Oral metastases from hepatocellular carcinoma are very rare. We encountered a case of hepatocellular carcinoma with a solitary metastasis to the mandible as an initial manifestation. The patient was a 76-year-old man who was admitted for left mandibular swelling. A biopsy specimen of mandible was suspected to be a metastatic tumor. The histological findings, abdominal computed tomography, bone scintigraphy, and F-18 fluorodeoxyglucose-positron emission tomography (FDG-PET) revealed it to be a solitary metastasis from hepatocellular carcinoma. As a result, he was diagnosed to have liver cirrhosis due to a hepatitis C virus infection and hepatocellular carcinoma with a solitary metastasis to the mandible. The primary lesion was treated with transcatheter arterial embolization (TAE), and the metastasis to the mandible was surgically resected. The patient survived for 9 months after treatment without recurrence

Hashida, Tetsu

Hoshino, Keiko

Kakizaki, Satoru

Mogi, Kenji

Mori, Masatomo

Sato, Ken

Sohara, Naondo

Takagi, Hitoshi

Teshigawara, Katsunobu

Tomizawa, Yoshio

Okayama University Scientific Achievement Repository

Acta Medica OkayamaVolume 60, Issue 4 2006 Article 7AUGUST 2006Solitary mandibular metastasis as an initialmanifestation of hepatocellular carcinoma.Katsunobu Teshigawara, Gunma UniversitySatoru Kakizaki, Gunma UniversityNaondo Sohara, Gunma UniversityTetsu Hashida, Gunma University, GunmaYoshio Tomizawa, Gunma UniversityKen Sato, Gunma UniversityHitoshi Takagi, Gunma UniversityMasatomo Mori, Gunma UniversityKeiko Hoshino, Gunma UniversityKenji Mogi, Gunma UniversityCopyright c©1999 OKAYAMA UNIVERSITY MEDICAL SCHOOL. All rights reserved.Solitary mandibular metastasis as an initialmanifestation of hepatocellular carcinoma.∗Katsunobu Teshigawara, Satoru Kakizaki, Naondo Sohara, Tetsu Hashida,Yoshio Tomizawa, Ken Sato, Hitoshi Takagi, Masatomo Mori, Keiko Hoshino,and Kenji MogiAbstractOral metastases from hepatocellular carcinoma are very rare. We encountered a case of hep-atocellular carcinoma with a solitary metastasis to the mandible as an initial manifestation. Thepatient was a 76-year-old man who was admitted for left mandibular swelling. A biopsy specimenof mandible was suspected to be a metastatic tumor. The histological findings, abdominal com-puted tomography, bone scintigraphy, and F-18 fluorodeoxyglucose-positron emission tomogra-phy (FDG-PET) revealed it to be a solitary metastasis from hepatocellular carcinoma. As a result,he was diagnosed to have liver cirrhosis due to a hepatitis C virus infection and hepatocellularcarcinoma with a solitary metastasis to the mandible. The primary lesion was treated with tran-scatheter arterial embolization (TAE), and the metastasis to the mandible was surgically resected.The patient survived for 9 months after treatment without recurrence.KEYWORDS: hepatocellular carcinoma, mandibular metastasis, oral metastasis∗PMID: 16943863 [PubMed - indexed for MEDLINE]Copyright (C) OKAYAMA UNIVERSITY MEDICAL SCHOOLepatocellular carcinoma (HCC) most frequently metastasizes to the lung,  lymph nodes,  bone, and adrenal glands [1,  2].  Metastases of HCC to the oral cavity and jaws are uncommon,  with only 70 cases being reported in the literature [3ﾝ24] since its ﬁ rst description by Dick et al. [4] in 1957.  Only 1ﾝ3ｵ of oral malignancies are metastatic carcinomas from a distant primary [25].  We experienced a rare case of HCC with a solitary metastasis to the mandi-ble as a ﬁ rst manifestation.Case Report　　A 76-year-old man was admitted to the Department of Stomatology and Maxillofacial Surgery,  Gunma University Hospital,  because of left mandibular swelling and pain.  The patient reported that numbness of the left mandible had been present for approximately 10 months,  during which time the lesion had exhibited progressive growth.  Computed tomography (CT) revealed an osteolytic lesion in the left mandible (Fig.  1A).  