Background: It is common for biopsies of concerning pulmonary nodules to result in cytologic “atypia” on biopsy, which may represent a benign response or a false negative finding. This investigation evaluated time to diagnosis and factors which may predict an ultimate diagnosis of lung cancer in these patients with atypia cytology on lung nodule biopsy. Methods: This retrospective study included patients of the Stony Brook Lung Cancer Evaluation Center who had a biopsy baseline diagnosis of atypia between 2010 and 2020 and were either diagnosed with cancer or remained disease free by the end of the observation period. Cox Proportional Hazard (CPH) Models were used to assess factor effects on outcomes. Results: Among 106 patients with an initial diagnosis of atypia, 80 (75%) were diagnosed with lung cancer. Of those, over three-quarters were diagnosed within 6 months. The CPH models indicated that PET positivity (SUV ≥ 2.5) (HR = 1.74 (1.03, 2.94)), nodule size > 3.5 cm (HR = 2.83, 95% CI (1.47, 5.45)) and the presence of mixed ground glass opacities (HR = 2.15 (1.05, 4.43)) significantly increased risk of lung cancer. Conclusion: Given the high conversion rate to cancer within 6 months, at least tight monitoring, if not repeat biopsy may be warranted during this time period for patients diagnosed with atypia.

In cytologic analysis of lung nodules, specimens classified as atypia cannot be definitively diagnosed as benign or malignant. Atypia patients are typically subject to additional procedures to obtain repeat samples, thus delaying diagnosis. We evaluate morphologic categories predictive of lung cancer in atypia patients. This retrospective study stratified patients evaluated for primary lung nodules based on cytologic diagnoses. Atypia patients were further stratified based on the most severe verbiage used to describe the atypical cytology. Logistic regressions and receiver operator characteristic curves were performed. Of 129 patients with cytologic atypia, 62.8% later had cytologically or histologically confirmed lung cancer and 37.2% had benign respiratory processes. Atypia severity significantly predicted final diagnosis even while controlling for pack years and modified Herder score (p = 0.012). Pack years, atypia severity, and modified Herder score predicted final diagnosis independently and while adjusting for covariates (all p < 0.001). This model generated a significantly improved area under the curve compared to pack years, atypia severity, and modified Herder score (all p < 0.001) alone. Patients with severe atypia may benefit from repeat sampling for cytologic confirmation within one month due to high likelihood of malignancy, while those with milder atypia may be followed clinically.