Original Research—Head and Neck Surgery
Otolaryngology–
Recurrence and Progression of Head and
Neck Paragangliomas after Treatment
Kevin J. Contrera, MD, MPH1, Valeda Yong, MD2,
Chandana A. Reddy, MS3, Sara W. Liu, MD1,
and Robert R. Lorenz, MD, MBA1
No sponsorships or competing interests have been disclosed for this article.
Abstract
Objective. To characterize the recurrence of head and neck
paragangliomas and the factors associated with disease pro-
gression after treatment.
Study Design. Retrospective cohort study.
Setting. Tertiary care center.
Subjects and Methods. In total, 173 adults with 189 paraganglio-
mas (41.3% carotid body, 29.1% glomus jugulare, 19.0% glomus
tympanicum, and 10.6% glomus vagale) treated between 1990
and 2010 were evaluated to determine the incidence and risk
of recurrence using Cox proportional hazards.
Results. The mean (SD) follow-up duration was 8.6 (9.1)
years. The incidence was 2.92 recurrences per 100 person-
years. The rate of recurrence was 8.2% (95% confidence
interval [CI], 3.7-12.7) after 4 years and 17.1% (95% CI,
10.2-24.0) after 10 years. Glomus jugulare tumors were
more likely to recur (hazard ratio [HR], 3.69; 95% CI, 1.70-
8.01; P \ .001) while carotid body tumors were less likely
(HR, 0.44; 95% CI, 0.21-0.97; P = .041). Radiation had a
lower risk of recurrence or progression compared to surgical
excision (HR, 0.30; 95% CI, 0.10-.94; P = .040). Recurrence
was associated with right-sided paragangliomas (HR, 3.60;
95% CI, 1.63-7.75; P = .001). The median time to recurrence
was 18.4 years. Six (3.2%) patients developed metastasis,
which was more common with local recurrence (9.5% vs
1.4%, P = .015).
Conclusions. Recurrence is more common with glomus jugu-
lare tumors and less common with carotid body tumors.
Radiation may have a lower risk of recurrence or progres-
sion than surgery for some paraganglioma types. Metastasis
is rare but more likely with recurrent disease. Surveillance
neck imaging is recommended every several years for
decades after treatment.
Keywords
paraganglioma, recurrence, metastasis, imaging, radiation
Received July 27, 2019; accepted January 8, 2020.
Head and Neck Surgery
2020, Vol. 162(4) 504–511
Ó American Academy of
Otolaryngology–Head and Neck
Surgery Foundation 2020
Reprints and permission:
sagepub.com/journalsPermissions.nav
DOI: 10.1177/0194599820902702
http://otojournal.org
P
aragangliomas are characterized as slow-growing
neuroendocrine tumors, occurring in an estimated 1
in 30,000 to 100,000 people.1,2 The head and neck is
the most common location for extra-adrenal parasympathetic
paragangliomas, including carotid body, glomus vagale, glomus
tympanicum, and glomus jugulare tumors.3 Once head and
neck paragangliomas are treated by radiation or surgery,
there are minimal evidence-based guidelines on how they
should be followed to evaluate for recurrence, metastasis, or
progression of disease.
The incidence of recurrent paragangliomas of the neck has
not been reported. Most important, it is unknown what factors
increase the risk of recurrent disease. As such, there are con-
flicting surveillance practices.4,5 With ‘‘very low’’ quality of
evidence, the European Society of Endocrinology recom-
mended repeat imaging every 1 to 2 years after treatment.6
Given paragangliomas’ slow growth rate and indolent nature,
annual imaging may be resulting in excessive costs and radia-
tion exposure.7-9 Numerous studies have noted a need for
more long-term data to inform validated protocols on serial
imaging of patients with paragangliomas.5-7,10,11
In this long-term, retrospective cohort study, we investi-
gate the incidence of paraganglioma recurrence/progression
after treatment with surgery or radiation. By characterizing
metastasis and the factors associated with greater risk of
recurrence, we aim to guide clinicians on optimal posttreat-
ment surveillance.
Materials and Methods
Study Design and Participants
A retrospective chart review was conducted of patients
treated for a head and neck paraganglioma between 1990
1
Head & Neck Institute, Cleveland Clinic, Cleveland, Ohio, USA
2
School of Medicine, Case Western Reserve University, Cleveland, Ohio,
USA
3
Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio, USA
This article was presented as a podium presentation at AAO-HNSF 2019
Annual Meeting & OTO Experience; September 15-18, 2019; New Orleans,
Louisiana.
Corresponding Author:
Robert R. Lorenz, MD, MBA, Head and Neck Institute, Cleveland Clinic,
9500 Euclid Ave, A71, Cleveland, OH 44195, USA.
Email: lorenzr@ccf.org
Contrera et al
and 2010 based on International Classification of Diseases,
Ninth Revision (ICD-9) codes 194.5, 194.6, 227.5, 227.6,
and 237.3. Our analytic cohort comprised individuals with
at least 1 posttreatment computed tomography (CT) or mag-
netic resonance imaging (MRI) of the head, neck, chest,
abdomen, or pelvis that could evaluate for recurrence/pro-
gression and metastasis. Ultrasounds were included only if
they were intended to evaluate for paragangliomas of the
neck. CT and MRI not intended for paraganglioma surveil-
lance but appropriately sensitive for paragangliomas were
included.12-14 This study was approved by the Cleveland
Clinic Institutional Review Board (IRB 17-728).
Treatment and Outcomes
Patients were recorded as having undergone surgical exci-
