Novel Pathologic Factors for Risk Stratification of Gastric “Indefinite for Dysplasia” Lesions

Abstract

Background/Aims. “Indefinite for dysplasia” (IND) conditions of the stomach have high malignancy rates (22.6%–75.0%). Endoscopic resection is sometimes used for follow-up, but criteria for selecting this follow-up method are not established. We investigated pathologic factors to subclassify the IND of the stomach and select appropriate follow-up methods. Methods. In total, 123 IND cases with final diagnoses of cancer (29.3%), high-grade dysplasia (6.5%), low-grade dysplasia (11.4%), and nonneoplasm (52.8%) were randomly divided into test set ( n = 27 ) and validation set ( n = 96 ). By the image analysis, size, pleomorphism, hyperchromasia, irregularity of nuclei, and ratios of structural atypia area (SAA) to total IND area were measured in the test set. Using the validation set, consensus meetings were held for the evaluation of pathologic factors that predict the final diagnosis. Results. By image analysis, the only ratio of SAA to total IND area was associated with the final diagnosis ( p < 0.001 ). In the consensus meeting for validation, the nuclear factors, except loss of nuclear polarity ( p = 0.004 – 0.026 ), could not predict the final diagnosis. Conversely, most structural factors could predict the final diagnosis. In particular, SAA > 25 % was the most powerful predictive factor. We proposed criteria of risk stratification by using SAA > 25 % , loss of surface maturation (LOSM), and loss of nuclear polarity (LONP) (Malignancy rate; Category 0: SAA ≤ 25 % without LOSM and LONP; 0%, Category 1: SAA ≤ 25 % with any of LOSM or LONP; 15.2%–16.7%, Category 2: SAA > 25 % without LOSM and LONP; 44.4%–50.0%, Category 3: SAA > 25 % with any of LOSM or LONP 54.5%–55.6%). Conclusions. Structural atypia was more helpful than nuclear atypia and SAA > 25 % was the most powerful predictor for the diagnosis of INDs of the stomach. We propose shortening the follow-up period to six months for Category 1, endoscopic resection for Category 2 and 3, postresection follow-up periods of one year for Category 2, and six months for Category 3.