1 Introduction to Lung Cytopathology and Small Tissue Biopsy

Application of the cytologic method to specifically examine respiratory specimens was used first in Europe by the mid1800s, though exfoliated epithelial cells were described as early as the 18th century. Hampeln’s 1897 paper is credited with the first thorough description of normal and nonmalignant cellular elements seen in sputum. And, about two decades later, his was one of the first publications to document the use of sputum cytology to diagnose pulmonary carcinoma in a series of 25 cases rather than a single report. Only sporadic and limited publications of respiratory cytology occurred in the early decades of the 20th century. A 3-year study of sputum cytology that culminated in a 1944 publication is considered as one of the most important contributions to clinical cytology of chest diseases in the first half of the 20th century. Nonetheless, it was only with the 1943 seminal publication by Papanicolaou and Traut that a major impetus to apply clinical exfoliative cytology to a variety of body sites really resulted in a renaissance of respiratory tract cytology. The consequence was a profusion of papers (only a handful referenced here) by the early 1950s concentrating in particular on the application of cytology to diagnose various forms of bronchogenic carcinoma, but also documenting the advantages that respiratory cytopathology offered in the recognition of fungal, parasitic, and viral diseases. Optimal design of the rigid bronchoscope occurred in 1904 when Jackson added a suction channel and a light to its distal end. It was used primarily for removing purulent secretions from the airways, and was the only instrument capable of examining the lower airway up to the late 1960s. However, the exceptional technical skill required to perform needle aspiration with this instrument led to its limited use. The flexible fiberoptic bronchoscope was first introduced by Ikeda et al. With this technical advance, physicians could now visualize and sample segmental and subsegmental bronchi of all lobes, and obtain samples from infants and children. By 1973 its use had become widespread. The flexible bronchoscope allows for passage of brushes, biopsy forceps, and needles through their lumens for diagnostic sampling, and has few complications. Therefore, fiberoptic bronchoscopy ushered in the most common form of cytologic sampling of the respiratory tract in use today. One of the earliest descriptions of transbronchial needle aspiration to sample mediastinal lymph nodes occurred in 1949, and that same author reported his results with the technique in a series of 83 patients 9 years later. Modern transbronchial fine needle aspiration (TBNA), often referred to asWang needle after its inventor, was introduced in the late 1970s in the US for diagnosis and staging of bronchogenic carcinoma. Wang and colleagues showed that paratracheal lymph nodes, lesions within the bronchial wall, and masses compressing the tracheobronchial tree could be sampled using esophageal varices needles. This method increased the diagnostic yield over forceps biopsy alone in the detection of submucosal carcinoma. TBNA is typically performed prior to bronchial washing, brushing to minimize contamination of the aspirate with blood and mechanically exfoliated cells. In the last few years endobronchial ultrasound-guided fine needle aspiration (EBUS) has developed as an offshoot of TBNA in that it allows aspiration of mediastinal, hilar lymph nodes as well as pulmonary and mediastinal lesions under direct ultrasound control and in “real-time.” Although reports of percutaneous transthoracic lung aspiration appeared in the late 19th century, these aspiration procedures were employed primarily in patients with suspected pneumonia. Martin and Ellis pioneered the application of percutaneous transthoracic needle lung biopsy (using an 18-gauge needle) to lung cancer by reporting on a series of 41 cases. This was followed by a number of favorable