Adenocarcinoma In Situ of Lung

Adenocarcinoma In Situ of Lung

Article
Healthy Lungs
Diseases & Conditions
+1
Contributed byKrish Tangella MD, MBADec 13, 2022

What are the other Names for this Condition? (Also known as/Synonyms)

  • AIS of Lung
  • Pulmonary Adenocarcinoma In Situ
  • Pulmonary AIS

What is Adenocarcinoma In Situ of Lung? (Definition/Background Information)

  • Adenocarcinoma In Situ (AIS) of Lung is a small-sized, localized, premalignant adenocarcinoma. In order to establish a diagnosis of adenocarcinoma in situ, no invasion of the lymphatic and vascular system should be seen. Also, pleural involvement should not be noted
  • Adenocarcinoma In Situ of Lung is usually non-mucinous type; though extremely rarely, it can be of mucinous type too. No histological pattern, such as acinar, papillary, or micropapillary, is noted
  • The cause of Adenocarcinoma In Situ of Lung is generally unknown, but it is influenced by smoking. The cancer can cause chest pain, breathing difficulties, fatigue, and other general signs and symptoms, such as fever, weight loss, and appetite loss
  • Surgery is the mainstay of treatment, although chemotherapy and radiation therapy may be used for treating Adenocarcinoma In Situ of Lung based on the assessment of the physician. With complete surgical removal of the tumor, the prognosis is excellent

Who gets Adenocarcinoma In Situ of Lung? (Age and Sex Distribution)

  • Individuals under the age of 40 years are rarely diagnosed with lung cancer. The majority of Adenocarcinoma In Situ of Lung cases are detected and diagnosed in adults over the age of 65 years
  • Both males and females are affected
  • Current studies do not show any racial or ethnic predilection

What are the Risk Factors for Adenocarcinoma In Situ of Lung? (Predisposing Factors)

There are no specific risk factors that have been identified for Adenocarcinoma In Situ of Lung. However, it has been associated with smoking.

In general, physicians believe that certain factors may increase an individual’s risk for lung cancers and these include:

  • Advancing age: The risk increases with age and most cases occur in individuals over the age of 65 years
  • Smoking: Smoking cigarettes, cigars, or pipes, increase the risk due to damaging chemicals being inhaled into the lungs. Prolonged smoking damages the lung, resulting in reduced clearance of the chemical carcinogens that accumulate in the lungs. This can lead to an increased risk of developing lung cancer
  • Exposure to secondhand smoke: Individuals, who do not smoke, but live with smokers, also have an increased risk
  • Air pollution: Exposure to polluted air may increase any individual’s risk. This is true, especially in the case of smokers, who are exposed to air pollution, than non-smokers
  • Exposure to asbestos and other harmful chemicals: Prolonged exposure to asbestos and other harmful chemicals including arsenic, chromium, nickel, and tar
  • Radon causing indoor air pollution: Radon, a colorless, odorless, and tasteless radioactive gas is produced by the natural breakdown of uranium in soil and rocks. In certain geographical regions, hazardous levels of radon gas can develop inside building or households. Individuals exposed to excessive amounts of radon gas are vulnerable to lung cancer
  • Family history: Individuals with one or more immediate family members or relatives with a history of lung cancer
  • Personal history: Individuals who have previously had lung cancer have an increased risk of its recurrence
  • Certain longstanding lung diseases: Lung diseases, such as lung fibrosis, tuberculosis, bronchitis, or chronic obstructive pulmonary disease (COPD) over a prolonged period of time, may increase an individual’s risk
  • Radiation therapy to the chest: Individuals who had radiation therapy to the chest for another cancer are increasingly prone to lung cancer
  • Working in mines
  • The presence of alpha 1 antitrypsin deficiency disorder

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one's chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Adenocarcinoma In Situ of Lung? (Etiology)

The exact cause of Adenocarcinoma In Situ of Lung is unknown.

