Original Research
Otolaryngology–
Incidence and Significance of
Hypermetabolic PET-CT Findings in
Unilateral TVF Motion Impairment
Luke Stanisce, MD1,2, Timothy Renzi2, Nikita Paripati2,
Nadir Ahmad, MD1,2, Thomas C. Spalla, MD1,2,
Howard L. Roth, MD2,3, and Yekaterina Koshkareva, MD1,2
No sponsorships or competing interests have been disclosed for this article.
Abstract
Objective. To determine the incidence and significance of asym-
metric hypermetabolic laryngeal findings on positron emission
tomography–computed tomography (PET-CT) in patients with
unilateral true vocal fold (TVF) motion abnormalities.
Study Design. Retrospective cohort.
Setting. Single-center tertiary care institution.
Subjects and Methods. The medical records of patients with
unilateral TVF motion abnormalities were reviewed. The
incidence of normal and asymmetric hypermetabolic laryn-
geal findings was calculated in patients who underwent PET-
CT and laryngeal examination, operative laryngoscopy with
biopsy, or injection medialization laryngoplasty.
Results. A total of 135 patients with unilateral TVF motion
abnormalities underwent PET-CT. After exclusion of patients
who completed new or surveillance imaging for a laryngeal
neoplasm (n = 27), asymmetric hypermetabolic findings in the
larynx were noted in 21 (19%) cases: 13 (12%) on the con-
tralateral side of the impaired TVF, 8 (7%) on the ipsilateral
side. Two (25%) patients with ipsilateral hypermetabolism had
concerning subsequent fiberoptic laryngeal examinations
prompting operative biopsy. There was no evidence of inflam-
matory or neoplastic disease in all patients with contralateral
hypermetabolic findings. Fifteen patients completed PET-CT
scans after injection medialization procedures; 6 (40%) dis-
played avidity ipsilateral to the side of the injection. The
median time from injection to scan was 27 days, as opposed
to 193 days in the unremarkable scans (P = .011).
Conclusion. Contralateral hypermetabolism in patients with uni-
lateral TVF motion abnormalities may represent a false-positive
finding. Ipsilateral hypermetabolic uptake without recent fold
instrumentation warrants prompt diagnostic evaluation.
Keywords
vocal fold paralysis, PET-CT, false positive, laryngeal cancer
Received April 2, 2019; accepted July 9, 2019.
Head and Neck Surgery
1–6
Ó American Academy of
Otolaryngology–Head and Neck
Surgery Foundation 2019
Reprints and permission:
sagepub.com/journalsPermissions.nav
DOI: 10.1177/0194599819866403
http://otojournal.org
P
ositron emission tomography–computed tomography
(PET-CT) imaging plays a major role in the detection
and surveillance of cancer in the head and neck
region. While increased uptake of radioisotope-labeled
fluorodeoxyglucose (FDG) is used to visually represent neo-
plastic tissue, a variety of inflammatory conditions, benign
lesions, and normal physiologic activity may also demon-
strate hypermetabolic findings.1-5 Resulting from an inher-
ent lack of specificity, the predictive value and diagnostic
accuracy of this modality have been a contemporary focus
of head and neck investigation.6-9
In the setting of a unilateral true vocal fold (TVF)
motion impairment, the contralateral vocal fold may
develop increased activity in a compensatory effort to
achieve glottic closure.10,11 Select reports have shown that
this augmented activity can yield asymmetric increased
FDG avidity on the contralateral side of the impaired vocal
fold.12,13 However, asymmetrical hypermetabolism in the
larynx should also raise suspicion for a primary or meta-
static glottic neoplasm. Otolaryngologists are often tasked
with discerning the underlying cause for these incidental
imaging findings.
Despite the need to reconcile PET-CT scan interpretation
difficulties, the rate of true- and false-positive findings attri-
butable to TVF motion impairment has yet to be defined.
Previous reports attempted to examine asymmetric laryngeal
PET scans without considering the incidence of normal
scans in this patient demographic, inaccurately drawing con-
clusions about diagnostic efficacy.14,15 To date, no studies
have comprehensively determined the rate of normal, abnor-
mal, or false-positive laryngeal PET-CT findings in patients
1
Division of Otolaryngology–Head and Neck Surgery, Cooper University
Hospital, Camden, New Jersey, USA
2
Cooper Medical School at Rowan University, Camden, New Jersey, USA
3
Department of Radiology, Cooper University Hospital, Camden, New
Jersey, USA
Corresponding Author:
Luke Stanisce, MD, Division of Otolaryngology–Head and Neck Surgery,
Cooper University Hospital, Three Cooper Plaza, Suite 404, Camden, NJ
08103, USA.
