- Email: [email protected]
Initial presentation of hepatocellular carcinoma as a mandibular mass
Initial presentation of hepatocellular carcinoma as a mandibular mass Case report and review of the literature Andrew Chin, DDS, a Tina S. Liang, DMD, b and Alan J. Borislow, DDS, c Philadelphia, Pa ALBERT EINSTEIN MEDICAL CENTER Hepatocellular carcinoma metastatic to the oral cavity is a rare phenomenon. From 1957 to date, 51 cases have been documented in the English literature. In this report we describe a case of metastatic hepatocellular carcinoma manifesting itself as unilateral mandibular paresthesia before the discovery of the primary tumor. In addition, we review the literature related to metastatic hepatocellular carcinoma and the pathways of metastasis. (Oral Surg Oral Med Oral Pathol Oral
Radiol Endod 1998;86:457-60)
It is well known that hepatocellular carcinoma is the most common primary hepatic tumor. However, in no more than 1% of cases is there oral involvement, t,2 Only 1% to 4% of oral malignancies are metastatic carcinomas from a distant primary s i t e - i n decreasing order, from the breast, lung, kidney, thyroid, and prostate. Hepatocellular carcinoma with extrahepatic metastasis has been reported in approximately 50% of cases, with the lung, diaphragm, or skeleton usually involved) Bone metastasis has been reported b y Yoshimora et al 4 in 10.1% of patients, with the vertebrae being most frequently affected, followed by (in decreasing order) the ribs, sternum, and pelvis. W h e n metastatic tumor involves the oral cavity, the most frequent site is the posterior angle of the mandible.5, 6 Frequency of metastasis to the angle of the mandible is thought to be due to the abundance of hematopoietic tissue, which may enable tumor emboli to implant and proliferate. 6 Review of all reported metastatic carcinomas to the oral cavity since 19573,4, 8-53 has shown that most patients are male (male-female ratio, 46:4), that 90% of patients are more than 50 years of age (range, 15 to 88 years), and that most cases involve the mandible (40 mandible only, 8 maxilla only, 1 mandible and maxilla, 1 tonsil). The intraoral mass was discovered before the p r i m a r y tumor in 73% of cases.3,4, 8-53 Patients with metastasis to the oral cavity are often s y m p t o m a t i c with swelling, paresthesia, or excessive tissue growth. The following study reviews the case of a patient who appeared for evaluation and treatment at the Dental aClaiefGeneral Practice Resident, The Maxwell S. Fogel Department of Dental Medicine. bDirector, General Practice Residency Program, The Maxwell S. Fogel Department of Dental Medicine. CChairman, The Maxwell S. Fogel Department of Dental Medicine. Received for publication Dec. 29, 1997; returned for revision Mar. 10, 1998; accepted for publication May 21, 1998. Copyright © 1998 by Mosby, Inc. 1079-2104/98/$5.00 + 0 7/14/92093
Center of Albert Einstein Medical Center with a previously undiagnosed oral lesion.
CASE REPORT The Albert Einstein Dental Center evaluated a 70-year-old man before possible partial liver resection or full liver transplant because of hepatocellular carcinoma. Approximately 3 months previously, the patient had complained to his dentist of sudden paresthesia of the right mandible to the midline of the lower lip. At that time, the patient did not have any clinical signs of intraoral or extraoral swelling or gingival enlargement. Soon after, the patient was found to have an enlarged liver. Needle biopsy of the liver revealed hepatocellular carcinoma. The patient continued to have paresthesia of the mandible, but he was not evaluated at that time. When he came to our dental center with right mandibular swelling and paresthesia, it was deemed likely that the hepatocellular carcinoma had metastasized to the mandible and other skeletal areas. The patient was an occasional social drinker and had a history of smoking (1 pack of cigarettes per day for 26 years); he had stopped smoking in 1963. Two sisters and his mother had died from carcinomas of unknown type. The patient manifested general malaise and a systolic ejection murmur of III/VI. At the date of admission the patient showed signs of anemia (hemoglobin, 10.3 g/dL [normal range, 13-17 g/dL]; hemocrit, 31.5% [normal range, 39% to 50%]). Several liver enzymes were abnormal (aspartate aminotransferase, 61 IU/L [normal range, 8-54 IU/L]; gamma-glutamyl transferase, 142 IU/L [normal range, 8-78 IU/L]; alkaline phosphatase, 141 IU/L [normal range, 34-124 IU/L]), and several liver function tests were abnormal as well (albumin, 3.0 g/dL [normal range, 3.5-5.2 g/dL]; prothrombin time, 13.3 seconds [normal range, 11.3-13.1 seconds]). The patient had a firm, nontender, asymptomatic extraoral 3.5-cm lesion in the area of the right parotid gland and angle of the mandible. The patient had no clinical evidence of lymph node involvement. Intraorally the parotid duct was patent, with good salivary flow and no evidence of purulence or drainage. Distal to the right second molar, a 0.5 x 0,7-cm firm, ulcerated soft tissue nodule was seen (Fig 1). There was no evidence of cortical expansion. 457
458 Chin, Liang, andBorislow
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY
October 1998
Fig 1. Intraoral clinical presentation of lesion involving right mandibular molar region.
Fig 3. Axial computed tomography image of maxilla shows right coronoid and left maxilla lesions in area of canine.
Fig 2.Panoramic radiograph taken at initial consult visit shows radiolucent lesion distal to last molar on right side and ranging superiorly up ascending ramus.
