By Tim D. Sands, DDS, Dip OMFS and Bruce R. Pynn, Msc, DDS, FRCDS(C)
Oral malignant metastases are a relatively rare finding considering the incidence of metastatic tumors in the body. They account for less than one percent of all metastatic malignancies, which prefer to spread to the spine, pelvis, skull or ribs.1 Most oral malignancy develops as a result of local extension of primary disease that originates in the oral cavity and surrounding tissues.2 Metastasis is defined as the transfer of disease cells from one organ or part to another site not directly connected with it.3 Thus, a metastatic tumor is of a similar histology with the primary malignancy and is separated from it by an amount of intervening healthy tissue.4 The ability to metastasize is a characteristic of malignant tumors.
Carcinoma is the most prevalent oral metastatic tumor and the most common primary origin is the female breast, followed by the lung and then kidney.5 Metastasis to bone are the most frequent metastatic tumors of the oral cavity, and are far more often involved than the oral soft tissues.6 The main location is the posterior mandible accounting for more than 70 percent of all oral metastases.2 Unfortunately, the discovery of an oralmetastatic tumor usually represents a terminal disease and a poor overall prognosis.5
A 73-year-old gentleman presented to the emergency department with combination of jaw pain, decreased mouth opening and increasing chin numbness. The patient’s medical history indicated that he had been treated for prostate cancer several years prior but has recently developed para-arotic and supra-clavicular nodes for which he was undergoing a palliative course of radiation therapy. His PSA has recently doubled over the past few months. He was taking MS-Contin and Decadron to control the pain.
The intraoral exam showed a healing socket from an extraction of #35 carried out three weeks previously and an expanded buccal cortex in the premolar region. The inferior border of his mandible was very tender to palpation. He had no visible or palpable lymphadenopathy in his neck.
The radiographic appearance on both the panorex and CT scan revealed a moth-eaten radiolucency with a minimally displaced pathologic fracture at the site (Figs. 1 & 2). The patient was placed on a course of Clindamycin while he finished his radiation therapy and plans were made to reassess his situation in 10 days time. Unfortunately, he succumbed to his disease prior to reassessment and treatment for his metastatic disease.
Generally it is accepted that oral cancer constitutes about five percent of all malignant neoplasms in the body,2 and only one percent of these represent metastatic lesions.6 Hirshberg and Bushner7 in an overview of oral metastasis suggest that the true prevalence of oral cavity metastasis is difficult to assess and may be under reported.
This opinion arises since literature reviews may pool information from case reports, a small series of patients or tend to combine metastatic tumors to the oral soft tissues with those of bone.
Also influential is that a skeletal survey in a metastatic work up to identify other secondary lesions may not routinely include the jaws or that the most recent publications tend to be based on unusual cases involving unique primary sites or unusual oral presentations. These trends tend to bias opinion on the statistics of oral metastases.
Although varied among reports, it appears most primary tumors metastasizing to the oral cavity are from the breast, lung or kidney.1,5 Other origins with a reduced frequency include but are not limited to: colon, adrenal gland, prostate, thyroid, ovary and testes. Most frequently the tumor is a carcinoma, a malignant new growth of epithelial cell origin; however, neuroblastoma, retinoblastoma, hepatoma and melanoma have been reported.1,2,6
AGE AND SEX
Patients are usually identified between the ages of 40 to 702 with a mean age of 45.7 Most authors report a female to male ratio of 3 to 2.2 This female predilection is influenced by the obvious gender specific sites of malignancy origin; for example, metastatic breast adenocarcinoma is more common in women.
In an analysis of 390 cases of metastatic lesions to the jawbone and grouping gender and primary location, in males the most common primary is the lung followed by the prostate, kidney, bone and adrenal gland. In females and in decreasing frequency, the breast, adrenal gland, colon, genital organs (uterus, ovary, cervix), and thyroid represent origins.8
In the development of any metastatic lesion, the tumor cells must penetrate a number of barriers. Cells detach from the primary and travel in the lymphatic or blood vessel circulation, to invade and proliferate within the target recipient tissue.7 It is believed that the spread of most metastatic disease is hematogenous.2
The lungs and liver account for the majority of all metastatic deposits. Malignant emboli drain into the portal vein and land in the liver or travel via the inferior or superior vena cava to the heart and then are deposited in the lungs.2 The main mechanism proposed for metastatic spread to the oral region is backflow though the venous system.5
Batson10 accounted for the head and neck distribution of tumor cells by the valveless para vertebral venous plexus. This route allows and explains a bypass of the filtering liver or lung circulation.
In a series of papers,7,8,11 attempts are made to emphasize the importance of separating tumors to the oral soft tissues from those affecting the jawbones. Bone metastasis may be 20 times more common than oral mucosal metastatic lesions.5 It appears that despite a common blood supply that site of malignant origin influences the location of metastasis.
