Mandibular metastasis in hepatocellular carcinoma
D. S. B. C.
C. Doval, V. Kannan, V. Kumaraswamy, K. M. Reddy, P. P. Bapsy, Rama Rao
Kidwai Memorial Institute of Oncology, Bangalore, India
D. C. Doval, V. Kannan, S. V. Kumaraswamy, B. K. M. Reddy, P P Bapsy, C. Rama Rao: Mandibular metastasis in hepatocellular carcinoma. Int. J. Oral Maxillofac. Surg. 1992. 21." 9~98. Abstract. Hepatocellular c a r c i n o m a ( H C C ) p r e s e n t i n g initially as a b o n y metastasis is rare. I n v o l v e m e n t o f maxillofacial b o n e s is even m o r e rare a n d only 20 cases h a v e b e e n reported. A case o f a 65-year-old male p a t i e n t presenting with m e t a s t a sis to the m a n d i b l e f r o m a p r i m a r y H C C is described.
M e t a s t a t i c spread of m a l i g n a n t t u r n o u t s to the oral cavity is u n c o m m o n , a n d a c c o u n t s for 1% of all oral m a l i g n a n cies 9. T h e c o m m o n e s t intra-oral site for metastasis is the m o l a r a n d p r e m o l a r region o f the m a n d i b l e s . H a e m a t o g e n o u s spread f r o m hepatocellular c a r c i n o m a ( H C C ) occurs frequently in the lungs 2. Osseous m e t a s t a sis is usually a s y m p t o m a t i c a n d is f o u n d in 1-20% o f cases at a u t o p s y 5. Involvem e n t o f maxillofacial b o n e s is rare a n d only 20 cases o f H C C m e t a s t a t i c to the oral cavity have been r e p o r t e d in the literature 7. A case of H C C is r e p o r t e d with s y m p t o m s p e r t a i n i n g to oral metastasis.
increasing swelling over the left mandible of 1½months' duration. Examination revealed a swelling in the left lower edentulous area, retromolar area and over the angle of the left mandible. The swelling measured 3 x 3 cm and was firm in consistency. The covering mucosa was stretched and shiny but not ulcerated. The skin over the cheek was normal and neck nodes were not palpable. Systemic examination revealed a febrile man with a pulse rate of 90, BP 160/90 mmHg, no icterus or pedal oedema. Abdominal palpation revealed a minimally enlarged liver. Laboratory tests revealed normal haemogram and biochemistry. Radiographs of the mandible showed a large osteolytic area in the angle of the left mandible with ill-defined borders. There was no surrounding sclerotic
Key words: hepatocellular carcinoma; metastasis. Accepted for publication 6 December 1991
reaction (Fig. 1). The chest X-ray was normal. Biopsy and histopathological examination of the mandibular swelling showed a turnout composed of cells arranged in broad trabeculae with intervening sinusoids. The individual tumour cells showed moderate to abundant eosinophilic cytoplasm with vesicular nuclei, prominent nucleoli and one to 2 mitosis/high-power field. Areas of necrosis and haemorrhage were present. The possibility of metastasis from a primary HCC was entertained (Fig. 2). Abdominal ultrasound examination revealed minimal hepatomegaly with a hyperechoic area of 3.5 cm in the right lobe of the liver. A radio-isotope scan of the liver confirmed the presence of a space-occupying lesion in the right lobe. A radio-isotope bone scan showed an increased uptake over the posterior aspect of the left mandible. The
Case report A 65-year-old man was seen at our hospital with complaints of a painful and gradually
Fig. 1. X-ray mandible showing the osteolytic lesion,
Fig. 2. a. Polygonal tumor cells arranged in a trabecular pattern, HE x 120. b. High power showing the vesicular nuclei and prominent nucleoli in the tumor cells, HE x 756.
