Ashdin Publishing
Journal of Case Reports in Medicine
Vol. 6 (2017), Article ID 235995, 3 pages
doi:10.4303/jcrm/235995
ASHDIN
publishing
Case Report
Multiple Parotid Masses: A Rare Case of De Novo Monomorphic and
Pleomorphic Adenomas in a Patient with Myotonic Dystrophy
Chloe Matovina, Andrew Birkeland, and Matthew E. Spector
Department of Otolaryngology—Head and Neck Surgery, University of Michigan, Ann Arbor, MI 48109, USA
Address correspondence to Matthew E. Spector, [email protected]
Received 27 July 2016; Accepted 30 December 2016
Copyright © 2017 Chloe Matovina et al. This is an open access article distributed under the terms of the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract Objective/background. This is a case presentation of a
primary multifocal monomorphic and pleomorphic adenoma, with
possible association with myotonic dystrophy. Methods/presentation.
The patient was a 36-year old woman with myotonic dystrophy
with multiple left parotid masses. Biopsy and final pathology
demonstrated discrete de novo pleomorphic and monomorphic
adenomas. Conclusions/impact. There is increasing investigation into
association between myotonic dystrophy and neoplasia, including
salivary gland tumors. Here we present a patient with multiple parotid
neoplasms and discuss this unique case in regards to the risk of tumors
in patients with muscular dystrophy.
to myotonic dystrophy that could also play a role in
tumorigenesis [4, 6, 7].
We present a patient with a history of myotonic
dystrophy who displayed three distinct masses within
the left parotid gland, ranging from 1.4 cm to 3.5 cm, arising
from the superficial, deep, and parapharyngeal portions of
the parotid gland.
Keywords parotid mass; monomorphic adenoma; pleomorphic adenoma; myotonic dystrophy
A 36-year-old female presented with a left parotid mass
that had been slowly increasing in size and tenderness
over the course of two months. The patient had a history
of deep venous thrombosis and adult-onset myotonic
dystrophy, with facial, hand, and gait motor instabilities.
She denied use of cigarettes or smokeless tobacco products
and reported no alcohol consumption. Of note, she had
a significant family history of myotonic dystrophy in her
mother, maternal aunts, and grandmother, with earlier onset
and worsening symptoms with each generation. Because of
her strong family history, the patient had declined formal
genetic testing. Notably, the patient had no history of prior
fine needle aspiration, radiation, trauma or surgery of the
head and neck.
On physical examination, a firm, 2–3 cm mass was
palpated within the left parotid gland. An ultrasoundguided fine needle aspiration biopsy was performed with
preliminary consistent with a pleomorphic adenoma, with
no malignant cells identified. Computed tomography (CT)
scans showed multiple discrete nodular enhancing lesions
within the left parotid gland (Figures 1(a) and 1(b)). The
deeper areas were not seen on ultrasound examination and
were not biopsied. After discussion with the patient, these
could be removed in a single surgery.
The patient underwent a left parotidectomy with facial
nerve monitoring. Findings included a 1.4 cm circumscribed
mass in the superficial lobe, a 3.5 cm circumscribed mass in
1. Introduction
Pleomorphic and monomorphic adenomas are rarely
multifocal. Reports of the incidence of de novo multifocal
pleomorphic adenomas are in the range of 0.14%–0.6% [1].
Moreover, there are no reports of multifocal monomorphic
adenomas and no reports of both pleomorphic and
monomorphic adenomas arising within the parotid gland.
Myotonic dystrophy is a progressive muscular disorder,
often starting in childhood or in the 20s, and progresses
throughout life [2]. It is most noticeable in the hands
and facial muscles, with ptosis, reduced facial expression,
dysarthria, and gait abnormalities among the first signs and
symptoms [3]. The most common form of myotonic dystrophy is caused by mutations in the DMPK gene with trinucleotide (CTG) repeat expansion leading to a dysfunctional
gene product. Notably this disease is subject to anticipation,
with increased CTG repeats in subsequent generations,
resulting in earlier onset and more severe symptoms [3].
Interestingly, there are some case reports that suggest
a relationship between myotonic dystrophy and cancer
risk and tumor formation, including pleomorphic adenomas [4, 5]. This relationship is hypothesized to arise
from the genetic mutations and genetic instability (with
unstable nucleotide triplet repeat sequences) contributing
2. Case presentation
2
Journal of Case Reports in Medicine
(a)
(b)
Figure 1: CT scans showing multiple discrete nodular
enhancing lesions within the left parotid gland. (a) Parapharyngeal (arrow, 1) and deep lobe parotid tumor (arrow, 2).
(b) A more inferior section of the deep lobe parotid tumor
(arrow, 2) and the superficial parotid lobe tumor (arrow, 3).
(a)
the deep lobe of the left parotid gland, and a 3.5 cm circumscribed mass in the left parapharyngeal space. Each mass
was completely excised with negative margins. The patient
was seen back in follow up approximately one month after
surgery. All incisions were well healed without complications. Final pathology results confirmed that the superficial
mass was a pleomorphic adenoma and the two deep masses
were discrete monomorphic adenomas (Figures 2(a)–2(c)).
3. Discussion
De novo multifocal salivary gland tumors are uncommon
in general, and even more so in the case of pleomorphic
adenomas and monomorphic adenomas [8]. There are no
reports of the presence of both monomorphic and pleomorphic adenomas arising within the same gland. The majority
of reported cases of primary multiple pleomorphic adenoma
in previously untreated patients involve two dominant nodules; however, some have been reported with a larger number of nodules [9].
Given this patient’s history of myotonic dystrophy, the
presented case is unique in the sense that it may provide
insight into the potential relationship between germline
mutations associated with myotonic dystrophy and the
appearance of pleomorphic adenomas.