sion if they had complete resection (95 patients), resection
without specification of completeness (30), or subtotal
resection (6). The analysis comparing radiation and surgery
excluded patients with subtotal resection (6) given the risk
for progression of residual disease, as well as patients pri-
marily treated with both surgery and radiation (13).
Recurrence was defined as reappearance of paraganglioma
in the same anatomic location after a complete surgical
excision or progression of residual disease for patients
treated with radiation or subtotal resection. In limited cases
where determination of tumor growth was equivocal on
imaging, we used a threshold of 3 mm of size increase in
a single dimension over an interval of \5 years. Metastasis
was defined as spread of disease to local or distant nonendo-
crine tissue after treatment.15
Covariates
Age was based on time of treatment. Tumor type (ie, carotid
body tumor, glomus jugulare, glomus vagale, or glomus
tympanicum) was determined based on surgical pathology
or diagnostic radiology. Tumor types were compared to all
other tumor types combined when estimating risk of recur-
rence. Patients who were found to have more than 1 para-
ganglioma at the time of initial diagnosis were noted to
have multiple paragangliomas on presentation. Each tumor
was followed individually; hence, patients with multiple
tumors contributed separate episodes of follow-up. Patients
were noted to have a positive genetic analysis if they were
found to have mutations in succinate dehydrogenase (SDH)
B, C, and D; Von Hippel Lindau; or RET oncogene.
Statistical Analysis
Univariate and multivariate Cox proportional hazards
regression analysis was performed to evaluate factors asso-
ciated with a risk of recurrent paraganglioma. The final
multivariate model included age, glomus jugulare, genetics,
multiple paragangliomas on presentation, side, and treat-
ment. Patient follow-up began on the date of treatment and
continued until the patient was found to have a recurrence.
Patients without recurrence were censored at the time of
their last head and neck imaging. Significance testing was
performed using 2-sided tests with a type I error rate of .05.
505
Statistical analyses were done using SAS v 9.4 (SAS
Institute, Cary, North Carolina).
Results
Table 1 describes the demographic and clinical characteris-
tics of the study population. The cohort included patients
with a primary diagnosis of carotid body (41.3%), glomus
jugulare (29.1%), glomus tympanicum (19.0%), and glomus
vagale tumors (10.6%). Most patients underwent surgical
resection (69.3%), followed by radiation (23.8%) and surgery
with radiation (6.9%). The mean (SD) follow-up duration
was 8.6 (9.1; median, 5.8) years. Patients had a mean (SD) of
7.3 (8.3) posttreatment images of the head and neck.
The incidence was 2.92 recurrences per 100 person-
years, meaning 1 in 10 patients would have a recurrence if
reimaged every 3.4 years after treatment. In recurrences per
100 person-years, the incidence for each type of paragan-
glioma was 4.9 for glomus jugulare, 2.78 for glomus tympa-
nicum, 1.73 for carotid body, and 1.25 for glomus vagale.
Figure 1 depicts recurrence-free survival after treatment
of a head and neck paraganglioma. The median time to
recurrence was 18.4 years after treatment (16.8 years for
surgery, median not reached for radiation). At 4 years of
follow-up, 8.2% (95% confidence interval [CI], 3.7-12.7) of
paragangliomas recurred. At 10 years of follow-up, 17.1%
(95% CI, 10.2-24.0) of paragangliomas recurred. Figure 2
compares survival between the different types of head and
neck paragangliomas. At 10 years of follow-up, the rates of
recurrence were 28.2% (95% CI, 14.2-42.1) for glomus
jugulare, 12.4% (95% CI, 1.8-23.1) for carotid body, 10.5%
(95% CI, 0.0-30.0) for glomus vagale, and 9.7% (95% CI,
0.0-20.2) for glomus typmanicum.
Table 2 describes the multivariate Cox proportional
hazards model. There was a significantly greater risk of
recurrence with glomus jugulare tumors (hazard ratio [HR],
3.69; 95% CI, 1.70-8.01; P \ .001). Carotid body tumors
were significantly less likely to recur (HR, 0.44; 95% CI,
0.21-0.97; P = .041). Right-sided paragangliomas had a
higher risk of recurrence (HR, 3.60; 95% CI, 1.63-7.75; P =
.001).
In comparing radiation to surgical excision (subtotal resec-
tion not included in analysis), we found that overall, radiation
had a lower risk of recurrence/progression compared to com-
plete surgical excision (HR, 0.30; 95% CI, 0.10-.94; P =
.040). Figure 3 depicts the survival between paragangliomas
treated with radiation vs surgical excision. When this analysis
is dichotomized to individual tumor types (Table 3), radia-
tion had a lower rate of recurrence for glomus jugulare
tumors (3.4% vs 94.1%, P \ .001); however, surgery had a
lower rate of recurrence for carotid body tumors (9.0% vs
42.9%, P = .037). Of the 6 patients with recurrent carotid
body tumor after surgery, 4 (66.6%) ultimately had metastatic
disease. No patients recurred after radiation for glomus tym-
panicum and vagale; however, the difference compared to
surgery was not statistically significant.
There was no greater risk of recurrence for patients with
positive genetic analysis (HR, 1.29; 95% CI, 0.47-3.56; P =
506 Otolaryngology–Head and Neck Surgery 162(4)

