Diagnosing inflammatory myofibroblastic tumour involves a combination of imaging techniques, tissue analysis, and molecular testing to distinguish this rare condition from other tumours and infections, helping doctors determine the most appropriate treatment approach.

Introduction: When to Seek Diagnostic Evaluation

Inflammatory myofibroblastic tumour (IMT) presents a unique challenge because it can develop without causing noticeable symptoms for quite some time. Many people discover they have this condition during routine health checkups or when investigating unrelated concerns.^[1] The tumour can grow silently until it reaches a size that begins to interfere with nearby organs or structures, at which point symptoms become apparent.^[1]

If you experience persistent symptoms such as unexplained fever, night sweats, unintentional weight loss, or a general feeling of unwellness that doesn’t go away, it’s important to seek medical attention.^[12] These symptoms can mimic many other conditions, including infections or other types of tumours, which is why proper diagnostic testing is essential. Pain at a specific location in the body, particularly if it’s associated with a lump or mass that can be felt, should also prompt a visit to your doctor.^[12]

The symptoms you experience will largely depend on where the tumour is located and how large it has grown.^[8] For instance, if an IMT develops in the lungs, you might have a cough, difficulty breathing, or chest pain that feels similar to a respiratory infection.^[15] If the tumour is in the abdomen, you might feel abdominal pain or notice a mass during physical examination.^[13] Because IMT occurs most commonly in children and young adults, any unusual symptoms in this age group warrant careful evaluation.^[1]

Diagnostic Methods for Identifying IMT

Imaging Studies

When doctors suspect an inflammatory myofibroblastic tumour, they typically begin with imaging studies to locate the mass and understand its characteristics. Computed tomography, commonly called a CT scan, is one of the primary imaging tools used to evaluate IMT.^[1] This test creates detailed cross-sectional images of the body that help doctors determine the tumour’s size, exact location, and whether it has spread to surrounding tissues.^[13]

For tumours in the lungs, a chest CT scan will show a mass that is typically large, peripherally located, and lobulated in appearance.^[10] The tumour may show signs of invading the chest wall, blood vessels, or structures in the middle of the chest called the mediastinum. Sometimes calcification—deposits of calcium that appear bright white on the scan—can be seen within the tumour.^[10] When contrast dye is injected during the scan, IMTs typically show a heterogeneous pattern of enhancement, meaning some areas light up more than others.^[10]

Magnetic resonance imaging, or MRI, is another imaging technique that can be useful, particularly for tumours in certain locations.^[10] MRI uses powerful magnets and radio waves instead of radiation to create detailed images of soft tissues. When an MRI is performed on an IMT, the tumour may appear similar in brightness to skeletal muscle, though the appearance can vary.^[10]

Ultrasound imaging may be employed for tumours in the abdomen or pelvis, as it can help visualize soft tissue masses and their relationship to nearby organs without using radiation.^[2] For abdominal IMTs, ultrasound or CT scans can reveal a soft tissue mass that may be pressing on or surrounding important blood vessels or organs.^[13]

Advanced Imaging: PET Scans

In some cases, doctors may order a specialized test called positron emission tomography, or PET scan, often combined with a CT scan (PET-CT).^[17] This test uses a small amount of radioactive glucose that is injected into your bloodstream. Cancer cells and some inflammatory cells take up this glucose more readily than normal cells, causing them to light up on the scan. This test helps doctors understand how active the tumour is.

However, PET scans can be confusing when evaluating IMT because these tumours contain many inflammatory cells. The amount of radioactive glucose uptake by an IMT can vary considerably depending on factors like how densely packed the cells are, how quickly they’re dividing, and how many plasma cells (a type of white blood cell) are present.^[15] This means that an IMT can sometimes look very “hot” or active on a PET scan, making it difficult to distinguish from a malignant tumour based on imaging alone.^[17]

Biopsy: The Gold Standard for Diagnosis

While imaging studies can show that a mass is present and provide information about its characteristics, they cannot definitively determine whether the tumour is an IMT or something else. To make an accurate diagnosis, doctors need to examine the actual tumour cells under a microscope, which requires taking a sample through a procedure called a biopsy.^[12]

There are different ways to obtain a biopsy sample. For tumours that are easily accessible, a doctor may perform a needle biopsy, using a thin needle to remove a small sample of tissue.^[17] This procedure is often guided by CT scanning or ultrasound to ensure the needle reaches the correct location.^[17] However, because IMTs can have variable appearances and the needle samples are small, they may not always provide enough tissue to make a confident diagnosis.^[15]

For lung tumours, doctors might attempt to obtain samples through bronchoscopy, a procedure where a flexible tube with a camera is inserted through the mouth or nose and into the airways.^[17] However, this approach may not always reach the tumour if it’s located on the outer edges of the lung, and even when samples are obtained, the small amount of tissue may not be representative of the entire tumour.^[15]

In many cases, the most reliable way to diagnose IMT is through surgical biopsy or complete surgical removal of the tumour.^[1] This provides pathologists with enough tissue to thoroughly examine the tumour’s characteristics and perform additional specialized tests. The surgical approach allows doctors to see the tumour in its entirety and understand how it relates to surrounding structures.^[15]

Microscopic Examination and Pathology

Once tissue is obtained, a specialist called a pathologist examines it under a microscope. IMTs have a distinctive appearance characterized by spindle-shaped cells that are longer than they are wide, mixed with numerous inflammatory cells.^[1] The inflammatory cells are predominantly plasma cells and lymphocytes, which are types of white blood cells, along with some eosinophils—cells typically involved in allergic reactions and parasite infections.^[1]