  • Adenocarcinoma In Situ of Lung develops following atypical adenomatous hyperplasia and is considered a preinvasive lesion to minimally invasive adenocarcinoma. It is an intermediate step to pulmonary adenocarcinoma development
  • In general, lung adenocarcinomas have been shown to have a variety of different genetic mutations. This includes the involvement of ALK, KRAS, and EGFR genes. Studies have found that EGFR mutations are seen during transformation of adenocarcinoma in situ to minimally invasive adenocarcinoma
  • Genetic mutations have been noted in early invasive adenocarcinoma development. Around 40-85% of them show mutations on gene EGFR, while up to 4% of them show KRAS gene mutations
  • In general, it is known that cancers form when normal, healthy cells begin transforming into abnormal cells - these cancer cells grow and divide uncontrollably (and lose their ability to die), resulting in the formation of a mass or a tumor
  • The transformation of normally healthy cells into cancerous cells may be the result of genetic mutations. Mutations allow the cancer cells to grow and multiply uncontrollably to form new cancer cells
  • These tumors can invade nearby tissues and adjoining body organs, and even metastasize and spread to other regions of the body

What are the Signs and Symptoms of Adenocarcinoma In Situ of Lung?

Early-stage lung cancer rarely causes any signs and symptoms and initially makes for a difficult diagnosis. The signs and symptoms of Adenocarcinoma In Situ of Lung may include the following:

  • Shortness of breath that gets worse with time; difficulty in breathing
  • Cough that may be persistent; blood in cough/sputum (hemoptysis)
  • Chest pain, heaviness in the chest
  • Changes to voice, hoarseness, or loss of voice

Signs and symptoms that may emerge during the later stages of the condition include:

  • High temperatures (fever) and excessive night sweats (may be recurrent)
  • Headache
  • Low blood pressure

Some features of the tumor include:

  • A majority of the tumors originate from the smaller airways (peripheral lung, near the pleura). However, tumors may be present anywhere in the lung
  • The tumor appears as single poorly-defined adenocarcinoma that is less than 3 cm in size (most are less than 2 cm in size). It is extremely rare to observed tumors greater than 3 cm in sizes
  • No invasion of the blood vessels or lymphatics is observed; also, the pleura is not involved

How is Adenocarcinoma In Situ of Lung Diagnosed?

The following procedures and tools may be used in the diagnosis of Adenocarcinoma In Situ of Lung:

  • Physical examination: During a physical exam, a physician will check the individual’s overall health status, listen to their breathing, and check for possible fluid buildup in the lungs (auscultation)
  • Pulmonary function tests can help determine the extent of lung damage; it can also help the healthcare provider assess the ability of lungs to deliver oxygen to the body
  • Chest X-ray: Two-dimensional pictures using tiny amounts of radiation are taken, in order to detect any tumors or other medical issues associated with the lungs, such as pneumonia. Tumors inside the lung can be detected using a chest X-ray; although sometimes, these tumors are too small to visualize (tumors less than 1 cm in size may be missed on a chest X-ray)
  • Computerized tomography (CT) scan: Also known as CAT scan, this radiological procedure creates detailed three-dimensional images of structures inside the body. CT scans may be helpful in detecting recurrences, or if the cancer has metastasized to the surrounding lymph nodes of the lungs
  • Magnetic resonance imaging (MRI) scan: An MRI scan uses magnetic fields that create high quality pictures of certain body parts, such as tissues, muscles, nerves, and bones. These high-quality images may indicate to a physician, if any tumor is present
  • Positron emission tomography (PET): A PET scan is a nuclear medicine imaging technique that uses three-dimensional images to show how tissue and organs are functioning. A small amount of radioactive material may be injected into a vein, inhaled or swallowed. A PET scan is also helpful in detecting recurrences, or if any metastasis (to the surrounding lymph nodes of the lungs) has occurred
  • Sputum cytology: Sputum cytology is test that involves the collection of mucus (sputum), coughed-up by a patient. After the mucus is collected, a pathologist examines it in an anatomic pathology laboratory, to see if any cell abnormalities are present indicative of pulmonary adenocarcinoma
  • Bone scan: A bone scan is a nuclear imaging test that involves injecting a radioactive tracer into an individual’s vein. Bone scans are primarily used to detect if the cancerous cells have metastasized to the bones and formed secondary tumors
  • Bone marrow biopsy: Bone marrow is a soft tissue found within bones. A bone marrow biopsy is used to detect blood abnormalities, or if a physician believes that metastasis to the bone marrow may have occurred