Table 1. Demographic and Clinical Characteristics of Patients Treated for Head and Neck Paraganglioma by Recurrence or Progression.
Characteristic No Recurrence (n = 147) Recurrence (n = 42) Total (N = 189) P Value

Age at treatment, mean (SD), y 53.1 (15.6) 43.0 (14.8) 50.9 (15.9) .164
Sex, No. (%)
Female 103 (70.1) 30 (71.4) 133 (70.4) .601
Male 44 (29.9) 12 (28.6) 56 (30.1)
Diagnosis, No. (%)
Carotid body tumor 69 (46.9) 9 (21.4) 78 (41.3) .026
Glomus jugulare 32 (21.8) 23 (54.8) 55 (29.1)
Glomus tympanicum 28 (19.0) 8 (19.0) 36 (19.0)
Glomus vagale 18 (12.2) 2 (4.8) 20 (10.6)
Multiple paragangliomas on presentation, No. (%) 20 (13.6) 7 (16.7) 27 (14.3) .593
Genetics, No. (%)
Positive 19 (12.9) 9 (21.4) 28 (14.8) .826
Negative or unknown 128 (87.1) 33 (78.6) 161 (85.0)
Treatment, No. (%)a
Surgery 95 (74.5) 30 (88.2) 125 (73.5) .108
Radiation 41 (25.5) 4 (11.8) 45 (26.5)
Metastasis, No. (%) 2 (1.4) 4 (9.5) 6 (3.2) .016

Abbreviation: SD, standard deviation.

a
Does not add up to 189 because excluded patients without designated complete resection or underwent both surgery and radiation.

Figure 1. Kaplan-Meier curve for recurrence-free survival after

treatment of all paragangliomas. Tick marks represent censored Figure 2. Kaplan-Meier curve for recurrence-free survival after
observations. treatment comparing types of paragangliomas. Tick marks repre-
sent censored observations.

.620) compared to patients with negative or no genetic anal-

ysis. Patients without multiple paragangliomas on presenta-
tion were not at lower risk of recurrence (HR, 0.79; 95%
CI, 0.24-2.69; P = .717). There was not a greater risk of
recurrence associated with patients who were younger (HR,
0.98; 95% CI, 0.95-1.01; P = .106) or female (HR, 1.21;
95% CI, 0.59-2.49; P = .601 [univariate]).
Six patients (3.2%) developed metastasis after treatment.
The tumor subtypes included 4 carotid body tumors, 1 glomus
vagale, and 1 glomus jugulare. Locations of metastasis were
cavernous sinus, diffuse osseous and liver, epidural, spinal,
and 2 cervical metastases. Patients with recurrence were statis-
tically more likely to develop metastasis than patients without
recurrence (9.5% vs 1.4%, P = .015). All patients who devel-
oped metastasis did so after their recurrence.
Discussion
This study presents the first reported incidence of recurrent
head and neck paragangliomas in one of the largest cohorts
of this population in the literature. In patients with a history
of head and neck paraganglioma, recurrence is gradual and
often late. Glomus jugulare tumors were more likely to recur
while carotid body tumors were less likely. Rates of metasta-
sis were low but more likely with locally recurrent disease.
Contrera et al 507

