1. CLINICAL NOTE
A Cytomegalovirus-Associated Mass
Presenting With Laryngeal Obstruction
Aaron D. Friedman, MD; Walter G. Maurer, MD; Michael C. Byrd, MD; James R. Cook, MD, PhD; Robert R. Lorenz, MD
C
ytomegalovirus (CMV) is a ubiquitous, opportunistic pathogen. Primary CMV infec-
tion occasionally causes a mononucleosis syndrome in immunocompetent patients
but is more often asymptomatic. Congenital involvement leads to hearing loss and a
host of irreversible neurologic sequelae, whereas the immunocompromised patient
can experience chorioretinitis, enteritis, pneumonitis, or central nervous system involvement. Cy-
tomegalovirus–related mucosal ulcerations of the oral cavity and pharynx are not uncommon to
this patient population.1
Rarely, CMV infection produces a mass le-
sion that mimics a tumor. Cytomegalovi-
rus pseudotumors in the head and neck
have been reported in the brain,2
subman-
dibular gland,3
hypopharynx,4
and tra-
chea.5
Although there are a few reports6,7
of CMV infection in the larynx resulting
in mucosal ulceration, and a single case8
of an extranodal, supraglottic lymphoma
in the setting of CMV laryngitis, to the best
of our knowledge, there has not been a de-
scription of a discrete mass in the larynx
due to CMV alone. We report the case of
an individual who presented with airway
obstruction resulting from such a lesion.
REPORT OF A CASE
A 62-year-old man with neurofibromato-
sis type 1 presented to the operating room
for elective removal of a neurofibroma on
his foot. Despite a normal voice, he was
noted to have inspiratory stridor, and ques-
tioning revealed that he had suffered from
shortness of breath for the past 2 weeks. A
short course of corticosteroids and bron-
chodilators, prescribed by his family phy-
sician, had failed to alleviate his symp-
toms. A physical examination revealed
normal oral and oropharyngeal mucosa.
There were multiple cutaneous neurofibro-
mas of the neck but no thyromegaly or
lymphadenopathy,andhistracheawasmid-
line. Flexible fiberoptic laryngoscopy
showedapedunculatedsubglotticmass,oc-
cluding approximately 75% of the airway.
Findings from the remainder of the pha-
ryngeal and laryngeal examination (includ-
ing true vocal cord mobility) were unre-
markable. Laboratory values demonstrated
anelevatedwhitebloodcellcountof14000/
µL.
Given the degree of airway occlusion,
excision of patient’s foot lesion was
aborted, and he was taken to the operat-
ing room for removal of the subglottic
mass. After intravenous anesthetic induc-
tion, the patient was mask ventilated and
turned over to the otolaryngology team.
A laryngoscope was passed transorally, and
the larynx was suspended. The mass was
well defined, with a verrucous surface
(Figure 1), and had a single point of at-
tachmenttothesubglottisatthe11-o’clock
position.Underapneicconditions,straight-
cupforcepswereusedtograbthelesionand
remove it at its stalk. Measurement on the
operative table revealed an approximately
2.5ϫ2-cm lesion. Flexible tracheoscopy
and bronchoscopy findings revealed no
other airway lesions. The patient emerged
from anesthesia without complications.
Routinehematoxylin-eosin–stainedsec-
tions of the mass lesion revealed a lym-
phoplasmacytic infiltrate with accompa-
nying giant cells. There were intranuclear
and intracytoplasmic inclusions sugges-
tive of CMV (Figure 2). Immunohisto-
Author Affiliations: Head and Neck Institute (Drs Friedman, Byrd, and Lorenz)
and Departments of General Anesthesiology (Dr Maurer) and Clinical Pathology
(Dr Cook), Cleveland Clinic, Cleveland, Ohio.
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2. chemical analysis demonstrated nu-
merous anti–CMV-positive cells
(Figure 3). Further immunostain-
ing and flow cytometry showed no
evidence of a lymphoproliferative
disorder. Fungal and acid-fast ba-
cilli stains as well as a cytokeratin im-
munostain were negative for organ-
isms.
Infectious disease consultation
was obtained, but antiviral treat-
ment was deemed unnecessary given
the resolution of this patient’s symp-
toms following the surgery. A test for
human immunodeficiency virus
(HIV) was negative for organisms.
Given the lack of any other symp-
toms to suggest immunodeficiency,
nofurtherworkupwasperformed.As
of 9 months after the procedure, the
patient had no complaints. His voice
was normal, and he did not have dys-
pnea or stridor. Flexible laryngos-
copy demonstrates no evidence of re-
currence and does not suggest any
new airway lesions.
COMMENT
Cytomegalovirus pseudotumors
have been described in several head
and neck locations. One article,4
titled “Mass Lesions of the Larynx
Due to Cytomegalovirus Infection in
a Patient Infected With the Human
Immunodeficiency Virus,” re-
counts a CMV mass lesion of the
pyriform sinus and posterior hypo-
pharyngeal wall but not of the lar-
ynx proper, as its title suggests.