A biopsy refers to a medical procedure that involves the removal of cells or tissues, which are then examined by a pathologist. Different biopsy procedures include:

  • Tissue biopsy from the affected lung:
    • A biopsy of the tumor is performed and sent to a laboratory for a pathological examination. A pathologist examines the biopsy under a microscope. After putting together clinical findings, special studies on tissues (if needed) and with microscope findings, the pathologist arrives at a definitive diagnosis. Examination of the biopsy under a microscope by a pathologist is considered to be gold standard in arriving at a conclusive diagnosis
    • Biopsy specimens are studied initially using Hematoxylin and Eosin staining. The pathologist then decides on additional studies depending on the clinical situation
    • Sometimes, the pathologist may perform special studies, which may include immunohistochemical stains, molecular testing, flow cytometric analysis and very rarely, electron microscopic studies, to assist in the diagnosis
  • The biopsy may be performed through any of the following procedures:
    • Bronchoscopy: A special medical instrument, called a bronchoscope, is inserted through the nose and into the lungs to collect small tissue samples
    • Thoracentesis: During thoracentesis, physicians use a special medical device called a cannula, to remove fluid between the lungs and the chest wall for examination
    • Thoracoscopy: A medical instrument called a thoracoscope is inserted into the chest through tiny incisions, in order to examine and remove tissue from the chest wall, which is then analyzed further
    • Thoracotomy: Thoracotomy is a surgical invasive procedure with special medical instruments to open-up the chest and remove tissue from the chest wall or the surrounding lymph nodes of the lungs
    • Mediastinoscopy: A medical instrument called a mediastinoscope is inserted into the chest wall to examine and remove samples
    • Fine needle aspiration biopsy (FNAB) or transthoracic needle biopsy: A device called a cannula is used to extract tissue or fluid from the lungs, or surrounding lymph nodes
    • Open lung biopsy

A differential diagnosis with respect to other lung cancer types may be necessary prior to establishing a definite diagnosis, by excluding the following cancers:

  • Minimally invasive adenocarcinoma of the lung, especially for non-mucinous AIS
  • Secondary lung tumors that may have metastasized from other regions (pancreas, gastrointestinal tract) to the lung

Diagnostic criteria for Pulmonary Adenocarcinoma In Situ include the following parameters:

  • Presence of small, solitary adenocarcinoma less than (or equal to) 3 cm in size
  • Pure lepidic growth pattern should be noted
  • No invasion of blood vessels, lymphatic tissues, or pleura seen (including no stromal invasion is observed)
  • Absence of any invasive adenocarcinoma pattern (such as solid, papillary, micropapillary, acinar, colloid, fetal, enteric, or invasive mucinous adenocarcinoma)
  • No aerogenous spread (spread through the air cavities) is noted
  • Cell type is mostly mucinous (occasionally, they may be non-mucinous)
  • Absent or unseen nuclear atypia
  • Septal widening occurring with sclerosis or fibrosis

Note: Pulmonary Adenocarcinoma In Situ is normally detected incidentally through CT scans, when used for other medical reasons.

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Adenocarcinoma In Situ of Lung?

The complications of Adenocarcinoma In Situ of Lung can include:

  • Dyspnea (shortness of breath): If the cancerous tumor expands to block important, large, or small airways of the chest or lung
  • Hemoptysis (coughing-up blood): Individuals may cough-up blood, due to excessive amounts of blood in the airways
  • Recurrence following a complete surgical removal of the tumor is extremely rare
  • There may be complications related to the methods used in treating the condition

How is Adenocarcinoma In Situ of Lung Treated?