98
Doval et al.
alpha feto protein level was 128 Iu/ml and serum Australia antigen was negative. Needle biopsy of the liver showed areas of necrosis and a few groups of cells showing both vesicular and hyperchromatic nuclei and a moderate amount of eosinophilic cytoplasm. An occasional multi-nucleated turnout giant cell was identified. These histological features were consistent with that of a moderately differentiated HCC. A final diagnosis of HCC metastic to the left mandible was made. The patient was started on systemic 5 Flurouracil (5 FU) therapy at a dose of 1000 rag/ iv weekly. Local radiotherapy to the mandible, 30 Gy in 10 fractions over 2 weeks was delivered. After 2 months, (total dose of 5 FU 8 g) the patient was reassessed. Partial regression was noted over the left mandible and ultrasound examination of the abdomen also revealed partial regression of the hepatic turnout. 5 F U was continued at 1000 mg/ iv but given once in 3 weeks. The patient remained in partial remission for 10 months after which the mandibular tumour started increasing in size. The hepatic turnout also increased in size. The total dose of 5 FU given at that time was 19 g. As the disease started progressing, definitive antineoplastic therapy was stopped, and due to the steady downhill course of the patient no new chemotherapeutic agents were tried. The patient finally succumbed 16 months after the initial diagnosis. Autopsy was not performed. Discussion The p a t i e n t described presented with s y m p t o m s o f m a n d i b u l a r metastasis of H C C . E x t r a h e p a t i c metastasis f r o m H C C c o m m o n l y occurs in regional l y m p h n o d e s a n d lungs b u t a u t o p s y rep o r t s d o c u m e n t u p to 20% o f osseous metastasis 6. The first case o f m a n d i b u l a r metastasis o f H C C was r e p o r t e d by DIcK et al. in 1957 I. Since then, 20 cases o f H C C m e t a s t a t i c to the oral region,
14 involving the m a n d i b l e , have been r e p o r t e d v. T h e literature regarding H C C metastasis to the oral cavity h a s been extensively reviewed 7' 9. T h e angle o f the m a n d i b l e is a c o m m o n site o f metastasis, p r o b a b l y due to its rich h a e m a t o poietic m a r r o w 13. These lesions are very h a e m o r r h a g i c a n d any surgical procedure - even biopsy - s h o u l d be a t t e m p t e d w i t h p r e c a u t i o n 7' 13. T h e histology of the osseous metastasis varied f r o m well-differentiated to anaplastic TM 13. I n o u r case the t u r n o u t was m o d e r ately differentiated. T h e prognosis in p a t i e n t s with H C C is poor, especially if surgery is n o t feasible. M e d i a n survival for patients with unresected t u m o u r s is usually reported to be 3 to 4 m o n t h s 12. C h e m o t h e r a p y is m a i n l y palliative, especially in a metastatic H C C . I n a study o f the n a t u r a l history o f H C C , the a d d i t i o n o f systemic c h e m o t h e r a p y showed a dismal survival rate 1°. T h e c o m m o n l y used c h e m o t h e r a p e u t i c agents for H C C are 5 F U a n d D o x o r u b i c i n 4 with response rates o f 15% a n d 23%, respectively 3,12. I n spite o f p o o r survival in metastatic m a n d i b u l a r H C C 13, the absence o f cirrhosis a n d the response to chemot h e r a p y m i g h t have c o n t r i b u t e d to the relative long survival o f 16 m o n t h s in the p a t i e n t described. References I. DICK A, MEAD SG, MENSH M, SCHATTEN WE. Primary hepatoma with metastasis to mandible. Am J Surg 1957: 94: 846-50. 2. EDMONDSON HA, STEINER PE. Primary carcinoma of the liver: A study of 100 cases among 48900 necropsies. Cancer 1954: 7: 462-503. 3. FALKSONG, MOERTEL CG, LAVIN P, PRE-