On radiographic examination, a 3.0 x 2.5-cm lytic lesion was seen to be present at the fight angle of the mandible. The lesion extended from the roots of the second molar to the ascending ramus and inferiorly involved the inferior alveolar canal (Fig 2). An abdominal computed tomography series showed a large right-lobe liver mass, 12.0 x 12.0 x 12.0 cm, with a central area of necrosis, and several satellite lesions of the left lobe, the largest being 1.5 cm in diameter. Computed tomography of the head and neck revealed involvement of the right coronoid process, the fight medial pterygoid muscle, and the left maxilla (Fig 3). Bone scan assessment showed probable bony metastasis to the proximal one third of the right femur, right tibia, and skull. An incisional biopsy of the gingival mass was obtained, and the histopathologic features were consistent with metastatic hepatocellular carcinoma with extensive necrosis (Fig 4). lmmunohistochemical studies showed that the lesion cells did not express c~-fetoprotein.
DISCUSSION Review of the literature has shown that in certain endemic areas of Africa and Southeast Asia, chronic hepatitis B virus (HBV) carriers have an increased inci-
Fig 4. Histopathologic section of right mandibular lesion shows nests of well-differentiated trabecular variant of hepatocellular carcinoma (hemotoxylin-eosin, original magnification x200).
dence of hepatocellular carcinoma. 32 Most carriers of H B V are a s y m p t o m a t i c , but viral D N A eventually becomes incorporated into the host genome of infected hepatocytes, which leads to m a l i g n a n t transformation. 54 In the subtropical region, ingestion of food contaminated with fungal aflatoxins is also believed to contribute to h e p a t o c e l l u l a r carcinoma. In the low prevalence area, North America and Europe, the underlying cause seems to be alcoholic, postnecrotic, and hemochromatic cirrhosis.l 6,39,54 There are b e l i e v e d to be 2 main routes o f t u m o r metastasis from the liver to the oral cavity by means of
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY
Chin, Liang, andBorislow 459
l/olume 86, Number 4 b l o o d b o r n e p a t h w a y s . 6,42 W i t h the portal h e m a t o g e nous route, the m a j o r vessels of the liver, hepatic artery, and portal veins are invaded; this leads to w i d e s p r e a d m e t a s t a s i s , f r e q u e n t l y to the lungs. A n o t h e r route, d e s c r i b e d by Batson, 55 consists o f a p a t h w a y of rich anastomoses of paravertebral veins that lack valves and m a y be c a p a b l e o f b y p a s s i n g o t h e r v e n o u s systems, such as the pulmonary, caval, and portal. W i t h c u r r e n t d i a g n o s t i c t e c h n o l o g y , w e are m o r e c a p a b l e o f d e t e c t i n g m a l i g n a n t le.sions. H o w e v e r , at t i m e s , the a b e r r a n t m a l i g n a n t l e s i o n m a y not be detectable until clinical signs such as swelling, paresthesia, m o b i l e teeth, and tissue necrosis are evident. M o s t patients w i t h metastatic hepatocellular c a r c i n o m a have had hepatic c a r c i n o m a for s o m e t i m e b e f o r e clinical detection. 3,4,39,56 Often, w h e n hepatic t u m o r cells infiltrate the g r e a t v e s s e l s , p a t i e n t s w i l l m a n i f e s t ascites or e v e n h y p o g l y c e m i a b e c a u s e o f d e c r e a s e d liver function. 57 Patients m a y h a v e liver-related b l o o d dyscrasias or aberrant liver lab values, such as elevated alkaline phosphatase levels. 58,59 D i a g n o s t i c laboratory studies p e r f o r m e d on our p a t i e n t r e v e a l e d a n e m i a , a b n o r m a l liver function, and elevated liver e n z y m e levels. T h e patien t did not h a v e any o f the underlying risk factors noted earlier; however, this is not u n c o m m o n . 57 S e r o l o g i c tests for hepatitis are often negative, and the h i g h l y diagnostic o~-fetoprotein values are often within n o r m a l limits, as in the case of our patient. 57 S y s t e m i c signs and/or a b n o r m a l laboratory values are not detected in m a n y patients until a metastatic lesion is diagnosed.56, 57 As noted, metastatic oral tumors are detected b e f o r e d i s c o v e r y of the primary hepatic lesions in 7 3 % o f r e p o r t e d cases.3,4, 8-53 T h e r e f o r e , the i m p o r tance o f b i o p s y and consideration o f the oral cavity as a site for metastatic disease f r o m r e m o t e sites must be e m p h a s i z e d . In a d d i t i o n , our p a t i e n t c o m p l a i n e d o f paresthesia 3 months b e f o r e there was any clinical evid e n c e of s w e l l i n g in the oral region. A p a n o r a m i c radiograph m i g h t have b e e n helpful w h e n the initial c o m plaint o f paresthesia was reported. U n f o r t u n a t e l y , w h e n oral m e t a s t a s i s has o c c u r r e d , prognosis is very poor. K a n a z a w a and Sato 33 reported a m e a n survival rate o f 21 w e e k s (range, 2 w e e k s to 2 years) after diagnosis o f metastatic disease to the oral region. Surgical e x c i s i o n m a y be p e r f o r m e d for functional or c o s m e t i c purposes; however, b e c a u s e of the w i d e s p r e a d nature of the tumor, often only palliative treatment is performed.