The spindle cells in IMT are special cells called myofibroblasts, which have features of both fibroblasts (cells that produce connective tissue) and smooth muscle cells.^[2] These cells help maintain the structure of organs and play a role in wound healing, but in IMT they grow abnormally. The pathologist will look for these characteristic cells scattered throughout tissue that contains abundant inflammatory cells.^[1]

To confirm the diagnosis, pathologists use special staining techniques that highlight specific proteins in the tumour cells. They may test for markers such as CD68 and vimentin, which are typically present in myofibroblastic cells.^[15] These additional tests help distinguish IMT from other conditions that might look similar under the microscope, such as infections, reactive inflammatory conditions, or other types of tumours.^[1]

Molecular and Genetic Testing

One of the most important advances in diagnosing IMT has been the discovery that many of these tumours have specific genetic abnormalities. In approximately 50 to 80 percent of IMT cases, there is a rearrangement involving a gene called ALK, which stands for anaplastic lymphoma kinase.^[5][8] This means that pieces of chromosomes—the structures in cells that contain genes—break apart and reconnect in abnormal ways.

When the ALK gene is rearranged, it fuses with other genes to create what scientists call fusion proteins. These abnormal proteins can drive the tumour’s growth.^[2] Pathologists can detect ALK protein in tumour tissue using a special staining technique called immunohistochemistry, which makes the ALK protein visible under the microscope.^[8] Finding ALK positivity not only helps confirm the diagnosis but also provides crucial information about treatment options, as there are now medications specifically designed to block these abnormal ALK proteins.^[3]

Some IMTs don’t have ALK rearrangements but instead have abnormalities in other genes such as ROS1, NTRK3, RET, or PDGFRB.^[10] Comprehensive molecular testing can identify these alternative genetic changes, which is particularly important because different genetic abnormalities may respond to different targeted treatments.^[3] In more than 90 percent of children with IMT, genetic abnormalities such as ALK gene rearrangement or ROS1 gene fusions can be identified.^[3]

Laboratory Blood Tests

While there is no single blood test that can diagnose IMT, certain laboratory findings may provide supporting evidence. Some patients with IMT have abnormal blood counts, including elevated levels of white blood cells or platelets.^[17] Others may show increased levels of certain proteins in the blood, such as polyclonal gamma-globulin, or elevated inflammatory markers like interleukin-6 (IL-6) and interleukin-1 beta (IL-1β).^[17]

However, these findings are not specific to IMT and can occur with many other conditions, including infections and different types of tumours.^[17] Therefore, blood tests are used as part of the overall clinical picture rather than as definitive diagnostic tools. They may be more helpful in monitoring the tumour’s response to treatment or detecting recurrence after treatment.

Diagnostics for Clinical Trial Qualification

When patients with IMT are being considered for enrollment in clinical trials, they typically need to undergo a more extensive evaluation beyond the standard diagnostic workup. Clinical trials have specific criteria that participants must meet to ensure the study can safely and accurately assess new treatments.

One of the most critical requirements for many clinical trials involving IMT is confirmation of the tumour’s molecular profile, particularly ALK status.^[10] Trials testing ALK-targeted medications require documented evidence that the tumour is ALK-positive through either immunohistochemistry or more sophisticated genetic testing methods such as fluorescence in situ hybridization (FISH) or next-generation sequencing.^[10] These molecular diagnostic techniques identify the specific genetic rearrangement present in the tumour cells.

Patients being screened for clinical trials usually need comprehensive imaging to establish a baseline measurement of the tumour and to confirm that it hasn’t spread to distant organs.^[8] This baseline is crucial because it allows researchers to accurately measure whether the treatment is shrinking the tumour or slowing its growth. Imaging studies may include CT scans of the chest, abdomen, and pelvis, as well as MRI scans of specific areas depending on where the tumour is located.

Clinical trials may also require tissue samples to be sent to specialized laboratories for additional molecular analysis. This can include testing for gene fusions beyond ALK, looking at the tumour’s complete genetic profile, or analyzing specific biomarkers that might predict how well the tumour will respond to the experimental treatment.^[11] Some trials collect fresh biopsy samples rather than using previously obtained tissue to ensure the molecular testing is as accurate and up-to-date as possible.

Blood tests are another standard component of clinical trial screening. These establish that patients have adequate organ function—particularly liver, kidney, and bone marrow function—to safely receive the experimental treatment.^[11] Researchers need to ensure that participants can metabolize and clear the study medication from their bodies and that they have sufficient blood cell counts to tolerate potential side effects.

Eligibility criteria often specify whether the IMT must be unresectable, meaning it cannot be safely removed by surgery, or whether it has recurred after previous treatment.^[10] This determination requires careful review of imaging studies by experienced surgeons and radiologists to confirm that surgical removal is not feasible or would not be in the patient’s best interest. Some trials specifically enroll patients whose tumours have progressed despite previous therapies, requiring documentation of treatment history and disease progression.

Age restrictions are common in clinical trials for rare tumours like IMT. Some studies focus exclusively on pediatric patients, while others include both children and adults.^[11] Documentation of the patient’s age and, for children, measurements of growth and developmental stage may be required. Patients or their legal guardians must also be able to understand and consent to participate in the trial, which involves additional documentation and educational processes.