What Is a Lung Granuloma?

Lung granulomas are grain-like nodules of immune cells that form in parts of the lung where there is an infection, toxic exposure, or inflammatory condition. Granulomas often form when the immune system tries to rein in the spread of disease-causing organisms like bacteria or fungi by creating a capsule around them.

Lung granulomas may or may not cause symptoms and are often found by accident when a person has a chest X-ray. Lung granulomas may be caused by a severe disease but are usually not cancerous.

Lung granulomas may also be referred to as granulomatous lung disease.

This article explains what lung granulomas are, including their possible symptoms and causes. It also describes what is involved in the diagnosis of this distinctive lung symptom.

What Are Lung Granulomas?

A lung granuloma is often first seen on a chest X-ray as a lung nodule. There may be a single granuloma or multiple granulomas scattered throughout the lungs.

They are typically the result of a normal body process in which the immune system attempts to contain something foreign in the lungs. The foreign material may be a microorganism, pieces of inhaled metals or toxins, or damaged tissues caused by inflammatory or autoimmune diseases.

Under the microscope, a granuloma is made up of immune cells called macrophages that surround and neutralize the foreign agent in the frontline immune defense. Other immune cells may be involved, including lymphocytes and Langerhan's cells.

Granulomas may be present only in the lungs but can affect other parts of the body such as the skin and lymph nodes based on the underlying cause.

There are also granulomas known as "necrotizing granulomas" in which necrosis (cell death) occurs around the area of inflammation. Necrotizing granulomas are commonly associated with lung infections.

Lung Granuloma Symptoms

The signs and symptoms of lung granulomas may range from no symptoms at all to widespread symptoms related to the underlying cause of the granuloma.

Asymptomatic vs. Symptomatic Granulomas

Many lung granulomas are detected accidentally during a chest X-ray for another medical condition. In such cases, the condition may be entirely asymptomatic (without symptoms) but nevertheless need medical treatment.

In fact, granulomas in and of themselves often do not cause any symptoms. Exceptions can occur, however, if the granulomas lie near the large airways of the lung or if there are a lot of granulomas. In addition, granulomatous lung disease may be associated with other lung diseases (such as interstitial pneumonia) that give rise to respiratory symptoms.

Symptoms may include a cough, wheezing, shortness of breath, or recurrent respiratory infections.

Symptoms Related to the Underlying Cause

When symptoms are present, they are frequently related to the underlying cause of the granuloma. By way of example:

• Tuberculosis (TB) may lead to symptoms such as fevers, night sweats, a chronic cough, and unintentional weight loss.
• Fungal pneumonia may cause symptoms similar to that of TB.
• Vasculitis (inflammation of blood vessels) can cause a variety of symptoms, including fever, night sweats, headaches, rash, neurological symptoms, and much more.

When considering the underlying causes of a granuloma, it's important for people to talk to their healthcare provider about any symptoms they are experiencing, including vague ones like fatigue.

Causes

Most lung granulomas are benign (non-cancerous). Possible causes can be broken down into the following broad categories:

Lung Infections

Infections are the most common cause of granulomas, and include:

Tuberculosis

Worldwide, tuberculosis is the most common cause of pulmonary granulomas, though the incidence has been increasing recently in the United States.

Non-Tubercular Mycobacterium

Mycobacterial infections such as Mycobacterium avium complex and Mycobacterium kansasii are important causes of granulomatous lung disease.

Fungal Infections

There are more than 140 types of fungal infections that can lead to lung granulomas, the most common being:

• Cryptococcosis
• Coccidioidomycosis (Valley Fever)
• Histoplasmosis
• Blastomycosis
• Aspergillosis

Parasitic Infections

Parasitic infections as a cause are less common in the United States, the most common of which include:

• Toxoplasmosis
• Dilofilariasis (dog heartworm)
• Ascariasis (roundworms)
  

Bacterial Infections

Bacterial infections are less common causes but may include:

• Aspiration pneumonia
• Brucellosis
• Nocardia

Inflammatory Conditions

The following conditions can cause lung granulomas by submitting the body to extreme or persistent inflammation:

Sarcoidosis

Sarcoidosis is an inflammatory disease that can affect many regions of the body and often begins with swollen glands, skin changes, fatigue, and joint pain and swelling.

