How should Inflammatory Myofibroblastic Tumor (IMT) be managed given its World Health Organization (WHO) classification as an intermediate (rarely metastasizing) fibroblastic/myofibroblastic neoplasm?

Management of Inflammatory Myofibroblastic Tumor (IMT)

Complete surgical resection is the standard treatment for Inflammatory Myofibroblastic Tumor (IMT), with close monitoring for recurrence due to its WHO classification as an intermediate (rarely metastasizing) fibroblastic/myofibroblastic neoplasm. 1

Understanding IMT Classification and Behavior

• IMT is classified by WHO as an intermediate (rarely metastasizing) fibroblastic/myofibroblastic neoplasm rather than a benign tumor 1
• Metastases are rare, occurring in less than 5% of cases, but local recurrence is common, especially in extrapulmonary IMT (25% of children) 1, 2
• IMT is a locally aggressive neoplasm with a median age at diagnosis of 9 years in children 1, 2
• Common locations include abdomen/pelvis, thorax, and head/neck regions 3

Diagnostic Approach

• Diagnosis requires comprehensive histopathologic evaluation with immunohistochemistry 1
• Approximately 50-60% of IMTs harbor ALK gene rearrangements, with ALK positivity detected by immunohistochemistry 1, 4
• Other molecular alterations may include ROS1 and NTRK gene fusions in ALK-negative tumors 1, 3
• Molecular testing should be performed to identify potential targetable alterations 1, 3

Treatment Algorithm

First-line Treatment

• Complete surgical resection is the standard treatment and is usually curative 1, 2
• Wide excision with negative margins (R0) should be the surgical goal 1
• For unresectable or partially resectable tumors, neoadjuvant therapy may be considered to facilitate subsequent complete resection 3

Management of ALK-positive IMT

• For ALK-positive unresectable or metastatic IMT, ALK inhibitor therapy with crizotinib is FDA-approved 1, 5
• Response rates of >80% have been reported with crizotinib in ALK fusion-positive IMT 1

Management of ALK-negative IMT

• ALK-negative IMTs may have a worse prognosis, with higher risk of metastasis 4
• Consider molecular testing for alternative targetable fusions (ROS1, NTRK) 1, 3
• For NTRK fusion-positive tumors, TRK inhibitors like larotrectinib or entrectinib may be considered 1

Prognostic Factors and Risk Stratification

• ALK-negative status is associated with older age, greater nuclear pleomorphism, and higher risk of metastasis 4
• Abdominal and pelvic IMTs have higher recurrence rates (up to 85%) 4
• Thoracic location is associated with higher risk of recurrence in pediatric patients 3
• Epithelioid variant of IMT with nuclear membrane or perinuclear ALK staining pattern represents a more aggressive subtype ("epithelioid inflammatory myofibroblastic sarcoma") with higher risk of recurrence and mortality 6

Follow-up Recommendations

• Close clinical follow-up is essential due to risk of recurrence 2, 4
• Follow-up should include regular imaging of the primary tumor site 1
• For high-risk tumors (ALK-negative, incomplete resection, epithelioid variant), more intensive surveillance is warranted 4
• Recurrences typically occur within the first 2 years after treatment 3, 4

Special Considerations

• Incomplete surgical resection without adjuvant therapy is associated with higher risk of progression/recurrence 3
• In pediatric patients, organ-sparing approaches should be considered when feasible 3
• Systemic therapy options for recurrent/metastatic disease may include targeted therapy based on molecular profile or conventional chemotherapy 5
• Radiation therapy may be considered for local control in select cases, particularly when combined with targeted therapy 5