Expansion of the Concept of Micropapillary Adenocarcinoma to Include a Newly Recognized Filigree Pattern as Well as the Classical Pattern Based on 1468 Stage I Lung Adenocarcinomas

Introduction: The classical micropapillary (MIP) pattern is defined in the 2015 WHO classification as tumor cells growing in papillary tufts forming florets that lack fibrovascular cores, and it is associated with poor prognosis. We observed a novel pattern that we termed a filigree MIP pattern and investigated its relationship with the classical MIP pattern. Methods: Filigree pattern was defined as tumor cells growing in delicate, lace-like, narrow stacks of cells without fibrovascular cores. We required at least three piled-up nuclei from the alveolar wall basal layer, with a breadth of up to three cells across. To assess the relationship of the filigree pattern with the classical MIP pattern, we documented their frequencies in the context of the clinical and pathologic characteristics of 1468 stage I invasive adenocarcinomas, including survival analysis using cumulative incidence of recurrence by competing risks. Results: We observed the filigree MIP pattern in 35% of cases. By including the filigree pattern as an MIP pattern, we identified 57 more MIP predominant cases in addition to the previously diagnosed 87 MIP predominant adenocarcinomas. These 57 cases were reclassified from papillary (n = 37), acinar (n = 16), and solid (n = 4) predominant adenocarcinoma, respectively. Of the 144 MIP predominant adenocarcinomas, the filigree predominant MIP pattern (n = 78) showed a poor prognosis like the classical predominant MIP pattern (n = 66) (p = 0.464). In addition, like the classical MIP pattern (p = 0.010), even a small amount (≥5%) of filigree MIP pattern was significantly associated with worse cumulative incidence of recurrence (p = 0.001) in multivariable analysis. Conclusion: The frequent association with the classical MIP pattern and the similar poor prognosis supports inclusion of the filigree pattern in the MIP pattern subtype.