The breast is the most common primary to the jawbones whereas the lung and kidney are the commonest sources to the oral mucosa.7 Tumors from the adrenal gland, prostate and thyroid have not been reported in the oral mucosa and prefer bone as their target.7
Overall, the most common location for oral metastasis are the molar and premolar regions of the mandibular bone.2 The ratio of mandibular to maxillary bone involvement is 5 to 1.9
Remnants of active hematopoietic marrow in the posterior mandible may attract tumor cells and account for this unequal distribution of oral metastatic disease. Metastatic tumors are rare in the condyle with less than thirty reported cases in the literature.2
In the oral soft tissues, the most common location is the attached gingiva followed by the tongue.11 Gingival lesions are equally distributed to maxilla and mandible and appear correlated to the presence of teeth. It is proposed that there may be a role for inflammation attracting metastatic cells to the attached gingiva.11 Although muscle in general appears to resist seeding, the well vascularized base and posterior tongue may account for the higher incidence.
In a historical review12 of post extraction socket involvement only 55 cases were justifiably reported. With ruling out pre-existing metastatic disease, it was proposed that local factors in the extraction site may attract circulating tumor cells. They then could become entrapped in the rich capillary network of granulation tissue during socket healing.6,12
CLINICAL SIGNS AND SYMPTOMS
The site of primary origin rarely influences clinical oral presentation.5 Swelling and pain appears to be a common feature of mandibular metastatic tumors;2 however, some bony metastatic deposits may present as painless masses with an intact overlying mucosa.5
Patients may report an increased mobility of affected teeth and an altered or reduced sensation of the lower lip.2 With regards to soft tissue metastasis, most will resemble a hyperplastic or granuloma-like mass.11
Unfortunately, metastatic tumors do not possess a pathognomonic radiographic appearance. A polymorphous radiolucency with ill defined and irregular margins is the most common presen
Prostate and breast tumors are often associated with radiopaque metastatic lesions. The areas appear as patchy sclerosis due to new bone formation, arising from the stimulation of surrounding normal bone.1 Pharoah1 describes the tumors effects on surrounding structures. The resorption of teeth is rare; however, lesions destroy the lamina dura and widen the periodontal ligament space.
In situations with developing teeth, tumor seeding in the dental papilla can destroy the cortex of the tooth crypt. The cortical bone of adjacent structures such as the mandibular canal, maxillary sinus and nasal floor is resorbed. Extension through the cortical plate of the jaws may stimulate a spiculated periosteal reaction.
The diagnosis of a metastatic tumor in the oral region may be difficult due to their rare occurrence. Jaw lesions more commonly present with a known or previously treated primary. Yet, in nearly 30 percent of cases, the oral metastatic lesion is the first indication of an undiscovered malignancy.9 An intraoral incisional biopsy and histopathologic examination is the means to confirm and identify a malignant tumor and potentially it’s metastatic origin.2
The pathologist may not provide an exact diagnosis, since metastatic malignancy does not represent a single disease and histological appearance is variable. Usually a distinction of a metastatic tumor from a primary malignancy can be made.5
For differential diagnosis purposes, clinical radiographic presentation is more commonly consistent with a primary malignancy such as squamous cell carcinoma.5 Odontogenic cysts that become secondarily infected may provide a similar radiographic appearance to a metastatic lesion.1
A pyogenic granuloma, peripheral giant cell granuloma, peripheral ossifying fibroma and other benign exophytic lesions may be confused with otherwise asymptomatic oral mucosa metastases.5
Once a metastatic diagnosis is suspected an appropriate referral for an oncologic work up is required. Advanced imaging, scintigraphy and regional investigations based on the suspected source is instituted to find or confirm origin and identify any other areas of secondary spread.
TREATMENT AND PROGNOSIS
The treatment and prognosis is primarily based on the site of origin and the degree of metastatic spread.2 Unfortunately, the identification of a metastatic tumor usually represents a poor overall prognosis.
If the primary tumor was successfully treated and the patient’s medical condition permits, the metastatic lesion should be aggressively treated. Management may involve surgical resection, radiation, chemotherapy or a combination of these techniques.
If the primary is recurrent or there is widespread metastases the jaw lesion should be managed conservatively. This goal of palliative treatment is to reduce the patient’s pain and preserve oral function. This may involve reducing the size of the tumor though radiotherapy, chemotherapy or local surgical excision.13OH
Dr. Sands is an oral and maxillofacial surgeon in private practice in Woodbridge, ON. Dr. Pynn is an oral and maxillofacial surgeon in private practice in Thunder Bay, ON.
Oral Health welcomes this original article.
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