Pathology – Research and Practice 206 (2010) 66–72
Oncocytic lipoadenoma of the parotid gland: Immunohistochemical and
Marius Iliea, Ve ´ronique Hofmana,b,c, Florence Pedeutourd, Rita Attiasd,
Joseph Santinie, Paul Hofmana,b,c,?
aLaboratory of Clinical and Experimental Pathology, 30 Avenue de la Voie Romaine, Louis Pasteur Hospital, 06002 Nice, France
bEA 4319/ERI-21, Faculty of Medicine, Avenue de valombrose, Universite ´ of Nice Sophia Antipolis, 06101 Nice, France
cHuman Biobank CHUN, Louis Pasteur Hospital, 06002 Nice, France
dLaboratory of Solid Tumor Genetics, Faculty of Medicine, CNRS UMR, 6543 Nice, France
eDepartment of Otorhinolaryngology, Louis Pasteur Hospital, 06002 Nice, France
Received 28 September 2008; received in revised form 28 December 2008; accepted 2 February 2009
Salivary gland oncocytic lipoadenoma is an exceptional benign tumor composed of mature adipose tissue
associated with a mixture of oncocytes. We report a case of oncocytic lipoadenoma showing sebaceous
differentiation, and provide a cytogenetic analysis, which has not yet been described. A 64-year-old male developed
a left parotid gland, well-encapsulated tumor measuring 3.5?3cm2, showing mature fat cells associated
with oncocytic changes of epithelial components. Immunohistochemistry showed a dual epithelial population
with ductal (positivity for AE1/AE3, CK19, CK7 antibodies) and basal-cell (positivity for p63, CK14, CK5,6
antibodies) differentiation in oncocytic areas. Moreover, oncocytic cells were stained with anti-alpha-1 antic-
hymotrypsin antibody and phosphotungstic acid–hematoxylin staining. Molecular cytogenetic analysis showed a
translocation t(12;14), resulting in structural rearrangement of the region framing the HMGA2 gene at 12q14.3.
Such alterations in HMGA2 have been described in both lipomas and pleomorphic adenomas of the salivary
r 2009 Elsevier GmbH. All rights reserved.
Keywords: Oncocytic lipoadenoma; Parotid gland; Immunohistochemistry; Cytogenetic
Oncocytic lipoadenoma of the salivary glands is an
exceptional benign tumor arising in parotid and
submandibular glands [1,9,13,14]. This tumor is well
encapsulated and composed of large areas of mature
adipose tissue and areas of oncocytic cells [1,9,13,14].
These tumors belong to the group of salivary gland
tumors with both adipose and epithelial tissues, includ-
ing sialolipoma and lipoadenoma tumors [10,18,20,22].
The first case of oncocytic lipoadenoma of the salivary
gland was described by Hirokawa et al.  in 1998. Since
then, three supplementary cases have been published
[1,13,14]. The purpose of the present study is to report a
new case of oncocytic lipoadenoma of the parotid gland
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0344-0338/$-see front matter r 2009 Elsevier GmbH. All rights reserved.
?Corresponding author at: Laboratory of Clinical and Experimental
Pathology, 30 Avenue de la voie romaine, Ho ˆpital Louis Pasteur,
06002 Nice, France. Tel.: +33492038855; fax: +33492038750.
E-mail address: email@example.com (P. Hofman).
with immunohistochemical study. Moreover, we provide
the first cytogenetic analysis of such tumor.
A previously healthy 64-year-old male was seen in the
Department of ORL (Pasteur Hospital, Nice, France)
for evaluation of a painless swelling in the left
preauricular area of 2-year duration. The CT scan
revealed a deep lobe and an ill-defined lesion of low
density with a heterogeneous aspect that led to the
diagnosis of pleomorphic adenoma. A partial paroti-
dectomy was performed with preservation of the facial
nerve. The patient was followed up for 2 years without
any sign of recurrence.
