Lung cancer cytology. Something old, something new.

The diagnosis of lung cancer by cytologic methods is of historic interest because it was an early demonstration that malignancy could be diagnosed by examining exfoliated cells. As reviewed by Johnston and Frable,1 Donne and Walsh separately noted that exfoliated respiratory cells occurred in sputum in 1845. The first major series of patients in which the examination of sputum led to a diagnosis of lung cancer was by Hamplen in 1919; 13 of 25 cases were successfully diagnosed. After several years of quiescence, pulmonary cytology enjoyed a period of rapid development in the 1970s and 1980s, particularly as fine-needle aspiration (FNA) was validated as an alternative to open lung biopsy or transbronchial biopsy for the diagnosis of pulmonary malignant neoplasm and infectious and inflammatory lung diseases. During this time, technical advances in radiologic technique permitted the imaging of small lesions and guidance of aspiration biopsy, as well as improvements in the design of bronchoscopes. Despite the important advances we are observing in body imaging (eg, spiral computed tomography [CT] scanning of the chest) and molecular diagnostics, it is encouraging that the morphologic examination of respiratory material still contributes substantially to diagnosis and patient management. This is illustrated in the work by Sturgis and colleagues2 in this issue of the Journal. Their statistical analysis of the cytomorphologic features of small cell carcinoma (SCCa) of the lung provides insight into the morphologic subclassification of lung cancer. Before commenting on their observations, it is useful to summarize the 5 major techniques to obtain cellular material for the diagnosis of lung cancer. The oldest and most fundamental method is sputum collection, which depends on the spontaneous exfoliation of cells. There are 3 bronchoscopic techniques: bronchial washing, bronchial brushing, and bronchoalveolar lavage. Finally, FNA techniques can be performed through the chest wall under radiographic guidance or transbronchoscopically. No collection method is necessarily superior to the others. The choice of cell collection technique is shaped by factors such as the personal preference of the physician, the status of the patient, the location of the lesion, and the differential diagnosis. However, the cytologist should understand that while cells obtained by different techniques have substantially similar morphologic characteristics, important differences are caused by differences in cell preservation and specimen processing. An example is the different sensitivity for lung cancer detection between freshly smeared and fixed, blended sputum specimens. Artifacts caused by the mechanical blending of the specimen lower the sensitivity of disease detection for small cell undifferentiated carcinoma and adenocarcinoma. The mechanical blending disrupts cell fragments and shears mucin-containing vacuoles from cells, thus complicating the diagnosis of adenocarcinoma. Fixation affects the nuclear diameter and the staining quality of the nuclear chromatin. For example, nuclei of SCCa are larger and more vesicular in samples collected by brushing or needle aspiration compared with sputum samples. In recent years, liquid-based thin-layer methods have been adopted for specimen collection and processing. These methods create unique artifacts that also must be understood by the diagnostic cytologist. The key question addressed by Sturgis et al2 is the relative value of different morphologic features in discriminating SCCa from non-SCCa (NSCCa). Of course, SCCa is not a homogeneous diagnosis. The International Association for the Study of Lung Cancer has proposed 3 categories of