Email: lukestanisce@gmail.com
2 Otolaryngology–Head and Neck Surgery
with known unilateral vocal fold dysfunction. This study
aimed to define those frequencies with correlation to under-
lying pathologies and clinical outcomes in an effort to better
understand the significance of this imaging result.
Methods
We retrospectively reviewed the electronic medical records
of all adult patients diagnosed at our tertiary care institution
with unilateral TVF paralysis, paresis, palsy, motion impair-
ment, or dysfunction from September 2010 to December
2018. Approval from the Cooper Health System Institutional
Review Board was obtained prior to the beginning of the
study (18-129EX). The study cohort was identified with
ICD-9 and ICD-10 codes (International Classification of
Diseases) for each diagnosis. Physician in-hospital and outpa-
tient clinic notes were reviewed. Patients were excluded upon
chart review based on the absence of an endoscopic laryngeal
examination, the presence of bilateral TVF motion impair-
ment, or misdiagnosis/miscoding. The following information
was extracted: reason for presentation to care, date of initial
laryngeal diagnosis, laterality of the afflicted cord, the date
and results of diagnostic flexible fiberoptic laryngoscopy, the
date and results of subsequent laryngeal endoscopies, opera-
tive direct laryngoscopy with or without biopsy (when appli-
cable), biopsy results (when applicable), history of cancer,
history of head and neck cancer, and history and date of lar-
yngeal instrumentation, including injection medialization or
implantation procedures (when applicable).
The incidence of PET-CT imaging among the final cohort
was calculated. All available imaging reports were analyzed,
and mention of unilateral or asymmetric hypermetabolic
activity in the larynx was recorded with the study date and
the indication for each scan. When available, reported stan-
dardized uptake value (SUV) measurements were recorded.
When unavailable, a board-certified radiologist retrospec-
tively assigned SUVs for the noted FDG avidity.
For the purpose of this analysis, true-positive imaging
results were defined as PET-CT findings (ie, FDG avidity)
with corresponding findings on endoscopic laryngoscopy
warranting an operative biopsy, such as mucosal change
concerning for neoplasia. False-positive results were defined
as remarkable PET-CT findings without any concerning
findings on laryngoscopy. False-negative results were
defined as unremarkable PET-CT findings in the context of
a concerning laryngeal examination, while true-negative
results were defined as unremarkable PET-CT findings
without corresponding change on laryngoscopy.
Distributive statistics were performed with Poisson
counts to determine the incidence of the end points of inter-
est. When applicable, the time (days) from laryngeal injec-
tion procedures to imaging scans was calculated. Normally
distributed variables were analyzed via mean and standard
deviation and nonparametric variables via median and
range. Statistical differences in the time from injection to
PET-CT scan between select patient subgroups were calcu-
lated with the Mann-Whitney test and the Kruskal-Wallis
test. Differences in SUVs among various subgroups were
Table 1. Indications for PET-CT Imaging (N = 135).
Indication n (%)
Lung cancer 44 (33)
Breast cancer 16 (12)
New laryngeal cancer 15 (11)
New esophageal cancer 12 (9)
Unknown primary 9 (7)
Mediastinal LAD 8 (6)
Surveillance for previous head and neck cancer
Laryngeal 8 (6)
Esophageal 7 (5)
Oropharyngeal 6 (4)
Thyroid 4 (3)
Hypopharyngeal 4 (3)
Nasopharyngeal 1 (1)
Melanoma 1 (1)
Abbreviations: LAD, lymphadenopathy; PET-CT, positron emission topogra-
phy–computed topography.
calculated with Mann-Whitney test. Chi-square was used to
test the difference in incidence among the types of inject-
able materials. A 2-sided critical value of P \ .05 was used
to define significance. SPSS 23.0 software (IBM, Armonk,
New York) was used to perform all analyses.
Results
The medical records of 758 patients diagnosed with unilat-
eral TVF paralysis, paresis, palsy, motion impairment, or
dysfunction were identified and reviewed. Of these patients,
135 underwent PET-CT scans. For the scope of this analy-
sis, patients under surveillance for a history of subglottic,
supraglottic, or glottic cancer and patients who underwent
PET-CT for the initial staging of a newly diagnosed laryn-
geal malignancy were excluded (n = 27). The indications
for PET-CT imaging are summarized in Table 1. Sixty-two
(57%) patients had endoscopic confirmation of a unilateral
TVF motion impairment before undergoing PET-CT ima-
ging. The remaining 46 (43%) patients obtained imaging
without a prior documented laryngeal examination. Seven
of these patients were subsequently referred for formal eva-
luation based on their PET-CT results. All patients in the
cohort had a laryngeal examination after PET-CT.
