Pathology
As already stated, not all cancers of the upper aerodigestive tract are squamous cell cancers, and cancer may arise from minor salivary glands (e.g., adenocarcinoma, adenoid cystic carcinoma) or from the underlying submucosal tissue (various sarcomas and others). However, the vast majority are squamous cell carcinoma. Macroscopically, these cancers usually become evident late as an exophytic or fungating mass or as a superficial or deeply infiltrating ulcer with or without evidence of cervical lymphatic metastases.

Premalignant lesions are less easily identifiable but occasionally are noted. Of these, the most common is leukoplakia, which presents as a white patch (Plate IV-12). It should be appreciated, however, that the incidence of malignant transformation in these lesions is extremely rare (0.13% to 6%) and undue concern is inappropriate if these legions are identified, although they may require biopsy and careful follow-up. Of greater significance is the presence of erythroplakia, which presents as a red patch.

These patches have an extremely high incidence of malignant transformation (almost 100%). The erythroplastic character is related to a submucosal vascular proliferation and round cell infiltrate secondary to the malignant squamous cells (Plate IV-13). These cancers have a propensity to multicentricity within the field of growth (i.e. the mucosa of the upper aerodigestive tract), and it is not unusual to identify further cancers presenting either simultaneously or later during follow-up. Histologically the degree of differentiation has been shown to have no real practical significance, although these tumors are usually described as well, moderately well, and poorly differentiated. Probably of greater value in determining tumor behavior is whether the tumor infiltrates in a broad base or in columns of cells and depth of infiltration into the underlying soft tissue. Many histologic variants of squamous cell carcinoma have been described, including lymphoepithelioma, a tumor that arises in the lymphoid-bearing areas (i.e., the nasopharynx, faucial and lingual tonsils) and is exquisitely radiosensitive. Verrucous carcinoma is a cancer that is so well differentiated that it is difficult to establish the diagnosis histologically; it is preferably treated with surgery. These tumors tend to increase in size locally, infiltrating the surrounding structures, and metastasize to regional cervical nodes and then, in advanced stage, distantly to lung, liver, and bone.

The staging system used is that designed by the American Joint Committee on Cancer, which is updated every few years (

Box 98-1). This tumor staging system takes into account the surface dimensions of the tumor and infiltration into the surrounding structures, the presence and extent of nodal metastases, and the presence of distant metastases.

In general, tumors of the oral cavity and oropharynx are staged by their surface dimensions and tumors of the larynx, hypopharynx, and nasopharynx by their local extension. While quite useful as a means of standardization of description for reporting, the system does not take into account tumor behavior. For this reason, much effort has been directed to the identification of both histologic (e.g., tumor-host interface, tumor thickness, perineural and vascular invasion, angiogenesis) and molecular factors, to determine meaningful prognostic indicators.