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Squamous cell lung cancer represents between 20% and 30% of all primary lung malignancy.1 It is believed that most squamous cell cancers begin in the central airway and will evolve in a stepwise, predictable way. These cancers are preceded by premalignant lesions that include squamous metaplasia, squamous dysplasia, and carcinoma in situ (CIS). Evidence of premalignant change is detected inconsistently in the induced sputum of high-risk individuals. If the carcinogenesis progresses, eventually central airway tumors will shed malignant cells that can be detected in sputum cytology preparations. Early superficial central airway cancers do not shed malignant cells in a reliable way, and the large-scale lung cancer screening trials of the 1970s and 1980s failed to demonstrate a mortality benefit from lung cancer screening with sputum cytology. Nonetheless, a small percentage of patients were identified with positive sputum cytology despite a normal chest x-ray in these trials. Cancers in this category were termed radiographically occult lung cancers. Although radiographically occult, many of these cancers were found to be early invasive carcinomas, arising from the segmental bronchi with metastases to adjacent lymph nodes. Diagnoses of these lung cancers were confirmed typically with white-light bronchoscopy (WLB).

The stepwise theory of lung cancer evolution is based in part on sputum obtained from high-risk patients and evidence obtained at autopsy in patients with lung cancer. Bronchial epithelial dysplasia is a presumed premalignant lesion, and recent work suggests that persistence of high-grade dysplasia is associated with development of invasive squamous cell carcinoma.2,3 Further evidence suggests that the presence of dysplastic cells in sputum cytology may even be a marker for peripheral lung cancer.4 In addition, there appears to be a great deal of biologic variation, with some rapid transitions to deep invasion and metastases. The most recent 8th edition TNM lung cancer staging system has the designation of “T1a ss” for “superficial-spreading tumor of any size but confined to the wall of the trachea or mainstem bronchus” and the “Tis” designation for CIS.5 Although microinvasion may be present pathologically, these lesions are typically too thin to be detectable with CT or PET scans. The evaluation and treatment of this group of malignancies are the focus of this chapter.


Timed observations also support the progression of the disease—from occult sputum-positive malignancy to the radiographically detectable image 2 years later.6 This still represents a relatively late stage in the process of oncogenesis. For instance, a 3- to 5-mm nodule contains more than 500 million cells.6 It may be possible to detect small nodules like this by studying the epithelium at sites distant from primary tumors. Monoclonal patches (only 200–400 cells) can be detected that have characteristics very similar to the primary tumor.7 Given the oncogenesis and field cancerization hypotheses, exfoliated tumor cells may survive longer in the sputum because of their resistance to apoptosis once separated ...

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