REFERENCES 1. Bertelli AP, Costa FA, Miziara JFA. Metastatic tumors of the mandible. Oral Surg Oral Med Oral Pathol 1970;30:21-8. 2. Bhaskar SN. Oral manifestation of metastatic tumors. Postgrad Med 1971;49:155-8.
3. Morishita M, Fukuda J. Hepatocellular carcinoma metastatic to the maxillary incisal gingiva. J Oral Maxillofac Surg 1984; 42:812-5. 4. Yoshimura Y, Matsuda S, Naitoh SI. Hepatocellular carcinoma metastatic to the mandibular ramus and condyle. J Oral Maxillofac Surg 1997;55:297-306. 5. Buchner A, Ramon Y. Distant metastases to the jaws. J Oral Surg 1967;25:246-50. 6. van der Kwast WAM, van der Waal I. Jaw metastases. Oral Surg Oral Med Oral Pathol 1974;37:850-7. 7. Meyer I, Shklar G. Malignant tumors metastatic to mouth and jaws. Oral Surg Oral Med Oral Pathol 1965;20:350-62. 8. Dick A, Mead SG, Mensh M, et al. Primary hepatoma with metastasis to the mandible. Am J Surg 1957;94:846-50. 9. Cern~a R Creepy CL, Chom~ J, et al. Metastase mandibulaire d'un epithelioma pfimitif du foie. Rev Stomatol 1963;64:589-93. 10. Lapeyrolerie FM, Manhold JH Jr. Hepatoma metastatic to the gingiva. Oral Surg Oral Med Oral Pathol 1964;18:365-7. 11. Franchebois R Laux M, Souyris E Metatase mandibulaire d'un hepatoma malin. Rev Stomatol 1965;66:155-7. 12. Radden BG, Reade PC. Gingival metastasis from a hepatoma. Oral Surg Oral Med Oral Pathol 1966;21:621-5. 13. Lund BA, Soule EH, Moertel CG. Hepatocellular carcinoma with me(astasis to the gingival mucosa: report of case. J Oral Surg 1970; 28:604-7. 14. McDaniel RK, Luna MA, Stimson PG. Metastatic tumors in the jaws. Oral Surg Oral Meal Oral Pathol 1971;31:380-6. 15. Appenzeller J, Weitzner S, Long GW. Hepatocellular carcinoma metastatic to the mandible: report of case and review of literature. J Oral Surg 1971;29:668-71. 16. Yacabucci JE, Mainous EG, Kramer HS. Hepatocellular carcinoma, diagnosed following metastasis to the mandible: report of a case. Oral Surg Oral Med Oral Pathol 1972;33;188-93. 17. Lepesteur J, Dinhhy T, Valllant JM, et al. Metastasis mandibulares des hepatomes. A propos d'un nouveau cas et revue de la litterature. Rev Stomatol 1073;74:533-42. 18. Sasaki T, Ohosaki T. A case of metastatic hepatocellular carcinoma metastasized to the mandibular bone [abstract]. Bulletin of Stomatology of Kyoto University 1973; 13:25. 19. Sarrazin A, Nousquet O, Vaillant JM, et al. Metatase mandibulaire r~velant un hepatome. Ann Med Interne (Paris) 1974;125:61-4. 20. Muldon CJ. A hepatocarcinoma with osseous metastases. J Laryngol Otol 1974;88:891-2. 21. Yoshida Y, Tsududa T, Yoshinari M, et al. Two cases of metastatic tumors to the mouth. Japanese Journal of Oral Surgery 1976; 22:534-9. 22. Cadenat H, Fabert G, Combelles R, et al. Metastase mandibulalre r~v~latrice d'un cancer primitif du foie. Rev Stomatol Chir Maxillofac 1976;991-8. 23. Kuga Y, Kitamura A, Kusaba I, et al. Primary liver cancer with metastasis to gingiva: report of a case. Oral Surg Oral Med Oral Pathol 1976;22:541-5. 24. Goveia G, Bahn S. Asymptomatic hepatocellular carcinoma metastatic to the mandible: report of a case. Oral Surg Oral Med Oral Pathol 1978;45:424-30. 25. Wedgwood D, Rusen D, Balk S. Gingival metastases from primary hepatocellular carcinoma. Oral Surg Oral Med Oral Pathol 1979;47:263-6. 26. Kinoshita F, Yoshida Y, Ogata K, et al. A case of hepatocellular carcinoma with mandibular metastasis [abstract]. Japanese Journal of Oral Surgery 1980;26:1706. 27. Vigneul JC, Nouel O, Klap P, et al. Metastatic hepatocellular carcinoma of the manbilble. J Oral Maxillofac Surg 1982;40:745-9. 28. Ando F, Uchida E, Koga T, et al. Metastatic hepatocellular carcinoma of the mandible: report of a case [abstract]. Japanese Journal of Clinical and Experimental Medicine 1985; 62:3936. 29. Horie Y, Suou T, Hirayama C, et al. Hepatocellular carcinoma metastatic to the oral cavity including the maxilla and the mandible: report of two cases and review of the literature. Gastroenterologia Japonica (Tokyo) 1985;20;604-10.
