ISSN: 2754-8880
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Edited by
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Submitted 14 Feb. 2023
Accepted 16 Feb. 2023
Citation
S Ezuan, F Fahmy, and A
Azlanudin.Metastatic
Hepatocellular Carcinoma
To Oral Soft Tissue; A Case
Report.:BJOSS::2025:(4);104-
107
Metastatic Hepatocellular Carcinoma To Oral
Soft Tissue; A Case Report
S Ezuan
1*
, F Fahmy
1
, and A Azlanudin
1
1
Department of Surgery, Hospital Canselor Tuanku Muhriz, University Kebangasan Malaysia
Medical Centre, Kuala Lumpur, Malaysia
*
Corresponding author: E-mail: alequenaezai@gmail.com
Tel: +603-91455555, Fax: +603-91456640
Orcid ID: https://orcid.org/0000-0002-8793-9146
O R IGI N A L
Introduction
Hepatocellular carcinoma comprises approximately 90% of primary cancers of the liver. Unfor-
tunately, it carries a grave prognosis (
1
). There was been a well-known association between
chronic liver diseases and Hepatitis infection which are Hepatitis C and Hepatitis B. In addition,
alcohol sue, aflatoxin B1, autoimmune hepatitis, steatohepatitis, and primary biliary and sclerosing
cholangitis are known to be important etiological agents (
2
). Extrahepatic metastasis occurs in
about 30-50% of patients (
2
;
3
). They are commonly affecting the lungs, abdominal lymph nodes,
diaphragm, and skeleton (
4
). However, metastasis of hepatocellular carcinoma to the oral cavity
is uncommon, based on the fact that tumours of the oromaxillofacial region are mainly primary in
origin whereby metastatic cases account for only 1% (
5
). In regards to the incidence of metastatic
hepatocellular carcinoma to the head and neck, it frequently involves the mandible, with gingiva
being the second. These metastatic deposits are believed to follow hematogenous spread by the
primary tumour (5).
Case Report
A 71-year-old man presented with a two-month history of progressively increasing the size of his
oral cavity mass and occasionally bled upon oral feeding. Almost concurrently, he experienced
abdominal distension, worsening jaundice, and significant constitutional symptoms. He was a
smoker but not taking any alcohol or chewable recreational materials.
Generally, he was cachexic and deeply jaundiced. Oral cavity assessment demonstrated a right
posterior lower alveolar mass which measures 3 x 4 cm exophytic, irregular, and ulcerated
lesion, which is associated with palpable right cervical lymphadenopathy. Abdominal examination
revealed painless hepatomegaly with bilateral lower leg pitting oedema.
Contrasted CT staging showed a large heterogenous right liver necrotic mass largest measuring
11.8 x 11.6 x 12.3 cm with a scattered liver lesion in bilateral lobes. There was also an associated
tumour rupture on the right liver with a large arterioportal shunt is suggestive of hepatocellular
carcinoma. In addition, a large right mandibular mass measuring 5.3 x 5.7 x 6 cm with intra and
extra-oral extension with local infiltration and right cervical lymphadenopaties were also apparent.
The advanced disease was further proven by the presence of extensive regional and distant nodes,
spine, lungs, and brain metastasis.
Histopathological examination of the right retromolar soft tissue was consistent with metastatic
hepatocellular carcinoma evidenced by the presence of malignant cells arranged in a polygonal
shape. Immunohistochemically, the malignant cells show diffuse positivity for Hep Par-1 and
Glypican-3 but are negative for alpha-fetoprotein.
Serum Alpha-fetoprotein was markedly raised with the positivity of the Hepatitis C profile. Hence,
the diagnosis of advanced hepatocellular carcinoma secondary to Hepatitis C infection with was
established.
In addition to the grave prognosis, he was unfit for chemotherapy and subjected to palliative care.
Intermittently he was admitted to our oncological suit for pain and bleeding from the oral mass
requiring mechanical compression, suture, and even haemostatic radiotherapy.
Figure 1. Large heterogenous enhancing mass in the right liver with hypodence necrotic
component. Capsular breach at segment VI was suggestive of tumour rupture.
Figure 2. Bleeding from the right mandibular metastatic tumour of hepatocellular carcinoma.