An oral incisional biopsy was performed,  with a subsequent histopathologic examination revealing a malignant neoplasm that appeared to be a metastatic tumor (Fig.  2A).  A whole-body examination with F-18 ﬂ uorodeoxyglu-cose-positron emission tomography (FDG-PET) Solitary Mandibular Metastasis as an Initial Manifestation of Hepatocellular CarcinomaKatsunobu Teshigawaraa,  Satoru Kakizakia＊,  Naondo Soharaa,  Tetsu Hashidaa,  Yoshio Tomizawaa,  Ken Satoa,  Hitoshi Takagia,  Masatomo Moria,  Keiko Hoshinob,  and Kenji MogibDepartments of aMedicine and Molecular Science,  and bStomatology and Maxillofacial Surgery,  Gunma University Graduate School of Medicine,  Maebashi,  Gunma 371ﾝ8511,  JapanHOral metastases from hepatocellular carcinoma are very rare.  We encountered a case of hepatocel-lular carcinoma with a solitary metastasis to the mandible as an initial manifestation.  The patient was a 76-year-old man who was admitted for left mandibular swelling.  A biopsy specimen of mandi-ble was suspected to be a metastatic tumor.  The histological ﬁ ndings,  abdominal computed tomogra-phy,  bone scintigraphy,  and F-18 ﬂ uorodeoxyglucose-positron emission tomography (FDG-PET) revealed it to be a solitary metastasis from hepatocellular carcinoma.  As a result,  he was diagnosed to have liver cirrhosis due to a hepatitis C virus infection and hepatocellular carcinoma with a soli-tary metastasis to the mandible.  The primary lesion was treated with transcatheter arterial emboli-zation (TAE),  and the metastasis to the mandible was surgically resected.  The patient survived for 9 months after treatment without recurrence.Key words : hepatocellular carcinoma,  mandibular metastasis,  oral metastasisActa Med.  Okayama,  2006Vol.  60,  No.  4,  pp.  243ﾝ247http ://www.lib.okayama-u.ac.jp/www/acta/CopyrightⒸ 2006 by Okayama University Medical School.Case ReportReceived January 6, 2006 ; accepted March 14, 2006. ＊Corresponding author. Phone : ＋81ﾝ27ﾝ220ﾝ8127 ; Fax : ＋81ﾝ27ﾝ220ﾝ8136E-mail : kakizaki@showa.gunma-u.ac.jp (S. Kakizaki)1Teshigawara et al.: Solitary mandibular metastasis as an initial manifestation ofProduced by The Berkeley Electronic Press, 2006revealed a high uptake in the left mandible and the liver.  The standardized uptake values (SUV) of FDG were 4.77 and 3.42 in the left mandible and liver, respectively (Fig.  1B,  Fig.  3A).  Abdominal CT revealed 2 liver tumors located in the right anterior lobe,  measuring 3 and 5 cm in diameter,  respec-tively.  The laboratory examination ﬁ ndings were as follows : hemoglobin,  12.0 g/dl ; platelet,  15.7 × 104/mm3 ; prothrombin time,  89ｵ ; albumin,  3.9 g/dl ; total bilirubin,  0.7 mg/dl ; aspartate transami-nase,  37 IU/l ; alanine transaminase,  33 IU/l ; alka-line phosphatase,  298 IU/l ; γ-glutamyl transferase, 51 IU/l ; blood urea nitrogen,  19 mg/dl ; creatinine, 0.8 mg/dl ; amylase,  120 IU/l ; total cholesterol 162 mg/dl.  In addition,  the serum alpha-fetoprotein (AFP) ; 1096.4 ng/ml and protein induced by vitamin K antagonist (PIVKA)-II ; 3,078 AU/ml were ele-vated.  He was negative for hepatitis B surface anti-gen and positive for hepatitis C antibody.  A biopsy specimen from the liver tumor (Fig.  2B) revealed moderately diﬀ erentiated hepatocellular carcinoma identical to the biopsy specimen of mandibular tumor (Fig.  2A).  Bone scintigraphy and FDG-PET showed no obvious metastasis other than that found in the mandible.  CT angiography (Fig.  3B,  3 C,  3D) showed the typical ﬁ ndings of HCC.  He was thus diagnosed to have HCC with a solitary metastasis to the mandible.  He was also complicated with liver cir-rhosis due to a hepatitis C virus infection.  The liver function was classiﬁ ed as Child-Pugh grade A. Swelling of the mandible,  pain,  and bleeding from the tumor impeded the patient from eating.  Because the metastasis was solitary and he had relatively well-preserved liver function,  we selected radical treatment of mandibular metastasis instead of pallia-tion therapy with radiation.  After treatment,  the patient’s eating functions as well as his oral hygiene dramatically improved.  