Overall, 81% of patients with unilateral TVF motion
impairment demonstrated normal PET-CT findings in the
larynx (n = 87). Asymmetric hypermetabolic findings in the
larynx were noted in 21 (19%) cases. Specifically, hyperme-
tabolic activity on the contralateral side of the known
impaired TVF was noted in 13 (12%) patients. All 13
patients underwent subsequent flexible fiberoptic laryngeal
examination, and no cases were found to have findings con-
cerning for inflammatory or neoplastic disease.
Asymmetric uptake on the ipsilateral side of the impaired
TVF was noted in 8 (7%) patients. Subsequent laryngeal
visualization revealed irregularities prompting formal
Stanisce et al
Table 2. Incidence and Significance of PET-CT Findings (n = 108).
Findings n (%)
Unremarkable laryngeal imaging findings 87 (81)
Asymmetric laryngeal hyperactivity 21 (19)
Contralateral hyperactivity 13 (12)
Benign laryngeal examination 13 (100)
Ipsilateral hyperactivity 8 (7)
Benign laryngeal examination 6 (75)
Laryngeal examination prompting biopsy 2 (25)
Abbreviation: PET-CT, positron emission topography–computed topography.
Figure 1. (A) Axial positron emission tomography–computed
tomography exhibiting fluorodeoxyglucose avidity at the level of
the right vocal fold, contralateral to the known paralyzed cord. (B)
Focal hyperactivity noted at the left glottic fold. Patient underwent
medialization injection laryngoplasty 15 days prior to imaging.
operative laryngoscopy and biopsy in 2 of these patients,
both of which were benign. Of note, the 2 patients who
underwent biopsy had a remote history of chemoradiation
treatment for esophageal cancer. Both patients did not have
formal laryngeal endoscopic evaluation prior to PET-CT
imaging findings. The other 6 patients in the cohort with
ipsilateral asymmetric uptake were known to our practice
and had undergone injection medialization within 11 weeks
prior to the PET-CT scans. These results are summarized in
Table 2. Figure 1 demonstrates examples of both ipsilat-
eral and contralateral hypermetabolism observed.
Only 1 case was noted to have concerning vocal fold
pathology seen on laryngopharyngoscopy following an unre-
markable PET-CT scan that prompted an operative biopsy.
Although the biopsy revealed a benign lesion, this case
serves as the sole false negative in our analysis group.
The false-positive rate for the cohort was calculated to be
18%, while the false-negative rate was estimated at 33%.
The specificity, or true-negative rate, was calculated to be
82%. The sensitivity, or true-positive rate, was estimated at
67%. A positive likelihood ratio of 3.2 and a negative likeli-
hood ratio of 0.4 were calculated.
SUVs were reported or calculated in 18 of the 21 cases
with asymmetric uptake. In the group with contralateral
hyperactivity, the median SUV was 8.26 (n = 10; range, 4.3-
16.4). In the cases with ipsilateral activity, the median SUV
was 6.65 (n = 8; range, 4.3-13.24). No significant differences
in SUVs were observed between the groups (P = .203).
3
Of the 135 patients, 43 had a history of vocal fold media-
lization injection procedures. Two patients underwent type
1 thyroplasty procedures with Silastic implants without ary-
tenoid adduction. Fifteen patients completed subsequent
PET-CT imaging after the injection procedures; 1 patient
underwent PET-CT after the implant procedure.
Hypermetabolic activity on the ipsilateral side of the injec-
tion was noted in 6 (40%) cases; however, the median time
from injection to the scan was 27 days (range, 10-74 days).
Four of these patients underwent additional follow-up PET-
CT at a median 189 days (range, 186-247 days), all of
whom demonstrated resolved FDG avidity. The remaining 9
cases showed unremarkable findings within the larynx. The
median interval from injection to the unremarkable PET-CT
scans was 193 days (n = 13; range, 46-882 days). A statisti-
cal difference was observed between the time interval of the
2 groups (P = .011). PET-CT findings were unremarkable
464 days after the Silastic implant procedure.