TORIUS F J, CARBONE PP. Chemotherapy studies in primary liver cancer: A prospective randomized clinical trial. Cancer 1978: 42: 2149-56. 4. KEMENYN, SCHNEIDERA. Regional treatment of hepatic metastatic and hepatocellular carcinoma. Curr P robl Cancer 1989: XIII: 256. 5. LEE YTM, GEERDA DA. Primary liver cancer: pattern of metastasis. J Surg Oncol 1987: 36:26 31. 6. LIAW CC, NG KT, CHEN TJ, LIAW YF. Hepatocellular carcinoma presenting as bone metastasis. Cancer 1989: 64:1753 7. 7. MARKER P, CLAUSEN PP. Metastasis to mouth and jaws from hepatocellular carcinoma. Ir~t J Oral Maxillofac Surg 1991: 20: 371-4. 8. MEYER I, SHKLAR G. Malignant tumors metastatic to mouth and jaws. Oral Surg 1965: 20: 350-62. 9. MUCITELLIDR, ZUNERE, ARCHARD HO, BROOK S. Hepatocellular carcinoma presenting as an oral cavity lesion. Oral Surg 1988: 66: 701-5. 10. NAGASUEN, YUKAYAH, HAMADAT, HIROSE S, KANASHIMAR, INOKUCHI K. The natural history of hepatocellular carcinoma: A study of 100 untreated cases. Cancer 1984: 54:1461 5. 11. OKAZAKI N, YOSHINO M, YOSHIDAT, HIROrIASHI S, KISHI K, SHIMOSATOY. Bone metastasis in hepatocellular carcinoma. Cancer 1985: 55: 19914. 12. OEERFIELD RA, STEEL G, GOLLAN JL, Sr~ERMAN D. Liver cancer CA 1989: 39: 206-18. 13. VIGNEULJC, NotmL G, KLAP P, AL HELALI M. Metastatic hepatocellular carcinoma of the mandible. J Oral Maxillofac Surg 1982: 40: 745-9. Address: Dr. D. C. Doval Kidwai Memorial Institute of Oncology Hosur Road Bangalore 560029 India
D. S. B. C.
C. Doval, V. Kannan, V. Kumaraswamy, K. M. Reddy, P. P. Bapsy, Rama Rao
Kidwai Memorial Institute of Oncology, Bangalore, India
D. C. Doval, V. Kannan, S. V. Kumaraswamy, B. K. M. Reddy, P P Bapsy, C. Rama Rao: Mandibular metastasis in hepatocellular carcinoma. Int. J. Oral Maxillofac. Surg. 1992. 21." 9~98. Abstract. Hepatocellular c a r c i n o m a ( H C C ) p r e s e n t i n g initially as a b o n y metastasis is rare. I n v o l v e m e n t o f maxillofacial b o n e s is even m o r e rare a n d only 20 cases h a v e b e e n reported. A case o f a 65-year-old male p a t i e n t presenting with m e t a s t a sis to the m a n d i b l e f r o m a p r i m a r y H C C is described.
M e t a s t a t i c spread of m a l i g n a n t t u r n o u t s to the oral cavity is u n c o m m o n , a n d a c c o u n t s for 1% of all oral m a l i g n a n cies 9. T h e c o m m o n e s t intra-oral site for metastasis is the m o l a r a n d p r e m o l a r region o f the m a n d i b l e s . H a e m a t o g e n o u s spread f r o m hepatocellular c a r c i n o m a ( H C C ) occurs frequently in the lungs 2. Osseous m e t a s t a sis is usually a s y m p t o m a t i c a n d is f o u n d in 1-20% o f cases at a u t o p s y 5. Involvem e n t o f maxillofacial b o n e s is rare a n d only 20 cases o f H C C m e t a s t a t i c to the oral cavity have been r e p o r t e d in the literature 7. A case of H C C is r e p o r t e d with s y m p t o m s p e r t a i n i n g to oral metastasis.
