Benign and Infectious Respiratory Lesions

Many respiratory cytology specimens show benign reactive, reparative, or infectious changes rather than malignancy. Recognising the cytologic features of infection, granulomatous disease, and reactive epithelial atypia is essential both to make positive non-neoplastic diagnoses and to avoid mistaking reactive changes for cancer.

Definition

Benign and infectious respiratory lesions, in cytopathology, are the non-neoplastic reactive, inflammatory, and infectious processes of the respiratory tract identified in cytologic specimens by their characteristic cells, organisms, and reactive changes.

Scope

This topic covers the cytomorphology of common non-neoplastic respiratory processes: viral cytopathic effect, fungal organisms including Pneumocystis jirovecii, mycobacterial and bacterial infection, granulomatous inflammation, and reactive and reparative epithelial atypia. It is a reference-educational overview of recognising benign and infectious patterns, not a guide to anti-infective treatment.

Core questions

• Which cytologic features identify specific respiratory infections in airway and lavage specimens?
• How can reactive and reparative epithelial atypia be distinguished from malignancy?
• What does the cellular pattern of a benign specimen contribute to diagnosis?

Key concepts

• Viral cytopathic effect
• Pneumocystis jirovecii and fungal organisms on lavage
• Granulomatous inflammation and multinucleated giant cells
• Reactive and reparative epithelial atypia
• Ciliated cell changes and Creola bodies
• Distinguishing reactive atypia from malignancy

Mechanisms

Infectious agents produce characteristic cytologic signatures: viruses induce nuclear and cytoplasmic inclusions and cytopathic change, fungi and Pneumocystis appear as recognisable organisms or foamy alveolar casts, and mycobacterial and other infections elicit granulomatous inflammation with epithelioid histiocytes and multinucleated giant cells. Bronchoalveolar lavage is a key specimen for detecting opportunistic organisms such as Pneumocystis jirovecii, particularly in immunocompromised patients (Sung 2011). Injury and inflammation also drive epithelial regeneration, producing reactive and reparative atypia, enlarged nucleoli, and cohesive sheets that can closely mimic malignancy and are a recognised source of false-positive interpretation.

Clinical relevance

Identifying a benign or infectious cause in a respiratory specimen can establish a diagnosis non-invasively and helps avoid overcalling reactive changes as cancer; bronchoalveolar lavage in particular can detect opportunistic infection in vulnerable patients. This entry describes the cytologic recognition of these processes for reference; it does not provide diagnostic thresholds or treatment recommendations for individual patients.

Epidemiology

Pneumocystis jirovecii pneumonia is an important opportunistic infection in immunocompromised hosts, and bronchoalveolar lavage cytology is a recognised means of detecting the organism in such patients (Sung 2011).

Evidence & guidelines

An official American Thoracic Society clinical practice guideline standardises the interpretation of bronchoalveolar lavage cellular analysis, including in infectious and interstitial contexts (Meyer 2012). Case-series evidence documents the performance of lavage cytology for detecting Pneumocystis jirovecii (Sung 2011). The need to distinguish reactive atypia from malignancy is emphasised within diagnostic guidance for suspected lung cancer (Rivera 2013).

History

The cytologic recognition of respiratory infection and reactive change developed alongside diagnostic respiratory cytology in the twentieth century, becoming especially important with the rise of opportunistic infections in immunocompromised populations, for which bronchoalveolar lavage emerged as a key sampling method (Sung 2011).

Seminal works

• sung-2011
• meyer-2012

Frequently asked questions

Why is reactive atypia a problem in respiratory cytology?

Inflammation, infection, infarction, and prior therapy can cause epithelial cells to enlarge and show prominent nucleoli, mimicking malignant change and risking a false-positive interpretation; awareness of these patterns and clinical correlation help avoid it.

Can respiratory cytology diagnose infection?

Yes; many infections show characteristic organisms or cytopathic changes, and bronchoalveolar lavage is a recognised specimen for detecting organisms such as Pneumocystis jirovecii, especially in immunocompromised patients.