Injections were completed with aqueous/glycerin/carbox-
ymethylcellulose gel implant (Prolaryn Gel, Radiesse Voice
Gel) or synthetic calcium hydroxylapatite suspended in aqu-
eous/glycerin/carboxymethylcellulose gel (Prolaryn PLUS,
Radiesse Voice) based on the discretion of the operating
surgeon. Both type 1 thyroplasty procedures were completed
with the Montgomery Thyroplasty Implant System (Boston
Medical Products Inc, Shrewsbury, Massachusetts). No sta-
tistical differences were observed between the incidence of
hypermetabolism and the type of material injected nor
between SUV measurements and material injected.
Discussion
Our study aimed to determine the incidence of normal and
abnormal laryngeal PET-CT findings in patients with unilat-
eral TVF motion impairment. Eighty-one percent of scans
in our study had unremarkable laryngeal findings. Of those
who underwent PET-CT for reasons other than laryngeal
cancer, 19% demonstrated incidental asymmetric hyperme-
tabolic activity. Contralateral and ipsilateral FDG avidity
was observed in 12% and 7% of cases, respectively. None
of the patients with hypermetabolic activity on the contralat-
eral side of the impaired TVF had laryngeal examination
findings concerning for inflammatory or neoplastic disease.
Thus, when encountered, this imaging finding may represent
a false-positive result, secondary to physiologic compensa-
tion or normal activity of the contralateral functional TVF.
Although recent vocal fold injection was associated with
ipsilateral FDG avidity, one-quarter of the patients with
TVF motion impairment who demonstrated this finding had
endoscopic changes that warranted an operative biopsy. In
the absence of recent instrumentation, ipsilateral hyperactiv-
ity should prompt immediate referral to an otolaryngologist
for further evaluation.
When abnormal FDG avidity in the larynx is evaluated,
the following should be considered: the laterality of the
hypermetabolic activity, a history of head and neck cancer,
previous radiation therapy, or recent chemotherapy treat-
ment with vinca alkaloids.16 The 2 patients in our ipsilateral
4 Otolaryngology–Head and Neck Surgery
hyperactivity cohort who underwent biopsy had a remote
history of head and neck cancers (esophageal), which may
have lowered physician threshold to perform biopsy. A
known history of head and neck cancer is a significant risk
for recurrent lesion, and this history should prompt further
evaluation.
This study first identified patients with TVF motion
abnormalities and then analyzed PET-CT findings in the
cohort. Previous reports in the literature have utilized an
opposite approach: first identifying positive PET-CT scans,
then analyzing vocal fold pathology in these groups. We
believe that the former approach infers less bias and pro-
vides a more accurate incidence of the discussed findings.
In an analysis exclusively composed of PET-CT scans with
mention of laryngeal uptake from 23 patients, Seymour et al
proposed that nearly 60% of laryngeal findings represent a
true-positive result.14 However, the investigators defined
true positivity by the presence of any vocal fold pathology,
including malignancy or motion abnormality. Their analysis
did not exclude patients who underwent PET-CT for pri-
mary laryngeal cancer, nor did it account for asymmetry or
laterality. Lee et al found that 15 of 17 patients with unilat-
eral laryngeal findings on PET imaging had underlying
vocal fold paralysis.15 Twelve percent of all positive find-
ings in their study represented an underlying head and neck
malignancy. Note that all of the patients in this study had
known lung cancer. An association between primary glottic
tumors and chest malignancies is well described, introdu-
cing an inherent bias into the study.17
To our knowledge, this is the largest study to date that
assessed the effects of laryngeal instrumentation and injec-
tion medialization on PET-CT findings. Although ipsilateral
FDG avidity was observed in 40% of the scans following
injection laryngoplasty, these positive scans were completed
at a median 27 days following the procedures. Absence or
resolution of the hypermetabolic activity in the remaining
scans was noted after a median interval of 193 days.
Furthermore, there were no statistical associations observed
between the incidence of FDG avidity or SUV measure-
ments and the type of material injected. Limited by the
small sample size, a time interval for the expected resolu-
tion of the hypermetabolic activity cannot be concluded
from this report, nor can associations with the injectable
material. Previous reports hypothesized that materials with
larger surface areas of breakdown cause significant meta-
bolic activity over an increased time.18 However, we are
unable to discern if the acute hypermetabolic activity
observed in our study represents the local inflammatory
response of laryngeal instrumentation and foreign material
injection rather than the injectable material itself.19,20 By
providing new insight into the local response to injection
medialization procedures, this study may serve as a platform
for future investigations.
