A 54-year-old woman experienced migrating back pain and was treated with physical therapy in a local clinic, but the symptoms did not improve. Computed tomography revealed a mass in the left lobe of the liver, and she was thus referred to Yonsei Medical Center for further evaluation and treatment. Needle aspiration biopsy of the liver revealed intrahepatic cholangiocarcinoma (adenocarcinoma, well differentiated, T3NXM1; Fig. 1). Thoracic spine metastasis, which had caused a compression fracture at T11, was revealed on magnetic resonance imaging, and a whole-body bone scan was performed (Fig. 2). The liver mass was treated with chemotherapy for 12 months, and the spinal metastasis was treated with radiotherapy and laminectomy with facetectomy. After completion of the 11th chemotherapy cycle, the patient refused further treatment.

One month later, the patient returned to the medical center with a complaint of painful swelling in the right mandible. Computed tomography revealed an expansile 2.0 cm×1.2 cm soft-tissue mass involving the outer cortex of the body of the right posterior mandible. The buccal cortex of the mandible demonstrated osteolytic destruction and the lingual cortex was thinned (Fig. 3). A needle aspiration biopsy of the mandibular mass revealed metastatic mucin-forming adenocarcinoma from the liver. She refused a right hemimandibulectomy, and chose to receive radiotherapy. The patient was then referred from the Department of Radiation Oncology to the Department of General Dentistry at Yonsei University for dental evaluation and dental care prior to radiotherapy.

When she visited the dental clinic, she had no remarkable facial, bony, or vestibular swellings, and the cervical lymph nodes were not enlarged on palpation. Slight generalized gingival swelling and redness were noted, as well as heavy calculus deposition. A panoramic X-ray found a well-circumscribed radiolucent region on the right mental foramen of the mandible (Fig. 4). The right premolar had the vitality on ice test and had no mobility. No paresthesia was reported in the right lower lip. She was treated with scaling and tooth brushing instructions only. A biopsy was not performed.

The patient underwent palliative radiotherapy in the area of the mandibular metastasis in several fractions (35 Gy in ten fractions). One month after radiation therapy, the mandibular pain had disappeared, but a whole-body positronemission tomography/computed tomography (PET/CT) scan revealed hypermetabolism in the right liver, left humerus, sacrum, right ilium, and lumbar spine, mild hypermetabolism in the right mandible, and a small nodule in the right upper and lower lobes of the lung, suggesting multiple bone and lung metastases. The patient desired further treatment at another hospital, and did not return to Yonsei Medical Center.

The oral cavity is a very unusual metastasis site. Oral metastasis is usually evidence of widespread disease, and the actual incidence is difficult to determine with precision, since an unknown number of patients die without a workup for oral metastasis. The known cases of oral metastasis involve patients who show oral symptoms while living. Therefore, metastatic cholangiocarcinoma to the mandible is rare because metastatic spread to other vital organs prior to the mandible results in a low survival rate.

However, the number of case reports of metastatic cholangiocarcinoma in the oral and maxillofacial region is increasing worldwide due to improvements in the treatment of malignant tumors and the average patient survival time. Watts12 reported a case of cholangiocarcinoma of the right subcondyle, which showed a "hotspot" in a bone scan and the loss of definition of the signoid notch of the mandible in a panoramic view. Harding-Kaba et al.11 reported a case of cholangiocarcinoma where the patient presented with a painful cheek swelling that was found to be an osteolytic lesion of the lower jaw. Patrocinio et al.13 reported a cholangiocarcinoma that presented as trismus due to metastasis to the parotid gland, and was clearly separated from other structures by a capsule. McClure et al.7 described a single case of left mandibular condyle metastasis from a cholangiocarcinoma in a 15-year retrospective study of metastatic maxillofacial cancer, but no further information was presented about the cholangiocarinoma patient. The most recent case, reported by Nakanishi et al.,14 involved metastasis of a cholangiocarcinoma to the oral floor contiguous with the lingual mucosa. However, their report contained no description of mandibular metastasis (Table 1).

In our case, osteolytic destruction and a soft-tissue mass involving the outer cortex of the right mandibular body were observed, whereas lower-lip paresthesia, gingival lesions, and tooth mobility were not noted, although an osteolytic lesion was close to the mental foramen and premolar teeth. A whole-body bone scan that was performed on the patient's first visit to Yonsei Medical Center did not show hot uptake in the right mandible, but mild hypermetabolism was found in a whole-body PET/CT scan performed one month after radiation therapy of the mandible.

A whole-body bone scan was performed on the patient's first visit to Yonsei Medical Center, more than one year before the incidence of mandibular swelling. We therefore suspected that no mandibular metastasis had taken place when the whole-body bone scan was taken, although it is possible that the whole-body bone scan did not detect the mandibular metastasis.

The radiographic features of bone metastasis are characterized as osteolytic, osteoblastic, or mixed.15 Although most metastatic bony lesions are osteolytic, metastatic tumors from the prostate, lung, and breast are very often found to be osteoblastic.16 Tumors originating from the gastrointestinal tract and breast often appear as mixed-type.8 Bone scans are of considerable utility in detecting areas of osteoblastic activity in areas affected by trauma, infection, and arthropathy,17 but may not detect metastatic tumors that are primarily associated with bone destruction and minimal or no osteoblastic activity.1718 In contrast, PET/CT has been found to show higher sensitivity than bone scans in the detection of osteolytic metastatic tumors, but lower sensitivity in detecting osteoblastic bony lesions.19 We can therefore speculate that the bone scan did not detect mandibular metastasis, whereas the PET/CT scan showed mild hypermetabolism because our patient experienced osteolytic bone destruction in the right mandible.

Although a few anatomic routes have been suggested as the metastatic pathway, the precise mechanism of oral and maxillofacial metastasis remains unclear. Metastasis from the abdomen or thorax is thought to take place through the blood vessels, mainly through Batson's vertebral and paravertebral plexus of veins, which comprises a valveless venous system.20

In conclusion, metastatic cholangiocarcinoma to the oral cavity is rare; however, clinicians must consider it as a possibility, especially in patients with known risk factors, because the prognosis of oral metastasis is usually poor and most patients die within one year of diagnosis.21 Although most metastases to the oral region are noted after the diagnosis and treatment of the primary malignancy, in nearly 30% of patients with oral metastasis, an oral metastatic region is the first indication of an undiscovered malignancy at a distant site.22 Therefore, clinicians should be aware of the clinical and radiographic features of oral metastatic tumors.