The respiratory tract is comprised of upper and lower airways. The upper airway extends from the sinonasal tract to the larynx, and the lower tract extends from the trachea to the lungs. Although all sites are amenable to cytological sampling, the lower tract is usually the target for the detection of infections, benign lesions, and neoplastic processes. Various sampling techniques are utilized, occasionally with the use of concurrent needle core biopsies (NCB). In this chapter only the lower respiratory tract will be addressed.

Lung carcinoma is common and is the leading cause of death in men and women. According to the American Cancer Society, there will be approximately 225,000 new cases of lung cancer and about 158,080 deaths from the disease (accounting for one of four cancer deaths) in 2016. Only 20 % of lung cancers are diagnosed at an early stage when the disease is still localized within the lungs. At the time of diagnosis, 25 % of patients have regional metastasis, and 55 % of patients have distant spread of disease. Thus, early detection remains the major cornerstone for the successful treatment of pulmonary malignancies.

Carcinomas, both of the small cell and non-small cell types, are by far the most common malignancy of the respiratory tract. Non-small cell lung cancer (NSCLC) accounts for ~85 % of all lung cancers. Histologically, NSCLC is divided into adenocarcinoma, squamous cell carcinoma, and large cell neuroendocrine carcinoma. Patients with NSCLC require a complete staging workup to evaluate the extent of disease because stage plays a major role in determining the choice of treatment.

The accuracy of differentiating between small cell carcinoma and NSCLC on cytology specimens ranges from 94 to 100 % when compared with resection or autopsy specimens. The accuracy of subclassifying NSCLC into adenocarcinoma, squamous cell carcinoma, and large cell neuroendocrine carcinoma ranges from 66 to 91 %. Concordance between bronchoscopically obtained cytology and biopsy specimens is >95 % in recent studies. The overall sensitivity increases with a combined use of different sampling modalities.

Metastatic malignant neoplasms, from almost any site, can metastasize to the lung. Generally, lung metastases are identified in 30–55 % of all cancer patients. Tumors that commonly metastasize to the lung include carcinomas from the colon, breast, prostate, and urinary bladder, sarcomas, and melanomas.

The new Papanicolaou Society of Cytology guidelines for standardized terminology and nomenclature for respiratory cytology are designed to stratify the risk of malignancy with diagnostic categories for appropriate patient management [1]. The current guidelines provide diagnostic categories and criteria and also describe techniques for obtaining specimens, ancillary testing, and patient follow-up and management. A six-tiered system is recommended as the standardized nomenclature for reporting respiratory cytology diagnoses. The categories proposed are nondiagnostic, negative (for malignancy), atypical, neoplastic (benign and low-grade malignancy), suspicious for malignancy, and malignant. A multidisciplinary diagnostic approach is recommended. Patient management should be determined by correlating the clinical findings in concert with imaging features, cytological findings, and result of molecular analysis, if pertinent.

The examination of exfoliative respiratory cytology is an efficient and cost-effective method for diagnosing respiratory tract lesions. An accurate diagnosis relies on receiving an adequate sample, optimal specimen preparation using LBP, cell block, and expertise in interpretation of LBP.

The principal indications for exfoliative cytology of the respiratory tract are as follows:

Exfoliative respiratory tract specimens are usually processed as one Papanicolaou (Pap)-stained LBP. The collection specimen is rinsed in a preservative medium for LBP. Direct smears from brushings can also be made with a quick rolling motion of the brush on glass slides. The slides can be fixed in 95 % ethanol for Pap staining or air-dried for Romanowsky staining (e.g., Diff-Quik stain). Residual material can be rinsed in collection medium and used to process additional LBP for special stains, immunostains, or cell block preparation, especially if tissue fragments are noted. Please see Chap. 1 also.