The surgical specimen measured 5?4.5?3cm3and
weighed 15g. The tumor had a fatty consistency,
measured 3.5cm in its largest diameter, and was
completely encapsulated. Examination of crossing sec-
tions showed a yellowish tumor with small micronodules
of light gray tan measuring 0.2–0.4cm. A diagnosis of a
benign adipose tumor with oncocytic areas was made on
the basis of frozen sections. The surgical specimen was
fixed in formalin, embedded in paraffin, and deparaffi-
nized sections were stained with hematoxylin, eosin, and
saffron (HES) and phosphotungstic acid–hematoxylin
(PTAH). Immunohistochemical staining was performed
using an automated Ventana BenchMarks instrument
(Tucson, AZ, USA). A standard avidin–biotin–perox-
idase complex staining technique was performed using
the indicated primary antibodies (Table 1). Normal
salivary gland tissue adjacent to the tumor was used as a
control. After surgical excision, a fresh fragment from
the tumor was prepared for cytogenetic and fluorescence
in situ hybridization (FISH) analyses. Mechanical and
collagenase dissociation of the tumor sample was
performed according to Limon et al. . Bacterial
artificial chromosome (BAC) clones RP11-30I11 and
RP11-118B13 located proximal to the 50and distal
to the 30region of the HMGA2 gene (http://genome.
ucsc.edu) were used as a two-color break-apart probe to
detect rearrangements in the HMGA2 region, as
described previously . The BAC clones from the
Roswell Park Cancer Institute Library (Buffalo, NY)
were obtained from the Children’s Hospital Oakland
Research Institute (http://www.bacpac.chori.org). They
were hybridized to metaphase cells according to
Microscopic examination showed a well-circum-
scribed proliferation, consisting primarily of mature
adipose tissues (70% of the tumor area) surrounded by a
thin fibrous capsule with incomplete septae extending
into the tumor mass. Islands or less delimited zones
consisting of oncocytes were found in the lesion
(Figs. 1A and B). These cells exhibited abundant
eosinophilic fine granular cytoplasm and a single small
rounded nucleus, and were arranged in microglandular
or solid patterns or were isolated, and admixed with
adipocytes (Fig. 1C). A few oncocytic populations were
composed of small, densely eosinophilic cells with
pyknotic nuclei (Fig. 1D). Mature sebaceous glands
were present in some rare areas, admixed with oncocytic
cells, and more rarely with mature adipocytes (Figs. 1E
and F). Oncocytic cells and adipocytes showed no
mitotic figures and atypia, and invasion through the
fibrous capsulewas not
ductal structures were present in the adipose tissue and
in oncocyticnodules, surrounded
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Table 1. Primary antibodies used in this study and immunohistochemical profiling of the oncocytic component.
Antibodies ManufacturersClonesDilutionIntensityLabeled cell types
OV-TL 12/30 monoclonal
+ to +++
+ to +++
BC and MEC
BC, MEC, and LC
BC and LC
BC and MEC
BC and MEC
BC and LC
LC: luminal cells; BC: basal cells; MEC: myoepithelial cells. SMA: smooth muscle actin.
M. Ilie et al. / Pathology – Research and Practice 206 (2010) 66–7267
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Fig. 1. (A) Oncocytic nodule and mature adipose tissue (HES?100). (B). Oncocytic cells. (HES?200). (C) Oncocytes arranged in
a solid and microglandular (arrow) pattern (HES?400). (D) Dark cells (arrows) (HES?400). (E, F) Metaplastic sebaceous gland
(E: HES?200 and F: HES?400, inset?800). (G) Lymphocytic infiltration around the ducts (HES?200). (H) PTAH staining
(?200, inset ?800).
M. Ilie et al. / Pathology – Research and Practice 206 (2010) 66–7268
The surrounding normal salivary gland showed atrophy
of epithelial cells and chronic inflammatory cell infiltra-
tion, as well as some scattered adipocytes without
associated oncocytic cells. Histochemically, PTAH
staining revealed diffuse cytoplasmic granularity in
oncocytic cells (Fig. 1H)
Immunohistochemistry showed that oncocytic areas
were strongly and diffusely positive for AEI/AE3, CK7,
and alpha-1-antichymotrypsin, whereas CK19, CK14,
CK5,6, and p63-positive cells were present mainly at the
periphery of neoplastic acini (Figs. 2A–D). Immunos-
taining with an anti-EMA antibody stained the luminal
surface of the oncocytes (Fig. 2E), and differentiated
sebaceous cells were positive for CK14 and EMA.
