International Journal of Otolaryngology and Head & Neck Surgery, 2013, 2, 232-235
Published Online November 2013 (http://www.scirp.org/journal/ijohns)
http://dx.doi.org/10.4236/ijohns.2013.26048
Open Access IJOHNS
Unusual Metastases from a Pleomorphic Adenoma of the
Parotid Gland: A Case and Literature’s Review
Giuditta Mannelli*, Lucio Rucci, Oreste Gallo
First Clinic of Otorhinolaryngology-Head and Neck Surgery, University of Florence, Florence, Italy
Received October 19, 2012; revised November 20, 2012; accepted December 5, 2012
Copyright © 2013 Giuditta Mannelli et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
ABSTRACT
Background: Pleomorphic adenoma constitutes the most common benign parotid gland tumor. Local recurrence after
surgery has been described in 1% - 5% of cases, and malignant evolution in 2% - 9% of cases. Metastasizing pleomor-
phic adenomas has rarely been reported. No histologic or molecular parameters exist at the present time that could pre-
dict the development of metastasis in these neoplasms. Methods and Results: A 54-year-old woman had a superficial
left parotidectomy with facial nerve preservation for pleomorphic adenoma. She developed two recurrences in 2000 and
2001, but 25 years later the first operation she presented a metastasis in her right gluteal region with evidence of local
recurrence. Conclusion: Metastatizing pleomorphic adenoma is a rare pathologic situation but, in case of swelling or
lump appearance in patients with pleomorphic adenoma history, it should be taken in mind.
Keywords: Salivary Gland Tumors; Pleomorphic Adenoma; Metastases; Surgery; Gluteal Region
1. Introduction
Pleomorphic adenoma is the most common parotid tumor
in both adult and pediatric populations. It is also termed
mixed tumor and it is generally accepted as biologically
benign, showing a slow-growing and well-circumscribed
margin. By definition, this tumor does not metastasize at
all. However, tumor recurrence and/or malignant degen-
eration are known as possible complications. A rare and
controversial clinical entity is a metastasizing pleomor-
phic adenoma which, although histologically identical to
pleomorphic adenoma, metastasizes to regional and dis-
tant sites, usually after many years, and after treatment,
without demonstrating any malignant histopathological
features. Authors such as Wenig [1] suggest that Metas-
tatic Mixed Tumors appear after multiple recurrences of
an original pleomorphic adenoma in the primary site,
mainly because of many inappropriate surgical manipu-
lations that could promote the development of dissemi-
nating metastasis. Although apparently defined by pa-
thologists as benign, mortality can be as high as 22%,
according to Ellis and Auclair [2]. Metastasizing pleo-
morphic adenoma has neither age or gender predilection,
nor association with race or geographic location [3]. This
tumor usually presents multiple local recurrences, at least
two or more before the development of metastatic foci
[1]. Nevertheless, many reported cases in literature are
without prior evidence of local recurrence [4,5]. The in-
terval between diagnoses of the primary tumor and me-
tastases ranges from 3 to 52 years after the occurrence of
the primary lesion. Bone is the most common site for
metastases, followed by head and neck deposits such as
regional lymph nodes, the oral cavity and pharynx, then
skin, liver, retroperitoneum, kidney, calvarium and
nervous system which are the other less interested sites
of interess [3].
Here, we present a case of a parotid pleomorphic ade-
noma that metastasized to the right gluteal region with
evidence of local recurrence.
2. Case Report
A 54-year-old woman presented in 1983 with a slow
growing mass in tail of her left parotid gland. She un-
derwent a superficial left parotidectomy with facial nerve
preservation and the mass was histologically confirmed
as pleomorphic adenoma. Unfortunately, she presented
again, both in 2000 and 2001, a lesion in the surgical
field, localized immediately under previous skin incision,
which was excised and confirmed as a recurrent pleo-
morphic adenoma. During the last operation facial nerve
*Corresponding author.

G. MANNELLI ET AL. 233
was sacrificed. In January 2008, because of a recent ap-
pearance of a little, painless and smooth ovoid mass in
the right gluteal region, the patient underwent ultrasono-
graphy that confirmed the presence in this region of a
hypoechoic little mass, 17.4 × 12.3 × 16.1 mm, with pos-
terior wall reinforcement, showing slim, regular and not
vascularized walls. These features suggested a sebaceous
cyst or any dermatofibroma (Figure 1). In order to clar-
ify the nature of the lesion, a MR (magnetic resonance)
exam of the pelvis was performed in December 2008 and
confirmed the presence of an extra-muscolar and subfas-
cial mass in the right gluteal region (Figure 2). In Janu-
ary 2009, the patient underwent the surgical excision of
the lesion and the histological investigation documented
possible soft tissue’s metastasis from a pleomorphic
adenoma, without atypia, mytosis neither necrosis (Fig-
ure 3).
