Cancers of the Oral Mucosa Workup

The principles are to confirm the oral squamous cell carcinoma (OSCC) diagnosis histopathologically and to determine whether malignant disease is present elsewhere, including the following:

• Bone, muscle, or primary tumors: Other primary tumors are typically located in the upper aerodigestive tract (eg, mouth, nares, pharynx, larynx, esophagus). Whether endoscopy is warranted to detect such tumors in all cases remains controversial.
• Metastases: This initially occurs to regional lymph nodes and later to the liver, bones, and brain. Imaging studies may help detect abnormalities missed during the clinical examination.

Blood tests include the following:

• Liver function tests: Results may reveal metastases in persons with advanced disease.
• Complete blood cell count and hemoglobin value
• Urea and electrolyte measurements
• Blood group testing and cross-matching
• Calcium level: As many as 4% of patients with cancer in the head and neck may have elevated serum calcium levels. This is a poor prognostic indicator primarily found in persons with advanced disease.
• Serum ferritin, alpha-antitrypsin, and alpha-antiglycoprotein levels: Persons with high-stage cancer of the head and neck also have increased levels of serum ferritin, alpha-antitrypsin, and alpha-antiglycoprotein, while those at any stage of disease have increased haptoglobin levels (although not known if this is true specifically for oral cancer). Additionally, prealbumin levels are decreased slightly in persons at any stage. Results from assays of these serum constituents cannot be regarded as sufficiently specific or sensitive to be of reliable clinical value, and this, unfortunately, is also true of the many tissue markers thus far described.

Photography to create a photographic record is especially useful for monitoring the clinical state and site of premalignant lesions.

Chest radiography and endoscopy are valuable procedures for excluding synchronous SPTs. Chest radiography may be indicated because the lungs are the most common site for metastases and a site for second primary carcinomas. Radiography, sometimes including axial CT scanning or, possibly, other imaging techniques, may be needed to determine the degree of spread of some tumors, particularly to exclude bone invasion and lymph node involvement. Chest radiography is important as a preanesthetic check, especially in patients with known pulmonary or airway disease and to demonstrate metastasis to the lungs or hilar lymph nodes, ribs, or vertebrae. Jaw radiography (often rotating pantomography) may show invasion, although it is inadequate to exclude bone invasion.

Other imaging investigations include MRI or CT scanning of the primary site, of the head and neck, and of suspected sites of lymph node or distant metastases. Sentinel node biopsy, MRI, 18-fluorodeoxyglucose positron emission tomography (FDG-PET) scanning, or ultrasonography of the neck (or combinations) can be used to delineate the extent of cervical node metastasis.

Radionuclide scanning occasionally is useful. Bone scanning is of little value in screening because findings are positive only where bone involvement is symptomatic. Bone scanning is primarily used to determine the extent of tumor spread. Liver radionuclide scanning shows abnormal findings in as many as 6% of patients with cancer in the head and neck, but two thirds are false-positive findings; therefore, liver scanning normally is not indicated.

Routine panendoscopy helps identify simultaneous second primary carcinomas in the esophagus, larynx, or lungs in as many as 14% of patients. Endoscopy is widely recommended, although it is not performed in all centers. More than one third of SPTs are detectable by endoscopy at or within 1 year of diagnosis of the index tumor.

Electrocardiography may be useful.

Incisional biopsy, guided when appropriate by vital staining, is essential to confirm the diagnosis. A biopsy must be performed on any oral mucosal lesion suggestive of cancer, including any ulcer that does not heal within 2-3 weeks. An incisional biopsy is always required, usually with the patient under local anesthesia. Always take a biopsy specimen of the red lesions if both red and white lesions are present because red, rather than white, areas are more likely to show dysplasia.

