a background matrix containing gelatinous mucopolysaccharides and non-sulfated glycosaminoglycans); the matrix also contains inflammatory cells, particularly plasma cells and lymphocytes occasionally mixed with eosinophils and neutrophils. The epithelioid inflammatory myofibroblastic sarcoma subtype of IMT shows sheets of epithelioid to round cells within a myxoid (i.e. appears blue or purple compared to the normal red appearance of connective tissue when appropriately H&E stained and examined under the microscope), collagenous, or mixed myxoid-collagenous matrix, <5% spindle cells, and an inflammatory cell infiltrate that in most cases consists predominantly of neutrophils or, less often, small lymphocytes or eosinophils; plasma cells occur in only a minority of EIMS cases. The neoplastic cells in the tumors of 50% to 60% of IMT cases and 100% of EIMS cases express an ALK fusion protein. Other genetic abnormalities occur in these cells. Testing for the presence of the ALK fusion protein and other genetic abnormalities (see next section) can help diagnose IMT. Treatment
Many sources recommend that localized IMT be treated with total resection of all tumorous tissues. Localized tumor recurrences may likewise be treated by total resection. There is little support for adding radiation or systemic chemotherapy to this regimen. Tumors that are not resectable, occur in inaccessible sites, are multifocal, or have metastasized are treated with aggressive therapeutic regimens.In one retrospective study, 59 patients (all <25 years old) with IMT where treated with surgery. 31 had no residual disease post-surgery; 4 of these patients had local relapses, 3 of whom were again treated surgically and 1 with surgery plus chemotherapy.
A review of previously published IMT patients of all ages found that: 1) 4 patients (3 with unifocal, 1 with multifocal disease) without prior treatment had complete responses to crizotinin; 2) 2 patients (1 with unifocal, 1 with multifocal disease) that had persistent disease after surgery and previously treated with chemotherapy had partial responses to crizotinib while 1 patient previously treated with a corticosteroid, prednisone, continued to have progressive disease on crizotinib; and 3) 6 patients with progressive disease after surgery (due to multifocal or unifocal disease in inaccessible sites) had complete responses (2 cases), partial responses (2 cases), stable disease (1 case), or progressive disease (1 case) in response to crizotinib. Two of these crizotinib-treated patients with progressive disease had near complete responses to second generation ALK inhibitors Another study reviewed 29 pediatric patients (age 15 months to 17 years) who were treated with an ALK inhibitor followed by surgical removal of the tumor (5 cases), surgical tumor removal followed by an ALK inhibitor (12 cases), or an ALK inhibitor without surgery. Twelve patients had complete responses, 14 partial responses, 2 stable disease, and 2 recurrences after finishing ALK inhibitor treatment. The latter two patients obtained complete responses to retreatment with crizotinib (1 case) or a second generation ALK inhibitor, ceritinib (1 case). A study of 14 pediatric patients with metastatic or inoperable ALK-positive IMT were treated with crizotinib: 5 patients obtained complete responses, 7 partial responses, and 2 stable disease. Over the study period (2–63 months), no patient developed progressive disease.