Bronchocentric Granulomatosis

This an inflammatory condition that affects the smaller airways of the lung called bronchioles and is thought to be a response to some type of injury to the lungs.

Inflammatory Bowel Disease

With inflammatory bowel diseases (IBD), such as Crohn's disease and ulcerative colitis, granulomas may occur not only in the gastrointestinal (GI) tract but other parts of the body such as the lungs. In one study, 21% to 36% of people had evidence of lung granulomas outside of the GI tract.

Environmental Exposures

There are a number of different environmental exposures that can lead to lung granulomas:

Hypersensitivity Pneumonitis

Hypersensitivity pneumonitis, or inflammation of the lungs due to an allergic reaction, may occur with a number of different exposures. These include fungi and industrial chemicals such as dyes.

Toxic Metal Exposure

Exposure to the metal beryllium (used in industrial ceramic manufacturing) may result in berylliosis. A number of other metal dust exposures may result in symptoms similar to berylliosis. Some of these include aluminum, titanium, silica, zirconium, cobalt, and silica.

Talc granulomas are most often related to illicit drug use. It is seen primarily with the injection of crushed-up pills (such as opiates, barbiturates, and methylphenidate) that release excess talc into the bloodstream.

Medications

Adverse reactions to a number of different medications have been associated with the development of lung granulomas. This can be confusing, as some of these drugs are used to treat medical conditions that are associated with pulmonary granulomas.

Some of these include:

• Methotrexate
• Interferon
• Bacillus Calmette-Guerin (BCG) vaccine
• Remicade (infliximab)
• Enbrel (etanercept)
• Rapamune (sirolimus)
• Arava (leflunomide)
• Cimzia (certolizumab)
• Humira (adalimumab)
• Entyvio (vedolizumab)
• Imuran (azathioprine)

Autoimmune Diseases

Lung granulomas may occur in a number of different autoimmune conditions.

Rheumatoid Arthritis

Necrotizing granulomas are relatively common in people with rheumatoid arthritis and may occur in the lungs as well as under the skin (subcutaneous). They may occur related to the underlying disease or as an adverse reaction to medications used to treat the disease.

Sjogren's Syndrome

A number of lung diseases including lung granulomas are associated with Sjogren's syndrome, an autoimmune disease targeting moisture-producing tissues in the body.

Vasculitis

Vasculitis is a term that refers to chronic inflammation of blood vessels and may occur in blood vessels anywhere in the body. The most common sites, however, are the lungs and kidneys.

Types of vasculitis associated with granulomas include:

• Granulomatosis with polyangitis (formerly called Wegener's granulomatosis)
• Eosinophilic granulomatosis with polyangitis (formerly called Churg-Strauss syndrome)

Granulomatous Lymphocytic Interstitial Lung Disease

Granulomatous lymphocytic interstitial lung disease (GLILD) is a rare and potentially severe lung complication associated with immunodeficiency. It affects the tissues around the alveoli (air sacs) of the lungs, causing scarring and thickening of tissues.

GLILD may be secondary to an autoimmune disease or the result of a certain type of pneumonia that affects these tissues.

Cancer

Granulomas are usually associated with benign conditions, but may sometimes be seen with:

• Lymphomatoid granulomatosis (associated with leukemia or lymphoma)
• Sarcoid-like granulomatosis (caused by certain blood cancers or cancer drugs)
  

Diagnosis

Due to the wide range of potential causes, diagnosing lung granulomas can be challenging. In addition to a careful history and physical examination, lab tests, imaging tests, pulmonary function testing, and a lung biopsy may be needed.

History and Physical Exam

The diagnosis of a granuloma begins with a careful history of symptoms, including those that may be unrelated to the lungs. When symptoms are present, it's important to note whether these are of recent onset (acute) or have been ongoing (chronic).

