Pulmonary Adenocarcinoma: Symptoms, Causes, Diagnosis, Classification and Treatment

It is the most common type of lung cancer.

It is characterized by distinct cellular and molecular characteristics, including gland formation and the production of significant amounts of mucus.

It is also classified as one of several non-small cell lung cancer, to distinguish it from small cell lung cancer that has a different behavior and prognosis.

Signs and symptoms of lung adenocarcinoma

The most common signs of lung cancer include:

  • Cough that does not go away or gets worse.
  • Coughing up blood
  • Chest pain, which may be aggravated by deep breathing, coughing, or laughing.
  • Weight loss and loss of appetite.
  • Difficult breathing
  • In general, you feel tired or weak.
  • Recurrent or unresolved lung infections.
  • New onset of wheezing without a history of asthma .

Importantly, all of these signs are most commonly due to causes other than cancer.


The risk of lung adenocarcinoma increases substantially after a long duration of smoking , with a previous duration of smoking of 30-40 years, giving a relative risk of approximately 2.4 compared to non-smokers, and a duration of more than 40 years with a relative risk of approximately 5.

This cancer is generally seen peripherally in the lungs, unlike small cell lung cancer and squamous cell lung cancer, which tend to be more centrally located, although they can also appear as central lesions.

Smokers are more likely to develop lung adenocarcinoma.

Deeper inhalation of cigarette smoke produces peripheral lesions that are often the case in lung adenocarcinomas. In general, adenocarcinoma grows more slowly and forms smaller masses than the other subtypes. However, it tends to metastasize at an early stage.

Molecular biology

Chromosomal rearrangements

Three membrane-associated tyrosine kinase receptors are recurrently involved in rearrangements in adenocarcinomas: ALK, ROS1, and RET, and more than eighty other translocations have also been reported in lung adenocarcinomas.

Targeted therapies: The ALK and ROS1 fusion proteins are sensitive to treatment with the new ALK tyrosine kinase inhibitors (see Atlas of Genetics and Cytogenetics in Oncology and Hematology).

Genetic mutations

Common genetic mutations in lung adenocarcinoma affect many genes, including EGFR (20%), HER2 (2%), KRAS, ALK, BRAF, PIK3CA, MET (1%, associated with resistant disease), and ROS1.

Most of these genes are kinases and can be mutated in different ways, including amplification. The most commonly mutated gene in lung adenocarcinomas is TP53.

Diagnosis of lung adenocarcinoma

A diagnosis of lung cancer can be suspected on the basis of typical symptoms, particularly in a person with a history of smoking.

Symptoms like coughing up blood and unintentional weight loss may prompt further investigation, such as medical imaging.


A chest X-ray is often the first imaging test done when a person has a cough or chest pain, particularly in a primary care setting.

A chest x-ray can detect a lung mass / nodule suggestive of cancer, although sensitivity and specificity are limited.


If possible, a biopsy of any suspected lung cancer is performed to perform a microscopic evaluation of the cells involved.

Lung adenocarcinoma tends to stain mucin as it is derived from the mucus-producing glands of the lung.

Similar to other adenocarcinomas, if this tumor is well differentiated (low grade) it will resemble the normal glandular structure.

Poorly differentiated adenocarcinoma will not resemble normal glands (high grade) and will be detected by seeing that they stain positively for mucin (produced by the glands).

Adenocarcinoma can also be distinguished by staining for TTF-1, a cellular marker for adenocarcinoma.


The adenocarcinoma category includes a range of subtypes, and any tumor tends to be heterogeneous in composition.

Several main subtypes are currently recognized by the World Health Organization (WHO).

  • Non-invasive or minimally invasive adenocarcinoma.
  • Adenocarcinoma in situ of the lung (bronchioalveolar carcinoma).
  • Minimally invasive lung adenocarcinoma.
  • Adenocarcinoma invasivo.
  • Adenocarcinoma predominante acinar.
  • Predominant papillary adenocarcinoma.
  • Adenocarcinoma micropapilar predominante.
  • Solid predominant adenocarcinoma.
  • Adenocarcinoma mucinoso invasivo.

In up to 80% of these tumors, components of more than one subtype will be recognized. Surgically resected tumors should be classified by complete histologic subtypes, which describe patterns of involvement in 5% increments.

The predominant histological subtype is used to classify the tumor in general. The predominant subtype is the survival prognosis after complete resection.

Signet ring and clear cell adenocarcinoma are no longer histologic subtypes, but cytologic features that can appear in tumor cells of multiple histologic subtypes, most commonly solid adenocarcinoma.

Some variants are not clearly recognized by the WHO and IASLC / ATS / ERS classification:

  • Enteric lung adenocarcinoma.
  • Cribriform lung adenocarcinoma.

Treatment of lung adenocarcinoma

Adenocarcinoma is a non-small cell lung carcinoma and as such does not respond as much to radiation therapy as small cell lung carcinoma, but is treated surgically, for example by pneumonectomy or lobectomy .

Early-stage disease is treated surgically. Targeted therapy is available for lung adenocarcinomas with certain mutations.

Crizotinib is effective in tumors with fusions involving ALK or ROS1, while gefitinib, erlotinib, and afatinib are used in patients whose tumors have EGFR mutations.