Due to her anamnestic data, the patient was revalued
to investigate the presence of other distant metastasis and
possible local recurrence. Therefore, in June 2009 the CT
scans excluded metastasis at the chest, while the CT
scans of head and neck evidenced the presence of a mass
under the left petrosa which was penetrating the mastoid
cells and was in contact with the labyrinthine system
(Figures 4 (a) and (b)).
This was compatible with a recurrence of pleomorphic
adenoma. Even though imaging techniques spoke about a
local recurrence, patient did not complain any symptoms
at all before. Except for dizziness, confirmed by a vesti-
bular exam suggesting for the presence of a central ves-
tibular disorder. The pa t ient had normal heari ng .
3. Discussion
Since the 1940s a rare and unusual entity, distinct from
pleomorphic adenoma, has been recognised as its malig-
nant variants: metastasizing pleomorphic adenoma
(MPA). This one appears as a histologically benign le-
sion metastasizes to areas including skin (scapular region
etc.), cervical lymph nodes, paranasal sinuses, lungs,
liver, kidney, vertebrae and long bones, external audito ry
canal and larynx. Classification of salivary gland tumors
by Foote and Frazell in 1953 [6] gives insufficient clini-
cal or histological information about MPA; by reviewing
cases reported in literature is possible to make important
inferences about behavior and outcome of patients pre-
senting with enigmatic conditions. In fact, between 1953
and 2012, 57 global cases of MPA h ave been reported in
literature. The head and neck appears like the most
common site for metastasis (43.8%), followed by lungs
(33.3%), bones (33.3%), and abdominal viscera (10.5%).
Within the head and neck, there are 11 metastases
(19.3%) to regional lymph nodes, and 14 tumor deposits
(24.5%) are detected in nonlymphatic extracranial tissues
such as skin or paranasal sinuses. There is one case of
Figure 1. Ultrasonography exam of the right gluteal region
which shows the presence of a hypoechoic little mass, 17.4 ×
12.3 × 16.1 mm, with posterior wall renfoircement.
Figure 2. MR (magnetic resonance) section of the pelvis
confirming the presence of an extra-muscolar and subfas-
cial mass in the right gluteal region.
Figure 3. Histological exams documents pleomorphic ade-
noma’s soft tissue metastasis nature.
(a) (b)
Figure 4. CT (Computerized tomography) scans of head
and neck evidencing: (a) the presence of a mass under the
left petrosa penetrating the mastoid cells and (b) being in
contact with the labyrinthine system.
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G. MANNELLI ET AL. 234
intracranial metastases. All these cases derived from the
summation of the cases reviewed by Nouraei et al. [7]
and the new ones found in literature from 2005 to the
entire 2009. By comparing the most common location for
metastasis, the head and neck site has become the first
one interested by metastases of MPA, while bones from
being the first location has become the third one after
lungs. On Table 1, are reported several data regarding
overall series.
It is rare for a tumor appearing histologically benign to
have the capacity to metastasize; the metastasizing “be-
nign” pleomorphic adenoma is considered distinct from
the true malignant mixed tumor (carcinoma ex-pleo-
morphic adenoma and carcinosarcoma) because it re-
mains histologically benign [7]. That is why, in case of
previous benign head and neck neoplasia, the appearance
of new masses is not easily linked to the previous disease,
even if it should always lead towards a possible connec-
tion with the previous head and neck disease before
thinking about a new disorder. The MPA is an emblem-
atic possibility; in fact, b ecause of its diagnosis, which is
determined by histopathological analysis only, clinical
examinations could steer wrongly towards differential
diagnosis with many other kind of possible neoplasia
depending on the site of presentation. We saw above,
how head and neck is the most common site of metasta-
ses from MPA, in this case ultrasonography of the neck
or computer tomography scan or magnetic resonance
analysis may help in distinguishing the morphological
characteristics of the new lump, especially in identifying
its malignant or benign nature. The same critical attitude
should be applied in case of mass in other sites. More-
over, the historical records of the patients may help in
thinking about rare condition, such as the MPA. In fact,
even if the mechanism for the metastatic behaviour is not
clear, it seems to be more common when the original
pleomorphic adenoma is uncompletely excised, due to
repeated surgical manipulation in the attempt to excise
recurrences that could push neoplastic cells into vascular
spaces.
