YIJOM-1525; No of Pages 3

Int. J. Oral Maxillofac. Surg. 2009; xxx: xxx–xxx

doi:10.1016/j.ijom.2009.01.015, available online at http://www.sciencedirect.com

Case Report
Head and Neck Oncology

Metastatic hepatocellular A. R. Vitale1, D. Compilato2,

G. Coletti3, G. Calvisi1,
V. Ciuffitelli1, D. Barbera1,
A. Craxı̀4, G. Campisi2, P. Leocata1
carcinoma of the parotid region 1
Department of Experimental Medicine,
University of L’Aquila, L’Aquila, Italy;
2
Department of Oral Sciences, University of

without lung metastasis: a case Palermo, Palermo, Italy; 3Department of

Pathology, San Salvatore Hospital, L’Aquila,
Italy; 4Gastroenterology and Hepatology Unit,

report University of Palermo, Palermo, Italy

A. R. Vitale, D. Compilato, G. Coletti, G. Calvisi, V. Ciuffitelli, D. Barbera, A. Craxı̀,

G. Campisi, P. Leocata: Metastatic hepatocellular carcinoma of the parotid region
without lung metastasis: a case report. Int. J. Oral Maxillofac. Surg. 2009; xxx: xxx–
xxx. # 2009 International Association of Oral and Maxillofacial Surgeons. Published
by Elsevier Ltd. All rights reserved.

Abstract. Parotid gland metastatic tumours are rare, usually arising from a primary
mucosal or cutaneous cancer located in the ipsilateral head and neck region,
although metastases from a primary cancer outside the head and neck region are
possible. Hepatocellular carcinoma (HCC) rarely metastasizes to the head and neck
region and the parotid glands are an even more unusual site. The authors describe
the case of an 82-year-old male who presented with a right parotid mass.
Percutaneous incisional biopsy with histological and immunohistochemical studies
suggested metastatic HCC. Radiological investigations excluded other metastatic
lesions. This case illustrates the difficulties that may be encountered when seeking a Keywords: hepatocellular carcinoma; metas-
definitive diagnosis of parotid gland masses and underlines the need for tases; parotid gland.
collaboration between clinicians and pathologists when diagnosing a parotid
enlargement. Accepted for publication 29 January 2009

Metastatic involvement of the parotid
glands is uncommon, comprising 8% of
all parotid gland malignancies6. These
metastases usually arise from a primary
mucosal or cutaneous cancer, generally
melanomas and squamous cell carcino-
mas7, located in the ipsilateral head and
neck region3. Metastases arising from a
primary cancer outside the head and neck
region are also possible. Hepatocellular
carcinoma (HCC), the most frequent pri-
mary hepatic tumour, metastasizes in more
than 50% of cases, however, parotid gland
metastatic HCCs are uncommon, with only
two cases reported in the literature4,9. The
authors report a patient in whom the finding
of a right parotid mass led to the discovery
of HCC, without lung involvement.
Case report
A 82-year-old Caucasian male, with no
reported history of liver diseases, was
admitted to the San Salvatore Hospital
(L’Aquila, Italy) for a firm mass, painless
on palpation, located in the right parotid
gland. It was the size of a nut and was
covered by ulcerated skin with frequent
and abundant bleeding. Ultrasound exam-
ination revealed a 3.8  3.4  1.5 cm
mass with heterogeneous and hypo-
echogenous structure involving the right
parotid gland. A parotid fine-needle
aspiration biopsy (FNAB) to a cytomor-
phologic examination was performed.
Cellular specimens showed a cluster of