There are sporadic reports of HIV-
positive patients or organ trans-
plant recipients with ulceration of
thesupraglottis6,8
orsubglottis7
inthe
setting of localized or systemic CMV
disease. In 1 of these cases, a laryn-
geal mass was also described.8
Re-
sults of a biopsy of the lesion re-
vealed a superficial CMV cytopathic
effect, but the process in deeper tis-
sue was consistent with malignant
lymphoma.
Significant airway obstruction re-
sulting from a CMV mass lesion oc-
curred in the proximal trachea (4 cm
below the glottis) of a 42-year-old
patient with AIDS.5
He had a re-
mote history of prolonged intuba-
tion and was stridorous and dys-
pneic on physical examination. On
flexible bronchoscopy, the lesion
was described as an “exophytic mass
with severe ulcerations . . . almost
totally occluding the airway.”5(p884)
Findings from mucosal biopsies
demonstrated CMV inclusions, and
cultures of tracheal washings were
also positive for the organism. The
lesion partially regressed after the pa-
tient received ganciclovir sodium
therapy for 2 weeks, although he re-
mained symptomatic. Plans to en-
doscopically remove the mass were
aborted when he died from another
opportunistic disease.
The laryngeal case described
herein is unique: unlike the muco-
salulcerationspreviouslydescribed,
thispatientpresentedwithapedun-
culated, well-defined mass in the
subglottis that caused frank stridor
and obvious airway obstruction.
Physical examination was both di-
agnostic and therapeutic, in that re-
moval of the lesion was all that was
required for treatment. The patient
with a tracheal CMV mass lesion also
had a restricted airway but re-
ceived medical, not surgical, inter-
vention. Failure to investigate the
preoperative stridor in this patient
could have resulted in disastrous
consequences: the unrecognized
mass could have been dislodged by
an endotracheal tube and sent dis-
Figure 1. Subglottic mass, status postexcision.
Figure 2. Histologic sections of the mass lesion identified a lymphoplasmacytic infiltrate with scattered
histiocytes and prominent endothelial cells. Occasional cells show nuclear inclusions (arrows) suggestive
of cytomegalovirus (hematoxylin-eosin, original magnification ϫ400).
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3. tally into the trachea or one of the
mainstem bronchi. Finally, unlike
the patient who had laryngeal lym-
phoma and concurrent CMV infec-
tion, this patient did not exhibit a
malignant process on histopatho-
logic examination.
Previous reports of CMV-relat-
ed mass lesions describe involve-
ment in patients who were HIV posi-
tive (with or without AIDS) or
immunosuppressed for the pur-
pose of organ transplantation. This
patient’s HIV test result was nega-
tive. He also had no medical his-
tory of opportunistic infection, nor
has he developed any of them since
his surgery, 9 months ago.
A CMV infection has a charac-
teristic appearance in routine sec-
tions stained with hematoxylin-
eosin. As its name implies, CMV
enlarges the cells in affected tissue.
Infected cells typically have baso-
philic nuclear inclusions, and a clear
halo often lines the inner side of the
nuclear membrane. Smaller baso-
philic inclusions in the cytoplasm are
common as well.9
These cytopathic
effects may not be present, how-
ever, until 2 to 3 weeks after inocu-
lation.10
In addition, the character-
istic morphologic findings may not
be identified when the viral load is
low.11
Consequently, immunohis-
tochemical analysis is often used to
confirm the diagnosis,1
although the
lack of a positive test result does not
rule out CMV infection.10
Some reports of CMV manifest-
ing in the head and neck have de-
scribed serologic detection of the vi-
rus,3,4
but Griffths10
makes the
important point that CMV is pres-
ent in the tissue in question prior to
its dissemination into the blood.
Thus, efforts to detect the virus
should focus on analysis of biopsy
specimens. Moreover, although
findings from CMV tissue culture
samples may also confirm the diag-
nosis, at least 21 days are required
before biopsy findings are reported
as negative, and so the procedure is
not routinely performed.12
Finally,
the question arises of whether CMV
infection is causal or coincidental—
causality requires detection of the
virus in tissue and corresponding
clinical signs and symptoms.12
Even
though the diagnosis of CMV pseu-
dotumor seems less well defined,
previous reports3
have emphasized
the definition described herein of
pathogenic CMV infection in com-
bination with the presence of a
mass, often thought to be a malig-
nancy. Given the presence of cells
positive for CMV in an exophytic
lesion with symptomatic airway
obstruction, this description of a
subglottic CMV pseudotumor
meets these criteria.
In conclusion, this article joins
only a handful of articles that de-
scribe CMV infection in the larynx
and, to our knowledge, represents
the first account of a CMV-
associated mass lesion causing sig-
nificant airway obstruction in such
a location. Moreover, unlike previ-
ous reports of CMV pseudotumors,
there was no evidence of immuno-
compromise in this patient. Surgi-
cal excision of the laryngeal mass
was both diagnostic and curative. Al-
though a lesion of this nature is ex-
tremely rare, otolaryngologists are
obligated to thoroughly evaluate the
upper airway in any patient with stri-
dor, especially prior to intubation.
