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

• AAH of Lung
• Pulmonary AAH
• Pulmonary Atypical Adenomatous Hyperplasia

What is Atypical Adenomatous Hyperplasia of Lung? (Definition/Background Information)

• Atypical Adenomatous Hyperplasia (AAH) of Lung is a small-sized preinvasive lesion that is characterized by the abnormal growth of cells, which may be mild to moderately atypical, in the alveolar walls or bronchioles (smaller airways)
• This condition is difficult to diagnose through imaging studies. Atypical Adenomatous Hyperplasia of Lung is an incidental finding in many cases, when a surgery/biopsy is performed for other medical reasons
• The cause of Atypical Adenomatous Hyperplasia of Lung is generally unknown, but it may be influenced by smoking. The tumor can cause chest pain, breathing difficulties, and fatigue. However, no invasion of the lymphatic and vascular system is noted
• Surgery is the mainstay of treatment, although chemotherapy and radiation therapy may be used for treating Atypical Adenomatous Hyperplasia of Lung based on the assessment of the physician. With complete surgical removal of the tumor, the prognosis is excellent

Who gets Atypical Adenomatous Hyperplasia of Lung? (Age and Sex Distribution)

• No specific demographics are available for Atypical Adenomatous Hyperplasia of Lung
• However, individuals under the age of 40 years are rarely diagnosed with lung cancer. Also, the majority of lung adenocarcinomas 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

Note: AAH of Lung has been detected in lung cancer specimens; in about 20% of the specimens from women and in about 10% of specimens obtained from men. The incidence is higher when the cancer is adenocarcinoma of lung; at 30% for women and 18% for men.

What are the Risk Factors for Atypical Adenomatous Hyperplasia of Lung? (Predisposing Factors)

There are no specific risk factors that have been identified for Atypical Adenomatous Hyperplasia of Lung. Although, 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 ones 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 Atypical Adenomatous Hyperplasia of Lung? (Etiology)

The exact cause of Atypical Adenomatous Hyperplasia of Lung is unknown.

• It is believed that there are certain factors contributing to lung cancer development, which include smoking, exposure to radon, and prolonged exposure to asbestos and other harmful chemicals (arsenic, chromium, nickel, and tar)
• Adenocarcinoma in situ (AIS) develops following the formation of Atypical Adenomatous Hyperplasia of Lung. AIS is considered a preinvasive lesion to minimally invasive adenocarcinoma. Thus, AAH of Lung can be described as an early step towards pulmonary adenocarcinoma development
• The involvement of CYP19A1 gene is shown in Atypical Adenomatous Hyperplasia of Lung associated with adenocarcinoma of lung. The manner of disease development (pathogenesis) of both are reported to be similar
• Gene mutations have been noted involving KRAS and EGFR genes in about 35% of the cases, indicating that this lesion may be a precursor to pulmonary adenocarcinoma development
• 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 Atypical Adenomatous Hyperplasia of Lung?

Atypical Adenomatous Hyperplasia of Lung may not present any signs and symptoms thus making for a difficult diagnosis. However, in some cases, the signs and symptoms may include:

• 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)
• Sudden weight loss; unintentional weight loss; changes in appetite
• The individual is easily tired, resulting in fatigue even with minimal activity
• Headache
• Low blood pressure

Some features of the tumor include:

• Most of the lesions are small, at around or less than 5 mm; some are known to grow up to 12 mm in size
• The tumors (proliferation of cells forming a mass) are slow-growing and poorly-defined
• A majority of the tumors originate from the smaller airways (peripheral lung, near the pleura)
• No invasion or involvement of the blood vessels or lymphatics is observed; also, the pleura is not involved
• Local or distant metastasis is not present

However, individuals may have Atypical Adenomatous Hyperplasia of Lung occurring in the background of lung adenocarcinoma (occurring as multiple nodules or lesions).

How is Atypical Adenomatous Hyperplasia of Lung Diagnosed?

The following procedures and tools may be used in the diagnosis of Atypical Adenomatous Hyperplasia 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
• 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 carcinomas

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/conditions may be necessary prior to establishing a definite diagnosis, by excluding the following cancers:

• Lung fibrosis or lung inflammation resulting in reactive pneumocyte hyperplasia
• Adenocarcinoma in situ, non-mucinous type

Note:

• Pulmonary Atypical Adenomatous Hyperplasia is difficult to be detected through CT scans. The tumor is often diagnosed incidentally during a surgical procedure performed for other medical conditions
• The WHO does not recommend classifying AAH of Lung as either low-grade or high-grade

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 Atypical Adenomatous Hyperplasia of Lung?

The complications of Atypical Adenomatous Hyperplasia of Lung can include:

• Potential to develop into adenocarcinoma of the lung, if undetected or left untreated
• Dyspnea (shortness of breath): If the 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 not observed
• There may be complications related to the methods used in treating the condition

How is Atypical Adenomatous Hyperplasia of Lung Treated?

The most commonly used treatment for Atypical Adenomatous Hyperplasia 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 Atypical Adenomatous Hyperplasia of Lung be Prevented?

Currently, there is no known prevention method for Atypical Adenomatous Hyperplasia 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 the tumors early. It is generally known that CT scans are about 3-4 times better than X-ray studies

What is the Prognosis of Atypical Adenomatous Hyperplasia of Lung? (Outcomes/Resolutions)

• The prognosis of Atypical Adenomatous Hyperplasia 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
• In case AAH of Lung occurs in the backdrop of pulmonary adenocarcinoma, then the prognosis of the condition depends upon various factors including the stage of the adenocarcinoma, response to treatment, the age and health status of the individual

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 Atypical Adenomatous Hyperplasia 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