Clinicopathologic Analysis of Multiple (Five or More) Atypical Adenomatous Hyperplasias (AAHs) of the Lung Evidence for the AAH-Adenocarcinoma Sequence

Objective: Clarification of the clinicopathologic characteristics of patients with multiple atypical adenomatous hyperplasias (AAHs). Materials and Methods: The subjects were 1639 patients who underwent lobectomy or pneumonectomy for lung tumors. The clinicopathologic features of the AAHs in the lung background and the main tumors were examined with regard to the number and the size of the AAHs, the incidence and histology of adenocarcinomas (ADs), and the outcome. Results: Thirty-two patients (2.0%) had 5 or more AAHs (ranging from 5 to 171), being present predominantly in the upper lobe (86%) and in women (75%). Among the 794 AAHs, 495 (62%) measured less than 1 mm, 170 (22%) measured 1 to less than 2 mm, 118 (15%) measured 2 to less than 5 mm, and 11 (1%) measured 5 to less than 10 mm. Twenty-eight patients (88%) had AD (1 in 18 patients and 2 to 6 in 10 patients). Thirty-two of the 51 patients with ADs (63%) had an AAH component. The incidence of ADs among the total of both AAHs and ADs was 6.0% (51 of 845). The 5-year cancer-free survival rate was 71.4%. Conclusion: Five or more AAHs were seen in the background in 2.0% of lung tumors. Most of the AAHs were small, measuring less than 2 mm, and few exceeded 5 mm. Most of the patients had ADs, which were histologically suggested to be derived from AAH. However, the incidence of the AAH-AD sequence was considered to be low at the tumor basis, and the outcome of ADs was not very favorable.