Morphology and genetics of pre-invasive pulmonary disease

A Subset of Lung Adenocarcinomas and Atypical Adenomatous Hyperplasia–Associated Foci Are Genotypically Related

“…1 AAH is a focal, slightly atypical proliferation of monolayer cuboidal pneumocytes with distinct margins, measuring less than 5 mm in maximum diameter, and appears as a solitary or multifocal small ground-glass nodule in a high-resolution computed tomography scan. [1][2][3][4][5][6] Some authors subdivide AAH into low and high grade, but this issue remains controversial, and subdivision is not recommended by the 2004 WHO classification. The differential diagnosis between AAH and nonmucinous-type bronchioloalveolar carcinoma (nmBAC) may be difficult, and distinction is basically related to the size of the lesion and the cytologic characteristics of the cells.…”

“…The differential diagnosis between AAH and nonmucinous-type bronchioloalveolar carcinoma (nmBAC) may be difficult, and distinction is basically related to the size of the lesion and the cytologic characteristics of the cells. [1][2][3][4] Although AAH foci are mainly found in patients with multiple synchronous lung adenocarcinomas, it is hard to prove that the former is a precursor of the latter. Previous studies have highlighted the presence of several genetic alterations in AAH and then demonstrated the neoplastic nature of this lesion.…”

“…Previous studies have highlighted the presence of several genetic alterations in AAH and then demonstrated the neoplastic nature of this lesion. [1][2][3][4][5][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase (RTK) deeply involved in the carcinogenesis of non-small cell lung cancer (NSCLC), mainly adenocarcinomas. 24 A subset of patients with NSCLC experienced a significant improvement of symptoms and/or survival using orally dispensed small molecules acting as EGFR selective inhibitors (ie, erlotinib and gefitinib).…”

Current issues in pulmonary adenocarcinoma

“…Autopsy-based studies have found lesions in 2-4% of patients. 15 Some lesions are visible on the cut surface of well fixed, inflated lung but the majority are incidental microscopic findings, more frequently found in the upper lobes and in subpleural lung. The best prospective studies describe AAH in around 20-25% of adenocarcinomas, but in only 9% of squamous cell carcinoma resections.…”

“…4,7 This underpinned Miller's original proposal that there exists in the lung an adenoma−carcinoma sequence akin to that seen in the colon. 15 In early lung adenocarcinogenesis, some AAH lesions, probably only very few, transform into the next stage: pure localized non-mucinous bronchioloalveolar carcinoma (LNMBAC). There is now much detailed morphometric and molecular biological evidence to support the neoplastic, pre-invasive nature of AAH.…”