This type of growth is termed "lepidic" and is characteristic of adenocarcinoma of the lung in its earliest stages. Diagnosis
A diagnosis of lung cancer may be suspected on the basis of typical symptoms, particularly in a person with smoking history. Symptoms such as coughing up blood and unintentional weight loss may prompt further investigation, such as medical imaging. Classification
The majority of lung cancers can be characterized as either small cell lung cancer (SCLC) or non-small cell lung cancer (NSCLC). Lung adenocarcinoma is one of the three major subtypes of NSCLC, which also include squamous carcinoma and large cell carcinoma.Historically, there has been much debate in the most accurate method of describing adenocarcinoma of the lung and several revisions of classification systems have been published. Most recently, the International Multidisciplinary Classification of Lung Adenocarcinoma was published in 2011 and represents the consensus of several organizations to more accurately describe this specific type of lung cancer. The current classification system aims to more reliably predict prognosis and determination of therapeutic management.The tumor size, pattern of cell growth, and depth of cell invasion into normal lung tissue are considered in determining classification. The following names represent a step-wise pathologic progression in the natural course of adenocarcinoma development; Adenocarcinoma in situ (AIS), Minimally invasive adenocarcinoma (MIA), and Invasive adenocarcinoma. Invasive adenocarcinoma of the lung includes a heterogenous mixture of subtypes and variants. The 2011 consensus describes five subtypes of invasive adenocarcinomas based on the cell pattern that is most predominant.
Mechanism
Pathogenesis
Large scale studies such as The Cancer Genome Atlas (TCGA) have systematically characterized recurrent somatic alterations likely driving lung adenocarcinoma initiation and development. Gene mutations and copy number alterations
Since smoking is a strong mutagenic factor, lung adenocarcinoma is one of the tumor types with the highest number of mutations. Common somatic mutations in lung adenocarcinoma affect many oncogenes and tumor suppressor genes, including TP53 (mutated in 46% of cases), EGFR (27%), KRAS (32%), KEAP1, STK11 and NF1. EGFR and KRAS mutations tend to appear in a mutually exclusive fashion. KRAS mutations are associated with smoking habits, whereas EGFR mutations occur more frequently in females, people of Asian ethnicity and never-smokers.Copy number amplifications in oncogenes such as TERT, MDM2, EGFR, MET, and MYC have been reported, as well as deletions of tumor suppressor genes such as CDKN2A.Frequent alterations occur in genes belonging to the receptor tyrosine kinase pathway, of which EGFR is the most prominent example. This pathway is involved in cell proliferation and survival and it is often deregulated in cancer. As a consequence, targeted therapies have been developed to inhibit mutant pathway components. Chromosomal rearrangements
Three membrane associated tyrosine kinase receptors are recurrently involved in fusions or rearrangements in adenocarcinomas: ALK, ROS1, and RET, and more than eighty other translocations have also been reported in adenocarcinomas of the lung.In ALK rearrangements, the most common partner gene is EML4. EML4-ALK fusions tend to occur in tumors that do not carry EGFR or KRAS mutations and have also a lower frequency of TP53 mutations.