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

• DIPNECH (Diffuse Idiopathic Pulmonary Neuroendocrine Hyperplasia)

What is Diffuse Idiopathic Pulmonary Neuroendocrine Hyperplasia? (Definition/Background Information)

• Lung cancer is a high mortality cancer that affects the lungs. Any individual can develop lung cancer, although individuals who smoke cigarettes remain at the highest risk for the condition. It is the most common cause of cancer-related death in the world
• Diffuse Idiopathic Pulmonary Neuroendocrine Hyperplasia (DIPNECH) is a preinvasive condition that is caused by the abnormal growth of neuroendocrine cells of the lung, called pulmonary neuroendocrine cells (or PNC). This overgrowth is often localized to the lung airways and observed as nodules in the lung
• DIPNECH is often seen with longstanding (but mild) inflammation of the lymphocytes, and lung fibrosis at the site of the cell proliferation. There may be local invasion to form tumorlets (or small-sized tumors)
• Diffuse Idiopathic Pulmonary Neuroendocrine Hyperplasia is known to lead to the formation of carcinoid tumor (mostly typical carcinoid tumor), which is a type of neuroendocrine lung cancer, if appropriate treatment is not considered
• Diffuse Idiopathic Pulmonary Neuroendocrine Hyperplasia can cause asthma-like symptoms including breathing difficulties, chronic cough, and wheezing
• The usual line of treatment of Diffuse Idiopathic Pulmonary Neuroendocrine Hyperplasia is through steroids based on the assessment of the physician. However, other treatment measures, such as surgery, may be considered
• The prognosis depends of Diffuse Idiopathic Pulmonary Neuroendocrine Hyperplasia is generally good with early recognition and adequate treatment

Who gets Diffuse Idiopathic Pulmonary Neuroendocrine Hyperplasia? (Age and Sex Distribution)

• Diffuse Idiopathic Pulmonary Neuroendocrine Hyperplasia is often detected and diagnosed in adults in the 40-60 years age group
• In general, a male preference is noted for lung cancers. However with DIPNECH, a female predominance is noted
• Current studies do not show any specific racial or ethnic predilection

What are the Risk Factors for Diffuse Idiopathic Pulmonary Neuroendocrine Hyperplasia? (Predisposing Factors)

The following factors have been identified as increasing the risk for Diffuse Idiopathic Pulmonary Neuroendocrine Hyperplasia:

• Since lung fibrosis is noted in the context of DIPNECH, some researchers believe that the condition may be secondary to a lung injury
• In rare cases, an association with multiple endocrine neoplasia 1 (MEN 1, a genetic disorder) has been observed

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

• 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
• 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 arsenic and other hazardous substances
• Exposure to asbestos and other harmful chemicals and heavy metals: Prolonged exposure to asbestos and other harmful chemicals including chromium, nickel, and tar
• Exposure to secondhand smoke: Individuals, who do not smoke, but live with smokers, also have an increased risk
• 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, chronic obstructive pulmonary disease (COPD), asthma, and bronchitis, 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 Diffuse Idiopathic Pulmonary Neuroendocrine Hyperplasia? (Etiology)

The exact cause of Diffuse Idiopathic Pulmonary Neuroendocrine Hyperplasia is unknown; the condition is termed ‘idiopathic’.

• The proliferating cells (pulmonary neuroendocrine cells or PNCs) are known to release chemicals, called amines and peptides, which may be responsible for the fibrotic changes in the affected lung portion. DIPNECH may form at the site of these changes as a reactive process
• However, in case PNC overgrowth occurs due to other reasons (termed reactive proliferation), then carcinoid tumors are not observed and lung damage/injury may be noted
• Information on genetic abnormalities (if any present) involved in these tumors is currently unavailable. However, in rare cases, the hyperplasia is seen to be present against a background of multiple endocrine neoplasia type 1 (a genetic condition)

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 Diffuse Idiopathic Pulmonary Neuroendocrine Hyperplasia?

The features of Diffuse Idiopathic Pulmonary Neuroendocrine Hyperplasia may include:

• The presence of tumorlets, which are irregularly-shaped, small-sized tumors (about or less than 5 mm in overall size)
• The tumorlets may show an invasive growth pattern into the airways
• A nodular-shaped thickening may be observed on the bronchial wall on imaging studies
• The tumor may arise in the main bronchus and extend into bronchiolar wall, and sometimes into the lung tissues

The main signs and symptoms of DIPNECH may include:

• Cough that is longstanding
• Shortness of breath; difficulty in breathing
• Wheezing

All the initial symptoms that are observed may be indicative of asthma.

How is Diffuse Idiopathic Pulmonary Neuroendocrine Hyperplasia Diagnosed?

The following procedures and tools may be used in the diagnosis of Diffuse Idiopathic Pulmonary Neuroendocrine Hyperplasia:

• 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 the tumor

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

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 Diffuse Idiopathic Pulmonary Neuroendocrine Hyperplasia?

The complications of Diffuse Idiopathic Pulmonary Neuroendocrine Hyperplasia can include:

• Dyspnea (shortness of breath): If the tumor expands to block important, large, or small airways of the chest or lung
• Bronchiectasis, which is the irreversible damage to the bronchiole tubes (airways)
• In very few individuals with DIPNECH, the condition may develop to form carcinoid tumors. Even in such individuals, the development of typical carcinoid tumors occurs more often than the development of atypical carcinoid tumors. Typical carcinoids have a much better prognosis than atypical carcinoids
• Recurrence following surgical removal of the tumor

Note: Small cell lung carcinomas and large cell neuroendocrine carcinomas have not been associated with DIPNECH.

How is Diffuse Idiopathic Pulmonary Neuroendocrine Hyperplasia Treated?

The treatment options available for individuals with Diffuse Idiopathic Pulmonary Neuroendocrine Hyperplasia include the following:

• Administration of steroids is the usual line of treatment of DIPNECH
• Surgery may be performed based on evaluation by the healthcare provider
• Lung transplantation may be occasionally performed, in case of a progressive obstruction of the small bronchioles

How can Diffuse Idiopathic Pulmonary Neuroendocrine Hyperplasia be Prevented?

Currently, there is no known prevention method for Diffuse Idiopathic Pulmonary Neuroendocrine Hyperplasia. 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. It is generally known that CT scans are about 3-4 times better than X-ray studies

What is the Prognosis of Diffuse Idiopathic Pulmonary Neuroendocrine Hyperplasia? (Outcomes/Resolutions)

• Diffuse Idiopathic Pulmonary Neuroendocrine Hyperplasia is a preinvasive lesion that can be longstanding and slowly progressive. However, the prognosis of the condition is generally good with appropriate treatment
• In case of carcinoid tumor development, a majority of such tumors are typical carcinoid tumors that have a good prognosis with effective surgical treatment

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 Diffuse Idiopathic Pulmonary Neuroendocrine Hyperplasia:

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.