In vivo staining may help if difficultly arises when deciding which area is most appropriate for the biopsy, particularly if widespread lesions are present. Staining with toluidine blue followed by a rinse with 1% acetic acid and then saline may stain the areas most suggestive of findings and indicate which need a biopsy. Oral carcinoma in situ and early invasive carcinoma have an affinity for toluidine blue dye, and although several false-positive results may be encountered, these can be minimized by restaining after 14 days. Toluidine blue clearly is more effective in experienced hands and when used with appropriate clinical judgment. Counterstaining with Lugol iodine solution may enhance the usefulness of toluidine blue staining.

Various light sources are becoming available to help delineate areas for biopsy. The biopsy specimen should be sufficiently large to include enough suspect and apparently normal tissue to provide the pathologist an opportunity to make the diagnosis and to not have to request an additional specimen. Most patients tolerate (physically and psychologically) one biopsy session. Most biopsy wounds, whether 0.5 cm (too small) or 1.5 cm long (usually adequate), heal within 7-10 days; therefore, taking at least one ample specimen is better than having to repeat the procedure. Some clinicians always take several biopsy specimens at the first visit to avoid the delay, anxiety, and aggravation resulting from a negative pathology report for a patient in whom cancer is strongly suspected. Fix biopsies in 10% normal saline to prevent autolysis.

Avoid excisional biopsies unless the lesion is small because the procedure is unlikely to have achieved excision of an adequately wide margin of tissue if the lesion is malignant but will have destroyed clinical evidence of the site and character of the lesion for the surgeon or radiotherapist. This can be avoided by tattooing the site.

For lymph node biopsy, a biopsy is best performed on regional lymph nodes suggestive of cancer using a fine-bore needle to aspirate cells for cytologic examination. Ultrasound-guided fine-needle aspiration cytology is now favored. False-negative results are possible, but the primary danger of incisional biopsy is that it may seed malignant cells. In practical terms, ipsilateral, firm or hard, enlarged regional lymph nodes in a patient with an obvious oral carcinoma are likely to include metastases.

The epithelium forms islands resembling normal stratified squamous epithelium, except that the islands are invading the underlying tissues and undergoing aberrant keratinization. Instead of the keratin being formed and shed from the surface, it is formed within the substance of an epithelial island, producing a keratin whorl or epithelial pearl. This is a feature of well-differentiated carcinoma.

Epithelial islands may be discrete and circumscribed, although they are invading the underlying tissues quite extensively or appear more moth eaten with loss of basement membrane; however, loss of basement membrane is not a prerequisite of an invasive tumor. Occasionally, an endogenous foreign body giant cell reaction to the keratin from ruptured pearls occurs.

SCC consists of small islands of squamous cells with a high mitotic index and nuclear hyperchromatism but no obvious keratinization.

Poorly differentiated SCC consists of sheets of cells showing extreme pleomorphism, giant nuclei, and multiple and bizarre mitoses and often is difficult to distinguish from other malignancies, particularly poorly differentiated lymphoma or melanoma. In this instance, immunocytochemical markers such as keratins, common leukocyte antigen, and melanoma-specific antibodies are indicated.

The 1993 American Joint Committee on Cancer TNM classification and staging of oral cancer is as follows:

Classification

• Primary tumor

  • T0 - No primary tumor
  • Tis - Carcinoma in situ
  • T1 - Tumor 2 cm or smaller
  • T2 - Tumor 4 cm or smaller
  • T3 - Tumor larger than 4 cm
  • T4 - Tumor larger than 4 cm and deep invasion to muscle, bone, or deep structures (eg, antrum)
• Lymphatic node involvement

  • N0 - No nodes
  • N1 - Single homolateral node smaller than 3 cm
  • N2 - Nodes(s) homolateral smaller than 6 cm
  • N3 - Nodes(s) larger than 6 cm and/or bilateral
• Tumor metastasis

  • M0 - No metastasis
  • M1 - Metastasis noted

Staging

• Stage I - T1, N0, M0
• Stage II - T2, N0, M0
• Stage III

  • T3, N0, M0
  • T1, T2, T3, N1, M0
• Stage IV

  • T4, N0, M0
  • Any T, N2 or N3, M0
  • Any T, any N, any M