Effect of formalin fixation and tumour size in small-sized non-small-cell lung cancer: a prospective, single-centre study

Abstract

AIMS: Formalin fixation can cause tumour shrinkage. The aim of this study was to prospectively evaluate the effect of overnight formalin fixation on tumour size and the effect of clinicopathological parameters on changes in tumour 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 tumour diameters in the fresh and formalin-fixed specimens. Tumour size significantly differed (mean, 0.66 mm; P < 0.001) and was positively correlated (r2 = 0.982; P < 0.001) between fresh and formalin-fixed specimens. The percentage difference after fixation was 4.06%. Formalin fixation caused tumour shrinkage in 46.8%, tumour enlargement in 4.8%, and a tumour stage shift in 3.17%. The risk of a > 10% change in tumour size after formalin fixation was increased in tumours with a lepidic pattern [odds ratio (OR): 6.268; P = 0.001], in subsolid tumours (OR: 4.068; P = 0.011), and in the presence of adenocarcinoma in situ (AIS)/minimally invasive adenocarcinoma (MIA) histology (OR: 6.545; P = 0.003). Pleural dimpling lowered the risk of tumour 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 ischaemic time was the single risk factor for tumour shrinkage in the invasive adenocarcinoma subgroup (OR: 5.357; P = 0.021).

CONCLUSION: NSCLC tumours shrank or enlarged by 4.06% after overnight formalin fixation. A lepidic pattern and AIS/MIA histology were independent risk factors for both significant tumour shrinkage and growth after fixation. Longer ischaemic time was the single risk factor for significant tumour shrinkage in invasive adenocarcinoma.