Table 2. Multivariate Cox Proportional Hazards Model for Paraganglioma Recurrence or Progression.
Characteristic Hazard Ratio 95% Confidence Interval P Value

Age 0.98 0.95-1.01 .106

Tumor type (vs all other types combined)
Carotid body tumora 0.44 .20-.97 .041
Glomus jugulare 3.69 1.70-8.68 \.001
Glomus tympanicuma 1.00 .46-2.20 .994
Glomus vagalea 0.40 .10-1.68 .210
Genetics (positive vs unknown or negative) 1.29 .47-3.56 .624
Multiple paragangliomas on presentation (no vs yes) 0.80 .24-2.69 .717
Side (right vs left) 3.56 1.63-7.75 .001
Treatment (radiation vs surgery) 0.30 .10-.94 .040
a
Univariate analysis and not included in the multivariate model.

Table 3. Recurrence or Progression Comparing Surgery to Radiation for Each Paraganglioma Type.
Characteristic Treatment Recurrence (n = 34) No Recurrence (n = 136) P Value

Carotid body tumor Surgery 6 (9.0) 61 (91.0) .037

Radiation 3 (42.9) 4 (57.1)
Glomus jugulare Surgery 16 (94.1) 1 (5.9) \.001
Radiation 1 (3.4) 28 (96.6)
Glomus tympanicum Surgery 7 (25.0) 21 (75.0) .632
Radiation 0 (0.0) 5 (100.0)
Glomus vagale Surgery 1 (7.7) 12 (92.3) .439
Radiation 0 (0.0) 4 (100.0)