increasing swelling over the left mandible of 1½months' duration. Examination revealed a swelling in the left lower edentulous area, retromolar area and over the angle of the left mandible. The swelling measured 3 x 3 cm and was firm in consistency. The covering mucosa was stretched and shiny but not ulcerated. The skin over the cheek was normal and neck nodes were not palpable. Systemic examination revealed a febrile man with a pulse rate of 90, BP 160/90 mmHg, no icterus or pedal oedema. Abdominal palpation revealed a minimally enlarged liver. Laboratory tests revealed normal haemogram and biochemistry. Radiographs of the mandible showed a large osteolytic area in the angle of the left mandible with ill-defined borders. There was no surrounding sclerotic
Key words: hepatocellular carcinoma; metastasis. Accepted for publication 6 December 1991
reaction (Fig. 1). The chest X-ray was normal. Biopsy and histopathological examination of the mandibular swelling showed a turnout composed of cells arranged in broad trabeculae with intervening sinusoids. The individual tumour cells showed moderate to abundant eosinophilic cytoplasm with vesicular nuclei, prominent nucleoli and one to 2 mitosis/high-power field. Areas of necrosis and haemorrhage were present. The possibility of metastasis from a primary HCC was entertained (Fig. 2). Abdominal ultrasound examination revealed minimal hepatomegaly with a hyperechoic area of 3.5 cm in the right lobe of the liver. A radio-isotope scan of the liver confirmed the presence of a space-occupying lesion in the right lobe. A radio-isotope bone scan showed an increased uptake over the posterior aspect of the left mandible. The
Case report A 65-year-old man was seen at our hospital with complaints of a painful and gradually
Fig. 1. X-ray mandible showing the osteolytic lesion,
Fig. 2. a. Polygonal tumor cells arranged in a trabecular pattern, HE x 120. b. High power showing the vesicular nuclei and prominent nucleoli in the tumor cells, HE x 756.
98
Doval et al.
alpha feto protein level was 128 Iu/ml and serum Australia antigen was negative. Needle biopsy of the liver showed areas of necrosis and a few groups of cells showing both vesicular and hyperchromatic nuclei and a moderate amount of eosinophilic cytoplasm. An occasional multi-nucleated turnout giant cell was identified. These histological features were consistent with that of a moderately differentiated HCC. A final diagnosis of HCC metastic to the left mandible was made. The patient was started on systemic 5 Flurouracil (5 FU) therapy at a dose of 1000 rag/ iv weekly. Local radiotherapy to the mandible, 30 Gy in 10 fractions over 2 weeks was delivered. After 2 months, (total dose of 5 FU 8 g) the patient was reassessed. Partial regression was noted over the left mandible and ultrasound examination of the abdomen also revealed partial regression of the hepatic turnout. 5 F U was continued at 1000 mg/ iv but given once in 3 weeks. The patient remained in partial remission for 10 months after which the mandibular tumour started increasing in size. The hepatic turnout also increased in size. The total dose of 5 FU given at that time was 19 g. As the disease started progressing, definitive antineoplastic therapy was stopped, and due to the steady downhill course of the patient no new chemotherapeutic agents were tried. The patient finally succumbed 16 months after the initial diagnosis. Autopsy was not performed. Discussion The p a t i e n t described presented with s y m p t o m s o f m a n d i b u l a r metastasis of H C C . E x t r a h e p a t i c metastasis f r o m H C C c o m m o n l y occurs in regional l y m p h n o d e s a n d lungs b u t a u t o p s y rep o r t s d o c u m e n t u p to 20% o f osseous metastasis 6. The first case o f m a n d i b u l a r metastasis o f H C C was r e p o r t e d by DIcK et al. in 1957 I. Since then, 20 cases o f H C C m e t a s t a t i c to the oral region,
