Effect of Formalin Fixation and Tumor Size in Small-sized Non-Small Cell Lung Cancer: A Prospective, Single-Center Study

Aim Formalin fixation can cause tumor shrinkage. We prospectively evaluated the effect of overnight formalin fixation on tumor size and the effect of clinicopathological parameters on changes in tumor size in small-sized non-small cell lung cancer (NSCLC). Methods and results Our study included 126 surgically resected NSCLC specimens submitted in a fresh state. We measured the largest cross-sectional tumor diameters in the fresh and formalin-fixed specimens. Tumor size significantly differed (mean, 0.066 cm; p 10% change in tumor size after formalin fixation was increased in tumors with lepidic pattern (odds ratio [OR], 6.268; p=0.001), in subsolid tumors (OR, 4.068; p=0.011), and in adenocarcinoma in situ (AIS)/minimally invasive adenocarcinoma (MIA) histology (OR, 6.545; p=0.003). Pleural dimpling lowered the risk for tumor size change after fixation (OR, 0.162; p=0.019). On multivariate analysis, a lepidic pattern (OR, 4.601; p=0.010) and AIS/MIA histology (OR, 4.381; p=0.026) were still significant risk factors. Longer ischemic time was the single risk factor for tumor shrinkage in the invasive adenocarcinoma subgroup (OR, 5.357; p=0.021). Conclusion NSCLC tumors shrank or enlarged by 4.06% after overnight formalin fixation. A lepidic pattern and AIS/MIA histology were independent risk factors for both significant tumor shrinkage and growth after fixation. Longer ischemic time was the single risk factor for significant tumor shrinkage in invasive adenocarcinoma. This article is protected by copyright. All rights reserved.