460
Chin, Liang, andBorislow
ORAL SURGERY ORAL MEDICINE ORAL P A T H O L O G Y
October 1998 30. Fujiwara K, Tanaka T, Koga M, et al. A case of metastatic hepatocellular carcinoma to the oral region [abstract]. Japanese Journal of Stomatological Society 1986;35:359. 31. Katoh E, Miyagawa A, Nagai I, et al. A case of hepatocellular carcinoma metastasized to the mandible [abstract]. Japanese Journal of Oral and Maxillofacial Surgery 1988;34:2688. 32. Mucitelli DR, Zuna RE, Archard HO. Hepatocellualr carcinoma presenting as an oral cavity lesion. Oral Surg Oral Med Oral Pathol 1988;66:701-5. 33, Kanazawa H, Sato K. Gingival Metastasis from primary hepatocellular carcinoma: report of a case and review of literature. J Oral Maxillofac Surg 1989;47:987-90. 34. Kinoshita K, Kitagami K, Sakaguchi Y, et al. A case of hepatocellular carcinoma metastatic to the oral cavity [abstract]. Journal of the Japanese Society for Internal Medicine 1989; 78:102. 35. Kizukuri H, Oka T, Andoh H, et al. Metastatic hepatocellular carcinoma of the mandibular head: report of a case [abstract]. Japanese Journal of Oral and Maxillofacial Surgery 1989; 35:2781. 36. Nakamura Y, Torii Y, Hayashi T, et al. A case of mandibular metastasis from primary hepatocellular carcinoma. Japanese Journal of Clinical Radiology 1989;34:937-40. 37. Ichihara H, Okuda T, Toida M, et al. Maxillary metastasis of the hepatocellualr carcinoma: report of a case and review of the literature [abstract]. Japanese Journal of Oral and Maxillofacial Surgery 1990;36:1381. 38. Kitagawa Y, Hashimoto K, Akashi K, et al. Two cases of hepatocellular carcinoma metastatic to the oral and maxillofacial region [abstract]. Japanese Journal of Oral and Maxillofacial Surgery 1990;36:1381. 39. Marker R Clausen PR Metastases to the mouth and jaws from hepatocellular carcinomas: a case report. Int J Oral Maxillofac Surg 1991;20:371-4. 40. Sakai T, Oka Y, Kurokawa S, et al. Acase of hepatocellular carcinoma diagnosed by mandibular metastasis [abstract]. Japanese Journal of Gastroenterology 1991 ;88:962. 41. Doval DC, Kannan V, Kumaraswamy SV, et al. Mandibular metastasis in hepatocellular carcinoma. Int J Oral Maxillofac Surg 1992;21:97-8. 42. Lalikos JF, Sotereanos GC, Nawrocki JS, et al. Isolated mandibular metastasis of hepatocellular carcinoma. J Oral Maxillofac Surg 1992;50:754-9. 43. Kawahara K, Iida S, Ogi N, et al. A case of mandibular metastasis from primary hepatocellular carcinoma [abstract]. Japanese Journal of Oral and Maxillofacial Surgery 1992;38:673. 44. Tsurn S, Yamasaki K, Nomura T, et al. Two cases of metastatic carcinoma to the oral cavity [abstract]. Journal of the Japanese Society of Oral Tumors 1992;4:14t. 45. Yanagisawa T, Takahashi Y, Kishimoto H, et al. A case of metastasized tumor of the mandible from hepatocellular carcinoma
46.
47.
48.
49.
50.
51.
52.
53.
54.
55. 54.
56. 57. 58.
[abstract]. Japanese Journal of Oral and Maxillofacial Surgery 1992;38:311. Barrera-Franco JL, Flores-Flores G, Mosqueda-Taylor A. Mandibular metastasis as the first manifestation of hepatocellular carcinoma: report of a case and review of the literature. J Oral Maxillofac Surg 1993;51:318-21. Michizoe Ai Tanaka K, Ishikawa T, et al. A metastatic hepatocellular carcinoma of the mandible [abstract]. Journal of the Hiroshima University Dental Society 1993;25:410. Unoki S, Uchida M, Abe T, et al. A case of mandibular metastais from primary hepatocellular carcinoma [abstract]. Japanese Journal of Clinical Radiology 1993;38:1571. Funaoka K, Nakamura E, Inoue N, et al. A case of metastatic hepatocellular carcinoma of the mandible [abstract]. Japanese Journal of Oral and Maxillofacial Surgery 1994;40:792. Takagi S, Tone D, Lee U, et al. A case of hepatocellular carcinoma to the mandible [abstract]. Journal of the Japanese Society of Oral Tumors 1994;6:194. Nomura J, Inui M, Seki Y, et al. Metastatic hepatocellular carcinoma of the mandible: report of a case and a review of the Japanese literature [abstract]. Asian Journal of Oral and Maxillofacial Surgery 1994;6:59. Takinami S, Yahata H, Kanoshima A, et al. Hepatocellular carcinoma metastatic to the mandible. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1995;79:649-54. Llanes E Ortega JS, Suarez B, Esponera JS, et al. Hepatocellular carcinomas diagnosed following metastasis to the oral cavity: report of 2 cases. J Periodontol 1996;67:717-9. Simon JB. Hepatic and Biliary Disorders. In: Berdow R, Fletcher A, editors. The Merck manual. Rahway: Merck Research Laboratories; 1992. p. 864-930. Batson OV. The function of the vertebral veins and their role in the spread of metastases. Ann Surg 1940;112:138-49. Carroll O, Krolls SO, Mosca NG. Metastatic carcinoma to the mandible: report of two cases. Oral Surg Oral Med Oral Pathol 1993;76:368-74. Ihde DC, Sherlock R Winawer S J, Fortner JG. Clinical manifestations of hepatoma. Am J Med 1974;56:83-91. Shio H, Ueki T. A case of hepatocellular carcinoma found by metastasis to the femur. Jpn J Cancer Clin 1984;30:834-8. Talerman A, Magyar E. Hepatocellular carcinoma presenting with pathologic fracture due to bone metastases. Cancer 1973; 32:1477-81.
