Oral complaints caused from metastases to the mandible and maxilla

* Department of Cytology, Regional Hospital of Chania, Crete, Greece
* Department of Maxillofacial Surgery, General Hospital of Alexandroupolis
* Department of Histology-Embryology, Democritus University of Thrace, Alexandroupolis
* Department of Pathology, Ippokration General Hospital of Salonica
* Department of Pathology, General Hospital of Drama


Introduction
Bone secondaries commonly occur following primary malignancies but metastases to the jaws are very rare. Red marrow is believed to be necessary for the establishment and proliferation of metastases is scanty in the mature jaws; hence instances of tumour metastases to the jaws are very few (1). It is estimated that only one percent of all oral malignancies occur due to primary malignancies elsewhere (2-6, 7). While almost any types of malignancy can metastasise to the mouth, some are found more often than others (7). Cancers that commonly metastasize to the oral cavity originate from the breast, kidney, lung and the prostate (7-9). Metastatic lesions may mimic odontogenic infections and other disease conditions in the oral cavity in presentation leading to late diagnosis by the unwary clinician. In Greece, reports on jaw tumours from metastasis elsewhere are quite scarce. This report presents a series of histologically verified metastatic tumours to the jaws collected over 15- years in a Greek tertiary oral and maxillofacial care center highlighting the problems associated with late diagnosis and the multidisciplinary implications of the disease.

Patients and Methods
The materials for our study were obtained from records of malignant diseases of the jaws observed at the Maxillofacial Department of the University Hospital of Alexandroupolis, Thrace, Greece between 1989-2005. Records inspected were case notes, histology reports and operation notes. Jaw malignancy of histologically verifiable metastatic origin was selected out for analyses of age at diagnosis, gender, presenting complaints, clinical features, histological diagnosis and treatment. Follow -up records of referred cases was not available, also the only patient treated by us did not return for follow-up reviews.

Results
Out of 276 malignancies of the oral cavity seen between 1989-2005, four cases (1.4%) were of metastatic origin. The age range of the patients was from 47 to 69 years, two males and two females. Three patients presented with symptoms of jaw swellings and other features localized to the oral cavity. Only one case was managed at our department before referral, one referred to other specialists, and one patient discharged himself from hospital after tumor diagnosis. Clinical details of our cases of metastatic jaw neoplasms are in table 1. A 69 years old female deemed inoperable due to tumour extent at secondary site was administrated with palliative analgesics until passed away one month later at home. Magnetic resonance imaging scan revealed a bony metastasis (fig. 1). It was a metastatic papillary thyroid adenocarcinoma (fig. 2). No post-mortem examination was performed. The second patient diagnosed of metastatic thyroid carcinoma was treated by jaw resection and did not return for follow-up. One patient discharged himself from the hospital. He was diagnosed of metastatic hepatocellular carcinoma (Fig. 3). The last one was diagnosed of metastatic oesophageal adenocarcinoma (Fig. 4). No record of the entire reffered patients was available.

