The Inflammatory Myofibroblastic Tumor (IMT) is a rare soft tissue growth classified as a tumor of intermediate biological potential. This means its behavior falls between a benign growth and a fully malignant sarcoma. The name can be misleading because it implies a purely inflammatory process, yet IMT is a true neoplasm with the potential for aggressive local growth. Understanding this rare condition requires distinguishing its tumor-like nature from the prominent inflammatory features that give it its name. Its low incidence, estimated at 150 to 200 cases diagnosed annually in the United States, contributes to the complexity of its management.
Defining Inflammatory Myofibroblastic Tumor
IMT is characterized pathologically by two main components: proliferating myofibroblastic spindle cells and a dense collection of inflammatory cells. The spindle cells are mesenchymal, showing features of both fibroblasts and smooth muscle cells. The prominent inflammatory infiltrate consists primarily of plasma cells, lymphocytes, and eosinophils, leading to its historical misidentification as an “inflammatory pseudotumor.”
The World Health Organization (WHO) classifies IMT as an intermediate, rarely metastasizing fibroblastic and myofibroblastic neoplasm. This classification reflects its capacity for local invasion and a high rate of recurrence. Distant metastasis is rare, occurring in less than 5% of cases.
The tumor can arise in nearly any anatomical location but shows a preference for the lung, abdominal cavity, mesentery, and retroperitoneum. While IMT affects individuals of any age, it is most frequently diagnosed in children and young adults, often with a median onset around nine years in pediatric populations. Tumor size is highly variable, ranging from small nodules to large masses up to 25 centimeters.
Recognizing the Clinical Presentation
Symptoms prompting a medical visit for IMT are often non-specific, creating diagnostic difficulty. The presentation depends on the tumor’s size and location. For instance, a lung tumor might cause a persistent cough or shortness of breath, while an abdominal mass could result in vague, chronic abdominal pain.
The most distinguishing aspect is the presence of systemic inflammatory signs, driven by the immune cells within the tumor. Patients frequently experience constitutional symptoms such as unexplained fever, night sweats, and involuntary weight loss. These systemic effects can mimic an infectious process or an autoimmune condition, delaying diagnosis.
In some cases, the tumor is discovered incidentally during imaging for an unrelated issue. If located in the gastrointestinal tract, symptoms may include obstruction or bleeding. The mass may also be palpable as an abnormal lump or swelling, depending on its depth.
Diagnostic Procedures and Molecular Markers
Diagnosis typically begins with radiological imaging to locate and characterize the mass. Techniques like computed tomography (CT) and magnetic resonance imaging (MRI) determine the tumor’s size, relationship to surrounding organs, and composition. While radiographic features may suggest malignancy due to fibrous content, definitive diagnosis requires a biopsy.
A biopsy obtains a tissue sample for microscopic examination. The pathologist confirms the characteristic mixture of myofibroblastic spindle cells and the prominent plasma cell-rich inflammatory infiltrate. To further characterize the tumor, immunohistochemistry (IHC) staining is performed using antibodies to detect specific proteins.
IHC testing is crucial for identifying the Anaplastic Lymphoma Kinase (ALK) protein, a key molecular marker in IMT. Approximately 50% to 70% of IMTs harbor a genetic rearrangement, or fusion, involving the \(ALK\) gene. This fusion causes the gene to overexpress the ALK protein, driving uncontrolled cell proliferation.
Detecting the ALK protein by IHC or confirming the \(ALK\) gene rearrangement using Fluorescence In Situ Hybridization (FISH) is important for diagnosis and treatment planning. The presence of an \(ALK\) gene fusion is often associated with a more favorable prognosis. If the ALK marker is absent, pathologists may test for other less common gene fusions, such as those involving \(ROS1\) or \(NTRK\) genes, which can also be oncogenic drivers.
Treatment Strategies and Prognosis
The primary treatment for localized IMT is complete surgical resection (R0 resection), which involves removing the entire tumor with a margin of healthy tissue. Complete removal is generally considered curative and provides the best long-term outcome. However, achieving R0 resection can be challenging when the tumor involves vital structures, particularly in the abdomen or retroperitoneum.
For unresectable, recurrent, or metastatic tumors, systemic therapies are the focus. The identification of the \(ALK\) gene fusion provided a targeted treatment option: ALK inhibitors, such as crizotinib. These drugs block the abnormal ALK fusion protein, leading to high response rates in ALK-positive tumors.
Non-surgical management may include steroids or non-steroidal anti-inflammatory drugs (NSAIDs) to manage systemic inflammatory symptoms. While these provide symptomatic relief, they are not definitive treatments for the tumor. Radiation therapy may be considered for local control when surgery is not possible or resection was incomplete.
The overall prognosis for IMT is generally favorable following complete surgical excision. However, local recurrence is a significant risk, especially for tumors in the abdominal and pelvic regions. Patients require close, long-term follow-up monitoring with regular imaging to detect recurrence, which typically occurs within the first few years after treatment.