Atypical adenomatous hyperplasia of the lung: A probable forerunner in thedevelopment of adenocarcinoma of the lung

An increasingly large body of work suggests that atypical adenomatous hyper plasia (AAH) of the lung may be a forerunner of pulmonary adenocarcinoma. R ecognizing this fact, the World Health Organization now acknowledges the ex istence of AAH while noting difficulties that may be encountered in disting uishing AAH from the nonmucinous variant of bronchioloalveolar carcinoma. R egrettably, a universally acceptable definition of morphologic criteria for the diagnosis of AAH has not been achieved. This review of the literature examines the epidemiology, gross appearance, light microscopic findings, mo rphometry, immunohistochemistry, and molecular features of AAH and suggests a set of histopathologic features that may help the practicing pathologist identify this intriguing lesion. These features include the following: irr egularly bordered focal proliferations of atypical cells spreading along th e preexisting alveolar framework; prominent cuboidal to low columnar alveol ar epithelial cells with variable degree of atypia but less than that seen in adenocarcinoma; increased cell size and nuclear-cytoplasmic ratio with h yperchromasia and prominent nucleoli, generally intact intercellular attach ment of atypical cells with occasional empty-looking spaces between them wi thout high cellularity and without tufting or papillary structures; and sli ght thickening of the alveolar walls on which the AAH cells have spread, wi th some fibrosis but without scar formation or significant chronic inflamma tion of the surrounding lung tissue. Several lines of evidence indicate tha t AAN is a lesion closely associated with adenocarcinoma of the lung, sugge sting AAH may be involved in the early stage of a complex multistep carcino genesis of pulmonary adenocarcinoma.