No abstract

Pulmonary nodule characterization is currently being redefined as new clinical, radiologic, and pathologic data are reported, necessitating a reevaluation of the clinical management, especially of subsolid nodules. These are now known to frequently, although not invariably, fall into the spectrum of peripheral adenocarcinomas of the lung. Strong correlation between the Noguchi histologic classification and computed tomographic (CT) appearances of these lesions, in particular, has been reported. Serial CT findings have further documented that stepwise progression of lesions with ground-glass opacity, manifested as an increase in size or the appearance and/or subsequent increase of solid components, does occur in a select subset of patients. As a consequence, recognition of the potential association between subsolid nodules and peripheral adenocarcinomas requires a review of current guidelines for the management of these lesions, further necessitated by a differential diagnosis that includes benign lesions such as focal inflammation, focal fibrosis, and organizing pneumonia. Specific issues that need to be addressed are the need for consensus regarding an appropriate CT classification, methods for precise measurement of subsolid nodules, including the extent of both ground-glass and solid components, as well as accurate assessment of the growth rates as means for predicting malignancy and prognosis. It is anticipated that interim guidelines may serve to standardize our current management of these lesions, pending further clarification of their natural history.

No abstract

The mechanism by which anti-cancer immunity shapes early carcinogenesis of lung adenocarcinoma (ADC) is unknown. In this study, we characterize the immune contexture of invasive lung ADC and its precursors by transcriptomic immune profiling, T cell receptor (TCR) sequencing and multiplex immunofluorescence (mIF). Our results demonstrate that anti-tumor immunity evolved as a continuum from lung preneoplasia, to preinvasive ADC, minimally-invasive ADC and frankly invasive lung ADC with a gradually less effective and more intensively regulated immune response including down-regulation of immune-activation pathways, up-regulation of immunosuppressive pathways, lower infiltration of cytotoxic T cells (CTLs) and anti-tumor helper T cells (Th), higher infiltration of regulatory T cells (Tregs), decreased T cell clonality, and lower frequencies of top T cell clones in later-stages. Driver mutations, chromosomal copy number aberrations (CNAs) and aberrant DNA methylation may collectively impinge host immune responses and facilitate immune evasion, promoting the outgrowth of fit subclones in preneoplasia into dominant clones in invasive ADC.

A new classification of lung adenocarcinoma has been proposed recently-the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification. Abundant information from recent lung cancer computed tomography (CT) screening programs has increased our understanding of the strong, although imperfect, correlation between histologic findings of lung adenocarcinoma and subsolid pulmonary nodules on CT, including both "pure" ground-glass nodules (GGNs) and "part-solid" GGNs. Moreover, serial CT imaging has demonstrated stepwise progression of these nodules in a subset of patients, characterized by increase in size and density of GGNs and development of a solid component. Given the higher incidence of malignancy and the considerably lower growth rate of subsolid nodules, dedicated standardized guidelines for management of these nodules have been proposed, including long-term (≥3 y) CT follow-up using a low-dose technique. Radiologists should be familiar with the new terminology of lung adenocarcinomas and strategic management of subsolid pulmonary nodules.