Three recognized preinvasive lesions are precursors of invasive tumors in the bronchial tree and lung: squamous dysplasia and carcinoma in situ (SD/CIS) of the tracheobronchial mucosa, atypical adenomatous hyperplasia (AAH), and diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH). Both AAH and DIPNECH occur in the lung periphery.

SD/CIS lesions are generally invisible to the bronchoscopist during standard bronchoscopy but may be identified as nonspecific areas of abnormality at autofluorescence bronchoscopy (AFB). Bronchial biopsies taken from abnormal AFB mucosa generate more SD/CIS lesions but also inflamed or even normal mucosa. Squamous dysplasia is graded as mild, moderate, or severe by the degree of cytological atypia (mild dysplasia showing slight nuclear atypia; severe disease shows marked atypia) and architectural alteration of the bronchial epithelium. By definition, SD/CIS occurs in a full-thickness squamous (metaplastic) epithelium in which the distribution of atypical, often basaloid cells with vertically oriented nuclei occurs in the lower third, lower two thirds, or extends into the upper third in mild, moderate, and severe disease, respectively. Mitoses are found off the basal layer of the epithelium but confined to its lower third in moderate dysplasia and at higher levels in severe dysplasia. Carcinoma in situ is characterized by a completely chaotic epithelium of highly atypical cells and little or no evidence of organization or maturation. The basement membrane remains intact but varies in thickness and tends to be relatively straight, which is helpful in differentiation from invasive disease when subepithelial tissue is scant. Occasionally SD/CIS adopts a papillary architecture with vascular pegs of connective tissue protruding into the epithelium, so-called angiogenic squamous dysplasia.

Both AAH and DIPNECH are lesions of the peripheral lung, and neither is visible to the endoscopist or diagnosable on bronchial biopsy. It is conceivable that some alveoli showing AAH could, by chance, be sampled at transbronchial biopsy, but, depending on the degree of atypia, distinction between reactive changes or even bronchioloalveolar carcinoma may be impossible, so a certain diagnosis of AAH cannot be made at transbronchial biopsy. Similarly with DIPNECH, a carcinoid tumorlet or focus of bronchiolar neuroendocrine cell hyperplasia may be sampled by transbronchial biopsy, but the significance of such a finding cannot be ascertained.