Figure 1

Figure 2

Figure 3

Figure 4

Discussion
Metastatic jaw tumours originate from distant body sites and exclude lesions due to spread from adjacent sites or those due to local recurrence. Metastatic lesions are very significant, as their appearance may be the only symptom of an underlying malignancy and/or the first evidence of dissemination from the primary site (7, 10). The exact incidence of secondary malignancies in the jaws is difficult to ascertain, as skeletal radiographic surveys are not routinely done in Greece. Even when such scans are performed, the jaws are usually excluded. Also for religious and cultural factors, consent for post mortem examinations is difficult to obtain in Greece. In the opinion of several authors, only 1% of all oral malignant neoplasm is of metastatic origin (2-6, 7). The relative frequency of 1% obtained in this series agreed with this view. The age and sex distributions of metastatic tumours to the jaws are determined by the source. In a review of 110 cases of metastases to the maxilla, patients' ages ranged from 3 months to 81 years while the overall male to female ratio was 1.5:1 (11). From our study, in this relatively minimum settings there were 2 females and 2 males giving a sex ratio of 1:1. The age range was 47 to 69 years with all cases above the 4th decade of life. This agrees with the fact that cancer is uncommon in children.
According to Batsakis (5), only 6.1% of 115 metastasising jaw tumours originate from the thyroid while a review of 110 cases of upper jaw metastases found most (44%) to originate from the kidneys and the bronchus (13%). Fewer came from the breast (9%), testicles (7%), uterus (6%), thyroid (5%), colon and rectum (5%), stomach (5%) and the prostate (3%) (11).
Our results (table 1) show half (50%) cases were of thyroid gland origin. The rest came from the liver and the oesophagus. The high frequency of thyroid metastases to the jaws is suspicious and warrants further study of the hazard of occult thyroid malignancy among Greeks.
Hanahan and Weinberg (12), have brilliantly described the processes involved in the detachment of tumour cells from the primary cancer site, its transport through the lymphatics or blood stream and establishment of a metastatic tumour site. The literature indicates that metastases are more frequent in the mandible than the maxilla due to paucity of active red marrow in the latter (1, 4, 6, 13). Apart from the jawbones, other oral sites of metastatic tumour are the gingiva, buccal mucosa, soft palate and the tongue (7). Tumour metastases to the jaws occur via the blood stream by embolization as the jawbones lack lymphatics (6). Among 18 metastases to the jawbones, more were to the mandible (n=15, 83%) than the maxilla (17%) (7). In table 1 there were more mandibular (3) than maxillary (1) sites further demonstrating this predilection. Soft tissue sites also affected were the oral mucosa, which ulcerated and bled due to tumour invasion.
Oral metastases may present in various forms: as pain, cheek swelling, tooth loosening, paraesthesia, epistaxis and cervical lymphadenopathy (7, 11) or rarely as a pathological fracture in the mandible (14). It may also occur as a solitary radiolucency of the jawbone (10). Features in the jaws may be observed before those of the primary site or even after surgical extirpation of the primary malignancy (7, 10, 15, 16). Metastases to the jaws may be the only evidence of tumour dissemination or part of generalized spread (7, 10, 11).
In this report, three of four patients presented with features localized to the oral cavity such as jaw swelling, pain and mucosal ulceration. Only one case of adenocarcinoma of the thyroid came with symptoms of neck swelling which later ulcerated related to the primary malignancy. On the other hand, none of our cases came oblivious of the primary problem. Also all patients we studied came after a considerable delay period, as reports of previous extractions of mobile teeth, incision and drainage and antibiotic therapy at outlying care centers were common among patients. Since the complaints and features of metastases to the jaws are similar to those of odontogenic infections and other benign tumours in the jaws, a high index of clinical suspicion is necessary to allow for early diagnosis.
The presence of malignant tumour outside its organ of origin indicates spread that portends a poor outcome hence some authors advocate palliative treatment such as radiotherapy to the affected jawbone for pain relief (6, 13-15). Curative treatment of an oral metastatic tumour site is considered only if extensive search for other metastases reveal only the oral site combined with an identified primary tumour that is controlled or treated successfully (7).
The optimal therapy for differentiated thyroid cancer includes thyroidectomy and radiotherapy (10). Of two cases of metastatic jaw tumours of thyroid origin, one was managed by jaw resection and one inoperable with palliative analgesics. It is difficult to speculate on the benefit of the jaw resection performed, as patient did not return for follow-up reviews. The case sent to the oncologists for multidisciplinary management did not return to us while one patient discharged himself after diagnosis.
In conclusion, metastases to the oral cavity are quite uncommon among Greeks. They may present with features similar to odontogenic infections and benign tumours, which lead to, delayed diagnosis and therefore limited treatment options. Careful examination and high index of clinical suspicion would facilitate selection for investigations and multidisciplinary treatment.

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