Reprint requests: Alan J. Borislow, DDS The Maxwell S. Fogel Department of Dental Medicine Albert Einstein Medical Center Paley Building, 2nd Floor 5501 Old York Road Philadelphia, PA 19141
Radiol Endod 1998;86:457-60)
It is well known that hepatocellular carcinoma is the most common primary hepatic tumor. However, in no more than 1% of cases is there oral involvement, t,2 Only 1% to 4% of oral malignancies are metastatic carcinomas from a distant primary s i t e - i n decreasing order, from the breast, lung, kidney, thyroid, and prostate. Hepatocellular carcinoma with extrahepatic metastasis has been reported in approximately 50% of cases, with the lung, diaphragm, or skeleton usually involved) Bone metastasis has been reported b y Yoshimora et al 4 in 10.1% of patients, with the vertebrae being most frequently affected, followed by (in decreasing order) the ribs, sternum, and pelvis. W h e n metastatic tumor involves the oral cavity, the most frequent site is the posterior angle of the mandible.5, 6 Frequency of metastasis to the angle of the mandible is thought to be due to the abundance of hematopoietic tissue, which may enable tumor emboli to implant and proliferate. 6 Review of all reported metastatic carcinomas to the oral cavity since 19573,4, 8-53 has shown that most patients are male (male-female ratio, 46:4), that 90% of patients are more than 50 years of age (range, 15 to 88 years), and that most cases involve the mandible (40 mandible only, 8 maxilla only, 1 mandible and maxilla, 1 tonsil). The intraoral mass was discovered before the p r i m a r y tumor in 73% of cases.3,4, 8-53 Patients with metastasis to the oral cavity are often s y m p t o m a t i c with swelling, paresthesia, or excessive tissue growth. The following study reviews the case of a patient who appeared for evaluation and treatment at the Dental aClaiefGeneral Practice Resident, The Maxwell S. Fogel Department of Dental Medicine. bDirector, General Practice Residency Program, The Maxwell S. Fogel Department of Dental Medicine. CChairman, The Maxwell S. Fogel Department of Dental Medicine. Received for publication Dec. 29, 1997; returned for revision Mar. 10, 1998; accepted for publication May 21, 1998. Copyright © 1998 by Mosby, Inc. 1079-2104/98/$5.00 + 0 7/14/92093
Center of Albert Einstein Medical Center with a previously undiagnosed oral lesion.
CASE REPORT The Albert Einstein Dental Center evaluated a 70-year-old man before possible partial liver resection or full liver transplant because of hepatocellular carcinoma. Approximately 3 months previously, the patient had complained to his dentist of sudden paresthesia of the right mandible to the midline of the lower lip. At that time, the patient did not have any clinical signs of intraoral or extraoral swelling or gingival enlargement. Soon after, the patient was found to have an enlarged liver. Needle biopsy of the liver revealed hepatocellular carcinoma. The patient continued to have paresthesia of the mandible, but he was not evaluated at that time. When he came to our dental center with right mandibular swelling and paresthesia, it was deemed likely that the hepatocellular carcinoma had metastasized to the mandible and other skeletal areas. The patient was an occasional social drinker and had a history of smoking (1 pack of cigarettes per day for 26 years); he had stopped smoking in 1963. Two sisters and his mother had died from carcinomas of unknown type. The patient manifested general malaise and a systolic ejection murmur of III/VI. At the date of admission the patient showed signs of anemia (hemoglobin, 10.3 g/dL [normal range, 13-17 g/dL]; hemocrit, 31.5% [normal range, 39% to 50%]). Several liver enzymes were abnormal (aspartate aminotransferase, 61 IU/L [normal range, 8-54 IU/L]; gamma-glutamyl transferase, 142 IU/L [normal range, 8-78 IU/L]; alkaline phosphatase, 141 IU/L [normal range, 34-124 IU/L]), and several liver function tests were abnormal as well (albumin, 3.0 g/dL [normal range, 3.5-5.2 g/dL]; prothrombin time, 13.3 seconds [normal range, 11.3-13.1 seconds]). The patient had a firm, nontender, asymptomatic extraoral 3.5-cm lesion in the area of the right parotid gland and angle of the mandible. The patient had no clinical evidence of lymph node involvement. Intraorally the parotid duct was patent, with good salivary flow and no evidence of purulence or drainage. Distal to the right second molar, a 0.5 x 0,7-cm firm, ulcerated soft tissue nodule was seen (Fig 1). There was no evidence of cortical expansion. 457
458 Chin, Liang, andBorislow
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY
October 1998
Fig 1. Intraoral clinical presentation of lesion involving right mandibular molar region.
Fig 3. Axial computed tomography image of maxilla shows right coronoid and left maxilla lesions in area of canine.
Fig 2.Panoramic radiograph taken at initial consult visit shows radiolucent lesion distal to last molar on right side and ranging superiorly up ascending ramus.
