Metastatic Neoplasms to the Oral Cavity Workup

Updated: Jun 26, 2018
  • Author: Abraham Hirshberg, MD, DMD; Chief Editor: Jeff Burgess, DDS, MSD  more...
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Imaging Studies

The balance between the activities of osteoblasts and osteoclasts in general determines the phenotype of metastatic bone lesions, either osteolytic or osteoblastic. Metastases from prostate cancer usually form osteoblastic lesions in bone [22, 30] ; by contrast, bone metastases from kidney, lung, or breast cancers are more often osteolytic.

An oral radiographic survey may be helpful. The most common radiographic presentation is that of a lytic lesion with ill-defined margins. Occasional osteoblastic lesions are observed. In approximately 5% of the patients, the radiographs do not reveal any pathologic changes.

Periapical and panoramic radiographs, CT scans, and MRIs can be obtained to evaluate the extent of the lesion.

Lack of radiographic changes does not exclude the possible presence of a small metastatic deposit in the jawbone.



The following steps constitute the diagnostic algorithm for evaluation of oral metastases:

  • Review the clinical history.

  • Review the available radiographic findings.

  • If a history of a previous tumor exists, obtain the slides and reports for review.

  • Perform a biopsy of the lesion.

  • Evaluate the light microscopic features of the neoplasm. On the basis of the histologic features, determine the need for special studies (eg, histochemical staining, immunohistochemical tests, electron microscopy).

  • In cases in which the primary tumor is not found (unknown primary), look for signs and symptoms in an attempt to identify the potential primary. A standard diagnostic evaluation of patients with unknown primary tumor (UPT) should be based on medical history, physical examination, clinical symptoms, laboratory studies, histopathological review with immunohistochemical analyses and imaging evaluations. [31]

Medical history can define areas of concerns, such as the respiratory system in a smoker, cough and hemoptysis, or misdiagnosed breast nodules in a woman. Moreover, personal history of previous biopsies, removed or spontaneously regressed lesions, or family history. The standard battery of laboratory tests includes a complete blood cell count; iron metabolism (eg, iron deficiency may point toward an occult gastrointestinal malignancy leading to chronic blood loss); urinalysis (helpful for discovering microscopic hematuria or the presence of proteinuria); liver and renal functional tests, including hepatitis B (HBV) and hepatitis C (HCV) markers; and stool examination for occult blood. In addition, some selected tumor markers should be determined, such as alpha-fetoprotein (αFP) for hepatocellular carcinoma and germ cell tumors, beta-human chorionic gonadotropin (βHCG) for germ cell tumors, and prostate specific antigen (PSA) for prostate carcinoma. Other tumor markers, such as carcinoembryonic antigen (CEA), CA125, CA15.3, and CA19.9, can be useful; however, because of their low specificity, they cannot be used to establish definitive diagnoses. Whole-body CT scanning should be performed in all patients, and mammography should be performed in women. Functional imaging (ie, fludeoxyglucose [FDG] positron emission tomography [PET]/CT) has gained a main role in the detection of the site of origin of unknown primary cancers and is currently recommended by the European Association of Nuclear Medicine.

Cancers of unknown primary origin are defined as histologically confirmed metastatic tumors for which no known primary site has been identified following thorough physical examination and laboratory and imaging diagnostic tests. The proportion of unknown primary origins in oral metastases varies from 5-17%. These variations probably result from a less restricted definition of what is called carcinoma of unknown primary (CUP), and the prevalence is probably much less. CUP may retain the signature of the primary origin, and advancement in molecular technologies may lead to identification of the primary origin. [32] These various tests, using DNA microarrays, quantitative real-time polymerase-chain-reaction (rtPCR), or tissue-of-origin assays based on mRNA or microRNA (miRNA) are based on the premise that in analyzing a large number of genes, the metastatic tumors match their primary tumor. The accuracy of these tests varies from 70% for mRNA- to 90% for DNA-based tests. [33, 34]

Plan the treatment protocol based on the clinical, pathological, and radiographic information.


Histologic Findings

The diagnosis is always based on histologic findings from the biopsy specimen. [35] The clue to the diagnosis is the resemblance of the metastasis to the primary tumor. If a history of a previous tumor exists, compare the current histologic findings with those of the preexisting primary malignant tumor; it is often difficult to determine, for patients with a previous history of malignancy, whether a lesion represents a metastasis or a new primary neoplasm. Histochemical staining, immunohistochemical testing, [36] and sometimes molecular cDNA profiling should be performed to identify the primary source of the metastatic tumor. The accuracy of immunohistochemistry and molecular cDNA profiling (by either RT-PCR or chips) exceeding 80% according to most authors. [31, 32]

Most oral metastatic malignancies appear to be of epithelial origin, mainly adenocarcinomas, and a very useful tool in diagnosing the primary origin is the pattern of expression of cytokeratins 7 and 20. [22] Nonepithelial tumors such as melanoma, sarcoma, lymphoma, and germ cell tumors can be diagnosed using appropriate immunohistochemical testing, and they can be managed even without an identifiable site of origin.

Attend to the differentiation of the primary intraoral malignancies from metastatic tumors. Several primary intraoral malignancies (especially those originating from salivary glands) have histologic features similar to those of tumors in distant organs: for example, primary ductal carcinoma of a salivary gland origin versus metastatic breast carcinoma, primary intraoral clear cell carcinoma versus metastatic renal cell carcinoma, primary intraoral squamous cell carcinoma versus metastatic squamous cell carcinoma from the lung, or primary intraoral malignant melanoma versus metastatic malignant melanoma. Malignant soft tissue tumors may originate intraorally, but, because of their rarity, one should always consider a metastatic origin.