
Department of Otolaryngology Otolaryngology and Neurotology, Saint Louis University Hospital, 3635 Vista Ave, St. Louis 63104, MO, United States

A R T I C LE I N FO A B S T R A C T

Keywords: Glomus jugulare paragangliomas (PGLs) are rare, slow-growing, hypervascular lesions that represent a type of
Familial paraganglioma syndrome extra-adrenal PGL, originating within the wall of jugular bulb. We report the first case of a 59-year-old woman
Glomus jugulare tumor with hereditary PGL syndrome, who was initially diagnosed with mastoiditis as the only radiological finding of
Mastoiditis an evolving jugular foramen PGL. Mastoiditis can be the presenting symptom of a jugular PGL due to eustachian
tube dysfunction. High index of clinical suspicion is important before initiating treatment for mastoiditis in
patients with familial PGL syndromes, obviating the need for early work-up with magnetic resonance imaging.

1. Introduction complex subunit D (SDHD) gene mutation, hypertension, diabetes

Glomus jugulare tumors are rare, slow-growing, hypervascular le-
sions that represent a type of extra-adrenal paraganglioma (PGL), ori-
ginating within the wall of jugular bulb [1–5]. Jugular foramen PGLs
represent only 10% of the head and neck PGLs [1–5]. Although con-
sidered histologically benign, the management of jugular PGLs is
challenging because of their infiltrative nature, as well as close proxi-
mity to the lower cranial nerves and vascular bundles [1–7]. It is now
recognized that nearly 40% of all PGLs are hereditary in nature [8–11].
Hereditary PGL syndrome is an autosomal dominant, highly penetrant
disorder, that runs in families with novel germline mutations in the
gene encoding succinate dehydrogenase complex subunit D (SDHD)
[7–11]. The most common presenting symptom of jugular PGLs is
pulsatile tinnitus, followed by hearing loss [1,3,6,12,13]. Here, we
identified a 59-year-old female with a history of familial PGL syndrome
who was initially diagnosed with mastoiditis as the presenting symptom
of an underlying cryptogenic glomus jugulare PGL.
2. Case report
We report the first case of a 59-year-old female with a medical
history of hereditary PGL syndrome with a succinate dehydrogenase
mellitus, morbid obesity, gastroesophageal reflux disease, vertigo, who
was referred to our institution for worsening pulsatile headaches, and
episodic hypertension for evaluation of a right jugular foramen mass.
The patient had a surgical history of bilateral carotid body PGLs, which
were resected more than 20 years ago with sacrifice of the bilateral
external carotid arteries, also a laryngeal PGL that was also resected in
the past. She has multiple, first degree relatives, with SDHD gene mu-
tation positive, familial PGL syndrome. Upon genetic profiling, the
patient tested heterozygous for the presence of an SDHD c.242 > T
(p.Pro81Leu) pathogenic mutation.
Six months prior to the patient’s referral, she developed diminished
hearing of the right ear. An audiometric evaluation showed mild mixed
conductive and sensorineural hearing loss of the right ear, with un-
restricted hearing of the left ear. A tympanometry showed negative
pressure in the right middle ear cavity. A contrast-enhanced computed
tomography (CT) scan of the head revealed fluid density in the right
mastoid air space (Figs. A and B). The middle ear cavity appeared to be
normal. There were no definite bony lesions, or erosion of the jugular
foramen. The patient was diagnosed with eustachian tube dysfunction,
which could be accounting for her symptoms of earache, and head-
aches. As such, a right myringotomy without tube placement was per-
formed.

Abbreviations: CT, contrast-enhanced computed tomography; db, decibels; Hz, Hertz; MRI, magnetic resonance imaging; PGL, paraganglioma; PET-CT, positron
emission tomography–computed tomography; SDHD, succinate dehydrogenase complex subunit D
⁎
Corresponding author.
E-mail addresses: georgios.alexopoulos@health.slu.edu (G. Alexopoulos), joshua.sappington@health.slu.edu (J. Sappington),
philippe.mercier@health.slu.edu (P. Mercier), richard@bucholz.org (R. Bucholz), jeroen.coppens@health.slu.edu (J. Coppens).

