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Malignant cells populate the sputa of patients with lung cancers. These cells can be accessed for sampling and cytologic analysis by expectoration or bronchoscopy of the upper airway. Higher rates of malignant cells are observed for central as opposed to peripheral neoplasms (71% versus 49%).1 However, patients with suspected lung cancer do not generally benefit from routine sputum cytology because bronchoscopy or other definitive diagnostic procedures will be avoided in only a small percentage (1–2%) of patients. Although some clinicians recommend sputum analysis in situations where histologic diagnosis is needed but bronchoscopy is deemed unsuccessful or impractical, screening and surveillance remain the primary indications. Hence patients with atypical symptoms, high-risk characteristics, and a positive history of cancer are more likely to undergo this diagnostic procedure. Cancers in this category are termed radiographically occult lung cancers. As the term implies, these neoplasms are not radiologically evident on standard chest imaging. Intervals exceeding 5 years between evidence of positive cytology and subsequent confirmation of a specific bronchial carcinoma were described in reports emanating from the 1960s. Introduction of the flexible fiberoptic bronchoscope in 1969, however, probably has reduced this interval.

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When the first large-scale lung cancer screening programs were conducted in the late 1970s and 1980s, a small percentage of patients was identified with positive sputum cytology but a normal chest x-ray. Although radiographically occult, many of these cancers were determined to be early invasive carcinomas, arising from the segmental bronchus, with metastasis to adjacent lymph nodes.

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As with many other types of lung cancer, the symptoms seldom lead to the detection of occult disease, but a chronic change in the cough habits of an older smoker should heighten clinical suspicion. Bronchoscopic evaluation subsequent to a positive sputum cytology typically detects invasive or carcinoma in situ. Recovery of malignant cells from the same site on two separate bronchoscopic examinations is considered adequate proof for surgical resection.

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In comparative studies, 20% of squamous cell carcinomas determined by resection histology were interpreted as large cell and undifferentiated carcinomas on sputum cytology.2 Sputum showing small cell carcinoma almost always will have a concordant diagnosis. In contrast, a specific diagnosis of adenocarcinoma will be made in only two-thirds of patients with cytologically positive sputum samples.2

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Various factors influence the incidence of positive sputum. In patients producing sputum, three positive samples will achieve a correct cell type 90% of the time.2 Tumors (especially squamous cell) that approach T2 size yield a high sputum sensitivity, and this finding appears to be amplified in patients with severe obstructive disease, as defined by a forced expiratory volume in 1 second (FEV1) value of less than 50% of vital capacity.2 Centrally located tumors are more likely to produce a positive cytologic diagnosis.

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Sputum cytologic screening with its relatively low yield could become more practical with process automation, which would reduce the resources required to analyze ...

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