have a 10% chance of recurrence if reimaged every 3.4 years

Figure 3. Kaplan-Meier curve for paraganglioma recurrence-free
survival after treatment comparing surgery to radiation. Tick
marks represent censored observations.
Incidence of Recurrence
We found an overall incidence of 2.92 recurrences per 100 person-
years. This means, in general, head and neck paragangliomas
after treatment. Although incidence has never been reported
in the head and neck literature, Amar et al16 deduced a lower
rate for other paragangliomas. Based on a systematic review
of 36 studies of thoraco-abdomino-pelvic paragangliomas and
pheochromocytomas, they approximated an incidence of 0.98
recurrences per 100 person-years, although actual person-
time was not available for most studies. This difference may
be secondary to different tumor pathology for head and neck
paragangliomas. Alternatively, the greater rates of recurrence
in the head and neck could be explained by the relative diffi-
culty of achieving complete resection compared to thoraco-
abdomino-pelvic paragangliomas.
Several studies have calculated gross rates of recurrence
(ie, events per person), which is dependent on individual
duration of follow-up. Anttila et al17 found a rate of recur-
rence of 6% in a population of 64 patients with 74 head and
neck paragangliomas, followed for median of 4.6 years.
This is less than our recurrence rate of 8.2% at 4 years.
While their duration of follow-up was overall shorter, they
likewise found a considerable delay from treatment to recur-
rence of 2.5 to 10.8 years. Other studies have found recur-
rence rates between 0% and 18%.4,18-20
508
Risk of Recurrence
In comparing tumor types, we found that glomus jugulare
tumors were more likely to occur while carotid body tumors
were less likely. This appears consistent with prior litera-
ture. A study of 185 tympanojugular paragangliomas found
recurrence rates of 2.4% after mostly total resection and 3.7
years of follow-up.21 Hinerman et al20 reported 18% of 55
glomus jugulare tumors recurred after being followed for
9.3 years. This is in contrast with 2 studies of 21 and 40 car-
otid body tumors that found no recurrences after following
for 7 and 3 years, respectively.22,23
We found that overall, paragangliomas treated with radia-
tion were less likely to recur/progress than those treated with
complete surgical excision. Our results are similar to the very
few studies that have attempted to compare treatments for
paragangliomas. A systematic review of 15 studies by
Gottfried et al11 found recurrence rates of 3.1% for surgery
and 2.1% for radiation, although statistical testing for differ-
ences was not performed. Similarly, Elshaikh et al24 reported
significantly better control rates with salvage radiation com-
pared to surgery in a population of 29 patients with recurrent
paragangliomas. When radiation was compared to surgery for
individual paraganglioma types, we found that glomus jugu-
lare almost always recurred with surgery (compared to
almost never with radiation); however, carotid body tumors
were actually more likely to recur with radiation. Most caro-
tid body tumors that did recur after surgery were malignant,
suggesting a more aggressive pathology. It is important to
note that these differences represent generalizations to help
guide clinicians and are not intended to demonstrate universal
superiority of one treatment to another. The decision to surgi-
cally excise, radiate, or even observe paragangliomas is mul-
tifactorial and should be made on an individual patient basis.
Recurrence rates after radiation vary greatly, in part
based on the duration of follow-up.25 Even when restricted
to glomus jugulare tumors, reported rates of recurrence after
radiation range between 2.1% and 8.0%.11,26,27 This may
suggest that the lower rates of recurrence with radiation
may be secondary to a greater delay in progression. Indeed,
we found a median time to recurrence of 18.4 years, well
beyond the follow-up duration of any study to date. This
proposed rationale is supported by comparing short- and
long-term studies. For instance, Hinerman et al20 reported a
rate of 5.0% in 121 paragangliomas followed for 8.5 years
while Dupin et al28 found only a single recurrence in 81
paragangliomas followed for 4.1 years. Long-term studies
are needed to better compare surgery and radiation.
We did not find an association with risk of recurrence and
hereditary paraganglioma or presentation with multiple para-
gangliomas, which can serve as surrogate genetic marker for
patients not undergoing genetic testing.29 This may in part be
due to the small percentage of our cohort who underwent
genetic testing (see limitations). Evaluation for the role of
genetics in risk of recurrence in head and neck paraganglio-
mas appears novel, but prior studies have suggested higher
Otolaryngology–Head and Neck Surgery 162(4)
rates of recurrence with heredity paraganglioma.13,16,30 In the
aforementioned meta-analysis evaluating thoraco-abdomino-
pelvic paragangliomas and pheochromocytomas, recurrence
rates were more than doubled in studies of populations with
60% hereditary disease.16
Interestingly, we found that right-sided paragangliomas
were more likely to recur despite having an equal distribu-
tion of right- and left-sided tumors. This was significant