https://doi.org/10.1016/j.inat.2019.100657
Received 17 September 2019; Received in revised form 29 November 2019; Accepted 21 December 2019
2214-7519/ © 2019 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/BY-NC-ND/4.0/).
G. Alexopoulos, et al.
The patient continued to have evolving symptoms after the surgery.
A repeat follow up CT scan of the head, six months following the
myringotomy, revealed a mass centered in the right jugular foramen
with extension into the adjacent post-styloid space, causing bony ex-
pansion of the jugular foramen. Again, there was coexisting mastoiditis
(Figs. A and B), with occlusion of the right internal jugular vein, just
inferior to the mass. A magnetic resonance imaging (MRI) of the brain,
with and without contrast, showed the right jugular foramen vividly
enhancing mass, measuring 2.6 cm in the anteroposterior, 2.3 cm in the
traverse, and 2.8 cm in the craniocaudal dimensions. The mass had
numerous flow voids. The mass obliterated the right hypoglossal canal,
extending into the right cerebellopontine angle, right occipital phar-
yngeal tubercle, and inferior aspect of the clivus. The lesion appeared to
emanate from the pars vascularis of the right jugular foramen (Fig. C).
Given the patient’s prior history, the location and appearance of the
lesion suggested a possible glomus jugulare PGL.
A follow-up cerebral angiogram confirmed tumor blush coming off
the petro-cavernous segment of the right internal carotid artery, also
2
Interdisciplinary Neurosurgery 20 (2020) 100657
Fig. A. Axial CT scan at the level of the right jugular
foramen before (left) and after (right) the expansion
of the glomus tumor. There is partial opacification of
the mastoid air cells, and erosion of the mastoid air
cell bony septa (left), but no definite mass. Six
months following the myringotomy, a CT scan de-
monstrated rapid irregular erosion of the jugular
foramen with a moth-eaten pattern (right). There is
coexisting mastoiditis.
Fig. B. Coronal CT scan at the level of the right ju-
gular foramen before (left) and after (right) the ex-
pansion of the glomus tumor. Again, there is partial
opacification of the mastoid air cells, and erosion of
the mastoid air cell bony septa (left). Six months
following the myringotomy, a CT scan (right) de-
monstrated a new mass causing osteolytic expansion
of the jugular foramen on the right with extension
into the adjacent post-styloid space, and intracranial
space.
blush coming off capillary branches of the V4 segment of the right
vertebral artery (Fig. 3). Most of the tumor blush was suggestive of
capillary perfusion, without definitive arterial pedicles.
Further workup with a positron emission tomography-computed
tomography (PET-CT) scan showed an intensely hypermetabolic mass
in the right jugular foramen, which expanded and eroded the foramen
along with mild intracranial extension into the right cerebellopontine
angle, consistent with a diagnosis of glomus jugulare PGL. There were
several mildly hypermetabolic axillary lymph nodes bilaterally, which
appeared reactive in nature, but no evidence of metastatic disease. PET-
CT scan also revealed a pulmonary nodule in the left upper lobe
(1.4 × 1.7 cm) that did not demonstrate any significant radio-uptake
above the background surrounding lung parenchyma, consistent with a
benign lung nodule. A magnetic resonance imaging (MRI) of the ab-
domen with and without contrast showed normal adrenal glands, and
an otherwise unremarkable study. A repeat audiogram showed mild to
moderate sensorineural hearing loss at 500 Hz through 2000 Hz for the
right ear.
G. Alexopoulos, et al.
3. Discussion
Head and neck paragangliomas (PGLs) develop from the para-
sympathetic system and arise primarily in four distinct areas: carotid
body, jugular foramen, middle ear, and larynx. [1-6] Carotid body tu-
mors represent the majority (~60%) of the head and neck PGL cases. In
contrast, jugular foramen tumors represent only 10% of the head and
neck PGLs [1–6]. Jugular foramen PGLs are rare, benign neuroendo-
crine tumors, that are slow growing but locally aggressive. Jugular
PGLs are highly vascularized tumors, arising from the paraganglion
cells within the adventitia of the jugular bulb [4–6]. Malignant trans-
formation of a glomus jugulare PGL is extremely rare [3–5,8]. The age
of onset has been noted to be quite broad overall, with hereditary PGLs
presenting a decade earlier than sporadic tumors. Glomus jugulare PGLs
usually diagnosed during the fourth to fifth decades of life with a female
predominance (female to male ratio = 5 : 1) [1,2,4–6].
During the past decade the understanding of the genetic and mo-
lecular etiology has had an important clinical impact on the manage-
ment of these tumors [2,3,8–10]. It is now recognized that nearly 40%
of all PGLs are hereditary in nature, this is the highest degree of her-
itability among all human tumors [1,2,7,11]. In families with PGLs,
germline mutations have been demonstrated in the gene succinate
deydrogenase complex subunit D (SDHD), which encode subunits of
mitochondrial complex [1,7–9,11]. Succinate dehydrogenase (SDH)
enzyme is a multiprotein complex composed of SDHA, SDHB, SDHC,
and SDHD proteins in addition to SDHAF2 (a flavination/assembly
factor) [1,7,8,11]. SDH is a critical component between the Krebs cycle
and electron transport chain in the mitochondria for which loss of SDH
3
Interdisciplinary Neurosurgery 20 (2020) 100657
Fig. C. Axial (top left) and coronal (top right) MRI of
the brain with contrast demonstrating an avidly en-