14 involving the m a n d i b l e , have been r e p o r t e d v. T h e literature regarding H C C metastasis to the oral cavity h a s been extensively reviewed 7' 9. T h e angle o f the m a n d i b l e is a c o m m o n site o f metastasis, p r o b a b l y due to its rich h a e m a t o poietic m a r r o w 13. These lesions are very h a e m o r r h a g i c a n d any surgical procedure - even biopsy - s h o u l d be a t t e m p t e d w i t h p r e c a u t i o n 7' 13. T h e histology of the osseous metastasis varied f r o m well-differentiated to anaplastic TM 13. I n o u r case the t u r n o u t was m o d e r ately differentiated. T h e prognosis in p a t i e n t s with H C C is poor, especially if surgery is n o t feasible. M e d i a n survival for patients with unresected t u m o u r s is usually reported to be 3 to 4 m o n t h s 12. C h e m o t h e r a p y is m a i n l y palliative, especially in a metastatic H C C . I n a study o f the n a t u r a l history o f H C C , the a d d i t i o n o f systemic c h e m o t h e r a p y showed a dismal survival rate 1°. T h e c o m m o n l y used c h e m o t h e r a p e u t i c agents for H C C are 5 F U a n d D o x o r u b i c i n 4 with response rates o f 15% a n d 23%, respectively 3,12. I n spite o f p o o r survival in metastatic m a n d i b u l a r H C C 13, the absence o f cirrhosis a n d the response to chemot h e r a p y m i g h t have c o n t r i b u t e d to the relative long survival o f 16 m o n t h s in the p a t i e n t described. References I. DICK A, MEAD SG, MENSH M, SCHATTEN WE. Primary hepatoma with metastasis to mandible. Am J Surg 1957: 94: 846-50. 2. EDMONDSON HA, STEINER PE. Primary carcinoma of the liver: A study of 100 cases among 48900 necropsies. Cancer 1954: 7: 462-503. 3. FALKSONG, MOERTEL CG, LAVIN P, PRE-
TORIUS F J, CARBONE PP. Chemotherapy studies in primary liver cancer: A prospective randomized clinical trial. Cancer 1978: 42: 2149-56. 4. KEMENYN, SCHNEIDERA. Regional treatment of hepatic metastatic and hepatocellular carcinoma. Curr P robl Cancer 1989: XIII: 256. 5. LEE YTM, GEERDA DA. Primary liver cancer: pattern of metastasis. J Surg Oncol 1987: 36:26 31. 6. LIAW CC, NG KT, CHEN TJ, LIAW YF. Hepatocellular carcinoma presenting as bone metastasis. Cancer 1989: 64:1753 7. 7. MARKER P, CLAUSEN PP. Metastasis to mouth and jaws from hepatocellular carcinoma. Ir~t J Oral Maxillofac Surg 1991: 20: 371-4. 8. MEYER I, SHKLAR G. Malignant tumors metastatic to mouth and jaws. Oral Surg 1965: 20: 350-62. 9. MUCITELLIDR, ZUNERE, ARCHARD HO, BROOK S. Hepatocellular carcinoma presenting as an oral cavity lesion. Oral Surg 1988: 66: 701-5. 10. NAGASUEN, YUKAYAH, HAMADAT, HIROSE S, KANASHIMAR, INOKUCHI K. The natural history of hepatocellular carcinoma: A study of 100 untreated cases. Cancer 1984: 54:1461 5. 11. OKAZAKI N, YOSHINO M, YOSHIDAT, HIROrIASHI S, KISHI K, SHIMOSATOY. Bone metastasis in hepatocellular carcinoma. Cancer 1985: 55: 19914. 12. OEERFIELD RA, STEEL G, GOLLAN JL, Sr~ERMAN D. Liver cancer CA 1989: 39: 206-18. 13. VIGNEULJC, NotmL G, KLAP P, AL HELALI M. Metastatic hepatocellular carcinoma of the mandible. J Oral Maxillofac Surg 1982: 40: 745-9. Address: Dr. D. C. Doval Kidwai Memorial Institute of Oncology Hosur Road Bangalore 560029 India
