Respiratory Exfoliative Cytology

, Christopher VandenBussche2 and Syed A. Hoda3

CBL Path, Rye Brook, NY, USA

Department of Pathology, Johns Hopkins University Department of Pathology, Baltimore, MD, USA

New York Presbyterian Hospital Weill Cornell Medical College, New York, NY, USA



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.

Cytological Reporting Guidelines

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.

Indications, Collection, and Laboratory Processing of Exfoliative Respiratory Tract Samples

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:

  1. 1.

    Workup of a solitary pulmonary nodule detected on diagnostic or screening CT


  2. 2.

    Workup of a pulmonary nodule detected on CT in patients with a prior malignancy


  3. 3.

    Workup of pulmonary infiltrates to exclude infectious etiology


Methods of Collection for Exfoliative Cytological Samples

  • Sputum

  • Bronchial brush and bronchial wash

  • Bronchoalveolar lavage (BAL)


The cytological examination of a spontaneously expectorated sputum is a noninvasive technique and can be used for the detection of infectious lesions and large centrally located tumors. Diagnostic sensitivity of sputum cytology is directly proportional to the number of samples examined, and its accuracy approaches 95 % when five (5) sequential samples are examined. However, sputum cytology is not recommended for screening lung cancer. A post-bronchoscopic sputum may be examined when the expectorated sputum is negative.

Bronchial Brush and Bronchial Wash Specimens

Bronchial brushing and bronchial wash specimens are obtained via flexible fiber-optic bronchoscope (FOB). FOB can also obtain fine-needle aspiration (FNA) biopsies and transbronchial forceps biopsies. The advantages of FOB include an increased visual range, especially in the upper lobes, minimal discomfort to the patient, and sampling of previously inaccessible lesions such as peripheral nodules.

Both bronchial brushing and bronchial wash can detect infectious and neoplastic lesions. If indicated, microbiological cultures can also be performed concurrently. The diagnostic yield for bronchial brushing depends upon an adequate bronchoscopic sampling as well as the size and location of the lesion. For central tumors, the diagnostic sensitivity of bronchial brushing and bronchial wash is lower than that of transbronchial biopsy (TBBx). The sensitivity of bronchial brushing and bronchial wash is further decreased for peripheral lesions. The concordance rate of bronchial brushing and TBBx is ~97 %. The highest diagnostic yield for bronchial brushing and bronchial wash is for squamous cell carcinoma, adenocarcinoma, and small cell carcinoma (in that order).

Bronchoalveolar Lavage (BAL) Specimens

BAL also performed using FOB is a safe technique with a diagnostic accuracy comparable to TBBx. It is valuable for the detection of opportunistic infections, and since it samples multiple bronchi, it is also suitable for sampling diffuse lesions such as adenocarcinoma with a lepidic growth pattern. The diagnostic sensitivity of BAL for organisms in immunosuppressed people is 82 % for Pneumocystis jirovecii, 83 % for cytomegalovirus (CMV) and fungal pneumonia, and 80 % for mycobacterial disease. The overall reported diagnostic yield of BAL for malignancy is about 50 % with a lower yield for peripheral lesions. The diagnostic yield is improved with the addition of other modalities such as bronchial brushing, bronchial wash, and TBBx.

Laboratory Processing of LBP Specimens

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.

Advantages of Cytological Specimens for Respiratory Tract over Needle Core Biopsy (NCB)

Aug 10, 2017 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Respiratory Exfoliative Cytology
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