Respiratory cytology: differential diagnosis and pitfalls

Pulmonary cytology can be challenging and has its share of diagnostic pitfalls. Reactive atypia can occasionally be alarming, leading to diagnostic pitfall for a false-positive diagnosis of malignancy, even for experienced cytopathologists (Naryshkin and Young, Diagn Cytopathol 1993;9:89-97). In addition, cytologic preparations can show an absence of architectural clues, leading to diagnostic difficulties. Some conditions can cytologically as well as clinically and radiographically mimic malignancies, making these pitfalls even more frequent (Bedrossian et al., Lab Med 1983;14:86-95). A recent report stated that "no laboratory that aims to make definitive diagnoses in pulmonary cytology can be spared from false-positive results"(Policarpio-Nicolas and Wick, Diagn Cytopathol 2008;36:13-19). A false-positive finding could produce unnecessary treatment and morbidity, whereas false-negative diagnosis could result in delayed diagnosis and treatment. This review analyzes and illustrates cellular changes and benign entities that can mimic malignancy in respiratory cytology as well as neoplasms that could lead to a false-negative diagnosis. In addition, some specific challenging and difficult aspects in classification of pulmonary malignancies will be discussed. Guidelines and clues are presented to avoid such pitfalls.