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Biopsy specimens of “normal” mucous membrane of patients susceptible to the effects of the carcinogens of tobacco revealed morphologic abnormalities on electron microscopic examination that were consistent with the concept that carcinogenesis is a multistep process of sequential neoplastic development extending over a long period of time. Such changes in the upper aerodigestive tract are probably tobacco induced and may be reversible if tobacco exposure is eliminated. Use of the electron microscope can provide the clinician with an accurate assay of the severity of mucosal alterations induced by tobacco. The ability to detect such morphologic abnormalities should provide another deterrant to smoking and a useful tool in the further study of these phenomena.

Keratosis, atypia, carcinoma in situ, and microinvasive cancer occurring as white or red patches on the vocal cords are part of the diathesis of cancer of the aerodigestive tract and represented a sequential continuum. Excisional biopsy is the preferred treatment for identification and potential cure of the lesion. If the margins of excision are inadequate, further treatment options are either reexcision or radiotherapy. Radiotherapy should be used only when the need for voice conservation prevails. Cessation of smoking does not remove the potential for progression of the disease, therefore, all patients must be followed indefinitely. Excisional biopsy of keratosis, carcinoma in situ, and microinvasive cancer of the larynx offers an excellent prognosis for voice preservation and survival.

Eleven patients with unresectable or marginally resectable (stage III and IV) cancer of the head and neck were treated according to protocol with preoperative chemotherapy, surgical resection, and postoperative radiotherapy. Chemotherapy consisted of a combination of cis-diamminedichloroplatinum (II) (cis-DDP), 120 mg/M2, and bleomycin, 15 mg/M2, given sequentially during a three week treatment period. Seven patients initially had unresectable lesions which became amenable to surgical resection after chemotherapy. All eleven patients had approximately a 25 to 100 per cent reduction in tumor size. Histopathologic examination after chemotherapy showed a marked tendency towards cellular differentiation and keratin formation. Tumor necrosis was conspicuous by its absence. These histologic changes appear to be different from those seen after the use of other chemotherapeutic agents and radiotherapy. The histopathologic results closely resemble those found after the administration of bleomycin alone, although considerably accentuated.

In the larynx it is frequently difficult to identify carcinoma in situ, early infiltrating carcinoma, and the exact margins of an established carcinoma. It has been found that the use of toluidine blue as a supravital stain during direct laryngoscopy is a reliable adjunct to the early and precise diagnosis of carcinoma of the larynx.

A complete response to induction cis-platinum bleomycin chemotherapy significantly increases the probability of local tumor control and overall disease-free survival. Factors that favor a good response to chemotherapy are tumor histology (well differentiated), location of the primary site (oral cavity and oropharynx), nodal status (N 0 ) and size of the primary lesion (T 3 better than T 4 ). Increased cellular maturation after chemotherapy correlates with an improved clinical response. The importance of induction and maintenance chemotherapy in the treatment of advanced head and neck cancer still needs to be determined with larger randomized series. Reliable predictors of therapy outcome are needed for realistic treatment planning, especially when the potential morbidity is considered.

THE EARLY diagnosis and management of carcinoma of the oral cavity and pharynx continues to present a great challenge. Carcinoma in an early stage of development is hard to detect because the lesion may be impalpable and the color changes not very different from the color of the surrounding mucosa. When the tumor is still intraepithelial, the only evidence may be an area of "erosion" where the thin covering layer of keratin or flattened cells is missing. Because carcinoma in the oral cavity, pharynx, and larynx is often multicentric in origin, it is common to find satellite tumors adjacent to the main tumor mass; the satellite tumor may be inconspicuous and overlooked during definitive therapy. Many carcinomas of the oral cavity start out as surface lesions which spread over the mucosa much more than they infiltrate1; the margins of the tumor may be hard to define, especially if there is