after controlling for confounding factors with multivariate
regression. While it is understandable how laterality could
affect recurrence in treatment of diseases such as colon
cancer, it is harder to rationalize why right-sided paragan-
gliomas were associated with greater recurrence.31 Several
studies within the orthopedic literature have demonstrated
statistically different outcomes related to laterality and sur-
geon handedness.32,33 Differences have also been shown
regarding laterality of carotid endarterectomy.34,35 Further
research is needed to investigate the reproducibility of this
result.
Metastasis
We found a rate of metastasis of 3.2%. Although large
cohort studies are limited, reported rates of metastasis range
from 0% to 7.7%.4,19,36,37 This is the first study to empiri-
cally demonstrate metastasis is more common with
recurrence—in this case, 3 times more. Although we found
a general distribution of metastasis, prior research has found
containment to cervical lymph nodes in 70% of cases.38
Metastasis may be more likely in carotid body and vagal
paragangliomas.15,19 Evaluation for metastasis is of particu-
lar importance with hereditary paraganglioma, namely, with
mutations in SDHB.39
Surveillance Recommendations
Frequency of surveillance imaging is patient dependent but
should be guided by evidence and cost-effectiveness. While
the European Endocrine Society recommended imaging of
the neck every 1 to 2 years to evaluate for recurrence, this
does not seem to be supported by the findings of this
study.4 We found that patients, on average, would need to
undergo 35 years of annual MRIs or CTs to find 1 recur-
rence. Of note, they acknowledged that their opinion was
‘‘arbitrary,’’ as ‘‘there are no observational or randomized
studies that support any particular interval,’’ which was
accurate prior to the release of this study.6 Based on our
results, repeat imaging of the head and neck appears appro-
priate every several years, but with increased frequency in
patients with glomus jugulare or treated with surgery. Our
recommendation is further supported by studies demonstrat-
ing that most paragangliomas are slow-growing, indolent
tumors, and immediate intervention is rarely needed.8,9,40,41
Repeat imaging every several years is consistent with
recent studies evaluating screening new head and neck
paragangliomas. Namely, Eijkelenkamp et al42 used the
Poisson process to deduce an interval of 3.2 years for SDHB
Contrera et al
mutation carriers. These findings directly address questions
raised by the US Endocrine Society clinical practice guide-
lines, which had previously found ‘‘insufficient evidence to
formulate guidelines about when and how to perform ima-
ging studies in patients at risk for biochemically silent para-
gangliomas,’’ which is the case for most head and neck
paragangliomas.5,43
We found a median time to recurrence of 18.4 years after
treatment. As such, patients should be counseled that surveil-
lance should be continued for decades to identify what are
frequently late recurrences. This is consistent with Endocrine
Society guidelines recommending at least 10 years of surveil-
lance.6 Long-term follow-up is necessary to identify recur-
rences that frequently occur decades after treatment.
We did not identify any patients who developed metasta-
sis after treatment but prior to the development of recurrent
disease. This would suggest that screening for metastasis is
not necessary after treatment unless patients develop recur-
rence. Prior studies have evaluated screening for second pri-
mary paragangliomas.44
Limitations
Our sample size limited our comparison within different
types of paragangliomas. Pooling head and neck paragan-
gliomas together allowed for robust analysis of recurrence-
free survival. However, these general findings cannot
always be applied to individual paraganglioma types, as we
found for carotid body tumors in the analysis of radiation vs
surgery. Nevertheless, this study represents one the largest
long-term studies of head and neck paragangliomas to date,
and combining paraganglioma types in this region is a stan-
dard practice within the literature.4,10,17,41,45,46
This observational study is limited in the absence of stan-
dardized treatments (eg, radiation dosing and field range
varied between patients and tumor types) and surveillance
imaging. There is a potential for a selection bias as patients
with recurrent tumors are more likely to have follow-up
imaging, which is why imaging done for any reason was
included in the study. The potential of miscalculating tumor
recurrence would not affect comparisons between groups
and is partially mitigated by the fact that paraganglioma
growth is typically gradual and seldom necessitates immedi-
ate identification. We did not have an observational cohort
that would allow us to compare treated tumors to untreated,
nor did we evaluate for the potential impact of functional or
secreting paragangliomas.
Our population was limited by the number of patients
who underwent genetic testing. Given previously reported
rates of hereditary paraganglioma nearing 50%, our study
likely had a significant sampling bias for genetic testing.47-
49
Since so few patients (7 total) actually had negative test-