The most commonly used treatment for Adenocarcinoma In Situ of Lung is surgery. Surgery can be potentially curative, if the tumor is completely excised. Chemotherapy and radiation may also be used for treatment, if surgery is not a viable option.

The surgical options include:

  • Wedge resection: Wedge resection is a partial removal of the wedge-shape portion of the lung that contains cancerous cells (along with any surrounding healthy tissue)
  • Segmentectomy: It is the partial removal of the cancerous lung and any surrounding healthy tissue
  • Pulmonary lobectomy: It is a type of surgical procedure performed to partially remove a portion of a lung
  • Sleeve lobectomy: It is another surgical procedure to partially remove a portion of the lung and a part of the airway (bronchus)

Radiation therapy and chemotherapy can be used as a combination therapy. Combinational therapy increases the effects of both types of treatment. However, the side effects are cumulative.

How can Adenocarcinoma In Situ of Lung be Prevented?

Currently, there is no known prevention method for Adenocarcinoma In Situ of Lung. Although there are no preventable measures for lung cancer, in general, various steps can be taken to help decrease the risk of its formation. These measures include:

  • Complete smoking cessation and avoiding exposure to secondhand smoke: The risk for lung cancer decreases drastically following quitting or giving up smoking
  • Physical activity: Individuals, who participate in a moderate amount of physical activity, may decrease their risk
  • Adequate consumption of fruits and vegetables: A healthy diet, low in saturated fats and rich in many fruits and vegetables, may help decrease one’s risk for lung cancer
  • Avoid exposure to certain materials and chemicals (including asbestos, arsenic, chromium, nickel, and tar): Individuals who work with such substances should follow proper usage principles and occupational safety instructions, since a prolonged exposure to harmful chemicals may increase the risk for lung cancer. This risk is multiplied in smokers who are exposed to these harmful chemicals
  • Avoid exposure to radioactive gas: Radon, a radioactive gas, produced by the natural breakdown of uranium in soil and rocks, may develop to hazardous levels inside building spaces. Individuals exposed to excessive amounts of radon gas are vulnerable to lung cancer
  • Limit alcohol consumption: Alcoholic beverages have been linked to increasing an individual’s risk for certain types of cancers, such as those affecting the lungs, mouth, throat, esophagus, breast, colon, and liver
  • CT screening in high-risk groups can decrease the incidence of lung cancer, or at least help detect such cancers early. A low-dose CT scan is good to identify adenocarcinomas early. It is generally known that CT scans are about 3-4 times better than X-ray studies

What is the Prognosis of Adenocarcinoma In Situ of Lung? (Outcomes/Resolutions)

  • The prognosis of Adenocarcinoma In Situ of Lung is generally excellent with adequate treatment, which is a complete surgical excision of the tumor. The survival rate in such cases is 100% and no recurrence is observed
  • When the tumor size is over 3 cm, which is very uncommon, the prognosis of the condition is unclear. However, most tumors are less than 3 cm and report excellent outcomes on early detection and complete tumor excision

It is important to have follow-up appointments with a physician, to evaluate the effects of the current treatment method, and to monitor for any returning tumors.

Additional and Relevant Useful Information for Adenocarcinoma In Situ of Lung:

  • Lung cancer incidence is around 35 cases per 100,000 populations: The incidence of lung cancer in non-smokers is 1-2 cases per 20,000 populations per year; its incidence in smokers is 20-30 times higher than that of non-smokers
  • Studies under WHO indicate that the number of adenocarcinoma of lung cases is increasing (or has increased) due to design changes to cigarettes, composition of certain contents, and even better filtration of smoke through the cigarette. This is researched to be due to increased nitrosamines being inhaled through tobacco smoke
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Krish Tangella MD, MBA

Pathology, Medical Editorial Board, DoveMed Team

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