Discussion
Hepatocellular carcinoma (HCC) is most frequently found in men, with oral metastasis typically
presenting clinically as an ulcerated symptomatic mass. The frequent occurrence of oral metastasis
is at the mandible and gingiva, particularly at the posterior region, the angle, and the ramus,
105/107
attributed to the presence of haematopoietic tissues in this region (
4
). This is parallel with the
case that we reported here.
The possible pathophysiological mechanism of HCC to the oral cavity remains to be revealed.
Hematogenous route through a hepatic artery or portal vein is thought to be the preferred pathway
for oral metastasis (
6
). Due to the fact that more than half of cases of HCC are associated with
liver cirrhosis, it has been postulated that changes in haemodynamics in relation to esophageal
varices make it a potential pathway to the oral cavity (6).
During the histopathological examination, routine haematoxylin and eosin-stained section may
give a clue towards the hepatic origin. However, an immunohistochemical study is often needed
to verify the metastatic HCC from other variants of oral metastatic tumours. 30% metastatic
tissues may have positive alpha-fetoprotein (
4
) which did not happen in our case. On another
occasion, the Hep Par-1 monoclocal antibody has known reactivity to benign and malignant
cells of hepatocyte origin and also yields significant diagnostic value. The Hep Par-1 assay is
sensitive and specific for HCC by 90% whereas the remaining portion is attributed to metastatic
adenocarcinoma (
4
). The second parameter which is also exclusive for HCC is Glypican-3. It is a
variety of oncoproteins that are involved in the growth of most HCC. Immunoreactivity increases
with poorer tumour differentiation which supplements the staining pattern of Hep Par-1 (
1
). In
conjunction with the case report that we described here, his tissue immunohistochemical analysis
has proven the diffuse positivity towards Hep Par-1 and Glypican-3.
A literature review analysis carried out by Hou et al. (2019) has found that patients with an oral
mass as the first sign of HCC had a grave survival rate (
6
). This is because a majority of them
already had multiple extrahepatic metastasis at the time of detection, leading to the subsequent
poor surgical observation mainly due to the delayed diagnosis (
6
). Parallel with the case that we
report here, the initial CT staging at the time of presentation already demonstrated extensive
metastasis and subsequently poor outcome.
Conclusion
Oral metastatic hepatocellular carcinoma needs to be included in the differentials of rapidly
growing oral lesions. It is especially true in patients with underlying Hepatitis infection or patients
with stigmata of chronic liver disease. Comprehensive clinical, radiological, and histopathological
evaluation is crucial in determining the diagnosis. Yet, the survival rate and prognosis of this
condition are still in dismal.
Conflict Of Interest
All authors declare no conflict of interest of any kind.
References
[1]
Daley TD, Minett CP, Driman DK, Darling MR. Oral metastatic hepatocellular carcinoma: a
changing demographic in Europe and North America. Immunohistochemical advances in the
microscopic diagnosis. Oral Oncology. 2011;47(1):62-7.
[2]
Terada T, Maruo H. Unusual extrahepatic metastatic sites from hepatocellular carcinoma.
International journal of clinical and experimental pathology. 2013;6(5):816-20.
[3]
Alrumaih RA, Arian AA, Alhedyani AA, Al-Zaher N, Dababo MA. Hepatocellular carcinoma
first presenting as a tumor of the oral cavity. Hematology/Oncology and Stem Cell Therapy.
2015;8(3):130-5.
106/107
[4]
Pires FR, Sagarra R, Corrêa MEP, Pereira CM, Vargas PA, Lopes MA. Oral metastasis of a
hepatocellular carcinoma. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and
Endodontology. 2004;97(3):359-68.
[5]
Okada H, Kamino Y, Shimo M, Kitamura E, Katoh T, Nishimura H, et al. Metastatic hepato-
cellular carcinoma of the maxillary sinus: a rare autopsy case without lung metastasis and a
review. International journal of oral and maxillofacial surgery. 2003;32(1):97-100.
[6]
Hou Y, Deng W, Deng G, Hu L, Liu C, Xu L. Gingival metastasis from primary hepatocellular
carcinoma: a case report and literature review of 30 cases. BMC cancer. 2019;19(1):1-10.
107/107