hancing mass, emanating from the pars vascularis of
the right jugular foramen, measuring
2.6 cm × 2.3 cm × 2.8 cm with numerous flow
voids, that obliterates the right hypoglossal canal,
extending into the right cerebellopontine angle, and
inferior aspect of the clivus. There is persistent
complete opacification of the right mastoid air cells.
Cerebral angiography, right vertebral artery injec-
tion, anteroposterior (bottom left) and lateral views
(bottom right). Tumor blush off capillary branches of
the V4 segment of the right vertebral artery, without
definitive arterial pedicles.
results in ATP production through glycolysis [1,7–9]. SDH-mutated
PGLs show robust expression of hypoxia induced genes, and genomic
and histone hypermethylation [7–10]. Multi-focality and bilateral tu-
mors are common in 25% of cases that are associated with hereditary
syndromes, especially mutations in the SDHD gene [1,3,7,8]. Bodeker
and colleagues recommend molecular genetic screening for SDHB,
SDHC, and SDHD in all head and neck PGLs. [7] Here, we present a
patient with an heterozygous SDHD c.242 > T (p.Pro81Leu) patho-
genic mutation, upon genetic profiling.
The most common presenting symptom of glomus jugulare PGLs is
pulsatile tinnitus, followed by hearing decline [1,3,4,6,12,13]. Hearing
loss is usually conductive in nature but can be sensorineural or mixed
[4–6,13]. Lower cranial nerve palsies (IX, XI, and/or XI) from direct
compression resulting in dysphagia, hoarseness, shoulder weakness,
and tongue hemiparesis are less common and are usually seen with
larger tumors that extend through the medial wall of the jugular bulb
[3,4,6,13]. Glomus jugulare PGLs are rarely hormonally active in less
than 4% of tumors [1,3,4,12]. A rare case of glomus jugulare PGL has
been reported which presented as papilledema [14]. There are also rare
reports of primary fallopian canal glomus tumors that extend to the
middle ear and mastoids, presenting as facial nerve palsy [4,15]. To our
knowledge, there is no similar report to date of a jugular PGL with
presentation as mastoiditis. We identified a patient with hereditary PGL
syndrome, who was initially diagnosed with mastoiditis as the only
radiological finding of an evolving glomus jugulare tumor. Diagnosis of
glomus tumors can be masked by coexisting mastoiditis in these pa-
tients. A high index of clinical suspicion is important before treating
mastoiditis in patients with familial PGL syndromes. Here, we propose
G. Alexopoulos, et al.
that early work up of mastoiditis with MRI is essential in all patients
with a history of hereditary PGL syndrome.
Jugular PGLs continue to represent a management challenge.
Multiple proposed classifications have been used, and none has gained
universal acceptance. Tumor classifications described by Fisch and
Glasscock are the most commonly used [16,17]. The treatment options
for jugular foramen PGLs include surgical resection, conventional ra-
diation therapy, stereotactic radiosurgery, therapeutic embolization, or
a combination of these modalities [3,6,12,18]. Historically, the treat-
ment of choice for jugular PGLs has been microsurgery for gross total
resection via an infratemporal approach, as it is the only modality able
to totally eradicate the tumor [4,6,12,18]. Preoperative embolization is
generally performed 24–72 hours before surgery, commonly using non-
adhesive liquid embolic agents [6,7]. In an effort to minimize operative
morbidity and improve symptoms associated with the disease, subtotal
resection has been used with increasing frequency by many centers
[3,4,6,12]. However, surgery is still associated with an unacceptably
high complication rate for a benign tumor like jugular PGL, explaining
the growing place of radiotherapy in the management of these lesions
[6,12,18]. Conformal radiotherapy with or without intensity modula-
tion and stereotactic radiotherapy, can both achieve tumor control rates
ranging from 90% to almost 100% of cases, with an equivalent if not
better tumor control rate and considerably fewer iatrogenic effects than
surgery [3,12,18]. However, radiotherapy is contraindicated in the
presence of intracranial invasion or extensive osteomyelitis [12,18]. In
the elderly and medically unfit subjects with minimal symptoms, a close
observation is an alternate option, especially in patients without
brainstem compression or concerns for malignancy [4,6]. In patients
with recurrent glomus jugulare tumors salvage radiotherapy appears
superior to surgery and should be considered the treatment of choice
[19]. Our patient was managed successfully using stereotactic radiation
therapy.
4. Conclusion
Mastoiditis can be the initial presenting symptom of jugular
foramen PGLs. High index of clinical suspicion is important before in-
itiating treatment for mastoiditis, especially in patients with familial
PGL syndrome, obviating the need for an early MRI work-up.
Consent for publication
Not applicable.
Ethics approval and consent to participate
Not applicable.
Funding
This research did not receive any specific grant from funding
agencies in the public, commercial, or not-for-profit sectors.
Declaration of Competing Interest
The authors declare that they have no known competing financial
interests or personal relationships that could have appeared to
Interdisciplinary Neurosurgery 20 (2020) 100657
influence the work reported in this paper.
Acknowledgements
No.
Appendix A. Supplementary data
Supplementary data to this article can be found online at https://
doi.org/10.1016/j.inat.2019.100657.
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