Less than 1% of patients with adenocarcinoma of the lung will exhibit this finding, but when it does occur, it is a poor prognostic factor. The exact mechanism of HPO is unknown but it thought to be hormonal or neurogenic in etiology. The triad of HPO includes distal clubbing, arthritis, and bilateral symmetrical periosteal formation. Causes
Risk factors
According to the Nurses Health Study, the risk of pulmonary adenocarcinoma increases substantially after a long duration of tobacco smoking: smokers with a previous smoking duration of 30–40 years are more than twice as likely to develop lung adenocarcinoma compared to never-smokers (relative risk of approximately 2.4); a duration of more than 40 years increases relative risk to 5.This cancer usually is seen peripherally in the lungs, as opposed to small cell lung cancer and squamous cell lung cancer, which both tend to be more centrally located, although it may also occur as central lesions. For unknown reasons, it often arises in relation to peripheral lung scars. The current theory is that the scar probably occurred secondary to the tumor, rather than causing the tumor. The adenocarcinoma has an increased incidence in smokers, and is the most common type of lung cancer seen in non-smokers and women. Deeper inhalation of cigarette smoke results in peripheral lesions that are often the case in adenocarcinomas of the lung. Generally, adenocarcinoma grows more slowly and forms smaller masses than the other subtypes. However, it tends to metastasize at an early stage.
ALK and ROS fusions offer opportunities for targeted therapies with tyrosine kinase inhibitors. Pathophysiology
The respiratory tract can be divided into two main components: the conducting airways and the gas exchange airways. The gas exchange airways are made of alveoli, small microscopic air sacs that are responsible for the exchange of oxygen and carbon dioxide during normal breathing. Alveoli are composed of two cell types, type I and type II pneumocytes. Type I pneumocytes cover 95% of alveolar surfaces, and are not able to regenerate. Type II pneumocytes are more common, making up 60% of the cells within alveolar epithelium, but constitute only 3% of the alveolar surface.There are several factors that contribute to the transformation of normal alveolar epithelium into dysplastic, or pre-cancerous, lesions. Adenocarcinoma of the lung develops in a step-wise progression as type II pneumocytes undergo consecutive molecular changes that disrupt normal cell regulation and turnover. Atypical adenomatous hyperplasia (AAH) is considered a pre-cancerous lesion, and is thought to further progress to adenocarcinoma in situ and invasive adenocarcinoma of the lung. The lesions of AAH are <5 mm, can be single or multiple, and have a ground glass appearance on CT imaging. As more genetic mutations and dysregulation of normal cell signaling pathways accumulate, AAH can progress to adenocarcinoma in situ (AIS). AIS lesions are classified as small tumors <3 cm with abnormal type II pneumocyte cell growth that is limited to the alveolar spaces i.e. without invasion into the stroma, pleura, or vasculature.