Although simultaneous resec-tion for liver tumors was also considered,  the patient’s age led us to select transcatheter arterial embolization (TAE) for the primary liver tumors. Although he received additional TAE for 6 months after the ﬁ rst treatment,  the local control of HCC was good and there was no distant metastasis at 9 months after the initial treatment.Discussion　　Oral metastases from HCC are very rare [3ﾝ24]. The most common metastatic sites from HCC are the lung,  lymph nodes,  bone,  and adrenal glands [1,  2]. HCC metastases to the oral cavity and jaws have been reported in only 62 cases,  according to a review by Pires et al. [3] in 2004.  We have identiﬁ ed an additional 8 cases.  As a result,  our case was the 71 st case of metastatic HCC to the oral cavity. Regarding oral tumors,  only 1ﾝ3ｵ of oral malignan-cies are metastatic carcinomas from a distant pri-mary site,  in decreasing order,  from the breast, adrenal gland,  colorectal system,  genital organs,  and the thyroid gland in women ; and from the lung,  pros-tate,  kidney,  bone,  and adrenal gland for men [25].　　The establishment of a diagnosis of metastatic HCC in the oral region may be diﬃ  cult,  particularly when the primary tumor has not yet been identiﬁ ed. Pires et al. [3] have reported noting a metastatic oral tumor before the primary hepatic lesion in 66ｵ of patients (41 of 62).  Because of a lack of symptoms other than mandibular swelling,  our case was ini-tially considered to be a primary mandibular tumor until the biopsy results were revealed.  We analyzed all 71 cases of metastatic HCC to the oral region, including our case,  reported until now.  The mean age of these 71 patients was 62.0 ± 12.0 years old ; the median age was 63 years old ; and the age ranged from 16 to 88 years old.  Males were predom-inant (male : female : unknown,  58 : 7 : 6,  respec-tively),  and the most common site of metastasis is the mandible,  especially the posterior mandible,  fol-lowed by the gingiva.  Metastasis to the maxilla is quite rare in comparison to the mandible.  In addi-tion,  the oral tumor was found before the primary HCC in 42 of 71 cases.  The oral tumor was found after the diagnosis of HCC in 23 cases (6 cases were unknown).　　The way that HCC can disseminate into intraosse-ous mandibular metastasis has been thoroughly dis-cussed in the literature [8].  Basically,  there are 2 pathways from the liver to the maxillofacial territory [8].  When the hepatic artery and the portal vein are aﬀ ected,  metastatic dissemination must reach the lung ﬁ rst,  and it may later reach the maxillofacial area [8].  According to such evidence,  most of the registered cases of HCC with mandibular metastasis 244 Acta Med.  Okayama　Vol.  60,  No.  4Teshigawara et al.2Acta Medica Okayama, Vol. 60 [2006], Iss. 4, Art. 7http://escholarship.lib.okayama-u.ac.jp/amo/vol60/iss4/7245Solitary Mandibular Metastasis from HCCAugust 2006A BFig. 1　　A,  Computed tomography (CT) ﬁ ndings of the left mandible revealed an osteolytic lesion with expanding growth ; B,  FDG-PET showed a strong accumulation in the left mandible.  The standardized uptake value (SUV) of FDG was 4.77.A BFig. 2　　A,  A biopsy specimen from the tumor of the mandible.  The proliferation of atypical cells with high N/C ratio and clear cytoplasm were observed ; B,  The biopsy specimen from liver tumor revealed moderately diﬀ erentiated hepatocellular carcinoma identical to that found in the mandibular tumor (Fig. 2A).A BC DFig. 3　　Abdominal CT and angiography revealed the liver tumors to be located in the right upper lobe,  which was thus compatible with HCC.  A,  FDG-PET showed a strong accumulation in the liver tumor.  The standardized uptake value (SUV) of FDG was 3.42.  B,  CT angioportgraphy ; C,  CT hepatic angiography,  early phase ; D,  digital subtraction angiography.3Teshigawara et al.: Solitary mandibular metastasis as an initial manifestation ofProduced by The Berkeley Electronic Press, 2006tend to be accompanied by lung metastasis [6,  9]. However,  no lung metastases were identiﬁ ed in our case.  