Scattered myoepithelial cells stained with anti-a-smooth
muscle actin and S100 protein antibodies in residual
acini, but not in tumor areas (Fig. 2F). Data concerning
the immunostaining are summarized in Table 1.
Cytogenetic analysis showed a translocation involving
the long arms of chromosomes 12 and 14 (Fig. 3A). The
breakpoints were located at 12q14 and 14q24, respec-
tively. FISH analysis confirmed and assigned more
precisely the breakpoint at 12q14.3, and showed that it
was located in the region of the HMGA2 gene framed
by the RP11-30I11 and RP11-118B13 BAC probes
(Fig. 3B). The karyotype was 46, XY, t(12;14)
Benign soft-tissue tumors represent 2–5% of all sali-
vary glands neoplasms [3,5]. Oncocytic lipoadenomas of
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Fig. 2. Immunohistochemistry with anti-cytokeratin 7 (A), anti-alpha-1-antichymotrypsin (B), p63 (C), cytokeratin 5/6 (D), EMA
(E), and a-smooth muscle actin antibodies (F) (A–F, immunoperoxidase, ?200).
M. Ilie et al. / Pathology – Research and Practice 206 (2010) 66–7269
salivary glands are benign, exceptional tumors recently
described in the literature, but currently not included in
the WHO classification of the salivary gland tumors .
To our knowledge, four cases of oncocytic lipoadeno-
mas have previously been published in the literature
[1,9,13,14]. In those cases, the tumors were located in
major salivary glands (parotid gland: 3 cases; subman-
dibular gland: 1 case) of an adult man (1 case) or women
(3 cases), respectively [1,9,13,14]. As in the present case,
those tumors were always encapsulated, associating
mature adipose tumor tissue and micronodules or
islands of oncocytic areas with ‘‘light’’ and ‘‘dark’’
oncocytes without atypia and mitotic features. Residual
normal acini and ducts can be present in the mesench-
ymal and epithelial tumor components. Polycystic
changes in the tumor can be observed, with associated
non-specific inflammatory cell infiltrates. As for the
case described by Klieb and Perez-Ordon ˜ez , we
noted sebaceous metaplasia of a couple of oncocytes
and adipocytes. Interestingly, sebaceous metaplasia
can be noted in different lesions of the salivary glands,
such as pleomorphic adenoma, oncocytoma, Warthin’s
tumor, sialolipoma, and in the non-tumor salivary
gland parenchyma [14,5]. The oncocytic origin of the
cells described in the oncocytic lipoadenoma of the
salivary glands is easily confirmed by strong staining
of these cells with PTAH stain or with antibodies
against mitochondria and by electron microscopy
In the present case, immunohistochemical examina-
tion showed that oncocytic cells had both the phenotype
of typical normal ductal cells (positivity of staining with
AEI/AE3, CK19, and CK7) and of normal basal cells
(positivity of the staining with p63, CK14, and CK5/6).
As previously described, oncocytic cells showed positiv-
ity for staining with a1-antichymotrypsin and with
PTAH [14,19]. A few cells were stained with anti-smooth
muscle actin antibodies, confirming that a few myoe-
pithelial cells were present. These results confirmed a
previous case report showing a double subpopulation of
oncocytic cells in oncocytic lipoadenoma of the parotid
gland . For some authors, these latter tumors had
basal–myoepithelial differentiation [14,6,4]. Some onco-
cytic cells demonstrated the ultrastructural character-
istics of normal striated duct cells . Finally,
various oncocytic lesions of the salivary glands, includ-
ing benign oncocytoma, oncocytic carcinoma, and other
lesions, can be detected using an anti-mitochondria
As an exceptional tumor, oncocytic lipoadenoma of
salivary glands can have differential diagnoses, mainly
other tumors with a large adipose tissue component.
