Hepatocellular carcinoma metastatic to the mandible: a case involving severe hemorrhage

JUNQUERA L, RODRÍGUEZ-RECIO C, TORRE A, SÁNCHEZ-MAYORAL J, FRESNO MF. HEPATOCELLULAR CARCINOMA METASTATIC TO THE MANDIBLE: A CASE INVOLVING SEVERE HEMORRHAGE. MED ORAL 2004;9:345-9.

ABSTRACT

Hepatocellular carcinoma (HCC) is quite uncommon in Europe and USA, although in this last country more than 13,000 new cases are diagnosed every year. Mandibular metastases are unusual, with only 50 cases documented. In this article, we present a 54 year-old male patient with a metastasis of HCC in right mandibular body, one year after treating the primary tumor. Curettage and biopsy of the lesion was performed, followed by a profuse hemorrhage. The patient expired six months after the biopsy, with multiple metastases. We describe the different paths for hematogenic dissemination of the process.

Key Words: Hepatocellular carcinoma, jaw bone metastasis.

INTRODUCTION

Hepatocellular carcinoma (HCC) is a well-known pathology worldwide, although metastases to the head and neck are unusual. Only 1-3% of oral malignancies are metastatic carcinomas from a distant primary site-in decreasing order, from the breast, adrenal gland, colorectal system, genital organs and the thyroid gland in women; and lung, prostate, kidney, bone, and adrenal gland for men (1). Hepatocellular carcinoma with extrahepatic metastasis has been reported in approximately 50% of cases, with lungs, abdominal lymphatics, adrenals, great veins adjacent to the liver, the diaphragm, or the skeleton usually involved. Poor differentiation, large tumors and those with multilobar spread have increased risk for metastasis (2). Bone metastasis in HCC has been reported in 10.1% of patients, with the vertebrae being most frequently affected, followed by (in decreasing order) ribs, sternum, and pelvis (3). We found only 50 cases of metastasis to the mandibular or maxillary area in the English (26 cases), Japanese (18 cases) and French (6 cases) literature from 1957 to 2003 (4-6).

The objective of this report is to present a case of metastatic HCC to the mandible and to emphasize the potential hemorrhagic problems associated with any surgical intervention

CASE REPORT

A 54-year-old man was referred to our department on May 2003, with odontalgia in the lower right erupted third molar. Intraoral examination showed a buccolingual swelling extending from molar region to right mandibular body and distal decay in mandibular right molar. The oral mucosa covering this area was normal. There was no cervical lymphadenopathy. The patient felt hypoesthesia in the mental nerve region. A panoramic radiograph showed tooth decay in third molar and a poorly defined osteolytic lesion affecting the right mandibular body (Fig 1). Two days later, molar exodontia with curettage-biopsy was performed under local anesthesia, followed immediately by acute hemorrhage treated with Surgicel™ (Johnson & Johnson, New Brunswick, NJ) and bone wax packing in the biopsy site. Complete blood studies and coagulation profile were within the normal range. Histopathologyc diagnosis revealed a mandibular metastasis from well differentiated hepatocellular carcinoma (Fig. 2). Neoplastic cells could not be dyed neither with cytokeratins 19 and 20 nor alpha-fetoprotein, but they did show an intense granular cytoplasmatic tinction with hepatocyte N marker.

The past medical history revealed a 8 year-hystory of diabetes mellitus type II controlled with oral medication, heavy alcohol consumption during the last 30 years and positive history of cigarette smoking (40 cigarettes per day for 20 years). One year before, he had been diagnosed of liver cirrhosis (stadium A of Child Pugh classification: 5/15) and multicentric hepatocellular carcinoma in the II, III and VI liver segments. At that time, a though evaluation, including a whole-body technetium 99-MDP bone scan and computed tomography (CT) of the brain, chest, abdomen an pelvis failed to reveal any evidence of metastatic disease. The patient underwent hepatic resection 1 month after diagnosis. Laboratory analysis revealed normal alpha-fetoprotein level (3,6 ng/ml).

Two weeks after our biopsy, alpha-fetoprotein level increased to 221 ng/ml. Bone scintigraphy showed multiple hot spots in several vertebrae, left occipital bone, sternum and middle third of right femur (Fig 3). Vertebral palliative radiation was performed with 10 Gy of Co 60. The patient expired six months after our intervention.