Myotonic dystrophy (a specific form of muscular
dystrophy) is a multisystem disorder most commonly
caused by a CTG expansion in the noncoding region of
the DMPK gene, exhibiting effects on skeletal and smooth
muscle, the eye, heart, endocrine system, and central
nervous system [3, 4]. This disorder can cause a number
of symptoms ranging from muscle weakness to cardiac
abnormalities [3]. Various neoplasms have been reported in
patients with myotonic dystrophy. Most of these neoplasms
involve the Wnt/β-catenin signaling pathway, suggesting
(b)
(c)
Figure 2: Histologic features of tumors isolated during a
left parotidectomy; hematoxylin and eosin stained sections
at 40× magnification. (a) Representative section of 1.4 cm
pleomorphic adenoma isolated from the left superficial lobe.
(b) Representative section of 3.5 cm monomorphic adenoma
isolated from the left deep lobe. (c) Representative section
of 3.5 cm monomorphic adenoma isolated from the left
parapharyngeal space.
Journal of Case Reports in Medicine
that tumor progression in myotonic dystrophy may relate to
mutations in this pathway [4].
The association of pleomorphic adenoma and myotonic
dystrophy has been previously described in only three case
reports [10, 11, 12]. Johannesson and colleagues were the
first to describe two patients with pleomorphic adenoma and
myotonic dystrophy, and as they did not describe a mechanism, they argued statistically that the rarity of these two diseases makes their combination essentially impossible without an association [10]. Draper and Pickles expanded on this
concept, reporting two further cases [11]. One case was a
9-year-old female with a single pleomorphic adenoma, and
the second was a 29-year-old female with multifocal pleomorphic adenoma. Their conclusion was that these tumors
are even more rare in children, suggesting an inherited relationship. Ogata confirmed this finding using southern blot
analysis to show the parotid tumor, just as other abnormal
functioning tissues in myotonic dystrophy (DM), had CTG
repeats, suggesting a pathophysiologic mechanism of tumor
formation [12]. Our case is unique in that there were three
lesions noted in one patient, and that this is the first description of monomorphic adenoma as the pathology.
The probability of the repeated occurrence of these two
conditions simply by chance is incredibly low; thus, physicians should be aware of the possibility of an association
between myotonic dystrophy and salivary gland tumors,
including pleomorphic and monomorphic adenomas. For
patients with myotonic dystrophy, regular examination of
the salivary glands may be indicated to identify potential
masses. Further research into potential genetic drivers
in pleomorphic and monomorphic adenomas arising in
myotonic dystrophy patients, and comparisons of genetic
profiles with those derived from nonmyotonic dystrophy
patients may delineate both common and unique activated
pathways in both pleomorphic and monomorphic adenomas.
Acknowledgment Andrew Birkeland is funded by a T-32 training
grant (T32 DC005356).
Conflict of interest The authors declare that they have no conflict of
interest.
References
[1] J. R. Miliauskas and J. L. Hunt, Primary unilateral multifocal
pleomorphic adenoma of the parotid gland: molecular assessment and literature review, Head Neck Pathol, 2 (2008), 339–
342.
[2] C. A. Smith and L. Gutmann, Myotonic dystrophy type 1
management and therapeutics, Curr Treat Options Neurol, 18
(2016), 52.
[3] T. D. Bird, Myotonic dystrophy type 1, in GeneReviews
[Internet], R. A. Pagon, M. P. Adam, H. H. Ardinger, S. E.
Wallace, A. Amemiya, L. J. H. Bean, et al., eds., University of
Washington, Seattle, 2015.
[4] C. M. Mueller, J. E. Hilbert, W. Martens, C. A. Thornton, R. T.
Moxley, and M. H. Greene, Hypothesis: neoplasms in myotonic
dystrophy, Cancer Causes Control, 20 (2009), 2009–2020.
3
[5] S. M. Gadalla, M. Lund, R. M. Pfeiffer, S. Gørtz, C. M. Mueller,
R. T. Moxley, et al., Cancer risk among patients with myotonic
muscular dystrophy, JAMA, 306 (2011), 2480–2486.
[6] S. Panzer, D. P. Kuhl, and C. T. Caskey, Unstable triplet repeat
sequences: a source of cancer mutations?, Stem Cells, 13 (1995),
146–157.
[7] R. Osanai, M. Kinoshita, K. Hirose, T. Homma, and I. Kawabata,
CTG triplet repeat expansion in a laryngeal carcinoma from a
patient with myotonic dystrophy, Muscle Nerve, 23 (2000), 804–
806.
[8] G. Seifert and K. Donath, Multiple tumours of the salivary
glands—Terminology and nomenclature, Eur J Cancer B Oral
Oncol, 32B (1996), 3–7.
[9] S. L. van Egmond, W. W. de Leng, F. H. Morsink, G. J. Offerhaus,
and L. A. Brosens, Monoclonal origin of primary unilateral
multifocal pleomorphic adenoma of the parotid gland, Hum
Pathol, 44 (2013), 923–926.
[10] G. Johannesson, K. G. Henriksson, and L. Odkvist, Coincidence
of dystrophia myotonica and pleomorphic adenoma of the parotid
gland, Acta Neurol Scand, 57 (1978), 275–278.
[11] M. R. Draper and J. M. Pickles, Pleomorphic adenoma and
myotonic dystrophy: an association?, J Laryngol Otol, 114
(2000), 985–987.
[12] K. Ogata, A. Takahashi, N. Oguchi, J. Ishitoya, S. Fuse, and
T. Shimpo, Somatic mosaicism of p(CTG)n expansion in a case
of myotonic dystrophy with parotid tumor, Rinsho Shinkeigaku,
(1998).