On radiographic examination, a 3.0 x 2.5-cm lytic lesion was seen to be present at the fight angle of the mandible. The lesion extended from the roots of the second molar to the ascending ramus and inferiorly involved the inferior alveolar canal (Fig 2). An abdominal computed tomography series showed a large right-lobe liver mass, 12.0 x 12.0 x 12.0 cm, with a central area of necrosis, and several satellite lesions of the left lobe, the largest being 1.5 cm in diameter. Computed tomography of the head and neck revealed involvement of the right coronoid process, the fight medial pterygoid muscle, and the left maxilla (Fig 3). Bone scan assessment showed probable bony metastasis to the proximal one third of the right femur, right tibia, and skull. An incisional biopsy of the gingival mass was obtained, and the histopathologic features were consistent with metastatic hepatocellular carcinoma with extensive necrosis (Fig 4). lmmunohistochemical studies showed that the lesion cells did not express c~-fetoprotein.
DISCUSSION Review of the literature has shown that in certain endemic areas of Africa and Southeast Asia, chronic hepatitis B virus (HBV) carriers have an increased inci-
Fig 4. Histopathologic section of right mandibular lesion shows nests of well-differentiated trabecular variant of hepatocellular carcinoma (hemotoxylin-eosin, original magnification x200).
dence of hepatocellular carcinoma. 32 Most carriers of H B V are a s y m p t o m a t i c , but viral D N A eventually becomes incorporated into the host genome of infected hepatocytes, which leads to m a l i g n a n t transformation. 54 In the subtropical region, ingestion of food contaminated with fungal aflatoxins is also believed to contribute to h e p a t o c e l l u l a r carcinoma. In the low prevalence area, North America and Europe, the underlying cause seems to be alcoholic, postnecrotic, and hemochromatic cirrhosis.l 6,39,54 There are b e l i e v e d to be 2 main routes o f t u m o r metastasis from the liver to the oral cavity by means of
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY
Chin, Liang, andBorislow 459
l/olume 86, Number 4 b l o o d b o r n e p a t h w a y s . 6,42 W i t h the portal h e m a t o g e nous route, the m a j o r vessels of the liver, hepatic artery, and portal veins are invaded; this leads to w i d e s p r e a d m e t a s t a s i s , f r e q u e n t l y to the lungs. A n o t h e r route, d e s c r i b e d by Batson, 55 consists o f a p a t h w a y of rich anastomoses of paravertebral veins that lack valves and m a y be c a p a b l e o f b y p a s s i n g o t h e r v e n o u s systems, such as the pulmonary, caval, and portal. W i t h c u r r e n t d i a g n o s t i c t e c h n o l o g y , w e are m o r e c a p a b l e o f d e t e c t i n g m a l i g n a n t le.sions. H o w e v e r , at t i m e s , the a b e r r a n t m a l i g n a n t l e s i o n m a y not be detectable until clinical signs such as swelling, paresthesia, m o b i l e teeth, and tissue necrosis are evident. M o s t patients w i t h metastatic hepatocellular c a r c i n o m a have had hepatic c a r c i n o m a for s o m e t i m e b e f o r e clinical detection. 3,4,39,56 Often, w h e n hepatic t u m o r cells infiltrate the g r e a t v e s s e l s , p a t i e n t s w i l l m a n i f e s t ascites or e v e n h y p o g l y c e m i a b e c a u s e o f d e c r e a s e d liver function. 57 Patients m a y h a v e liver-related b l o o d dyscrasias or aberrant liver lab values, such as elevated alkaline phosphatase levels. 58,59 D i a g n o s t i c laboratory studies p e r f o r m e d on our p a t i e n t r e v e a l e d a n e m i a , a b n o r m a l liver function, and elevated liver e n z y m e levels. T h e patien t did not h a v e any o f the underlying risk factors noted earlier; however, this is not u n c o m m o n . 57 S e r o l o g i c tests for hepatitis are often negative, and the h i g h l y diagnostic o~-fetoprotein values are often within n o r m a l limits, as in the case of our patient. 57 S y s t e m i c signs and/or a b n o r m a l laboratory values are not detected in m a n y patients until a metastatic lesion is diagnosed.56, 57 As noted, metastatic oral tumors are detected b e f o r e d i s c o v e r y of the primary hepatic lesions in 7 3 % o f r e p o r t e d cases.3,4, 8-53 T h e r e f o r e , the i m p o r tance o f b i o p s y and consideration o f the oral cavity as a site for metastatic disease f r o m r e m o t e sites must be e m p h a s i z e d . In a d d i t i o n , our p a t i e n t c o m p l a i n e d o f paresthesia 3 months b e f o r e there was any clinical evid e n c e of s w e l l i n g in the oral region. A p a n o r a m i c radiograph m i g h t have b e e n helpful w h e n the initial c o m plaint o f paresthesia was reported. U n f o r t u n a t e l y , w h e n oral m e t a s t a s i s has o c c u r r e d , prognosis is very poor. K a n a z a w a and Sato 33 reported a m e a n survival rate o f 21 w e e k s (range, 2 w e e k s to 2 years) after diagnosis o f metastatic disease to the oral region. Surgical e x c i s i o n m a y be p e r f o r m e d for functional or c o s m e t i c purposes; however, b e c a u s e of the w i d e s p r e a d nature of the tumor, often only palliative treatment is performed.
REFERENCES 1. Bertelli AP, Costa FA, Miziara JFA. Metastatic tumors of the mandible. Oral Surg Oral Med Oral Pathol 1970;30:21-8. 2. Bhaskar SN. Oral manifestation of metastatic tumors. Postgrad Med 1971;49:155-8.