Sialolipomas are very rare tumors, which represent
0.5% of salivary tumors, and were recently described to
be distinct from lipomas . Lipoadenomas are very
rare tumors arising in salivary glands [10,22]. Glandular
structures are numerous, showing features of striated
ducts, without associated myoepithelial cells. No acini
are identified after immunohistochemical examination
. Oncocytic metaplasia can be observed focally.
Associated sclerotic and polycystic changes can be
described due to a chronic evolution . This entity is
under discussion. Some authors regard these tumors as
adenolipoma as described for the breast, thyroid, or skin
[20,4], whereas others consider them as different tumors
. It seems that lipoadenoma is rather a neoplastic
glandular tumor than a hamartoma . Pleomorphic
adenoma can show a large adipose tissue component
corresponding to a lipomatous pleomorphic adenoma or
a pleomorphic adenoma with extensive adipose meta-
plasia . A myoepithelial component, as well as
chondroid or myxoid stroma, must be demonstrated .
Finally, salivary gland oncocytoma can be easily
eliminated by the presence of associated adipose cells
in oncocytic lipoadenoma [5,2].
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Fig. 3. Cytogenetic and fluorescence in situ hybridization
(FISH) analysis: (A) partial RHG-banded karyotype showing
the translocation t(12;14)(q14.3;q24). The arrows indicate
der(12) and der(14), resulting from the t(12;14) translocation,
respectively. (B) Rearrangement of HMGA2 identified by
FISH analysis: the closely juxtaposed red–green signals
corresponding to the 50and 30regions of HMGA2 are located
at 12q14.3 on the normal chromosome 12, while the 50region
of HMGA2 (green signal; BAC probe RP11-30I11) stays on
der(12) at 12q14.3, and the 30region of HMGA2 (red signal;
BAC probe RP11-118B13) is translocated onto der(14) at
M. Ilie et al. / Pathology – Research and Practice 206 (2010) 66–72 70
We provide here the first cytogenetic analysis of an
oncocytic lipoadenoma. We observed a reciprocal
translocation involving chromosomes 12 and 14. The
breakpoint at 12q14.3 was located within or very close
to the HMGA2 gene, as demonstrated by FISH analysis.
The potential biological implication of HMGA2 altera-
tion in the pathogenesis of this tumor could be linked to
a fusion of HMGA2 with a gene located on the long arm
of chromosome 14, and this fusion gene onset might
play a direct role in cell proliferation in this case. It was
not possible to establish with certitude which of the
tumor cell components – adipose, oncocytic, and/or
basal cells – were the origin of the karyotypic anomaly,
since a whole fresh specimen of the tumor was prepared
for cell culture. However, cultured cells showed fibro-
blastic features, suggesting at least that the adipose
component contained the t(12;14) translocation. Re-
arrangements of HMGA2 are frequent in lipomas and
other benign tumors, such as uterine leiomyomas and
salivary gland pleomorphic adenomas . The alteration
most often consists of a fusion of the first three exons of
HMGA2 with the 30part of another gene. The fusion
partner genes of HMGA2 are highly variable, the most
frequent being LPP (for lipoma-preferred partner) at
3q28. Strikingly, lipomas and pleomorphic adenomas of
the salivary glands share some cytogenetic and mole-
cular similarities . While a majority of pleomorphic
adenomas of the salivary gland are characterized by a
rearrangement in the PLAG1 gene at 8q11, approxi-
mately 8% of these tumors show a rearrangement in
HMGA2 . The most frequent aberration is fusion of
HMGA2 with the NFIB gene at 9p22. This fusion
HMGA2-NFIB has also been described in lipomas .
Of note, HMGA2 structural rearrangements have also
been described in benign mesenchymal tumors, e.g.
uterine leiomyomas and hamartomas. However, it is
currently not known whether particular chromosomal
patterns are specifically associated with oncocytic type
tumors and, if so, whether they relate to a malignant
potential of these tumors .
Grant from the Association pour la Recherche sur le
Cancer (ARC 4008 to FP) and the Projet libre
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