Here we reported the case a 54 years old woman who
underwent in 1983 a superficial left parotidectomy with
facial nerve preservation for a pleomorphic adenoma
which recurred locally on twice without any distant me-
tastasis and ones in 2009, 25 years later the first surgical
operation at her left parotid gland, with a soft tissue me-
tastasis. Recurrence of the tumor at the primary site oc-
curs in about 90% of cases of metastasizing pleomorphic
adenoma with a usual long interval between the diagno-
sis of the primary lesion and the metastasis [1]. Nouraei
et al. [7] demonstrated about an 81% of local recurrence
prior the distant metastasis’s detection, with the mean
time of presentation to recurrence of 5.0 ± 4.9 years. The
mean ± SD time from initial presentation to the d etection
Table 1. Sites of metastasis: update of metastases’ locations.
Sites Numbers %
Total 57 100%
Head and Neck
Skin/scalp/skull 11 19.3
Cervical limph node 11 19.3
Paranasal sinuses 2 3.5
Intracranial 1 1.7
Visceral
Pulmonary 19 33.3
Renal 4 7
Hepatic 2 3.5
Mediastinal limph node 1 1.7
Larynx 1 1.7
Bone
Pelvic/sacrum 6 10.5
Vertebra 5 8.8
Femur 3 5.3
Humerus 2 3.5
Ribs 2 3.5
Scapula 1 1.7
Skin nodules (not within head and neck) 3 5.3
of metastases who had no intervening local recurrences
was 12.3 ± 8.6 years, while fo r patients with a history of
local recurrence this was 16.9 ± 13.3 years. That is why
it may also occur many years after its seemingly com-
plete excision at the primary site. There are a few reports
of cases of pleomorphic adenoma metastases without
local recurrence at the primary site frequently many
years after primary excision [5]. In our report the third
local r ecurrence h as been iden tified after the metastasis’s
detection, because patient did not claim any clinical
symptoms at all except after CT scans immediately.
Since no clinical criteria differentiate the typical be-
nign pleomorphic adenoma from the metastasizing one,
some authors tried to identify distinguishing histologic
characteristics. Wenig et al. [1] made a review of 11
cases; primary, recurrence and metastases had a similar
appearance, as well as histopathological features. The
primary site was recorded: eight from the parotid, two
submandibular glands, and one the nasal septum. The
majority had two or more recurrences before the devel-
opment of their metastatic focus. The metastases were
discovered at any time from 6 to 52 years after the pres-
entation of the primary tumor. The metastatic deposits
were identified in bone, lung , regional lymph nodes, skin,
kidney, retroperitoneum, oral cavity, pharynx, calvarium,
and brain. Mitotic rate, cellular pleomorphism, tumor
infiltration, evidence of vascular or lymphatic invasion
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G. MANNELLI ET AL.
Open Access IJOHNS
235
were compared. No differences existed. No evidence of
malignancy was identified. Two of these patients died as
a direct result of their metastases at 3 and 2 years, seven
patients were alive without disease, and two patients died
of unrelated causes. More probably, the metastatic capa-
bility reflects the accumulation of key genetic alterations,
a sequential process that causes histological and biologi-
cal progression [2]. El-Naggar et al. [8] considered that
the lack of recognized histologic parameters of malig-
nancy raises the possibility that a small subset of pleo-
morphic adenomas may have an area of submicroscopic
alterations that may subsequently pursue a malignant
course.
Some authors investigated the possible correlation
between expression of oncogenes and tumor suppressos
genes and metastasizing pleomorphic adenoma, in order
to find a genetic reason of its behavior [9]. Unfortunately,
no correlation has been found between specific chromo-
somal defects and tumor recurrence and/or metastases.
4. Conclusions
MPA is a low-grade malignant tumor [3], which shows
the 58% disease-specific 5-years survival and about 50%
of disease-free survival rate, with a mortality rate of
about 20% [1,10]. It should not be underestimated. Mul-
tiple metastases are fatal, and their developing and pres-
ence in multiple sites, within the first 10 years after the
initial diagnosis, are independent predictors of worse
survival [10].
Usually, local recurrence is detected first and metasta-
sis second, but in case of accidental metastasis in a pa-
tient with a history of pleomorphic adenoma or of its
local recurrences it would be better to investigate the
presence of a local recurrence, which is found in 80% of
cases. We recommend, in order to prevent possible local
recurrences and distant metastasis, performing superficial
parotidectomy with facial nerve preservation to obtain a
meticulous resection of the primary pleomorphic ade-
noma, which is usually curative. On the other hand, che-
motherapy and radiotherapy still present a limited value
[11] as well as hormonal treatment [12].
Due to the limited number of reported cases, it is dif-
ficult to understand the biology of MPA as distinct from
non-MPA and to identify a specific follow-up protocol,
but we agree that the metastatic disease should be treated
surgically.
5. Acknowledgements
This manuscript is approved by all authors and all of
them have participated in writing and correcting of this
work. Further, all authors assure that manuscript has not
been published nor is under approving by other journals
or editors and they have not any conflict of interest, fi-
ancial or otherwise. n
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