Although we report estimations for sensitivity, specifi-
city, false-positive and false-negative rates, and likelihood
ratios, the limited sample size and temporal restrictions of
this analysis secondary to its retrospective nature may influ-
ence the generalizability of these statistics. For example,
some patients had undergone laryngeal endoscopy a year
after the most recent PET-CT imaging was obtained. Any
vocal fold pathology that may have developed in the interim
would not have been captured by the imaging study, ulti-
mately influencing the incidence of true and false negatives.
Such statistical terminology should be reserved within refer-
ence to the gold standard of a diagnostic evaluation, of
which PET-CT is not for vocal fold pathology. Furthermore,
we presented likelihood ratio estimations instead of positive
and negative predictive values, as predictive values are
more dependent on the underlying prevalence of disease in
the study cohort. Probably affected by the pretest, which is
intrinsically low for patients similar to those included in this
analysis, the positive predictive value holds little utility in
guiding clinical decisions.
This analysis did not uncover any statistical associations
among SUVs and the laterality of the FDG avidity.
Komissarova et al found that SUV estimates for tumors and
vocal cord paresis alone overlap, preventing the distinction
between motion abnormalities and neoplasms.21 The data
from our study are congruent with this conclusion. Due to
the paucity of current data, SUV measurements should not
be used to determine the underlying etiology for this inci-
dental finding.
We acknowledge several limitations that may serve as
additional areas of future investigation. Pilot data were not
available to perform prospective power calculations, and
our incidence data should serve only as an estimation. As
this was a single-center retrospective review, a patient’s
medical history and treatment records may not be fully cap-
tured. For example, a remote history of TVF injections at an
outside institution may not be accurately reflected in our
medical records, ultimately influencing the rates derived
from our data. A similar analysis should be conducted at a
multi-institution or population-based level to calculate true
incidence rates. Finally, all PET-CT scans were not inter-
preted by the same radiologist. Only scanned reports from
outside hospital systems were available for 3 cases, each
demonstrating contralateral hyperactivity. This prevented
our radiologist from retrospectively assigning SUVs to these
cases. Additionally, the potential for interobserver bias
exists in both image interpretation and verbiage used to por-
tray the results. Our institutional protocol instructs patients
to relax and not speak during imaging capture; however, a
retrospective analysis cannot guarantee control for phona-
tion and physiologic motion artifact.
The data presented in this study contribute to the growing
knowledge regarding incidental imaging findings in the head
and neck and their clinical significances.22-24 This evidence
holds implications for not only practicing otolaryngologists
but also medical and radiation oncologists, pulmonologists,
and speech-language pathologists. This report will serve to
guide physicians encountering this clinical scenario when
caring for patients with TVF motion impairments.
Stanisce et al
Conclusions
Unilateral FDG avidity on PET-CT imaging has been
reported as an incidental finding in patients with TVF
motion abnormalities. Excluding those with primary laryn-
geal cancer, this report determined that 81% of these
patients demonstrated no laryngeal findings on PET-CT.
While 19% of the cohort showed asymmetric hyperactivity
in the larynx, the false-positive rate was estimated at 18%.
Contralateral asymmetric hypermetabolism in patients with
unilateral TVF motion abnormalities may represent a false-
positive finding. In contrast, ipsilateral hypermetabolic
uptake without recent fold instrumentation should prompt
laryngeal endoscopy. Recent vocal fold instrumentation and
injection medialization are associated with ipsilateral FDG
avidity. The evidence presented in this analysis will help
guide physicians encountering this imaging finding when
caring for patients with TVF motion impairments and serve
as a platform for future investigations.
Author Contributions
Luke Stanisce, conception and design, acquisition of data, analysis
and interpretation, statistical analysis, drafting the article, critical
revision of the article, final approval of the article, agreement to be
accountable for all aspects of the work; Timothy Renzi, acquisi-
tion of data, critical revision of the article, final approval of the
article, agreement to be accountable for all aspects of the work;
Nikita Paripati, acquisition of data, critical revision of the article,
final approval of the article, agreement to be accountable for all
aspects of the work; Nadir Ahmad, analysis and interpretation,
critical revision of the article, final approval of the article, agree-
ment to be accountable for all aspects of the work; Thomas C.
Spalla, analysis and interpretation, critical revision of the article,
final approval of the article, agreement to be accountable for all
aspects of the work; Howard L. Roth, acquisition of data, critical
revision of the article, final approval of the article, agreement to be
accountable for all aspects of the work; Yekaterina Koshkareva,
conception and design, acquisition of data, analysis and interpreta-
tion, statistical analysis, drafting the article, critical revision of the
article, final approval of the article, agreement to be accountable
for all aspects of the work.
Disclosures
Competing interests: None.
Sponsorships: None.
Funding source: None.
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