ing, genetic analysis was treated as a binary variable, with
negative and nontested patients combined. These findings
highlight the underutilization of genetic testing as a guide in
clinical management.
509
Conclusions
The slow-growing, indolent nature of paragangliomas pre-
sents a unique surveillance challenge for head and neck sur-
geons. To our knowledge, this is the first study reporting
the incidence of recurrent paragangliomas after treatment.
By evaluating the factors associated with a greater risk of
recurrence and metastasis, this study seeks to guide clini-
cians following patients treated for paragangliomas of the
head and neck based on one of the largest samples of this
population to date.
In patients treated for head and neck paragangliomas,
recurrence is gradual and metastasis is rare. Our results do
not support the utility of annual neck imaging for surveil-
lance. However, repeat imaging of the head and neck every
several years appears appropriate with greater frequency in
patients with glomus jugulare or treated with surgery. Long-
term follow-up is necessary to identify recurrences that fre-
quently occur decades after treatment.
Author Contributions
Kevin J. Contrera, designed study, collected data, draft article,
responsibility for content of manuscript; Valeda Yong, collected
data, revised article, responsibility for content of manuscript;
Chandana A. Reddy, analysis of data, revised article, responsibil-
ity for content of manuscript; Sara W. Liu, analysis of data,
revised article, responsibility for content of manuscript; Robert R.
Lorenz, designed study, analysis of data, revised article, responsi-
bility for content of manuscript.
Disclosures
Competing interests: None.
Sponsorships: None.
Funding source: None.
References
1. Milunsky JM, Maher TA, Michels VV, Milunsky A. Novel
mutations and the emergence of a common mutation in the
SDHD gene causing familial paraganglioma. Am J Med Genet.
2001;100:311-314.
2. Erickson D, Kudva YC, Ebersold MJ, et al. Benign paragan-
gliomas: clinical presentation and treatment outcomes in 236
patients. J Clin Endocrinol Metab. 2001;86:5210-5216.
3. Chen H, Sippel RS, O’Dorisio MS, et al. The North American
Neuroendocrine Tumor Society consensus guideline for the
diagnosis and management of neuroendocrine tumors: pheo-
chromocytoma, paraganglioma, and medullary thyroid cancer.
Pancreas. 2010;39:775-783.
4. Papaspyrou K, Mann WJ, Amedee RG. Management of head
and neck paragangliomas: review of 120 patients. Head Neck.
2009;31:381-387.
5. Lenders JW, Duh QY, Eisenhofer G, et al. Pheochromocytoma
and paraganglioma: an Endocrine Society clinical practice
guideline. J Clin Endocrinol Metab. 2014;99:1915-1942.
6. Plouin PF, Amar L, Dekkers OM, et al. European Society of
Endocrinology clinical practice guideline for long-term follow-up
510
of patients operated on for a phaeochromocytoma or a paragan-
glioma. Eur J Endocrinol. 2016;174:G1-G10.
7. Jansen TTG, Timmers HJLM, Marres HAM, Kunst HPM.
Feasibility of a wait-and-scan period as initial management
strategy for head and neck paraganglioma. Head Neck. 2017;
39:2088-2094.
8. Michalowska I, Ćwik1a JB, Michalski W, et al. Growth rate of
paragangliomas related to germline mutations of the SDHx
genes. Endocr Pract. 2017;23:342-352.
9. Wang JT, Wang AY, Cheng S, Gomes L, Da Cruz M. Growth
rate analysis of an untreated glomus vagale on MRI. Case Rep
Otolaryngol. 2016;2016:8756940.
10. Moore MG, Netterville JL, Mendenhall WM, Isaacson B,
Nussenbaum B. Head and neck paragangliomas: an update on
evaluation and management. Otolaryngol Head Neck Surg.
2016;154:597-605.
11. Gottfried ON, Liu JK, Couldwell WT. Comparison of radio-
surgery and conventional surgery for the treatment of glomus
jugulare tumors. Neurosurg Focus. 2004;17:E4.
12. Zuluaga A, Ocazionez D, Riascos R, Palacios E, Restrepo CS.
Paragangliomas of the head and neck: imaging assessment.
Ear Nose Throat J. 2014;93:E22-E24.
13. Gimenez-Roqueplo AP, Caumont-Prim A, Houzard C, et al.
Imaging work-up for screening of paraganglioma and pheochro-
mocytoma in SDHx mutation carriers: a multicenter prospective
study from the PGL.EVA Investigators. J Clin Endocrinol Metab.
2013;98:E162-E173.
14. Subedi N, Prestwich R, Chowdhury F, Patel C, Scarsbrook A.
Neuroendocrine tumours of the head and neck: anatomical,
functional and molecular imaging and contemporary manage-
ment. Cancer Imaging. 2013;13:407-422.
15. Fliedner SM, Lehnert H, Pacak K. Metastatic paraganglioma.
Semin Oncol. 2010;37:627-637.
16. Amar L, Lussey-Lepoutre C, Lenders JW, Djadi-Prat J, Plouin
PF, Steichen O. Management of endocrine disease: recurrence
or new tumors after complete resection of pheochromocytomas
and paragangliomas: a systematic review and meta-analysis.
Eur J Endocrinol. 2016;175:R135-R145.
17. Anttila T, Hayry V, Nicoli T, et al. A two-decade experience
of head and neck paragangliomas in a whole population-based
single centre cohort. Eur Arch Otorhinolaryngol. 2015;272:
2045-2053.
18. Scheick SM, Morris CG, Amdur RJ, Bova FJ, Friedman WA,
Mendenhall WM. Long-term outcomes after radiosurgery for tem-
poral bone paragangliomas. Am J Clin Oncol. 2018;41:223-226.
19. Mediouni A, Ammari S, Wassef M, et al. Malignant head/neck
paragangliomas: comparative study. Eur Ann Otorhinolaryngol
Head Neck Dis. 2014;131:159-166.
