Lung cytology in the diagnostic workflow: A real-world study of its clinical impact

In the era of precision oncology, lung cancer diagnosis still relies on small and often limited tissue samples, which may be insufficient for definitive tumor classification and predictive biomarker assessment. In this context, lung cytology is gaining increased attention as a complementary source of tumor cells. However, its position within the diagnostic workflow remains incompletely defined. This study aimed to evaluate the real-world diagnostic contribution of lung cytology in routine clinical practice.

We conducted a retrospective analysis of patients diagnosed with lung cancer between 2022 and 2025 at our institution who underwent cytological sampling. Cases without histological biopsy were included when cytology represented the only clinically accepted diagnostic material. Cytological samples were categorized according to their diagnostic contribution into four groups: primary diagnostic role, exclusive predictive role, supportive role, and non-contributory role. The impact of cytology was further analysed according to specimen type, tumor histology, and in patients with multiple cytological samples. Predictive yield for biomarker testing and statistical associations were evaluated using Fisher's exact test, odds ratios, and McNemar's test for paired comparisons.

A total of 572 patients with 691 cytological specimens were included. Cytology provided an important diagnostic contribution in 121 cases (21.2%), providing primary diagnosis in 99 cases (17.3%) and enabling predictive biomarker assessment in 22 cases (3.8%). A supportive role, defined as cytological findings concordant with histological results, was observed in additional 250 cases (43.7%), bringing the overall proportion of cases in which cytology provided any diagnostic contribution to 64.9%. Cytology was non-contributory in 201 cases (35.1%). Diagnostic and predictive performance varied significantly according to specimen type. Pleural effusions and conventional TBNA showed significantly higher adequacy for molecular and PD-L1 testing compared with bronchial aspirates (OR 35.19; p < 0.0001). In patients with multiple cytological samples, the integration of different sampling techniques significantly reduced non-diagnostic cases (from 40.4% to 12.8%; p < 0.001).

Cytological samples provided an independent diagnostic and predictive contribution in more than 20% of cases. It also supported histological findings in a further 43.7% of patients, making it clinically informative in nearly two-thirds of patients. Although its performance varied according to specimen type, combining multiple sampling strategies significantly improved diagnostic yield. These findings highlight the continued value of cytology and support its broader integration into contemporary lung cancer diagnostic algorithms.