Abstract
Metastasis of malignant tumors to the oral cavity is rare. The authors report a case of thyroid carcinoma with mandibular osteoblastic metastasis. An 83-year-old female presented with lower jaw swelling and pain. An elastic hard subcutaneous mass was observed in the median mandible. X-ray images confirmed a tumor lesion with periosteal reaction spreading radially from the mandible. A biopsy revealed nests of large, polygonal tumor cells growing in a supporting fibrovascular framework. The patient’s anamnesis included thyroid carcinoma with lung metastasis, 2 years ago, treated by total enucleation of the thyroid and excision of the superior lobe of the left lung. Biopsy, primary and metastatic tumor samples all tested positive for thyroglobulin, suggesting a thyroid follicular epithelial origin. Mandibular metastasis of poorly differentiated carcinoma of the thyroid gland was diagnosed. Consent for further treatment was not obtained. The patient died 1 year and 7 months later.
Malignant tumors in the oral cavity are generally primary cancers. In contrast, metastatic tumors are rare, constituting 2% of all cancers in this area . Mandibular metastases generally originate from primary tumors of the breast (25%), lung (13%), prostate (10%), colon (7%), kidney (3%) and thyroid (3%) .
Poorly differentiated carcinoma became an independent disease in the World Health Organization (WHO) classification in 2004. This type of tumor is defined as having a structure and biological characteristics in-between those of differentiated and anaplastic carcinomas. Poorly differentiated carcinoma has a funicular, solid or insular structure. Compared with differentiated carcinoma, it has a high rate of distant metastasis, and the 5-year survival rate is about 50% . Distant metastases of thyroid carcinoma occur most frequently in the lungs, followed by bone, vertebrae, pelvis and costa. There have been few reports of mandibular metastases, and those that have been described have been osteolytic. To the authors’ knowledge, this is the first report of thyroid carcinoma with mandibular osteoblastic metastasis.
Case report
An 83-year-old female presented complaining of swelling and pain in the median lower jaw. An elastic tumor mass with a clear boundary, 50 × 40 mm in diameter, which was causing tenderness, was observed in the subcutaneous part of the median mandible ( Fig. 1 a) . Intraoral findings indicated that the upper and lower jaws were edentulous, and no abnormal findings, such as tumor formation, ulceration or inflammation were observed. Occlusal radiography showed a sunray appearance in the median mandible ( Fig. 1 b). A contrast computed tomography (CT) scan revealed a tumor with periosteal reaction that spread radially from the median mandible ( Fig. 1 c and d). Based on these findings, the case was clinically diagnosed as a median mandibular tumor, and a biopsy was performed. The microscopic findings revealed a tumor structure consisting of large multangular cells, with broad and clear cytoplasm. The cells were arranged in nests and were growing in a supporting fibrovascular framework ( Fig. 2 a and b ), clearly suggesting a metastatic tumor. A comprehensive gene expression analysis was performed, using microarrays, on part of the mandibular tumor biopsy sample. Applied Biosystems Human Genome Survey Arrays (Applied Biosystems, Foster City, CA) were used to determine the transcriptional profile of the tumor RNA sample. Arrays were initially normalized, and genes were deemed undetectable and excluded from final gene lists if they had a signal-to-noise ratio of less than three. The tumor tissues showed an increase in gene expression of more than three-fold compared with normal tissues. The overexpression of thyroid-related genes such as thyroglobulin (TG), thyroid peroxidase, thyroid hormone responsive, and thyroid hormone stimulating receptor, was detected ( Table 1 ). The patient’s anamnesis included thyroid carcinoma with metastasis to the lung 2 years ago, which had been treated by total enucleation of the thyroid and excision of the superior lobe of the left lung. Thyroid carcinoma was suspected, and immunohistochemical staining of the biopsy sample was carried out with samples of the thyroid primary and metastatic lung tumors ( Table 2 ). The staining pattern of the biopsy sample was similar to the samples of the thyroid primary and metastatic lung tumors. All of the samples tested positive for TG, suggesting that the tumor originated in the thyroid follicular epithelial cells ( Fig. 2 c and d). All the samples tested negative for calcitonin and carcinoembryonic antigen (CEA) , which are medullary carcinoma markers. Based on these results, mandibular metastasis of poorly differentiated carcinoma of the thyroid gland was diagnosed.
| RefSeq | Fold change | Gene name |
|---|---|---|
| NM_003235 | 1,717 | Thyroglobulin |
| NM_000547 | 94.7 | Thyroid peroxidase |
| NM_003251 | 42.6 | Thyroid hormone responsive |
| NM_000369 | 25.2 | Thyroid stimulating hormone receptor |
| NM_005119 | 6.1 | Thyroid hormone receptor associated protein 3 |
| NM_000316 | 4.9 | Parathyroid hormone receptor 1 |
| NM_006475 | 33.6 | Periostin, osteoblast specific factor |
| NM_000478 | 23.2 | Alkaline phosphatase |
| NM_007361 | 19.2 | Osteonidogen |
| NM_001719 | 17.1 | Bone morphogenetic protein 7 |
| NM_000582 | 9.4 | Osteopontin |
| NM_004967 | 9.0 | Bone sialoprotein |
| NM_003118 | 8.0 | Osteonectin |
| NM_001199 | 7.0 | Bone morphogenetic protein 1 |
| NM_001797 | 3.4 | Cadherin 11, type 2, OB-cadherin (osteoblast) |
| NM_020203 | 3.3 | Matrix, extracellular phosphoglycoprotein with ASARM motif (bone) |
| NM_006812 | 3.3 | Amplified in osteosarcoma |
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