DISCUSSION

Hepatocellular carcinoma (HC) is considered to be quite uncommon in Europe and United States, although in this last country about 13,000 new cases are diagnosed every year, especially in patients with alcoholic cirrhosis or infection by hepatitis viruses B and C (7). Metastases into maxillofacial territory are unusual, affecting preferably to male patients (male-female relationship 46:4) over 50 years (15-88 years range), in mandibular body or angle (4-6,8,9).

Maxillofacial metastases preceded the knowledge of liver disease in 59% of documented cases (4), but not in our case. Clinical manifestations like swelling and mental nerve hypoesthesia appear both in our patient and other cases (6,9). Odontalgia is more unusual, but the presence of distal decay in tooth 4.8 and a radiolucent image in relation with distal root of third molar, made us suspect of a synchronic odontogenic infection with the metastatic lesion.

It is widely discussed in the literature the way in which hepatocellular carcinoma can disseminate into an intraosseous mandibular metastasis. Basically, there are two paths from the liver to the maxillofacial territory. When the hepatic artery and the portal vein are affected, metastatic dissemination must reach the lungs first, and only later may reach the maxillofacial area. According to this, most of the registered cases of HCC with mandibular metastasis presented lung metastasis too (9,10). Lung metastases could not be demonstrated, at least in our case and 11 more (4). It has been postulated that there must be a connection between the azygos and hemiazygos veins and the vertebral venous plexus (Batson’s plexus) to explain this mandibular affectation. (3,11). The distribution of the osseous metastasis in our case seems to confirm this hypothesis. Surgery and cirrhosis in our patient could generate retrograde alterations of the circulatory flow. It is well known the existence of free communication between neck, thorax, abdomen and pelvis venous systems with the non-valve vertebral venous plexus that extends from cranial base to coccyx; any pressure increment inside the abdomen can create an ascendant flow through the vertebral venous plexus. In our patient, it is reasonable to think that the first metastasis could grow in the vertebral bodies from the intervertebral and basivertebral veins (figure 3); from that point, the dissemination could reach the occipital and mandibular bones. The vertebral venous plexus anastomoses to posterior intercostal and lumbar venous ramus, which drain into the azygos (right side) and hemiazygos (left side) veins. Metastatic cells could follow the hemiazygos vein in our patient, due to the liver segments and vertebrae affected, penetrating then in the thorax by the left diaphragm crus, and ascending in intimate connection with the vertebral bodies until arriving to the level of vertebra D7, in which, following the venous vessels would reach the azygos vein. This could explain rib metastasis and mandibular affectation in our patient (12). Radiographs of documented mandibular HCC metastasis present a radiolucent image (osteolytic) with quite defined borders and no sclerotic reaction. Orthopantomography in our patient showed this image, but also another image more radiolucent similar to periapical infectious pathology.

Histologyc diagnosis is easy when the hepatic tumor has been previously diagnosed as in our patient, but in most cases metastasis occurs before. Immaturity and anaplasia of the metastatic cells difficultate the diagnosis, and immunohistoche-mical markers, such as alpha-fetoprotein may be needed to confirm it. In our patient immunohistochemical analysis was negative, as it is described in other studies (6).

Many authors have studied the hemorrhagic process that can occur after the manipulation of HCC mandibular metastasis. Most of them find the coagulation alterations due to the basal liver pathology to be the reason for this bleeding (3,4). Ashar et al. (13) described a case in which after practicing a biopsy under local anesthesia, three episodes of hemorrhage occurred, and needed ligation of external carotid artery with no success, failed attempt of embolization due to technical problems and finally application of local radiotherapy (Co 4,100 cGy). These authors suggest that hemorrhagic tendency of these tumors is consequence of their rich vascularization as it happens in the primary tumor. When mandibular metastasis of HCC is suspected, it should be confirmed with fine needle punction-aspiration, and if it is not, then perform the biopsy (8).

Prognosis of HCC is bad. Mean survival after maxillofacial metastasis diagnosis is 21 weeks (range: 2 weeks - 2 years) (10). Only if we cannot find systemic metastasis and the primary tumor is controlled, we would practice radical surgery of mandibular metastasis.

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