0901-5027/000001+03 $36.00/0 # 2009 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Please cite this article in press as: A.R.. Vitale, et al., Metastatic hepatocellular carcinoma of the parotid region without lung metastasis:
a case report, Int J Oral Maxillofac Surg (2009),
YIJOM-1525; No of Pages 3
2 Vitale et al.
Fig. 1. High magnification: cluster of epithelioid cells with granular cytoplasm (Papanicolau
staining).
atypical polyhedral epithelioid cells with
round nuclei, prominent single nucleoli
and abundant granular eosinophilic cyto-
plasm (Fig. 1). Morphologically these
cells resembled oncocytes and a primary
oncocytic tumour of the parotid was con-
sidered. For a definitive diagnosis an inci-
sional percutaneous biopsy of the parotid
lesion was performed and histopathologi-
cal examination confirmed malignancy.
Microscopically the lesion was made up
of solid sheets, trabeculae and pseudoduc-
tal structures of proliferating pleomorphic
polyhedral cells with eosinophilic cyto-
plasm and prominent nucleoli and hyper-
chromatic nuclei (Fig. 2). Occasional
acidophil bodies (Mallory hyalin) and
cytoplasmic bile pigments were observed.
Many trabecular structures were sur-
rounded by endothelial cells, highlighted
by staining for CD34, organized in a net-
work of sinusoidal vessels. Some of the
sinusoids were lined with neoplastic cells.
These histomorphological features and the
Fig. 2. Low magnification: polygonal cells with a trabecular pattern and a network of sinusoidal
vessels (E&E staining).
Please cite this article in press as: A.R.. Vitale, et al., Metastatic hepatocellular carcinoma of the parotid region without lung metastasis:
a case report, Int J Oral Maxillofac Surg (2009),
presence of cytoplasmic bile pigment,
suggested a metastic HCC. Immunohisto-
chemical studies demonstrated tumour
cell reactivity to antibodies directed
against CD10, cytokeratins 8 and 18, cyto-
plasmic a-fetoprotein and carcinoembryo-
nic antigen, but focally positive for K1-67
antigens. Immunohistochemical staining
for HepPar 1 (hepatocyte paraffin anti-
body 1) was positive only on the tumour
cells. These features confirmed the histo-
pathological suspicion of metastatic HCC.
Before this diagnosis was reached, chest
radiography and computed tomography
(CT) were performed which did not reveal
lung metastases; a total CT scan excluded
further localizations. No active treatment
for HCC was carried out and the patient
died 6 months after the diagnosis.
Discussion
HCC is the fifth most common cancer
and the third leading cause of cancer-
related deaths worldwide, with approxi-
mately 0.5–1 million new cases per
year1. Metastases of HCC, although
not clinically evident at presentation,
occur in more than 50% of patients over
a long-term follow up. They generally
affect the abdominal lymph nodes,
lungs, bone and adrenal glands5, but
rarely the head and neck region, includ-
ing the oral cavity and parotid glands.
HCC metastases to the oral cavity have
been reported in 71 cases8, but those to
the parotid gland in only 2 cases4,9. The
present case is the third case of meta-
static HCC to the parotid gland. Estab-
lishing a diagnosis of metastatic HCC in
the maxillofacial area may be difficult,
particularly when the primary tumour, as
in this case, has not been identified by
clinicians. All three cases of parotid
metastasis from HCC were initially
investigated by FNAB. Despite its accu-
racy, specificity and sensitivity, discre-
pancies between the cytomorphological
and histopathological examinations can
occur. In the other two cases of meta-
static HCC to the parotid gland, the
diagnosis was initially suggested by
FNAB and confirmed by incisional
biopsy4,9. In the present case, although
atypical cells were discovered, FNAB
did not show specific cytological fea-
tures that allowed a diagnosis of meta-
static HCC and a percutaneous incisional
biopsy with histological and immunohis-
tochemical examination was necessary
for a more accurate diagnosis.
HCC, primary or metastatic, often
presents cytological and histopathologi-
cal features sufficiently characteristic to
suggest its diagnosis, as in the present
case. The tumour was typically com-
posed of atypical polyhedral epithelioid
cells with round nuclei, prominent single
nucleoli, and abundant granular eosino-
philic cytoplasm arranged in trabeculae,
solid nets or pseudoductal structures
with the occasional presence of bile in
the ducts. The trabecular structures were
often surrounded by endothelial cells,
revealed by staining for CD34.
A number of other metastatic tumours,
notably from the breast, kidney and
adrenal glands, may mimic the trabecu-
lar, liver-like pattern of HCC. Im-
munohistochemical analysis, including
markers such as cytoplasmic a-fetopro-
tein (positive in approximately 30% of
metastatic HCC), ‘hepatic’ cytokeratins
8 and 18, carcinoembryonic antigen,
epithelial membrane antigen, CD10,
CD15, K1-67 and the recently developed
monoclonal antibody HepPar 1, are often
required to aid in distinguishing meta-
YIJOM-1525; No of Pages 3
static HCC from other parotid metastatic
tumours.
The current case, like that reported by
Romanas et al.9 was exceptional, because
of the parotid site and the absence of
lung parenchymal involvement. Typically,
metastases from the liver to the maxillofa-
cial area reach the lungs first, via the hepatic
artery and the portal vein10, and later reach
the maxillofacial area. To explain the par-
otid localization without lung involvement,
it has been suggested that HCC could dis-
seminated into Batson’s plexus (a connec-
tion between the azygos and hemiazygos
veins and the vertebral venuous plexus)
bypassing filtration through the lungs2.
The solitary parotid metastasis in this case
may confirm this hypothesis.
A final note of caution should be sent to
clinicians caring for patients with HCC.
All extrahepatic masses in a cirrhotic
patient, even without a diagnosis of
HCC, should be investigated, taking into
account the possibility of HCC metastatic
spread and giving the pathologist the
appropriate background information.
Please cite this article in press as: A.R.. Vitale, et al., Metastatic hepatocellular carcinoma of the parotid region without lung metastasis:
a case report, Int J Oral Maxillofac Surg (2009),
Metastatic hepatocellular carcinoma
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Address: Domenico Compilato
Tel: +39 091 6552221
Fax: +39 091 6552236
E-mail: compilato@odonto.unipa.it