PDGFβ receptor) proteins that contribute to the development and/or progression of IMF.A mutation in one of the two NOTCH3 genes has been reported to occur in a single family with autosomal dominant inheritance of IMF: 9 of this familys members had IMF plus the mutation while 7 of its members did not have IMF or the mutation. Since the mutated NOTCH3 gene in this family produces an overactive neurogenic locus notch homolog protein 3 product that in cell culture studies increases the expression of the PDGFRB genes product, the PDGFβ receptor, this NOTCH3 mutation may promote the development and/or progression of IMF in a manner similar to PDGFRB mutant genes, i.e. by increasing the number and therefore overall activity of the PDGFβ receptor. Further studies are needed to define NOTCH3 gene mutations frequency of occurrence in, and contribution to the development of, IMF. Solitary IMF tumors
Solitary IMF tumors represent 50 to 74% of all IMF cases. These tumors commonly present with a mass that infiltrates the surrounding tissue in the head and neck areas (e.g. in the ethmoid sinus/maxillary sinus, infratemporal fossa, tongue, hard palate, behind an ear, or temporal bone); less commonly in other sites such as the scapula/axilla area, lower back, or soft tissue/bone in the lower leg; and also less commonly in visceral organs such as the pancreas, spleen, lung, or heart. Solitary IMF tumors often (i.e. 25 to 61% of cases in different studies) regress spontaneously.
Cases where surgical resection of a single symptomatic tumor is not a good option and cases with multiple visceral tumors are treated by non-surgical methods. These tumors typically respond to conventional systemic chemotherapy with reductions in their sizes; these responses are usually observed only after several weeks of therapy. Chemotherapy regimes that have successfully treated these cases include low dosage: vincristine plus dactinomycin; vinblastine plus methotrexate; vinblastine plus the glucocorticoid, prednisolone; vincristine plus actinomycin D plus the glucocorticoid, prednisone; and vincristine plus dactinomycin plus cyclophosphamide. A cytokine, interferon alpha, has also been used as a single-drug treatment in at least one of these cases. Multiple tumors (with viscera involvement) have also been treated with surgical resection in combination with these drugs and/or with radiation therapy alone or combined with these drugs.Recently, tyrosine kinase inhibitors have been used to treat PDGFRB-associated IMF cases. Imatinib or imatinib plus a second tyrosine kinase inhibitor, sorafenib, have successful treated several cases and chemotherapy plus imatinib have successfully treated a few cases of life-threatening IMF. Studies suggest that: 1) the tyrosine kinase inhibitor should be selected based on the PDGFRB oncoproteins sensitivity to it (e.g. dasatinib or ponatinib should be used to treat patients with the imatinib-resistant p.Asp850Val PDGFRB gene mutation.