3. Morishita M, Fukuda J. Hepatocellular carcinoma metastatic to the maxillary incisal gingiva. J Oral Maxillofac Surg 1984; 42:812-5. 4. Yoshimura Y, Matsuda S, Naitoh SI. Hepatocellular carcinoma metastatic to the mandibular ramus and condyle. J Oral Maxillofac Surg 1997;55:297-306. 5. Buchner A, Ramon Y. Distant metastases to the jaws. J Oral Surg 1967;25:246-50. 6. van der Kwast WAM, van der Waal I. Jaw metastases. Oral Surg Oral Med Oral Pathol 1974;37:850-7. 7. Meyer I, Shklar G. Malignant tumors metastatic to mouth and jaws. Oral Surg Oral Med Oral Pathol 1965;20:350-62. 8. Dick A, Mead SG, Mensh M, et al. Primary hepatoma with metastasis to the mandible. Am J Surg 1957;94:846-50. 9. Cern~a R Creepy CL, Chom~ J, et al. Metastase mandibulaire d'un epithelioma pfimitif du foie. Rev Stomatol 1963;64:589-93. 10. Lapeyrolerie FM, Manhold JH Jr. Hepatoma metastatic to the gingiva. Oral Surg Oral Med Oral Pathol 1964;18:365-7. 11. Franchebois R Laux M, Souyris E Metatase mandibulaire d'un hepatoma malin. Rev Stomatol 1965;66:155-7. 12. Radden BG, Reade PC. Gingival metastasis from a hepatoma. Oral Surg Oral Med Oral Pathol 1966;21:621-5. 13. Lund BA, Soule EH, Moertel CG. Hepatocellular carcinoma with me(astasis to the gingival mucosa: report of case. J Oral Surg 1970; 28:604-7. 14. McDaniel RK, Luna MA, Stimson PG. Metastatic tumors in the jaws. Oral Surg Oral Meal Oral Pathol 1971;31:380-6. 15. Appenzeller J, Weitzner S, Long GW. Hepatocellular carcinoma metastatic to the mandible: report of case and review of literature. J Oral Surg 1971;29:668-71. 16. Yacabucci JE, Mainous EG, Kramer HS. Hepatocellular carcinoma, diagnosed following metastasis to the mandible: report of a case. Oral Surg Oral Med Oral Pathol 1972;33;188-93. 17. Lepesteur J, Dinhhy T, Valllant JM, et al. Metastasis mandibulares des hepatomes. A propos d'un nouveau cas et revue de la litterature. Rev Stomatol 1073;74:533-42. 18. Sasaki T, Ohosaki T. A case of metastatic hepatocellular carcinoma metastasized to the mandibular bone [abstract]. Bulletin of Stomatology of Kyoto University 1973; 13:25. 19. Sarrazin A, Nousquet O, Vaillant JM, et al. Metatase mandibulaire r~velant un hepatome. Ann Med Interne (Paris) 1974;125:61-4. 20. Muldon CJ. A hepatocarcinoma with osseous metastases. J Laryngol Otol 1974;88:891-2. 21. Yoshida Y, Tsududa T, Yoshinari M, et al. Two cases of metastatic tumors to the mouth. Japanese Journal of Oral Surgery 1976; 22:534-9. 22. Cadenat H, Fabert G, Combelles R, et al. Metastase mandibulalre r~v~latrice d'un cancer primitif du foie. Rev Stomatol Chir Maxillofac 1976;991-8. 23. Kuga Y, Kitamura A, Kusaba I, et al. Primary liver cancer with metastasis to gingiva: report of a case. Oral Surg Oral Med Oral Pathol 1976;22:541-5. 24. Goveia G, Bahn S. Asymptomatic hepatocellular carcinoma metastatic to the mandible: report of a case. Oral Surg Oral Med Oral Pathol 1978;45:424-30. 25. Wedgwood D, Rusen D, Balk S. Gingival metastases from primary hepatocellular carcinoma. Oral Surg Oral Med Oral Pathol 1979;47:263-6. 26. Kinoshita F, Yoshida Y, Ogata K, et al. A case of hepatocellular carcinoma with mandibular metastasis [abstract]. Japanese Journal of Oral Surgery 1980;26:1706. 27. Vigneul JC, Nouel O, Klap P, et al. Metastatic hepatocellular carcinoma of the manbilble. J Oral Maxillofac Surg 1982;40:745-9. 28. Ando F, Uchida E, Koga T, et al. Metastatic hepatocellular carcinoma of the mandible: report of a case [abstract]. Japanese Journal of Clinical and Experimental Medicine 1985; 62:3936. 29. Horie Y, Suou T, Hirayama C, et al. Hepatocellular carcinoma metastatic to the oral cavity including the maxilla and the mandible: report of two cases and review of the literature. Gastroenterologia Japonica (Tokyo) 1985;20;604-10.