20. Hinerman RW, Amdur RJ, Morris CG, Kirwan J, Mendenhall
WM. Definitive radiotherapy in the management of paragan-
gliomas arising in the head and neck: a 35-year experience.
Head Neck. 2008;30:1431-1438.
21. Prasad SC, Mimoune HA, Khardaly M, Piazza P, Russo A,
Sanna M. Strategies and long-term outcomes in the surgical
management of tympanojugular paragangliomas. Head Neck.
2016;38:871-885.
Otolaryngology–Head and Neck Surgery 162(4)
22. Law Y, Chan YC, Cheng SW. Surgical management of carotid
body tumor: is Shamblin classification sufficient to predict sur-
gical outcome? Vascular. 2017;25:184-189.
23. Metheetrairut C, Chotikavanich C, Keskool P, Suphaphongs N.
Carotid body tumor: a 25-year experience. Eur Arch
Otorhinolaryngol. 2016;273:2171-2179.
24. Elshaikh MA, Mahmoud-Ahmed AS, Kinney SE, et al.
Recurrent head-and-neck chemodectomas: a comparison of
surgical and radiotherapeutic results. Int J Radiat Oncol Biol
Phys. 2002;52(4):953-956.
25. Gilbo P, Morris CG, Amdur RJ, et al. Radiotherapy for benign
head and neck paragangliomas: a 45-year experience. Cancer.
2014;120:3738-3743.
26. Guss ZD, Batra S, Limb CJ, et al. Radiosurgery of glomus
jugulare tumors: a meta-analysis. Int J Radiat Oncol Biol
Phys. 2011;81:e497-e502.
27. Shapiro S, Kellermeyer B, Ramadan J, Jones G, Wiseman B,
Cassis A. Outcomes of primary radiosurgery treatment of
glomus jugulare tumors: systematic review with meta-analysis.
Otol Neurotol. 2018;39:1079-1087.
28. Dupin C, Lang P, Dessard-Diana B, et al. Treatment of head
and neck paragangliomas with external beam radiation ther-
apy. Int J Radiat Oncol Biol Phys. 2014;89:353-359.
29. Szymańska A, Szymański M, Czekajska-Chehab E, Golabek
W, Szczerbo-Trojanowska M. Diagnosis and management of
multiple paragangliomas of the head and neck. Eur Arch
Otorhinolaryngol. 2015;272:1991-1999.
30. Martin TP, Irving RM, Maher ER. The genetics of paragan-
gliomas: a review. Clin Otolaryngol. 2007;32:7-11.
31. Yahagi M, Okabayashi K, Hasegawa H, Tsuruta M, Kitagawa
Y. The worse prognosis of right-sided compared with left-
sided colon cancers: a systematic review and meta-analysis.
J Gastrointest Surg. 2016;20:648-655.
32. Pennington N, Redmond A, Stewart T, Stone M. The impact
of surgeon handedness in total hip replacement. Ann R Coll
Surg Engl. 2014;96:437-441.
33. Mehta S, Lotke PA. Impact of surgeon handedness and lateral-
ity on outcomes of total knee arthroplasties: should right-
handed surgeons do only right TKAs? Am J Orthop (Belle
Mead NJ). 2007;36:530-533.
34. Girard LP, Feasby TE, Eliasziw M, et al. Complication rates
after left- versus right-sided carotid endarterectomy. Circ
Cardiovasc Qual Outcomes. 2009;2:642-647.
35. Maxwell BG, Maxwell JG, Brinker CC. Left-side preference
in carotid endarterectomies. Am Surg. 2000;66:793-796.
36. Ferrante AM, Boscarino G, Crea MA, Minelli F, Snider F.
Cervical paragangliomas: single centre experience with 44
cases. Acta Otorhinolaryngol Ital. 2015;35:88-92.
37. Papaspyrou K, Mewes T, Rossmann H, et al. Head and neck
paragangliomas: report of 175 patients (1989-2010). Head
Neck. 2012;34:632-637.
38. Lee JH, Barich F, Karnell LH, et al. National Cancer Data
Base report on malignant paragangliomas of the head and
neck. Cancer. 2002;94:730-737.
39. Baysal BE, Maher ER. 15 Years of paraganglioma: genetics and
mechanism of pheochromocytoma-paraganglioma syndromes
Contrera et al
characterized by germline SDHB and SDHD mutations. Endocr
Relat Cancer. 2015;22:T71-T82.
40. Smith JD, Harvey RN, Darr OA, et al. Head and neck paragan-
gliomas: a two-decade institutional experience and algorithm for
management. Laryngoscope Investig Otolaryngol. 2017;2:380-389.
41. Harrison L, Corbridge R. Active surveillance management of
head and neck paragangliomas: case series and review of the
literature. J Laryngol Otol. 2017;131:580-584.
42. Eijkelenkamp K, Osinga TE, de Jong MM, et al. Calculating
the optimal surveillance for head and neck paraganglioma in
SDHB-mutation carriers. Fam Cancer. 2017;16:123-130.
43. van Duinen N, Steenvoorden D, Kema IP, et al. Increased
urinary excretion of 3-methoxytyramine in patients with head
and neck paragangliomas. J Clin Endocrinol Metab. 2010;95:
209-214.
44. Contrera KJ, Yong V, Reddy CA, Berber E, Lorenz RR.
Second primary tumors in patients with a head and neck para-
ganglioma. Head Neck. 2019;41:3356-3361.
511
45. McCrary HC, Babajanian E, Calquin M, et al. Characterization
of malignant head and neck paragangliomas at a single institu-
tion across multiple decades. JAMA Otolaryngol Head Neck
Surg. 2019;145:641-646.
46. Mendenhall WM, Morris CG, Amdur RJ, Hitchcock KE,
Silver NL, Dziegielewski PT. Radiotherapy for benign head
and neck paragangliomas. Head Neck. 2019;41:2107-2110.
47. Cascón A, Pita G, Burnichon N, et al. Genetics of pheochro-
mocytoma and paraganglioma in Spanish patients. J Clin
Endocrinol Metab. 2009;94:1701-1705.
48. Gimenez-Roqueplo AP, Dahia PL, Robledo M. An update on
the genetics of paraganglioma, pheochromocytoma, and asso-
ciated hereditary syndromes. Horm Metab Res. 2012;44:328-
333.
49. Badenhop RF, Jansen JC, Fagan PA, et al. The prevalence of
SDHB, SDHC, and SDHD mutations in patients with head and
neck paraganglioma and association of mutations with clinical
features. J Med Genet. 2004;41:e99.