Metastatic Neoplasms to the Oral Cavity Workup

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^[21] ; by contrast, bone metastases from kidney, lung, or breast cancers are more often osteolytic. Note the following:

• An oral radiography 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.^[22]
• Note the following^[22] :

  • Medical history can define areas of concern, such as the respiratory system in a smoker, cough and hemoptysis, or misdiagnosed breast nodules in a woman. Moreover, the personal history may include previous biopsies or removed or spontaneously regressed lesions, as well as a family history of disease.
  • 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 for hepatocellular carcinoma and germ cell tumors, human chorionic gonadotropin for germ cell tumors, and prostate-specific antigen 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.
  • Radiological studies include whole-body CT scanning, which should be performed in all patients, and mammography in women.
  • Functional imaging (ie, ffluorodeoxyglucose positron emission tomography [FDG-PET]/CT scanning) 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. Molecular tests for tissue-of-origin determination in metastatic tumors are available and have the potential to significantly impact patient management.^[23] However, available validation data indicate that not all tests have shown adequate performance characteristics for clinical use.^[23] A novel class of global gene regulators called microRNAs (miRNAs) has been identified and has been found to be differentially expressed across different tumor types. Using miRNA-based classification and identification of cancers of unknown origin can pave the way to the use of more personalized and targeted therapeutic strategies.^[24]

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

The diagnosis is always based on histologic findings from the biopsy specimen.^[25] 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,^[26] 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.^[22]

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.