To explain this mandibular aﬀ ectation,  it has been postulated that there is a connection between the azygos or hemiazygos veins and the vertebral venous plexus (Batson’s plexus) [10,  26].  The soli-tary mandibular metastasis in our case may further conﬁ rm this hypothesis.　　The high vascularity of the metastatic lesion with HCC,  accompanied by concurrent coagulopathy caused by primary liver disease and often associated with this group of patients,  can lead to hemorrhagic episodes,  particularly in bone lesions [6,  11,  12]. Hemorrhagic events arising in the oral and maxillofa-cial region can usually be managed with hemostatic agents,  compression,  and wide sutures [6,  11ﾝ13]. However,  the hemorrhaging may occasionally be severe,  thus requiring the use of complex procedures such as external carotid ligation [11,  13]. Fortunately,  the parameters of coagulation were within normal limits in the case presented here-in ; more speciﬁ cally,  the patient was able to undergo surgical resection.  When such a case is not suitable for surgery,  then local radiation therapy with higher fractioned doses appears to be useful for achieving partial control of tumor growth and hemorrhaging [11,  12].　　Although the prognosis of patients with HCC has recently improved,  the prognosis of those with advanced stage HCC including distant metastases remains unsatisfactory [27].  The prognosis of patients with oral metastatic HCC is very poor,  with only palliative treatment frequently indicated to improve the local function [11].  Most patients die within 2 years after a diagnosis of oral metastasis [3].  In our case,  a metastatic tumor was completely resected by surgery and the primary lesions were well-controlled with TAE.  However,  we have contin-ually checked for the appearance of new metastases. Fortunately,  the clinical course of our patient was relatively good.  However,  the indications of radical treatment should be carefully considered because the prognosis of HCC depends on not only the tumor stage of HCC but also on the preserved liver func-tion.  A radical resection of metastasis will improve the quality of life only for patients with suﬃ  ciently preserved liver function.  Although a simultaneous resection for liver tumors was considered,  the patient’s age led us to select transcatheter arterial embolization (TAE) for the primary liver tumors.  A ﬂ exible treatment strategy based on the eﬀ ect and degree of invasiveness must be carefully taken into account when treating elderly patients.　　In conclusion,  oral metastatic HCC should be included in the diﬀ erential diagnosis of rapidly grow-ing oral tumors,  particularly in patients with a his-tory of chronic liver disease.  Even though most such cases tend to be clinically advanced,  an improved quality of life can be obtained by a radical resection of the metastatic oral lesion.References 1. Katyal S,  Oliver JH 3 rd,  Peterson MS,  Ferris JV,  Carr BS and Baron RL : Extrahepatic metastases of hepatocellular carcinoma. Radiology (2000) 216 : 698ﾝ703. 2. Kaczynski J,  Hansson G and Wallerstedt S : Metastases in cases with hepatocellular carcinoma in relation to clinicopathologic fea-tures of the tumor.  An autopsy study from a low endemic area. Acta Oncol (1995) 34 : 43ﾝ48. 3. Pires FR,  Sagarra R,  Correa ME,  Pereira CM,  Vargas PA and Lopes MA : Oral metastasis of a hepatocellular carcinoma.  Oral Surg Oral Med Oral Pathol Oral Radiol Endod (2004) 97 : 359ﾝ368. 4. Dick A,  Mead SG,  Mensh M and Schatten WE : Primary hepa-toma with metastasis to the mandible.  Am J Surg (1957) 94 : 846ﾝ850. 5. 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Solitary mandibular metastasis as an initial manifestation of hepatocellular carcinoma.

Solitary mandibular metastasis as an initial manifestation of hepatocellular carcinoma.

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