Submitted for Publication: April 28,
2006; final revision received June 15,
2006; accepted June 23, 2006.
Correspondence: Robert R. Lorenz,
MD, Head and Neck Surgery, The
Head and Neck Institute, The Cleve-
land Clinic Foundation, 9500 Eu-
clid Ave, A-71, Cleveland, OH 44195
(lorenzr@ccf.org).
Author Contributions: Dr Lorenz
had full access to all the data in the
study and takes responsibility for the
integrity of the data and the accu-
racy of the data analysis. Study con-
cept and design: Lorenz and Mau-
rer. Acquisition of data: Friedman,
Lorenz,Byrd,andCook.Analysisand
interpretation of data: Friedman,
Lorenz, and Cook. Drafting of the
manuscript: Friedman, Lorenz, and
Byrd. Critical revision of the manu-
script for important intellectual con-
tent: Lorenz, Maurer, and Cook. Ad-
ministrative, technical, and material
support: Friedman and Lorenz. Study
supervision: Lorenz and Cook.
Financial Disclosure: None re-
ported.
Previous Presentation: This study
was presented in part as a poster
presentation at the American Lar-
yngological Association/Com-
bined Otolaryngology Spring
Meeting; May 19-22, 2006; Chi-
cago, Ill.
Acknowledgment: We thank Muzaf-
far Ahmad, MD, for his pulmonary
expertise and clinical assistance with
this case.
REFERENCES
1. Wenig BM, Kuruvilla A, Goldrich MS, Heffner DK,
Tuur S. Pathologic manifestations of acquired im-
munodeficiency syndrome in the head and neck.
Ear Nose Throat J. 1990;69:406-415.
2. Vidal JE, Dauar RF, Penalva de Oliveira AC, Coelho
JF, Lins DL. Cerebral mass lesion due to cyto-
Figure 3. Immunohistochemical analysis confirmed the presence of cytomegalovirus (clone DDG9/CCH2;
Dako, Carpinteria, Calif) (hematoxylin-eosin, original magnification ϫ400).
(REPRINTED) ARCH OTOLARYNGOL HEAD NECK SURG/VOL 132, DEC 2006 WWW.ARCHOTO.COM
1377
©2006 American Medical Association. All rights reserved.

4. megalovirus in a patient with aids: case report and
literature review. Rev Inst Med Trop Sao Paulo.
2003;45:333-337.
3. Schellenberg DM, Desmond NM, Murphy SM, Tan-
ner AG. Aids-associated cytomegalovirus infec-
tion of the submandibular gland mimicking a
tumour. J R Soc Med. 1994;87:483-484.
4. Tinelli M, Castelnuovo P, Panigazzi A, D’Andrea
F, Caprioglio S. Mass lesions of the larynx due to
cytomegalovirus infection in a patient infected with
the human immunodeficiency virus. Clin Infect Dis.
1995;20:726-727.
5. Imoto EM, Stein RM, Shellito JE, Curtis JL. Cen-
tral airway obstruction due to cytomegalovirus-
induced necrotizing tracheitis in a patient with
AIDS. Am Rev Respir Dis. 1990;142:884-886.
6. Marelli RA, Biddinger PW, Gluckman JL. Cyto-
megalovirus infection of the larynx in the ac-
quired immunodeficiency syndrome. Otolaryn-
gol Head Neck Surg. 1992;106:296-301.
7. Lopez-Amado M, Yebra-Pimentel MT, Garcia-
Sarandeses A. Cytomegalovirus causing necro-
tizing laryngitis in a renal and cardiac transplant
recipient. Head Neck. 1996;18:455-458.
8. Siegel RJ, Browning D, Schwartz DA, Hudgins PA.
Cytomegaloviral laryngitis and probable malig-
nant lymphoma of the larynx in a patient with ac-
quired immunodeficiency syndrome. Arch Pathol
Lab Med. 1992;116:539-541.
9. McAdam AJ, Sharpe AH. Infectious diseases. In:
Kumar V, Abbas AK, Fausto N, Robbins SL, Co-
tran RS, eds. Robbins and Cotran’s Pathologic Ba-
sis of Disease. 7th ed. Philadelphia, Pa: Elsevier
Saunders; 2005:662-710.
10. Griffiths PD. Diagnosis of cytomegalovirus
infection. J Antimicrob Chemother. 1989;23
(suppl E):11-16.
11. Chemaly RF, Yen-Lieberman B, Castilla EA, et al.
Correlation between viral loads of cytomegalovi-
rus in blood and bronchoalveolar lavage speci-
mens from lung transplant recipients deter-
mined by histology and immunohistochemistry.
J Clin Microbiol. 2004;42:2168-2172.
12. Gandhi MK, Khanna R. Human cytomegalovirus:
clinical aspects, immune regulation, and emerg-
ing treatments. Lancet Infect Dis. 2004;4:725-
738.
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