Where a person lives may be helpful in narrowing down possible fungal causes, and a history of travel may raise the likelihood of tuberculosis. On-the-job exposures (such as to beryllium) should also be noted.

A history of repeated infections (such as sinusitis) may be noted in people who have immunodeficiency. Because immunodeficiency syndromes are a cause of repeated infections in both adults and children, it's important to let your healthcare provider know if you've had repeated sinus or other respiratory tract infections.

Imaging Studies

A lung granuloma or granulomas are often first spotted when a chest X-ray or chest computed tomography (CT) scan is done for another reason.

A high-resolution chest CT scan is a very important step in the diagnosis and evaluation of a lung granuloma as calcium deposits in granulomas often make them visible.

For people who have a lower-resolution CT scan, such as those done for lung cancer screening, a high-resolution scan should be done. In some cases, a chest magnetic resonance imaging (MRI) scan may be helpful.

A positron emission tomography (PET) scan is often done if there is concern about cancer, vasculitis, and inflammatory diseases, though the rate of false positives is high.

Laboratory Tests

A number of laboratory tests can help with determining the causes of lung granulomas:

• CBC: A complete blood count (CBC) can help detect infection based on which white blood cells are elevated.
  
• Serology: Fungal causes of lung granulomas are primarily detected with serology (blood tests). Serology may also be able to detect antibodies produced in response to certain infections or autoimmune conditions.
• TB testing: Testing for tuberculosis is important for anyone who has a lung granuloma if only to rule it out as a cause.

Procedures

There are non-invasive and invasive procedures used to indirectly or indirectly visualize the lungs:

Bronchoscopy

A bronchoscopy is often done as a way to directly visualize the airways. In a bronchoscopy, a flexible tube is inserted through the mouth and threaded down to the large airways of the lungs.

Endobronchial Ultrasound

An ultrasound probe may be attached to a bronchoscope to allow physicians to visualize regions in the lungs near the airways. With special tools, a biopsy may be done to extract granulomatous tissues near the airways.

Bronchoalveolar Lavage

Bronchoalveolar lavage is a procedure done during a bronchoscopy that can help diagnose hypersensitivity pneumonitis.

During the procedure, sterile saline is injected into the lungs through the bronchoscope and then suctioned out. The extracted cells can then be examined under the microscope.

Biopsy

Very often, a biopsy specimen is necessary to determine or confirm the precise cause of a lung granuloma. A lung biopsy specimen may be obtained in several ways:

Fine Needle Aspiration Biopsy

Fine needle aspiration (FNA) biopsy may be done by inserting a long, thin needle through the chest wall and into a granuloma. This is done under the guidance of either an ultrasound or CT scan.

Transbronchial Biopsy

A biopsy may be done during an endobronchial ultrasound, referred to as a transbronchial biopsy. With sarcoidosis, a transbronchial biopsy combined with a PET scan has largely replaced a more invasive procedure known as mediastinoscopy, which requires access through an incision in the chest wall.

Surgical Lung Biopsy

If an FNA or transbronchial biopsy does not provide a large enough sample, surgery may be needed. This may involve either video-assisted thoracoscopic surgery (VATS), utilizing a few small incisions with specialized instruments, or open lung surgery (thoracotomy).

Treatment

The treatment of lung granulomas will depend on the underlying cause. In general, most granulomas do not need to be surgically removed. Exceptions may occur if the granuloma or granulomas are causing symptoms or if the diagnosis is uncertain.

Some potential treatments include:

• Many fungal infections (such as histoplasmosis) don't require treatment as the body has already fought off the infection.
• The treatment of tuberculosis depends on many factors, including whether the strain is considered to be multi-drug resistant. Treatment is often lengthy and may include a combination of drugs.
• With hypersensitive pneumonitis and exposure to metals, eliminating the exposure is key.
• When granulomas are related to an autoimmune condition, treatment of the underlying condition is key.