460
Chin, Liang, andBorislow
ORAL SURGERY ORAL MEDICINE ORAL P A T H O L O G Y
October 1998 30. Fujiwara K, Tanaka T, Koga M, et al. A case of metastatic hepatocellular carcinoma to the oral region [abstract]. Japanese Journal of Stomatological Society 1986;35:359. 31. Katoh E, Miyagawa A, Nagai I, et al. A case of hepatocellular carcinoma metastasized to the mandible [abstract]. Japanese Journal of Oral and Maxillofacial Surgery 1988;34:2688. 32. Mucitelli DR, Zuna RE, Archard HO. Hepatocellualr carcinoma presenting as an oral cavity lesion. Oral Surg Oral Med Oral Pathol 1988;66:701-5. 33, Kanazawa H, Sato K. Gingival Metastasis from primary hepatocellular carcinoma: report of a case and review of literature. J Oral Maxillofac Surg 1989;47:987-90. 34. Kinoshita K, Kitagami K, Sakaguchi Y, et al. A case of hepatocellular carcinoma metastatic to the oral cavity [abstract]. Journal of the Japanese Society for Internal Medicine 1989; 78:102. 35. Kizukuri H, Oka T, Andoh H, et al. Metastatic hepatocellular carcinoma of the mandibular head: report of a case [abstract]. Japanese Journal of Oral and Maxillofacial Surgery 1989; 35:2781. 36. Nakamura Y, Torii Y, Hayashi T, et al. A case of mandibular metastasis from primary hepatocellular carcinoma. Japanese Journal of Clinical Radiology 1989;34:937-40. 37. Ichihara H, Okuda T, Toida M, et al. Maxillary metastasis of the hepatocellualr carcinoma: report of a case and review of the literature [abstract]. Japanese Journal of Oral and Maxillofacial Surgery 1990;36:1381. 38. Kitagawa Y, Hashimoto K, Akashi K, et al. Two cases of hepatocellular carcinoma metastatic to the oral and maxillofacial region [abstract]. Japanese Journal of Oral and Maxillofacial Surgery 1990;36:1381. 39. Marker R Clausen PR Metastases to the mouth and jaws from hepatocellular carcinomas: a case report. Int J Oral Maxillofac Surg 1991;20:371-4. 40. Sakai T, Oka Y, Kurokawa S, et al. Acase of hepatocellular carcinoma diagnosed by mandibular metastasis [abstract]. Japanese Journal of Gastroenterology 1991 ;88:962. 41. Doval DC, Kannan V, Kumaraswamy SV, et al. Mandibular metastasis in hepatocellular carcinoma. Int J Oral Maxillofac Surg 1992;21:97-8. 42. Lalikos JF, Sotereanos GC, Nawrocki JS, et al. Isolated mandibular metastasis of hepatocellular carcinoma. J Oral Maxillofac Surg 1992;50:754-9. 43. Kawahara K, Iida S, Ogi N, et al. A case of mandibular metastasis from primary hepatocellular carcinoma [abstract]. Japanese Journal of Oral and Maxillofacial Surgery 1992;38:673. 44. Tsurn S, Yamasaki K, Nomura T, et al. Two cases of metastatic carcinoma to the oral cavity [abstract]. Journal of the Japanese Society of Oral Tumors 1992;4:14t. 45. Yanagisawa T, Takahashi Y, Kishimoto H, et al. A case of metastasized tumor of the mandible from hepatocellular carcinoma
46.
47.
48.
49.
50.
51.
52.
53.
54.
55. 54.
56. 57. 58.
[abstract]. Japanese Journal of Oral and Maxillofacial Surgery 1992;38:311. Barrera-Franco JL, Flores-Flores G, Mosqueda-Taylor A. Mandibular metastasis as the first manifestation of hepatocellular carcinoma: report of a case and review of the literature. J Oral Maxillofac Surg 1993;51:318-21. Michizoe Ai Tanaka K, Ishikawa T, et al. A metastatic hepatocellular carcinoma of the mandible [abstract]. Journal of the Hiroshima University Dental Society 1993;25:410. Unoki S, Uchida M, Abe T, et al. A case of mandibular metastais from primary hepatocellular carcinoma [abstract]. Japanese Journal of Clinical Radiology 1993;38:1571. Funaoka K, Nakamura E, Inoue N, et al. A case of metastatic hepatocellular carcinoma of the mandible [abstract]. Japanese Journal of Oral and Maxillofacial Surgery 1994;40:792. Takagi S, Tone D, Lee U, et al. A case of hepatocellular carcinoma to the mandible [abstract]. Journal of the Japanese Society of Oral Tumors 1994;6:194. Nomura J, Inui M, Seki Y, et al. Metastatic hepatocellular carcinoma of the mandible: report of a case and a review of the Japanese literature [abstract]. Asian Journal of Oral and Maxillofacial Surgery 1994;6:59. Takinami S, Yahata H, Kanoshima A, et al. Hepatocellular carcinoma metastatic to the mandible. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1995;79:649-54. Llanes E Ortega JS, Suarez B, Esponera JS, et al. Hepatocellular carcinomas diagnosed following metastasis to the oral cavity: report of 2 cases. J Periodontol 1996;67:717-9. Simon JB. Hepatic and Biliary Disorders. In: Berdow R, Fletcher A, editors. The Merck manual. Rahway: Merck Research Laboratories; 1992. p. 864-930. Batson OV. The function of the vertebral veins and their role in the spread of metastases. Ann Surg 1940;112:138-49. Carroll O, Krolls SO, Mosca NG. Metastatic carcinoma to the mandible: report of two cases. Oral Surg Oral Med Oral Pathol 1993;76:368-74. Ihde DC, Sherlock R Winawer S J, Fortner JG. Clinical manifestations of hepatoma. Am J Med 1974;56:83-91. Shio H, Ueki T. A case of hepatocellular carcinoma found by metastasis to the femur. Jpn J Cancer Clin 1984;30:834-8. Talerman A, Magyar E. Hepatocellular carcinoma presenting with pathologic fracture due to bone metastases. Cancer 1973; 32:1477-81.
Reprint requests: Alan J. Borislow, DDS The Maxwell S. Fogel Department of Dental Medicine Albert Einstein Medical Center Paley Building, 2nd Floor 5501 Old York Road Philadelphia, PA 19141